CAP Profiles

Bio

Bio

Prof. Wang directs the Center for Magnetic Nanotechnology and is a leading expert in biosensors, information storage and spintronics. His research and inventions span across a variety of areas including magnetic biochips, in vitro diagnostics, cancer biomarkers, magnetic nanoparticles, magnetic sensors, magnetoresistive random access memory, and magnetic integrated inductors. He has over 300 publications, and holds 65 issued or pending patents in these and interdisciplinary areas. He was named an inaugural Fred Terman Fellow, and was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors. His team won the Grand Challenge Exploration Award from Gates Foundation (2010), the XCHALLENGE Distinguished Award (2014), and the Bold Epic Innovator Award from the XPRIZE Foundation (2017).

Dr. Wang cofounded three high-tech startups in Silicon Valley, including MagArray, Inc. and Flux Biosciences, Inc. In 2018 MagArray launched a first of its kind lung cancer early diagnostic assay based on protein cancer biomarkers and support vector machine (SVM). In 2019, Flux Biosciences launched a human trial to offer at-home testing of fertility based on hormones and magneto-nanosensors. Through his participation in the Center for Cancer Nanotechnology Excellence (as co-PI of the CCNE) and the Joint University Microelectronics Program (JUMP), he is actively engaged in the transformative research of healthcare and is developing emerging memories for energy efficient computing.

Academic Appointments

Administrative Appointments

  • Associate Chair, Materials Science and Engineering (2014 - 2019)

Honors & Awards

  • Leland T. Edwards Professor, Stanford University (2018)
  • Bold Epic Innovator Award (Co-Winner), XPRIZE Foundation (2017)
  • Nokia Sensing XCHALLENGE Distinguished Award, XPRIZE Foundation (2014)
  • Faculty Award, IBM (2013-4)
  • Faculty Fellow, Stanford Center at Peking University (SCPKU) (2013)
  • Fellow, American Physical Society (APS) (2012)
  • Fellow, The Institute of Electrical and Electronics Engineers (IEEE) (2009)
  • Distinguished Lecturer, IEEE Magnetics Society (2001)
  • Partnership Award, IBM (1999)
  • Inaugural Frederick Terman Faculty Fellow, Stanford University (1994-97)
  • CUSPEA Scholarship, Organized by Nobel Laureate TD Lee (1986)

Professional Education

  • PhD, Carnegie Mellon University, Electrical and Computer Engineering (1993)

Community and International Work

  • Fellow, Center for Innovation in Global Health (CIGH), Asia, Africa, America

    Topic

    Mobile Health, POCT

    Partnering Organization(s)

    Stanford University

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Contact

Links

Research & Scholarship

Current Research and Scholarly Interests

Dr. Wang is the Leland T. Edwards Professor in the School of Engineering, Stanford University. He is a Professor of Materials Science & Engineering and jointly a Professor of Electrical Engineering, and by courtesy, a Professor of Radiology (Stanford School of Medicine). He directs the Center for Magnetic Nanotechnology and is a leading expert in biosensors, information storage and spintronics. His research and inventions span across a variety of areas including magnetic biochips, in vitro diagnostics, cancer biomarkers, magnetic nanoparticles, magnetic sensors, magnetoresistive random access memory, and magnetic integrated inductors. He has over 300 publications, and holds 65 issued or pending patents in these and interdisciplinary areas. He was named an inaugural Fred Terman Fellow, and was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors. His team won the Grand Challenge Exploration Award from Gates Foundation (2010), the XCHALLENGE Distinguished Award (2014), and the Bold Epic Innovator Award from the XPRIZE Foundation (2017).

Dr. Wang cofounded three high-tech startups in Silicon Valley, including MagArray, Inc. and Flux Biosciences, Inc. In 2018 MagArray launched a first of its kind lung cancer early diagnostic assay based on protein cancer biomarkers and support vector machine (SVM). In 2019, Flux Biosciences launched a human trial to offer at-home testing of fertility based on hormones and magneto-nanosensors. Through his participation in the Center for Cancer Nanotechnology Excellence (as co-PI of the CCNE) and the Joint University Microelectronics Program (JUMP), he is actively engaged in the transformative research of healthcare and is developing emerging memories for energy efficient computing.

Dr. Wang obtained his PhD in Electrical and Computer Engineering from Carnegie Mellon University in 1993, MS in Physics from Iowa State University in 1988, and BS in Physics from the University of Science and Technology of China in 1986.

Clinical Trials

  • Identification of Circulating Tumor Cells in the Peripheral Blood of Lung Cancer Patients Recruiting

    The primary aim of this study is to determine whether we can identify human lung cancer tumor cells in the peripheral blood of lung cancer patients.

    View full details

Teaching

2020-21 Courses

Stanford Advisees

Graduate and Fellowship Programs

Publications

All Publications

  • Giant Magnetoresistive Nanosensor Analysis of Circulating Tumor DNA Epidermal Growth Factor Receptor Mutations for Diagnosis and Therapy Response Monitoring. Clinical chemistry Nesvet, J. C., Antilla, K. A., Pancirer, D. S., Lozano, A. X., Preiss, J. S., Ma, W., Fu, A., Park, S. M., Gambhir, S. S., Fan, A. C., Neal, J. W., Padda, S. K., Das, M., Li, T., Wakelee, H. A., Wang, S. X. 2021

    Abstract

    Liquid biopsy circulating tumor DNA (ctDNA) mutational analysis holds great promises for precision medicine targeted therapy and more effective cancer management. However, its wide adoption is hampered by high cost and long turnaround time of sequencing assays, or by inadequate analytical sensitivity of existing portable nucleic acid tests to mutant allelic fraction in ctDNA.We developed a ctDNA Epidermal Growth Factor Receptor (EGFR) mutational assay using giant magnetoresistive (GMR) nanosensors. This assay was validated in 36 plasma samples of non-small cell lung cancer patients with known EGFR mutations. We assessed therapy response through follow-up blood draws, determined concordance between the GMR assay and radiographic response, and ascertained progression-free survival of patients.The GMR assay achieved analytical sensitivities of 0.01% mutant allelic fraction. In clinical samples, the assay had 87.5% sensitivity (95% CI = 64.0-97.8%) for Exon19 deletion and 90% sensitivity (95% CI = 69.9-98.2%) for L858R mutation with 100% specificity; our assay detected T790M resistance with 96.3% specificity (95% CI = 81.7-99.8%) with 100% sensitivity. After 2 weeks of therapy, 10 patients showed disappearance of ctDNA by GMR (predicted responders), whereas 3 patients did not (predicted nonresponders). These predictions were 100% concordant with radiographic response. Kaplan-Meier analysis showed responders had significantly (P < 0.0001) longer PFS compared to nonresponders (N/A vs. 12 weeks, respectively).The GMR assay has high diagnostic sensitivity and specificity and is well suited for detecting EGFR mutations at diagnosis and noninvasively monitoring treatment response at the point-of-care.

    View details for DOI 10.1093/clinchem/hvaa307

    View details for PubMedID 33393992

  • A Novel Current Reconstruction Method Based on Elastic Net Regularization IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT Zhao, G., Hu, J., He, J., Wang, S. X. 2020; 69 (10): 7484–93

    View details for DOI 10.1109/TIM.2020.2984819

    View details for Web of Science ID 000571849100015

  • Diagnostics for SARS-CoV-2 detection: A comprehensive review of the FDA-EUA COVID-19 testing landscape. Biosensors & bioelectronics Ravi, N., Cortade, D. L., Ng, E., Wang, S. X. 2020; 165: 112454

    Abstract

    The rapidly spreading outbreak of COVID-19 disease is caused by the SARS-CoV-2 virus, first reported in December 2019 in Wuhan, China. As of June 17, 2020, this virus has infected over 8.2 million people but ranges in symptom severity, making it difficult to assess its overall infection rate. There is a need for rapid and accurate diagnostics to better monitor and prevent the spread of COVID-19. In this review, we present and evaluate two main types of diagnostics with FDA-EUA status for COVID-19: nucleic acid testing for detection of SARS-CoV-2 RNA, and serological assays for detection of SARS-CoV-2 specific IgG and IgM patient antibodies, along with the necessary sample preparation for accurate diagnoses. In particular, we cover and compare tests such as the CDC 2019-nCoV RT-PCR Diagnostic Panel, Cellex's qSARS-CoV-2 IgG/IgM Rapid Test, and point-of-care tests such as Abbott's ID NOW COVID-19 Test. Antibody testing is especially important in understanding the prevalence of the virus in the community and to identify those who have gained immunity. We conclude by highlighting the future of COVID-19 diagnostics, which include the need for quantitative testing and the development of emerging biosensors as point-of-care tests.

    View details for DOI 10.1016/j.bios.2020.112454

    View details for PubMedID 32729549

  • Parametric Reconstruction of Multiple Line Currents Based on Magnetic Sensor Array IEEE TRANSACTIONS ON MAGNETICS Zhao, G., Hu, J., Ma, H., He, J., Wang, S. X. 2020; 56 (7)

    View details for DOI 10.1109/TMAG.2020.2995500

    View details for Web of Science ID 000543621800011

  • Drive-Current-Free Switch With Internal Transduction in a Magneto Piezo-Electronic Transistor IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS Xue, F., Guo, Y., Sato, N., Ouyang, Y., Han, Z., Wang, S. X., Hu, J., He, J. 2020; 67 (4): 3257–66

    View details for DOI 10.1109/TIE.2019.2910050

    View details for Web of Science ID 000507307000072

  • Flow Homogenization Enables a Massively Parallel Fluidic Design for High-Throughput and Multiplexed Cell Isolation ADVANCED MATERIALS TECHNOLOGIES Ooi, C., Earhart, C. M., Hughes, C. E., Lee, J., Wong, D. J., Wilson, R. J., Rohatgi, R., Wang, S. X. 2020

    View details for DOI 10.1002/admt.201900960

    View details for Web of Science ID 000520259400001

  • Publisher Correction: A mountable toilet system for personalized health monitoring via the analysis of excreta. Nature biomedical engineering Park, S. M., Won, D. D., Lee, B. J., Escobedo, D., Esteva, A., Aalipour, A., Ge, T. J., Kim, J. H., Suh, S., Choi, E. H., Lozano, A. X., Yao, C., Bodapati, S., Achterberg, F. B., Kim, J., Park, H., Choi, Y., Kim, W. J., Yu, J. H., Bhatt, A. M., Lee, J. K., Spitler, R., Wang, S. X., Gambhir, S. S. 2020

    Abstract

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    View details for DOI 10.1038/s41551-020-0562-5

    View details for PubMedID 32382068

  • Piezoelectric-Piezoresistive Coupling MEMS Sensors for Measurement of Electric Fields of Broad Bandwidth and Large Dynamic Range IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS Xue, F., Hu, J., Guo, Y., Han, G., Ouyang, Y., Wang, S. X., He, J. 2020; 67 (1): 551–59

    View details for DOI 10.1109/TIE.2019.2893837

    View details for Web of Science ID 000490858500050

  • A mountable toilet system for personalized health monitoring via the analysis of excreta. Nature biomedical engineering Park, S. M., Won, D. D., Lee, B. J., Escobedo, D., Esteva, A., Aalipour, A., Ge, T. J., Kim, J. H., Suh, S., Choi, E. H., Lozano, A. X., Yao, C., Bodapati, S., Achterberg, F. B., Kim, J., Park, H., Choi, Y., Kim, W. J., Yu, J. H., Bhatt, A. M., Lee, J. K., Spitler, R., Wang, S. X., Gambhir, S. S. 2020

    Abstract

    Technologies for the longitudinal monitoring of a person's health are poorly integrated with clinical workflows, and have rarely produced actionable biometric data for healthcare providers. Here, we describe easily deployable hardware and software for the long-term analysis of a user's excreta through data collection and models of human health. The 'smart' toilet, which is self-contained and operates autonomously by leveraging pressure and motion sensors, analyses the user's urine using a standard-of-care colorimetric assay that traces red-green-blue values from images of urinalysis strips, calculates the flow rate and volume of urine using computer vision as a uroflowmeter, and classifies stool according to the Bristol stool form scale using deep learning, with performance that is comparable to the performance of trained medical personnel. Each user of the toilet is identified through their fingerprint and the distinctive features of their anoderm, and the data are securely stored and analysed in an encrypted cloud server. The toilet may find uses in the screening, diagnosis and longitudinal monitoring of specific patient populations.

    View details for DOI 10.1038/s41551-020-0534-9

    View details for PubMedID 32251391

  • Flow Homogenization Enables a Massively Parallel Fluidic Design for High-throughput and Multiplexed Cell Isolation. Advanced materials technologies Ooi, C., Earhart, C. M., Hughes, C. E., Lee, J. R., Wong, D. J., Wilson, R. J., Rohatgi, R., Wang, S. X. 2020; 5 (5)

    Abstract

    Microfluidic devices are widely used for applications such as cell isolation. Currently, the most common method to improve throughput for microfluidic devices involves fabrication of multiple, identical channels in parallel. However, this 'numbering up' only occurs in one dimension, thereby limiting gains in volumetric throughput. In contrast, macro-fluidic devices permit high volumetric flow-rates but lack the finer control of microfluidics. Here, we demonstrate how a micro-pore array design enables flow homogenization across a magnetic cell capture device, thus creating a massively parallel series of micro-scale flow channels with consistent fluidic and magnetic properties, regardless of spatial location. This design enables scaling in 2-dimensions, allowing flow-rates exceeding 100 mL/hr while maintaining >90% capture efficiencies of spiked lung cancer cells from blood in a simulated circulating tumor cell system. Additionally, this design facilitates modularity in operation, which we demonstrate by combining two different devices in tandem for multiplexed cell separation in a single pass with no additional cell losses from processing.

    View details for DOI 10.1002/admt.201900960

    View details for PubMedID 33072854

    View details for PubMedCentralID PMC7567302

  • Early multiplexed detection of cirrhosis by giant magnetoresistive biosensors with protein biomarkers. ACS sensors Ng, E., Le, A. K., Nguyen, M. H., Wang, S. X. 2020

    Abstract

    Liver cirrhosis is one of the leading causes of death in adults worldwide. It is highly prevalent in developing countries and is growing in prevalence in developed countries mostly due to chronic liver diseases, such as chronic hepatitis B and C, and alcoholic and nonalcoholic fatty liver disease. However, the prevalence of cirrhosis may be highly underestimated because early stages are asymptomatic and current early detection methods are inadequate. Here, we evaluate the potential of a set of novel cirrhotic protein biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1) and mac-2 binding protein glycosylation isomer (M2BPGi), for early detection of cirrhosis in a multiplexed assay using our giant magnetoresistive (GMR) sensor arrays. We evaluated the diagnostic performance of the biomarkers, individually and in combination, using multivariate logistic regression and random forest in a blinded proof-of-concept retrospective case-controlled study. The biomarkers in combination exhibited high diagnostic performance in both logistic regression and random forest models, with area under the curve (AUC) of 0.98 (0.94 - 1.00). In addition, the combination of biomarkers resulted in high sensitivity of 0.97 (0.95 - 1.00) and high specificity of 1.00. We showed that the diagnostic performance of our novel set of cirrhotic protein biomarkers on our multiplexed GMR sensor arrays is higher than the performance of currently used clinical biomarkers and factors (i.e. age, sex, alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc.). With this combination of novel biomarkers and the GMR technology, we could potentially boost the diagnostic power of early cirrhosis detection.

    View details for DOI 10.1021/acssensors.0c00232

    View details for PubMedID 32896123

  • Carbon-coated FeCo nanoparticles as sensitive magnetic-particle-imaging tracers with photothermal and magnetothermal properties. Nature biomedical engineering Song, G., Kenney, M., Chen, Y. S., Zheng, X., Deng, Y., Chen, Z., Wang, S. X., Gambhir, S. S., Dai, H., Rao, J. 2020

    Abstract

    The low magnetic saturation of iron oxide nanoparticles, which are developed primarily as contrast agents for magnetic resonance imaging, limits the sensitivity of their detection using magnetic particle imaging (MPI). Here, we show that FeCo nanoparticles that have a core diameter of 10 nm and bear a graphitic carbon shell decorated with poly(ethylene glycol) provide an MPI signal intensity that is sixfold and fifteenfold higher than the signals from the superparamagnetic iron oxide tracers VivoTrax and Feraheme, respectively, at the same molar concentration of iron. We also show that the nanoparticles have photothermal and magnetothermal properties and can therefore be used for tumour ablation in mice, and that they have high optical absorbance in a broad near-infrared region spectral range (wavelength, 700-1,200 nm), making them suitable as tracers for photoacoustic imaging. As sensitive multifunctional and multimodal imaging tracers, carbon-coated FeCo nanoparticles may confer advantages in cancer imaging and hyperthermia therapy.

    View details for DOI 10.1038/s41551-019-0506-0

    View details for PubMedID 32015409

  • Method of inter-turn fault detection for next-generation smart transformers based on deep learning algorithm HIGH VOLTAGE Duan, L., Hu, J., Zhao, G., Chen, K., Wang, S. X., He, J. 2019; 4 (4): 282–91

    View details for DOI 10.1049/hve.2019.0067

    View details for Web of Science ID 000506150400005

  • Efficient spin current generation in low-damping Mg(Al, Fe)(2)O-4 thin films APPLIED PHYSICS LETTERS Riddiford, L. J., Wisser, J. J., Emori, S., Li, P., Roy, D., Cogulu, E., van't Erve, O., Deng, Y., Wang, S. X., Jonker, B. T., Kent, A. D., Suzuki, Y. 2019; 115 (12)

    View details for DOI 10.1063/1.5119726

    View details for Web of Science ID 000487038900007

  • Current sensors based on GMR effect for smart grid applications SENSORS AND ACTUATORS A-PHYSICAL Ouyang, Y., Wang, Z., Zhao, G., Hu, J., Ji, S., He, P., Wang, S. X. 2019; 294: 8–16

    View details for DOI 10.1016/j.sna.2019.05.002

    View details for Web of Science ID 000472988800002

  • Identification of Partial Discharge Defects Based on Deep Learning Method IEEE TRANSACTIONS ON POWER DELIVERY Duan, L., Hu, J., Zhao, G., Chen, K., He, J., Wang, S. X. 2019; 34 (4): 1557–68

    View details for DOI 10.1109/TPWRD.2019.2910583

    View details for Web of Science ID 000477724800038

  • Overhead Transmission Line Parameter Reconstruction for UAV Inspection Based on Tunneling Magnetoresistive Sensors and Inverse Models IEEE TRANSACTIONS ON POWER DELIVERY Wu, Y., Zhao, G., Hu, J., Ouyang, Y., Wang, S. X., He, J., Gao, F., Wang, S. 2019; 34 (3): 819–27

    View details for DOI 10.1109/TPWRD.2019.2891119

    View details for Web of Science ID 000469337200004

  • Magnetoresistive Sensor Development Roadmap (Non-Recording Applications) IEEE TRANSACTIONS ON MAGNETICS Zheng, C., Zhu, K., de Freitas, S., Chang, J., Davies, J. E., Eames, P., Freitas, P. P., Kazakova, O., Kim, C., Leung, C., Liou, S., Ognev, A., Piramanayagam, S. N., Ripka, P., Samardak, A., Shin, K., Tong, S., Tung, M., Wang, S. X., Xue, S., Yin, X., Pong, P. T. 2019; 55 (4)

    View details for DOI 10.1109/TMAG.2019.2896036

    View details for Web of Science ID 000461841100001

  • Self-healing of electrical damage in polymers using superparamagnetic nanoparticles NATURE NANOTECHNOLOGY Yang, Y., He, J., Li, Q., Gao, L., Hu, J., Zeng, R., Qin, J., Wang, S. X., Wang, Q. 2019; 14 (2): 151-+

    View details for DOI 10.1038/s41565-018-0327-4

    View details for Web of Science ID 000457765800017

  • Magneto-nanosensor smartphone platform for the detection of HIV and leukocytosis at point-of-care NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE Ng, E., Yao, C., Shultz, T. O., Ross-Howe, S., Wang, S. X. 2019; 16: 10–19

    View details for DOI 10.1016/j.nano.2018.11.007

    View details for Web of Science ID 000460167000002

  • Highly sensitive detection of DNA hypermethylation in melanoma cancer cells BIOSENSORS & BIOELECTRONICS Nesvet, J., Rizzi, G., Wang, S. X. 2019; 124: 136–42

    View details for DOI 10.1016/j.bios.2018.10.018

    View details for Web of Science ID 000451935500017

  • An electrodynamic energy harvester with a 3D printed magnet and optimized topology APPLIED PHYSICS LETTERS Wang, Z., Huber, C., Hu, J., He, J., Suess, D., Wang, S. X. 2019; 114 (1)

    View details for DOI 10.1063/1.5074123

    View details for Web of Science ID 000455893000049

  • Improved detection of prostate cancer using a magneto-nanosensor assay for serum circulating autoantibodies. PloS one Xu, L., Lee, J., Hao, S., Ling, X. B., Brooks, J. D., Wang, S. X., Gambhir, S. S. 2019; 14 (8): e0221051

    Abstract

    PURPOSE: To develop a magneto-nanosensor (MNS) based multiplex assay to measure protein and autoantibody biomarkers from human serum for prostate cancer (CaP) diagnosis.MATERIALS AND METHODS: A 4-panel MNS autoantibody assay and a MNS protein assay were developed and optimized in our labs. Using these assays, serum concentration of six biomarkers including prostate-specific antigen (PSA) protein, free/total PSA ratio, as well as four autoantibodies against Parkinson disease 7 (PARK7), TAR DNA-binding protein 43 (TARDBP), Talin 1 (TLN1), and Caldesmon 1 (CALD1) and were analyzed. Human serum samples from 99 patients (50 with non-cancer and 49 with clinically localized CaP) were evaluated.RESULTS: The MNS assay showed excellent performance characteristics and no cross-reactivity. All autoantibody assays showed a statistically significant difference between CaP and non-cancer samples except for PARK7. The most significant difference was the combination of the four autoantibodies as a panel in addition to the free/total PSA ratio. This combination had the highest area under the curve (AUC)- 0.916 in ROC analysis.CONCLUSIONS: Our results suggest that this autoantibody panel along with PSA and free PSA have potential to segregate patients without cancer from those with prostate cancer with higher sensitivity and specificity than PSA alone.

    View details for DOI 10.1371/journal.pone.0221051

    View details for PubMedID 31404106

  • An Automated, Quantitative, and Multiplexed Assay Suitable for Point-of-Care Hepatitis B Virus Diagnostics. Scientific reports Gani, A. W., Wei, W., Shi, R. Z., Ng, E., Nguyen, M., Chua, M. S., So, S., Wang, S. X. 2019; 9 (1): 15615

    Abstract

    Hepatitis B virus (HBV) infection has a global reach with high prevalence in resource-limited areas like China and Africa. HBV patients in these areas have limited access to the currently used, costly HBV assays, which are performed in centralized clinical laboratories using single-plexed assays with bulky and expensive instruments. We aim to overcome these limitations by developing a simple and affordable HBV diagnostic platform to allow for timelier diagnosis and intervention of HBV infection. Using giant magnetoresistive (GMR) biosensor chips, we developed an automated and multiplexed quantitative platform for the measurement of a panel of HBV serology markers, including HBV "e" antigen (HBeAg), HBV surface antigen (HBsAg), and the antibody against HBsAg (anti-HBs). Our assay platform was able to detect each HBV marker with high specificity and sensitivity (with three orders of magnitude in dynamic range for each marker). Blinded analysis of HBV patient sera showed excellent correlation between our multiplexed quantitative HBsAg results and the qualitative results obtained using FDA-approved immunoassays, as well as those obtained using quantitative, single-plexed, enzyme-linked immunosorbent assays (ELISAs). The portable, automated, multiplexed, quantitative HBV serology assay platform we designed shows great promise as a more accessible alternative for HBV screening, diagnosis, and treatment monitoring.

    View details for DOI 10.1038/s41598-019-52147-z

    View details for PubMedID 31666635

  • In Vitro Cancer Diagnostics NANOTHERANOSTICS FOR CANCER APPLICATIONS Lee, J., Ooi, C., Wang, S. X., Rai, P., Morris, S. A. 2019; 5: 109–32

    View details for DOI 10.1007/978-3-030-01775-0_6

    View details for Web of Science ID 000576804300006

  • GMR Spin-Valve Biosensors SPINTRONICS HANDBOOK: SPIN TRANSPORT AND MAGNETISM: NANOSCALE SPINTRONICS AND APPLICATIONS, VOL 3, 2ND EDITION Lee, J., Gaster, R. S., Hall, D. A., Wang, S. X., Tsymbal, E. Y., Zutic 2019: 471–97

    View details for Web of Science ID 000576730200017

  • Self-healing of electrical damage in polymers using superparamagnetic nanoparticles. Nature nanotechnology Yang, Y., He, J., Li, Q., Gao, L., Hu, J., Zeng, R., Qin, J., Wang, S. X., Wang, Q. 2018

    Abstract

    High-voltage power transmission in electrical grids requires reliable and durable dielectric polymers for wire insulation1,2. Electrical treeing caused by high, local electric fields is a damaging process that leads to structure degradation and electrical conduction of dielectric materials, and ultimately, to catastrophic failure of the devices3-5. Here, we demonstrate that the addition of less than 0.1 volume per cent of superparamagnetic nanoparticles into a thermoplastic polymer enables the repair of regions damaged by electrical treeing and the restoration of the insulating properties. Under the application of an oscillating magnetic field, the embedded nanoparticles migrate to the electrical trees and generate a higher local temperature, which heals the electrical tree channels in the polymer. Our method allows us to regenerate the dielectric strength and electrical resistivity over multiple cycles of tree formation and healing, which could be used to increase the lifespan and sustainability of power cables for electronics and energy applications.

    View details for PubMedID 30598524

  • Magneto-nanosensor Smartphone Platform for the Detection of HIV and Leukocytosis at Point-of-Care. Nanomedicine : nanotechnology, biology, and medicine Ng, E., Yao, C., Shultz, T. O., Ross-Howe, S., Wang, S. X. 2018

    Abstract

    The advent of personalized medicine has brought an increased interest in personal health among general consumers. As a result, there is a great need for user-centric point-of-care (POC) health devices. Such devices are equally pertinent in developing countries or resource-limited settings for performing diagnostic tests. However, current POC tests for diseases such as human immunodeficiency virus (HIV) or leukocytosis, do not provide adequate levels of sensitivity or do not exist at all. Here, we extend our mobile magneto-nanosensor platform to point-of-care HIV and leukocytosis detection. The platform can be multiplexed, and the circuitry enables portability and sensitivity in the POC setting. A smartphone application simplifies operation and provides guidance to facilitate self-testing. Commercially available POC test kits typically provide only qualitative or semi-quantitative results of a single analyte. The magneto-nanosensor platform can provide users with pleasant user-experience while demonstrating robust sensitive and specific multiplexed quantification and detection of common diseases.

    View details for PubMedID 30502420

  • Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling SCIENTIFIC REPORTS Kim, K., Hall, D. A., Yao, C., Lee, J., Ooi, C. C., Bechstein, D. B., Guo, Y., Wang, S. X. 2018; 8

    View details for DOI 10.1038/s41598-018-34720-0

    View details for Web of Science ID 000449367700039

  • Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling. Scientific reports Kim, K., Hall, D. A., Yao, C., Lee, J., Ooi, C. C., Bechstein, D. J., Guo, Y., Wang, S. X. 2018; 8 (1): 16493

    Abstract

    Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20ms, approximately 50* faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings.

    View details for PubMedID 30405155

  • Highly sensitive detection of DNA hypermethylation in melanoma cancer cells. Biosensors & bioelectronics Nesvet, J., Rizzi, G., Wang, S. X. 2018; 124-125: 136–42

    Abstract

    Aberrant hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a promising biomarker for early cancer detection. This methylation status is reflected in the methylation pattern of ctDNA shed from the primary tumor; however, to realize the full clinical utility of ctDNA methylation detection via liquid biopsy for early cancer diagnosis, improvements in the sensitivity and multiplexability of existing technologies must be improved. Additionally, the assay must be cheap and easy to perform in a clinical setting. We report the integration of methylation specific PCR (MSP) to melt curve analysis on giant magnetoresistive (GMR) biosensors to greatly enhance the sensitivity of our DNA hybridization assay for methylation detection. Our GMR sensor is functionalized with synthetic DNA probes that target methylated or unmethylated CpG sites in the MSP amplicon, and measures the difference in melting temperature (Tm) between the two probes (DeltaTm), giving an analytical limit of detection down to 0.1% methylated DNA in solution. Additionally, linear regression of DeltaTm's for serial dilutions of methylated:unmethylated mixtures allows for quantification of methylation percentage, which could have diagnostic and prognostic utility. Lastly, we performed multiplexed MSP on two different genes, and show the ability of our GMR assay to resolve this mixture, despite their amplicons' overlapping Tm's in standard EvaGreen melt analysis. The multiplexing ability of our assay and its enhanced sensitivity, without necessitating deep sequencing, represent important steps toward realizing an assay for the detection of methylated ctDNA in plasma for early cancer detection in a clinical setting.

    View details for PubMedID 30366258

  • Quantification of cDNA on GMR biosensor array towards point-of-care gene expression analysis. Biosensors & bioelectronics Ravi, N., Rizzi, G., Chang, S. E., Cheung, P., Utz, P. J., Wang, S. X. 2018

    Abstract

    Gene expression analysis at the point-of-care is important for rapid disease diagnosis, but traditional techniques are limited by multiplexing capabilities, bulky equipment, and cost. We present a gene expression analysis platform using a giant magnetoresistive (GMR) biosensor array, which allows multiplexed transcript detection and quantification through cost-effective magnetic detection. In this work, we have characterized the sensitivity, dynamic range, and quantification accuracy of Polymerase chain reaction (PCR)-amplified complementary DNA (cDNA) on the GMR for the reference gene GAPDH. A synthetic GAPDH single-stranded DNA (ssDNA) standard was used to calibrate the detection, and ssDNA dilutions were qPCR-amplified to obtain a standard curve. We demonstrate that the GMR platform provides a dynamic range of 4 orders of magnitude and a limit of detection of 1 pM and 0.1 pM respectively for 15 and 18-cycle amplified synthetic GAPDH PCR products. The quantitative results of GMR analysis of cell-line RNA were confirmed by qPCR.

    View details for PubMedID 30269961

  • An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo NATURE BIOMEDICAL ENGINEERING Vermesh, O., Aalipour, A., Ge, T., Saenz, Y., Guo, Y., Alam, I. S., Park, S., Adelson, C. N., Mitsutake, Y., Vilches-Moure, J., Godoy, E., Bachmann, M. H., Ooi, C., Lyons, J. K., Mueller, K., Arami, H., Green, A., Solomon, E., Wang, S. X., Gambhir, S. S. 2018; 2 (9): 696–705

    View details for DOI 10.1038/s41551-018-0257-3

    View details for Web of Science ID 000444282800014

  • Two-terminal spin-orbit torque magnetoresistive random access memory NATURE ELECTRONICS Sato, N., Xue, F., White, R. M., Bi, C., Wang, S. X. 2018; 1 (9): 508–11

    View details for DOI 10.1038/s41928-018-0131-z

    View details for Web of Science ID 000454039700014

  • A blood biomarker for monitoring response to anti-EGFR therapy. Cancer biomarkers : section A of Disease markers Hughes, N. P., Xu, L., Nielsen, C. H., Chang, E., Hori, S. S., Natarajan, A., Lee, S., Kjar, A., Kani, K., Wang, S. X., Mallick, P., Gambhir, S. S. 2018

    Abstract

    BACKGROUND AND OBJECTIVE: To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents.METHODS: We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment.RESULTS: PRDX6 levels in cell media from sensitive cell lines increased significantly after gefitinib treatment vs. vehicle, whereas there was no significant difference for resistant lines. PRDX6 accumulation over time correlated positively with gefitinib sensitivity. Serum PRDX6 levels in gefitinib-sensitive xenograft models increased markedly during the first 24 hours of treatment and then decreased dramatically during the following 48 hours. Differences in serum PRDX6 levels between vehicle and gefitinib-treated animals could not be explained by differences in tumor burden.CONCLUSIONS: Our results show that changes in serum PRDX6 during the course of gefitinib treatment of xenograft models provide insight into tumor response and such an approach offers several advantages over imaging-based strategies for monitoring response to anti-EGFR agents.

    View details for PubMedID 29689709

  • Learning-based Data Analytics: Moving Towards Transparent Power Grids CSEE JOURNAL OF POWER AND ENERGY SYSTEMS Chen, K., He, Z., Wang, S. X., Hu, J., Li, L., He, J. 2018; 4 (1): 67–82

    View details for DOI 10.17775/CSEEJPES.2017.01070

    View details for Web of Science ID 000435855400008

  • A blood biomarker for monitoring response to anti-EGFR therapy CANCER BIOMARKERS Hughes, N. P., Xu, L., Nielsen, C. H., Chang, E., Hori, S. S., Natarajan, A., Lee, S., Kjaer, A., Kani, K., Wang, S. X., Mallick, P., Gambhir, S. 2018; 22 (2): 333–44

    View details for DOI 10.3233/CBM-171149

    View details for Web of Science ID 000437251500016

  • An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nature biomedical engineering Vermesh, O., Aalipour, A., Ge, T. J., Saenz, Y., Guo, Y., Alam, I. S., Park, S., Adelson, C. N., Mitsutake, Y., Vilches-Moure, J., Godoy, E., Bachmann, M., Ooi, C. C., Lyons, J. K., Mueller, K., Arami, H., Green, A., Solomon, E. I., Wang, S. X., Gambhir, S. S. 2018; 2: 696–705

    Abstract

    The detection and analysis of rare blood biomarkers is necessary for early cancer diagnosis and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumor cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 mL of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. We have developed a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labeled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labeling and single-pass capture of viable model CTCs in less than 10 seconds. The wire achieves capture efficiencies that correspond to enrichments of 10-80 times the amount of CTCs in a 5-mL blood draw, and to 500-5,000 times the enrichments achieved by the commercially available Gilupi CellCollector.

    View details for PubMedID 30524876

  • Gigahertz-Band Integrated Magnetic Inductors IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES El-Ghazaly, A., White, R. M., Wang, S. X. 2017; 65 (12): 4893–4900

    View details for DOI 10.1109/TMTT.2017.2728040

    View details for Web of Science ID 000418391300013

  • Denaturation strategies for detection of double stranded PCR products on GMR magnetic biosensor array BIOSENSORS & BIOELECTRONICS Rizzi, G., Lee, J., Guldberg, P., Dufva, M., Wang, S. X., Hansen, M. F. 2017; 93: 155-160

    Abstract

    Microarrays and other surface-based nucleic acid detection schemes rely on the hybridization of the target to surface-bound detection probes. We present the first comparison of two strategies to detect DNA using a giant magnetoresistive (GMR) biosensor platform starting from an initially double-stranded DNA target. The target strand of interest is biotinylated and detected by the GMR sensor by linking streptavidin magnetic nanoparticles (MNPs) to the sensor surface. The sensor platform has a dynamic detection range from 40pM to 40nM with highly reproducible results and is used to monitor real-time binding signals. The first strategy, using off-chip heat denaturation followed by sequential on-chip incubation of the nucleic acids and MNPs, produces a signal that stabilizes quickly but the signal magnitude is reduced due to competitive rehybridization of the target in solution. The second strategy, using magnetic capture of the double-stranded product followed by denaturing, produces a higher signal but the signal increase is limited by diffusion of the MNPs. Our results show that both strategies give highly reproducible results but that the signal obtained using magnetic capture is higher and insensitive to rehybridization.

    View details for DOI 10.1016/j.bios.2016.09.031

    View details for Web of Science ID 000399259000022

  • Capture and Genetic Analysis of Circulating Tumor Cells Using a Magnetic Separation Device (Magnetic Sifter). Methods in molecular biology (Clifton, N.J.) Ooi, C. C., Park, S. M., Wong, D. J., Gambhir, S. S., Wang, S. X. 2017; 1634: 153–62

    Abstract

    Circulating tumor cells (CTCs) are currently widely studied for their potential application as part of a liquid biopsy. These cells are shed from the primary tumor into the circulation, and are postulated to provide insight into the molecular makeup of the actual tumor in a minimally invasive manner. However, they are extremely rare in blood, with typical concentrations of 1-100 in a milliliter of blood; hence, a need exists for a rapid and high-purity method for isolating CTCs from whole blood. Here, we describe the application of a microfabricated magnetic sifter toward isolation of CTCs from whole blood at volumetric flow rates of 10 mL/h, along with the use of a PDMS-based nanowell system for single-cell gene expression profiling. This method allows rapid isolation of CTCs and subsequent integration with downstream genetic profiling methods for clinical applications such as targeted therapy, therapy monitoring, or further biological studies.

    View details for PubMedID 28819848

  • Simultaneous Profiling of DNA Mutation and Methylation by Melting Analysis Using Magnetoresistive Biosensor Array. ACS nano Rizzi, G., Lee, J. R., Dahl, C., Guldberg, P., Dufva, M., Wang, S. X., Hansen, M. F. 2017; 11 (9): 8864–70

    Abstract

    Epigenetic modifications, in particular DNA methylation, are gaining increasing interest as complementary information to DNA mutations for cancer diagnostics and prognostics. We introduce a method to simultaneously profile DNA mutation and methylation events for an array of sites with single site specificity. Genomic (mutation) or bisulphite-treated (methylation) DNA is amplified using nondiscriminatory primers, and the amplicons are then hybridized to a giant magnetoresistive (GMR) biosensor array followed by melting curve measurements. The GMR biosensor platform offers scalable multiplexed detection of DNA hybridization, which is insensitive to temperature variation. The melting curve approach further enhances the assay specificity and tolerance to variations in probe length. We demonstrate the utility of this method by simultaneously profiling five mutation and four methylation sites in human melanoma cell lines. The method correctly identified all mutation and methylation events and further provided quantitative assessment of methylation density validated by bisulphite pyrosequencing.

    View details for PubMedID 28832112

  • Capture and Genetic Analysis of Circulating Tumor Cells Using a Magnetic Separation Device (Magnetic Sifter) CIRCULATING TUMOR CELLS: METHODS AND PROTOCOLS Ooi, C., Park, S., Wong, D. J., Gambhir, S. S., Wang, S. X., Magbanua, M. J., Park, J. W. 2017; 1634: 153–62

    View details for DOI 10.1007/978-1-4939-7144-2_12

    View details for Web of Science ID 000449398600014

  • Simultaneous Profiling of DNA Mutation and Methylation by Melting Analysis Using Magnetoresistive Biosensor Array ACS Nano Rizzi, G., Lee, J., Dahl, C., Guldberg, P., Dufva, M., Wang, S. X. 2017; 11 (9): 8864–8870

    Abstract

    Epigenetic modifications, in particular DNA methylation, are gaining increasing interest as complementary information to DNA mutations for cancer diagnostics and prognostics. We introduce a method to simultaneously profile DNA mutation and methylation events for an array of sites with single site specificity. Genomic (mutation) or bisulphite-treated (methylation) DNA is amplified using nondiscriminatory primers, and the amplicons are then hybridized to a giant magnetoresistive (GMR) biosensor array followed by melting curve measurements. The GMR biosensor platform offers scalable multiplexed detection of DNA hybridization, which is insensitive to temperature variation. The melting curve approach further enhances the assay specificity and tolerance to variations in probe length. We demonstrate the utility of this method by simultaneously profiling five mutation and four methylation sites in human melanoma cell lines. The method correctly identified all mutation and methylation events and further provided quantitative assessment of methylation density validated by bisulphite pyrosequencing.

    View details for DOI 10.1021/acsnano.7b03053

    View details for PubMedCentralID PMC5810360

  • Multigene profiling of single circulating tumor cells. Molecular & cellular oncology Park, S., Wong, D. J., Ooi, C. C., Nesvet, J. C., Nair, V. S., Wang, S. X., Gambhir, S. S. 2017; 4 (2)

    Abstract

    Numerous techniques for isolating circulating tumor cells (CTCs) have been developed. Concurrently, single-cell techniques that can reveal molecular components of CTCs have become widely available. We discuss how the combination of isolation and multigene profiling of single CTCs in our platform can facilitate eventual translation to the clinic.

    View details for DOI 10.1080/23723556.2017.1289295

    View details for PubMedID 28401190

    View details for PubMedCentralID PMC5383366

  • High-throughput full-length single-cell mRNA-seq of rare cells. PloS one Ooi, C. C., Mantalas, G. L., Koh, W., Neff, N. F., Fuchigami, T., Wong, D. J., Wilson, R. J., Park, S. M., Gambhir, S. S., Quake, S. R., Wang, S. X. 2017; 12 (11): e0188510

    Abstract

    Single-cell characterization techniques, such as mRNA-seq, have been applied to a diverse range of applications in cancer biology, yielding great insight into mechanisms leading to therapy resistance and tumor clonality. While single-cell techniques can yield a wealth of information, a common bottleneck is the lack of throughput, with many current processing methods being limited to the analysis of small volumes of single cell suspensions with cell densities on the order of 107 per mL. In this work, we present a high-throughput full-length mRNA-seq protocol incorporating a magnetic sifter and magnetic nanoparticle-antibody conjugates for rare cell enrichment, and Smart-seq2 chemistry for sequencing. We evaluate the efficiency and quality of this protocol with a simulated circulating tumor cell system, whereby non-small-cell lung cancer cell lines (NCI-H1650 and NCI-H1975) are spiked into whole blood, before being enriched for single-cell mRNA-seq by EpCAM-functionalized magnetic nanoparticles and the magnetic sifter. We obtain high efficiency (> 90%) capture and release of these simulated rare cells via the magnetic sifter, with reproducible transcriptome data. In addition, while mRNA-seq data is typically only used for gene expression analysis of transcriptomic data, we demonstrate the use of full-length mRNA-seq chemistries like Smart-seq2 to facilitate variant analysis of expressed genes. This enables the use of mRNA-seq data for differentiating cells in a heterogeneous population by both their phenotypic and variant profile. In a simulated heterogeneous mixture of circulating tumor cells in whole blood, we utilize this high-throughput protocol to differentiate these heterogeneous cells by both their phenotype (lung cancer versus white blood cells), and mutational profile (H1650 versus H1975 cells), in a single sequencing run. This high-throughput method can help facilitate single-cell analysis of rare cell populations, such as circulating tumor or endothelial cells, with demonstrably high-quality transcriptomic data.

    View details for PubMedID 29186152

    View details for PubMedCentralID PMC5706670

  • Longitudinal Monitoring of Antibody Responses against Tumor Cells Using Magneto-nanosensors with a Nanoliter of Blood. Nano letters Lee, J. R., Chan, C. T., Ruderman, D., Chuang, H. Y., Gaster, R. S., Atallah, M., Mallick, P., Lowe, S. W., Gambhir, S. S., Wang, S. X. 2017; 17 (11): 6644–52

    Abstract

    Each immunoglobulin isotype has unique immune effector functions. The contribution of these functions in the elimination of pathogens and tumors can be determined by monitoring quantitative temporal changes in isotype levels. Here, we developed a novel technique using magneto-nanosensors based on the effect of giant magnetoresistance (GMR) for longitudinal monitoring of total and antigen-specific isotype levels with high precision, using as little as 1 nL of serum. Combining in vitro serologic measurements with in vivo imaging techniques, we investigated the role of the antibody response in the regression of firefly luciferase (FL)-labeled lymphoma cells in spleen, kidney, and lymph nodes in a syngeneic Burkitt's lymphoma mouse model. Regression status was determined by whole body bioluminescent imaging (BLI). The magneto-nanosensors revealed that anti-FL IgG2a and total IgG2a were elevated and sustained in regression mice compared to non-regression mice (p < 0.05). This platform shows promise for monitoring immunotherapy, vaccination, and autoimmunity.

    View details for PubMedID 28990786

  • Molecular profiling of single circulating tumor cells from lung cancer patients PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Park, S., Wong, D. J., Ooi, C. C., Kurtz, D. M., Vermesh, O., Aalipour, A., Suh, S., Pian, K. L., Chabon, J. J., Lee, S. H., Jamali, M., Say, C., Carter, J. N., Lee, L. P., Kuschner, W. G., Schwartz, E. J., Shrager, J. B., Neal, J. W., Wakelee, H. A., Diehn, M., Nair, V. S., Wang, S. X., Gambhir, S. S. 2016; 113 (52): E8379-E8386

    Abstract

    Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.

    View details for DOI 10.1073/pnas.1608461113

    View details for PubMedID 27956614

  • Portable, one-step, and rapid GMR biosensor platform with smartphone interface. Biosensors & bioelectronics Choi, J., Gani, A. W., Bechstein, D. J., Lee, J., Utz, P. J., Wang, S. X. 2016; 85: 1-7

    Abstract

    Quantitative immunoassay tests in clinical laboratories require trained technicians, take hours to complete with multiple steps, and the instruments used are generally immobile-patient samples have to be sent in to the labs for analysis. This prevents quantitative immunoassay tests to be performed outside laboratory settings. A portable, quantitative immunoassay device will be valuable in rural and resource-limited areas, where access to healthcare is scarce or far away. We have invented Eigen Diagnosis Platform (EDP), a portable quantitative immunoassay platform based on Giant Magnetoresistance (GMR) biosensor technology. The platform does not require a trained technician to operate, and only requires one-step user involvement. It displays quantitative results in less than 15min after sample insertion, and each test costs less than US$4. The GMR biosensor employed in EDP is capable of detecting multiple biomarkers in one test, enabling a wide array of immune diagnostics to be performed simultaneously. In this paper, we describe the design of EDP, and demonstrate its capability. Multiplexed assay of human immunoglobulin G and M (IgG and IgM) antibodies with EDP achieves sensitivities down to 0.07 and 0.33 nanomolar, respectively. The platform will allow lab testing to be performed in remote areas, and open up applications of immunoassay testing in other non-clinical settings, such as home, school, and office.

    View details for DOI 10.1016/j.bios.2016.04.046

    View details for PubMedID 27148826

  • Denaturation strategies for detection of double stranded PCR products on GMR magnetic biosensor array. Biosensors & bioelectronics Rizzi, G., Lee, J., Guldberg, P., Dufva, M., Wang, S. X., Hansen, M. F. 2016

    Abstract

    Microarrays and other surface-based nucleic acid detection schemes rely on the hybridization of the target to surface-bound detection probes. We present the first comparison of two strategies to detect DNA using a giant magnetoresistive (GMR) biosensor platform starting from an initially double-stranded DNA target. The target strand of interest is biotinylated and detected by the GMR sensor by linking streptavidin magnetic nanoparticles (MNPs) to the sensor surface. The sensor platform has a dynamic detection range from 40pM to 40nM with highly reproducible results and is used to monitor real-time binding signals. The first strategy, using off-chip heat denaturation followed by sequential on-chip incubation of the nucleic acids and MNPs, produces a signal that stabilizes quickly but the signal magnitude is reduced due to competitive rehybridization of the target in solution. The second strategy, using magnetic capture of the double-stranded product followed by denaturing, produces a higher signal but the signal increase is limited by diffusion of the MNPs. Our results show that both strategies give highly reproducible results but that the signal obtained using magnetic capture is higher and insensitive to rehybridization.

    View details for DOI 10.1016/j.bios.2016.09.031

    View details for PubMedID 27650710

  • Small Molecule Detection in Saliva Facilitates Portable Tests of Marijuana Abuse. Analytical chemistry Lee, J., Choi, J., Shultz, T. O., Wang, S. X. 2016; 88 (15): 7457-7461

    Abstract

    As medical and recreational use of cannabis, or marijuana, becomes more prevalent, law enforcement needs a tool to evaluate whether drivers are operating vehicles under the influence of cannabis, specifically the psychoactive substance, tetrahydrocannabinol (THC). However, the cutoff concentration of THC that causes impairment is still controversial, and current on-site screening tools are not sensitive enough to detect trace amounts of THC in oral fluids. Here we present a novel sensing platform that employs giant magnetoresistive (GMR) biosensors integrated with a portable reader system and smartphone to detect THC in saliva using competitive assays. With a simple saliva collection scheme, we have optimized the assay to measure THC in the range from 0 to 50 ng/mL, covering most cutoff values proposed in previous studies. This work facilitates on-site screening for THC and shows potential for testing of other small molecule drugs and analytes in point-of-care (POC) settings.

    View details for DOI 10.1021/acs.analchem.6b01688

    View details for PubMedID 27434697

  • Effect of Mg Oxidation Degree on Rashba-Effect-Induced Torques in Ta/CoFeB/Mg(MgO) Multilayer IEEE TRANSACTIONS ON MAGNETICS Sato, N., El-Ghazaly, A., White, R. M., Wang, S. X. 2016; 52 (7)

    View details for DOI 10.1109/TMAG.2016.2515025

    View details for Web of Science ID 000379924800013

  • Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection BIOSENSORS & BIOELECTRONICS Ng, E., Nadeau, K. C., Wang, S. X. 2016; 80: 359-365

    Abstract

    Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive and specific detection of multiple food allergens is thus imperative as food allergies are becoming increasingly recognized as a major healthcare concern, affecting an estimated 4% of the total population. We demonstrate first instance of sensitive and specific multiplexed detection of major peanut allergens Ara h 1 and Ara h 2, and wheat allergen Gliadin using giant magnetoresistive (GMR) sensor arrays. Commercialized ELISA kits for Ara h 1 and Ara h 2 report limits of detection (LODs) at 31.5 ng/mL and 0.2 ng/mL, respectively. In addition, the 96-well-based ELISA developed in-house for Gliadin was found to have a LOD of 40 ng/mL. Our multiplexed GMR-based assay demonstrates the ability to perform all three assays on the same chip specifically and with sensitivities at LODs about an order of magnitude lower than those of 96-well-based ELISAs. LODs of GMR-based assays developed for Ara h 1, Ara h 2, and Gliadin were 7.0 ng/mL, 0.2 ng/mL, and 1.5 ng/mL, respectively, with little to no cross-reactivity. These LODs are clinically important as some patients could react strongly against such low allergen levels. Given the limitations of current industrial detection technology, multiplexed GMR-based assays provide a method for highly sensitive and specific simultaneous detection of any combination of food-product allergens, thus protecting allergic patients from life-threatening events, including anaphylaxis, by unintentional consumption.

    View details for DOI 10.1016/j.bios.2016.02.002

    View details for Web of Science ID 000372558500051

  • Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection. Biosensors & bioelectronics Ng, E., Nadeau, K. C., Wang, S. X. 2016; 80: 359-365

    Abstract

    Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive and specific detection of multiple food allergens is thus imperative as food allergies are becoming increasingly recognized as a major healthcare concern, affecting an estimated 4% of the total population. We demonstrate first instance of sensitive and specific multiplexed detection of major peanut allergens Ara h 1 and Ara h 2, and wheat allergen Gliadin using giant magnetoresistive (GMR) sensor arrays. Commercialized ELISA kits for Ara h 1 and Ara h 2 report limits of detection (LODs) at 31.5 ng/mL and 0.2 ng/mL, respectively. In addition, the 96-well-based ELISA developed in-house for Gliadin was found to have a LOD of 40 ng/mL. Our multiplexed GMR-based assay demonstrates the ability to perform all three assays on the same chip specifically and with sensitivities at LODs about an order of magnitude lower than those of 96-well-based ELISAs. LODs of GMR-based assays developed for Ara h 1, Ara h 2, and Gliadin were 7.0 ng/mL, 0.2 ng/mL, and 1.5 ng/mL, respectively, with little to no cross-reactivity. These LODs are clinically important as some patients could react strongly against such low allergen levels. Given the limitations of current industrial detection technology, multiplexed GMR-based assays provide a method for highly sensitive and specific simultaneous detection of any combination of food-product allergens, thus protecting allergic patients from life-threatening events, including anaphylaxis, by unintentional consumption.

    View details for DOI 10.1016/j.bios.2016.02.002

    View details for PubMedID 26859787

  • Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus SCIENTIFIC REPORTS Lee, J., Haddon, D. J., Wand, H. E., Price, J. V., Diep, V. K., Hall, D. A., Petri, M., Baechler, E. C., Balboni, I. M., Utz, P. J., Wang, S. X. 2016; 6

    Abstract

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.

    View details for DOI 10.1038/srep27623

    View details for Web of Science ID 000377358700002

    View details for PubMedID 27279139

  • Effect of annealing on exchange stiffness of ultrathin CoFeB film with perpendicular magnetic anisotropy APPLIED PHYSICS LETTERS Sato, N., White, R. M., Wang, S. X. 2016; 108 (15)

    View details for DOI 10.1063/1.4945039

    View details for Web of Science ID 000374314000032

  • Bio-Inspired Stretchable Absolute Pressure Sensor Network. Sensors Guo, Y., Li, Y., Guo, Z., Kim, K., Chang, F., Wang, S. X. 2016; 16 (1)

    Abstract

    A bio-inspired absolute pressure sensor network has been developed. Absolute pressure sensors, distributed on multiple silicon islands, are connected as a network by stretchable polyimide wires. This sensor network, made on a 4'' wafer, has 77 nodes and can be mounted on various curved surfaces to cover an area up to 0.64 m × 0.64 m, which is 100 times larger than its original size. Due to Micro Electro-Mechanical system (MEMS) surface micromachining technology, ultrathin sensing nodes can be realized with thicknesses of less than 100 µm. Additionally, good linearity and high sensitivity (~14 mV/V/bar) have been achieved. Since the MEMS sensor process has also been well integrated with a flexible polymer substrate process, the entire sensor network can be fabricated in a time-efficient and cost-effective manner. Moreover, an accurate pressure contour can be obtained from the sensor network. Therefore, this absolute pressure sensor network holds significant promise for smart vehicle applications, especially for unmanned aerial vehicles.

    View details for DOI 10.3390/s16010055

    View details for PubMedID 26729134

    View details for PubMedCentralID PMC4732088

  • Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors. Scientific reports Lee, J. R., Sato, N., Bechstein, D. J., Osterfeld, S. J., Wang, J., Gani, A. W., Hall, D. A., Wang, S. X. 2016; 6: 18692

    Abstract

    Giant magnetoresistive (GMR) biosensors consisting of many rectangular stripes are being developed for high sensitivity medical diagnostics of diseases at early stages, but many aspects of the sensing mechanism remain to be clarified. Using e-beam patterned masks on the sensors, we showed that the magnetic nanoparticles with a diameter of 50 nm located between the stripes predominantly determine the sensor signals over those located on the sensor stripes. Based on computational analysis, it was confirmed that the particles in the trench, particularly those near the edges of the stripes, mainly affect the sensor signals due to additional field from the stripe under an applied field. We also demonstrated that the direction of the average magnetic field from the particles that contributes to the signal is indeed the same as that of the applied field, indicating that the particles in the trench are pivotal to produce sensor signal. Importantly, the same detection principle was validated with a duplex protein assay. Also, 8 different types of sensor stripes were fabricated and design parameters were explored. According to the detection principle uncovered, GMR biosensors can be further optimized to improve their sensitivity, which is highly desirable for early diagnosis of diseases.

    View details for PubMedID 26728870

  • Linear Control of Magneto-Electric Effect With Small Electric Fields IEEE MAGNETICS LETTERS Xue, F., Hu, J., Wang, S. X., He, J. 2016; 7

    View details for DOI 10.1109/LMAG.2016.2551694

    View details for Web of Science ID 000399976300001

  • Magneto-nanosensor platform for probing low-affinity protein-protein interactions and identification of a low-affinity PD-L1/PD-L2 interaction. Nature communications Lee, J., Bechstein, D. J., Ooi, C. C., Patel, A., Gaster, R. S., Ng, E., Gonzalez, L. C., Wang, S. X. 2016; 7: 12220-?

    Abstract

    Substantial efforts have been made to understand the interactions between immune checkpoint receptors and their ligands targeted in immunotherapies against cancer. To carefully characterize the complete network of interactions involved and the binding affinities between their extracellular domains, an improved kinetic assay is needed to overcome limitations with surface plasmon resonance (SPR). Here, we present a magneto-nanosensor platform integrated with a microfluidic chip that allows measurement of dissociation constants in the micromolar-range. High-density conjugation of magnetic nanoparticles with prey proteins allows multivalent receptor interactions with sensor-immobilized bait proteins, more closely mimicking natural-receptor clustering on cells. The platform has advantages over traditional SPR in terms of insensitivity of signal responses to pH and salinity, less consumption of proteins and better sensitivities. Using this platform, we characterized the binding affinities of the PD-1-PD-L1/PD-L2 co-inhibitory receptor system, and discovered an unexpected interaction between the two known PD-1 ligands, PD-L1 and PD-L2.

    View details for DOI 10.1038/ncomms12220

    View details for PubMedID 27447090

  • Microfluidic multiplexed partitioning enables flexible and effective utilization of magnetic sensor arrays. Lab on a chip Bechstein, D. J., Ng, E., Lee, J., Cone, S. G., Gaster, R. S., Osterfeld, S. J., Hall, D. A., Weaver, J. A., Wilson, R. J., Wang, S. X. 2015; 15 (22): 4273-4276

    Abstract

    We demonstrate microfluidic partitioning of a giant magnetoresistive sensor array into individually addressable compartments that enhances its effective use. Using different samples and reagents in each compartment enables measuring of cross-reactive species and wide dynamic ranges on a single chip. This compartmentalization technique motivates the employment of high density sensor arrays for highly parallelized measurements in lab-on-a-chip devices.

    View details for DOI 10.1039/c5lc00953g

    View details for PubMedID 26395039

  • Achieving Isotropic Permeability for Integrated Inductors IEEE TRANSACTIONS ON MAGNETICS El-Ghazaly, A., Sato, N., White, R. M., Wang, S. X. 2015; 51 (11)

    View details for DOI 10.1109/TMAG.2015.2441091

    View details for Web of Science ID 000364770500227

  • Magnetoelectric effect in shear-mode Pb(Zr, Ti)O-3/NdFeB composite cantilever APPLIED PHYSICS LETTERS Han, J., Hu, J., Wang, Z., Wang, S. X., He, J. 2015; 106 (18)

    View details for DOI 10.1063/1.4919738

    View details for Web of Science ID 000354259200032

  • Enhanced performance of magnetoelectric energy harvester based on compound magnetic coupling effect JOURNAL OF APPLIED PHYSICS Han, J., Hu, J., Wang, Z., Wang, S. X., He, J. 2015; 117 (14)

    View details for DOI 10.1063/1.4917214

    View details for Web of Science ID 000352967400020

  • In-plane longitudinal converse magnetoelectric effect in laminated composites: Aiming at sensing wide range electric field APPLIED PHYSICS LETTERS Xue, F., Hu, J., Wang, S. X., He, J. 2015; 106 (8)

    View details for DOI 10.1063/1.4913619

    View details for Web of Science ID 000350546600053

  • A novel cylindrical torsional magnetoelectric composite based on d(15) shear-mode response JOURNAL OF PHYSICS D-APPLIED PHYSICS Han, J., Hu, J., Wang, S. X., He, J. 2015; 48 (4)

    View details for DOI 10.1088/0022-3727/48/4/045001

    View details for Web of Science ID 000348300900001

  • Hysteretic Modeling of Output Characteristics of Giant Magnetoresistive Current Sensors IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS Han, J., Hu, J., Ouyang, Y., Wang, S. X., He, J. 2015; 62 (1): 516-524

    View details for DOI 10.1109/TIE.2014.2326989

    View details for Web of Science ID 000346767400053

  • Pilot Application of Magnetic Nanoparticle-Based Biosensor for Necrotizing Enterocolitis. Journal of proteomics & bioinformatics Kim, D., Fu, C., Ling, X. B., Hu, Z., Tao, G., Zhao, Y., Kastenberg, Z. J., Sylvester, K. G., Wang, S. X. 2015

    Abstract

    Necrotizing Enterocolitis (NEC) is a major source of neonatal morbidity and mortality. There is an ongoing need for a sensitive diagnostic instrument to discriminate NEC from neonatal sepsis. We hypothesized that magnetic nanopartile-based biosensor analysis of gut injury-associated biomarkers would provide such an instrument.We designed a magnetic multiplexed biosensor platform, allowing the parallel plasma analysis of C-reactive protein (CRP), matrix metalloproteinase-7 (MMp7), and epithelial cell adhesion molecule (EpCAM). Neonatal subjects with sepsis (n=5) or NEC (n=10) were compared to control (n=5) subjects to perform a proof of concept pilot study for the diagnosis of NEC using our ultra-sensitive biosensor platform.Our multiplexed NEC magnetic nanoparticle-based biosensor platform was robust, ultrasensitive (Limit of detection LOD: CRP 0.6 pg/ml; MMp7 20 pg/ml; and EpCAM 20 pg/ml), and displayed no cross-reactivity among analyte reporting regents. To gauge the diagnostic performance, bootstrapping procedure (500 runs) was applied: MMp7 and EpCAM collectively differentiated infants with NEC from control infants with ROC AUC of 0.96, and infants with NEC from those with sepsis with ROC AUC of 1.00. The 3-marker panel comprising of EpCAM, MMp7 and CRP had a corresponding ROC AUC of 0.956 and 0.975, respectively.The exploration of the multiplexed nano-biosensor platform shows promise to deliver an ultrasensitive instrument for the diagnosis of NEC in the clinical setting.

    View details for PubMedID 26798207

  • Microfluidic multiplexed partitioning enables flexible and effective utilization of magnetic sensor arrays LAB ON A CHIP Bechstein, D. J., Ng, E., Lee, J., Cone, S. G., Gaster, R. S., Osterfeld, S. J., Hall, D. A., Weaver, J. A., Wilson, R. J., Wang, S. X. 2015; 15 (22): 4273-4276

    Abstract

    We demonstrate microfluidic partitioning of a giant magnetoresistive sensor array into individually addressable compartments that enhances its effective use. Using different samples and reagents in each compartment enables measuring of cross-reactive species and wide dynamic ranges on a single chip. This compartmentalization technique motivates the employment of high density sensor arrays for highly parallelized measurements in lab-on-a-chip devices.

    View details for DOI 10.1039/c5lc00953g

    View details for Web of Science ID 000364072300003

    View details for PubMedID 26395039

  • High performance wash-free magnetic bioassays through microfluidically enhanced particle specificity. Scientific reports Bechstein, D. J., Lee, J., Ooi, C. C., Gani, A. W., Kim, K., Wilson, R. J., Wang, S. X. 2015; 5: 11693-?

    Abstract

    Magnetic biosensors have emerged as a sensitive and versatile platform for high performance medical diagnostics. These magnetic biosensors require well-tailored magnetic particles as detection probes, which need to give rise to a large and specific biological signal while showing very low nonspecific binding. This is especially important in wash-free bioassay protocols, which do not require removal of particles before measurement, often a necessity in point of care diagnostics. Here we show that magnetic interactions between magnetic particles and magnetized sensors dramatically impact particle transport and magnetic adhesion to the sensor surfaces. We investigate the dynamics of magnetic particles' biomolecular binding and magnetic adhesion to the sensor surface using microfluidic experiments. We elucidate how flow forces can inhibit magnetic adhesion, greatly diminishing or even eliminating nonspecific signals in wash-free magnetic bioassays, and enhancing signal to noise ratios by several orders of magnitude. Our method is useful for selecting and optimizing magnetic particles for a wide range of magnetic sensor platforms.

    View details for DOI 10.1038/srep11693

    View details for PubMedID 26123868

  • Modeling the Frequency Dependence of Packaged Linear Magnetoresisitive Sensors Based on MTJ IEEE TRANSACTIONS ON MAGNETICS Ouyang, Y., Hu, J., He, J., Zhao, G., Xue, F., Wang, Z., Wang, S. X., Yuan, Z., Ding, Z. 2014; 50 (11)

    View details for DOI 10.1109/TMAG.2014.2331369

    View details for Web of Science ID 000349465900256

  • Spin-wave resonances in the presence of a Bloch wall PHYSICAL REVIEW B Mullenix, J., El-Ghazaly, A., Lee, D. W., Wang, S. X., White, R. M. 2014; 89 (22)

    View details for DOI 10.1103/PhysRevB.89.224406

    View details for Web of Science ID 000338016900002

  • Magnetic energy harvesting properties of piezofiber bimorph/NdFeB composites APPLIED PHYSICS LETTERS Han, J., Hu, J., Wang, S. X., He, J. 2014; 104 (9)

    View details for DOI 10.1063/1.4867889

    View details for Web of Science ID 000332729200115

  • Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips LAB ON A CHIP Earhart, C. M., Hughes, C. E., Gaster, R. S., Ooi, C. C., Wilson, R. J., Zhou, L. Y., Humke, E. W., Xu, L., Wong, D. J., Willingham, S. B., Schwartz, E. J., Weissman, I. L., Jeffrey, S. S., Neal, J. W., Rohatgi, R., Wakeleebe, H. A., Wang, S. X. 2014; 14 (1): 78-88

    View details for DOI 10.1039/c3lc50580d

    View details for Web of Science ID 000327669000008

  • Wafer-Scale Synthesis of Monodisperse Synthetic Magnetic Multilayer Nanorods NANO LETTERS Zhang, M., Bechstein, D. J., Wilson, R. J., Wang, S. X. 2014; 14 (1): 333-338

    Abstract

    A double exposure technique has been used to fabricate nanoimprint stamps for making monodisperse nanorods with controllable lengths. The nanorod length is defined by a normal photolithography projection process whereas the nanorod width is defined by an edge-lithography process using a soft polydimethylsiloxane (PDMS) contact mask. Taking advantage of edge-lithography, the nanorod width can be less than the diffraction limit of the exposure light. Using these nanorod stamps, synthetic magnetic multilayer (SMM) nanorods have been fabricated using nanoimprint lithography, resulting in a length variation of ∼3%. Nanorod magnetic properties have been characterized in both longitudinal and in-plane transverse directions of the nanorods. A theoretical model has been established to explain the magnetic responses and has revealed that both shape anisotropy and interlayer interactions are important in determining the properties of SMM nanorods.

    View details for DOI 10.1021/nl404089t

    View details for Web of Science ID 000329586700053

    View details for PubMedID 24329003

    View details for PubMedCentralID PMC3931460

  • Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips. Lab on a chip Earhart, C. M., Hughes, C. E., Gaster, R. S., Ooi, C. C., Wilson, R. J., Zhou, L. Y., Humke, E. W., Xu, L., Wong, D. J., Willingham, S. B., Schwartz, E. J., Weissman, I. L., Jeffrey, S. S., Neal, J. W., Rohatgi, R., Wakelee, H. A., Wang, S. X. 2013; 14 (1): 78-88

    Abstract

    Detection and characterization of circulating tumor cells (CTCs) may reveal insights into the diagnosis and treatment of malignant disease. Technologies for isolating CTCs developed thus far suffer from one or more limitations, such as low throughput, inability to release captured cells, and reliance on expensive instrumentation for enrichment or subsequent characterization. We report a continuing development of a magnetic separation device, the magnetic sifter, which is a miniature microfluidic chip with a dense array of magnetic pores. It offers high efficiency capture of tumor cells, labeled with magnetic nanoparticles, from whole blood with high throughput and efficient release of captured cells. For subsequent characterization of CTCs, an assay, using a protein chip with giant magnetoresistive nanosensors, has been implemented for mutational analysis of CTCs enriched with the magnetic sifter. The use of these magnetic technologies, which are separate devices, may lead the way to routine preparation and characterization of "liquid biopsies" from cancer patients.

    View details for DOI 10.1039/c3lc50580d

    View details for PubMedID 23969419

  • Functionalization of high-moment magnetic nanodisks for cell manipulation and separation NANO RESEARCH Zhang, M., Earhart, C. M., Ooi, C., Wilson, R. J., Tang, M., Wang, S. X. 2013; 6 (10): 745-751

    View details for DOI 10.1007/s12274-013-0352-4

    View details for Web of Science ID 000325819000006

  • Modeling and experiments of magneto-nanosensors for diagnostics of radiation exposure and cancer. Biomedical microdevices Kim, D., Lee, J., Shen, E., Wang, S. X. 2013; 15 (4): 665-671

    Abstract

    We present a resistive network model, protein assay data, and outlook of the giant magnetoresistive (GMR) spin-valve magneto-nanosensor platform ideal for multiplexed detection of protein biomarkers in solutions. The magneto-nanosensors are designed to have optimal performance considering several factors such as sensor dimension, shape anisotropy, and magnetic nanoparticle tags. The resistive network model indicates that thinner spin-valve sensors with narrower width lead to higher signals from magnetic nanoparticle tags. Standard curves and real-time measurements showed a sensitivity of ~10 pM for phosphorylated-structural maintenance of chromosome 1 (phosphor-SMC1), ~53 fM for granulocyte colony stimulation factor (GCSF), and ~460 fM for interleukin-6 (IL6), which are among the representative biomarkers for radiation exposure and cancer.

    View details for DOI 10.1007/s10544-012-9678-z

    View details for PubMedID 22763391

    View details for PubMedCentralID PMC3674217

  • Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation SCIENTIFIC REPORTS Kim, D., Marchetti, F., Chen, Z., Zaric, S., Wilson, R. J., Hall, D. A., Gaster, R. S., Lee, J., Wang, J., Osterfeld, S. J., Yu, H., White, R. M., Blakely, W. F., Peterson, L. E., Bhatnagar, S., Mannion, B., Tseng, S., Roth, K., Coleman, M., Snijders, A. M., Wyrobek, A. J., Wang, S. X. 2013; 3

    Abstract

    Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry.

    View details for DOI 10.1038/srep02234

    View details for Web of Science ID 000322001200002

    View details for PubMedID 23868657

    View details for PubMedCentralID PMC3715761

  • Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation IEEE TRANSACTIONS ON MAGNETICS Ooi, C., Earhart, C. M., Wilson, R. J., Wang, S. X. 2013; 49 (7): 3434-3437

    Abstract

    NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen were previously shown to be captured at high efficiencies by a microfabricated magnetic sifter. If fine control and optimization of the magnetic separation process is to be achieved, it is vital to be able to characterize the labeled cells' magnetic moment rapidly. We have thus adapted a rapid prototyping method to obtain the saturation magnetic moment of these cells. This method utilizes a cross-correlation algorithm to analyze the cells' motion in a simple fluidic channel to obtain their magnetophoretic velocity, and is effective even when the magnetic moments of cells are small. This rapid characterization is proven useful in optimizing our microfabricated magnetic sifter procedures for magnetic cell capture.

    View details for DOI 10.1109/TMAG.2013.2245310

    View details for Web of Science ID 000322483200092

    View details for PubMedCentralID PMC3996843

  • Kerr-Imaged Edge-Curling Wall Effects of Narrow Magnetic Cores IEEE TRANSACTIONS ON MAGNETICS El-Ghazaly, A., Mullenix, J. M., White, R. M., Wang, S. X. 2013; 49 (7): 4017-4020

    View details for DOI 10.1109/TMAG.2013.2237759

    View details for Web of Science ID 000322483200240

  • Integrated Transformers With Sputtered Laminated Magnetic Core IEEE TRANSACTIONS ON MAGNETICS Mullenix, J., El-Ghazaly, A., Wang, S. X. 2013; 49 (7): 4021-4027

    View details for DOI 10.1109/TMAG.2013.2242865

    View details for Web of Science ID 000322483200241

  • Emerging protein array technologies for proteomics EXPERT REVIEW OF PROTEOMICS Lee, J., Magee, D. M., Gaster, R. S., LaBaer, J., Wang, S. X. 2013; 10 (1): 65-75

    Abstract

    Numerous efforts have been made to understand fundamental biology of diseases based on gene expression. However, the relationship between gene expression and onset of disease often remains obscure. The great advances in protein microarrays allow us to investigate this unclear question through protein profiles, which are regarded as more reliable than gene expressions to serve as the harbinger of disease onset or as the biomarker of disease treatment monitoring. The authors review two relatively new platforms of protein arrays, along with an introduction to the common basis of protein array technologies. Immobilization of proteins on the surface of arrays and neutralizing reactive areas after the immobilization are key practical issues in the field of protein array. One of the emerging protein array technologies is the magneto-nanosensor array, where giant magnetoresistive sensors are used to quantitatively measure the analytes of interest, which are labeled with magnetic nanoparticles. Similar to giant magnetoresistive sensors, several different ways of utilizing magnetic properties for biomolecular detection have been developed and are reviewed here. Another emerging protein array technology is nucleic acid programmable protein arrays, which have thousands of protein features directly expressed by nucleic acids on the array surface. The authors anticipate that these two emerging protein array platforms can be combined to produce synergistic benefits and open new applications in proteomics and clinical diagnostics.

    View details for DOI 10.1586/EPR.12.67

    View details for PubMedID 23414360

  • Magnetically ultraresponsive nanoscavengers for next-generation water purification systems. Nature communications Zhang, M., Xie, X., Tang, M., Criddle, C. S., Cui, Y., Wang, S. X. 2013; 4: 1866-?

    Abstract

    The development of sustainable, robust and energy efficient water purification technology is still challenging. Although use of nanoparticles is promising, methods are needed for their efficient recovery post treatment. Here we address this issue by fabrication of magnetically ultraresponsive 'nanoscavengers', nanoparticles containing synthetic antiferromagnetic core layers and functional capping layers. When dispersed in water, the nanoscavengers efficiently interact with contaminants to remove them from the water. They are then quickly collected (<5 min) with a permanent magnet, owing to their magnetically ultraresponsive core layers. Specifically, we demonstrate fabrication and deployment of Ag-capped nanoscavengers for disinfection followed by application of an external magnetic field for separation. We also develop and validate a collision-based model for pathogen inactivation, and propose a cyclical water purification scheme in which nanoscavengers are recovered and recycled for contaminant removal.

    View details for DOI 10.1038/ncomms2892

    View details for PubMedID 23673651

  • Effect of Magnetic Field Gradient on Effectiveness of the Magnetic Sifter for Cell Purification. IEEE transactions on magnetics Ooi, C., Earhart, C. M., Wilson, R. J., Wang, S. X. 2013; 49 (1): 316–20

    Abstract

    In our experiments with NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen, we demonstrate capture efficiencies above 90% even at sample flow rates of 5 ml/h through our microfabricated magnetic sifter. We also improve the elution efficiencies from between 50% and 60% to close to 90% via optimization of the permanent magnet size and position used to magnetize the sifter. We then explain our observations via the use of finite element software for magnetic field and field gradient distributions, and a particle tracing algorithm, illustrating the impact of magnetic field gradients on the performance of the magnetic sifter. The high capture and elution efficiencies observed here is especially significant for magnetic separation of biologically interesting but rare moieties such as cancer stem cells for downstream analysis.

    View details for PubMedID 23515873

  • A 256 pixel magnetoresistive biosensor microarray in 0.18μm CMOS. IEEE journal of solid-state circuits Hall, D. A., Gaster, R. S., Makinwa, K., Wang, S. X., Murmann, B. 2013; 48 (5): 1290–1301

    Abstract

    Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 μm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring.

    View details for PubMedID 24761029

  • Effect of Magnetic Field Gradient on Effectiveness of the Magnetic Sifter for Cell Purification IEEE TRANSACTIONS ON MAGNETICS Ooi, C., Earhart, C. M., Wilson, R. J., Wang, S. X. 2013; 49 (1): 316-320

    Abstract

    In our experiments with NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen, we demonstrate capture efficiencies above 90% even at sample flow rates of 5 ml/h through our microfabricated magnetic sifter. We also improve the elution efficiencies from between 50% and 60% to close to 90% via optimization of the permanent magnet size and position used to magnetize the sifter. We then explain our observations via the use of finite element software for magnetic field and field gradient distributions, and a particle tracing algorithm, illustrating the impact of magnetic field gradients on the performance of the magnetic sifter. The high capture and elution efficiencies observed here is especially significant for magnetic separation of biologically interesting but rare moieties such as cancer stem cells for downstream analysis.

    View details for DOI 10.1109/TMAG.2012.2224851

    View details for Web of Science ID 000312831500027

    View details for PubMedCentralID PMC3600415

  • Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation. Scientific reports Kim, D., Marchetti, F., Chen, Z., Zaric, S., Wilson, R. J., Hall, D. A., Gaster, R. S., Lee, J., Wang, J., Osterfeld, S. J., Yu, H., White, R. M., Blakely, W. F., Peterson, L. E., Bhatnagar, S., Mannion, B., Tseng, S., Roth, K., Coleman, M., Snijders, A. M., Wyrobek, A. J., Wang, S. X. 2013; 3: 2234-?

    Abstract

    Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry.

    View details for DOI 10.1038/srep02234

    View details for PubMedID 23868657

  • DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood PLOS ONE Budworth, H., Snijders, A. M., Marchetti, F., Mannion, B., Bhatnagar, S., Kwoh, E., Tan, Y., Wang, S. X., Blakely, W. F., Coleman, M., Peterson, L., Wyrobek, A. J. 2012; 7 (11)

    Abstract

    DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS). Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06

    View details for DOI 10.1371/journal.pone.0048619

    View details for Web of Science ID 000311935800084

    View details for PubMedID 23144912

    View details for PubMedCentralID PMC3492462

  • A Current Sensor Based on the Giant Magnetoresistance Effect: Design and Potential Smart Grid Applications SENSORS Ouyang, Y., He, J., Hu, J., Wang, S. X. 2012; 12 (11): 15520-15541

    Abstract

    Advanced sensing and measurement techniques are key technologies to realize a smart grid. The giant magnetoresistance (GMR) effect has revolutionized the fields of data storage and magnetic measurement. In this work, a design of a GMR current sensor based on a commercial analog GMR chip for applications in a smart grid is presented and discussed. Static, dynamic and thermal properties of the sensor were characterized. The characterizations showed that in the operation range from 0 to ±5 A, the sensor had a sensitivity of 28 mV·A(-1), linearity of 99.97%, maximum deviation of 2.717%, frequency response of −1.5 dB at 10 kHz current measurement, and maximum change of the amplitude response of 0.0335%·°C(-1) with thermal compensation. In the distributed real-time measurement and monitoring of a smart grid system, the GMR current sensor shows excellent performance and is cost effective, making it suitable for applications such as steady-state and transient-state monitoring. With the advantages of having a high sensitivity, high linearity, small volume, low cost, and simple structure, the GMR current sensor is promising for the measurement and monitoring of smart grids.

    View details for DOI 10.3390/s121115520

    View details for Web of Science ID 000311429500064

    View details for PubMedID 23202221

    View details for PubMedCentralID PMC3522974

  • Fluorescent Magnetic Nanoparticles for Magnetically Enhanced Cancer Imaging and Targeting in Living Subjects ACS NANO Fu, A., Wilson, R. J., Smith, B. R., Mullenix, J., Earhart, C., Akin, D., Guccione, S., Wang, S. X., Gambhir, S. S. 2012; 6 (8): 6862-6869

    Abstract

    Early detection and targeted therapy are two major challenges in the battle against cancer. Novel imaging contrast agents and targeting approaches are greatly needed to improve the sensitivity and specificity of cancer theranostic agents. Here, we implemented a novel approach using a magnetic micromesh and biocompatible fluorescent magnetic nanoparticles (FMN) to magnetically enhance cancer targeting in living subjects. This approach enables magnetic targeting of systemically administered individual FMN, containing a single 8 nm superparamagnetic iron oxide core. Using a human glioblastoma mouse model, we show that nanoparticles can be magnetically retained in both the tumor neovasculature and surrounding tumor tissues. Magnetic accumulation of nanoparticles within the neovasculature was observable by fluorescence intravital microscopy in real time. Finally, we demonstrate that such magnetically enhanced cancer targeting augments the biological functions of molecules linked to the nanoparticle surface.

    View details for DOI 10.1021/nn301670a

    View details for Web of Science ID 000307988900039

    View details for PubMedID 22857784

    View details for PubMedCentralID PMC3601027

  • Spin wave modes in ferromagnetic tubes JOURNAL OF APPLIED PHYSICS Kozhanov, A., Popov, M., Zavislyak, I., Ouellette, D., Lee, D. W., Wang, S. X., Rodwell, M., Allen, S. J. 2012; 111 (1)

    View details for DOI 10.1063/1.3672835

    View details for Web of Science ID 000299127200058

  • A Magneto-Nanosensor Immunoassay for Sensitive Detection of Aspergillus Fumigatus Allergen Asp f 1. IEEE transactions on magnetics Kim, D., Wang, S. X. 2012; 48 (11): 3266–68

    Abstract

    We report a magneto-nanosensor biochip for fungal detection. The chip is made of arrays of giant magnetoresistive (GMR) spin-valve sensors, and is able to detect protein biomarkers at low concentrations in solutions. As a demonstration, a standard curve for fungal pathogen Asp f 1 was obtained by measuring signals from various concentrations of Asp f 1 spiked in PBS solutions, indicating a detection limit of ~100 pg/ml. Five positive and negative Asp f 1 solution samples were discriminated correctly in blind experiments. Our data suggest that the magneto-nanosensor biochips are very promising as sensitive diagnostic devices for fungal pathogens. Given the generality of the detection scheme used in the magneto-nanosensor, we anticipate that the platform will be very useful for the detection of many types of biomarkers.

    View details for PubMedID 23494403

  • Raman-Active Two-Tiered Ag Nanoparticles with a Concentric Cavity SMALL Wi, J., Sengupta, S., Wilson, R. J., Zhang, M., Tang, M., Wang, S. X. 2011; 7 (23): 3276-3280

    Abstract

    A two-tiered Ag nanoparticle containing a cavity at the center of each nanoparticle is generated by two simple steps of nano-imprinting and metal vacuum deposition. It enables sub-zeptomole detection of organic molecules and five orders of the dynamic sensing range.

    View details for DOI 10.1002/smll.201101523

    View details for Web of Science ID 000298288100004

    View details for PubMedID 21990231

    View details for PubMedCentralID PMC3595186

  • Sombrero-Shaped Plasmonic Nanoparticles with Molecular-Level Sensitivity and Multifunctionality ACS NANO Wi, J., Barnard, E. S., Wilson, R. J., Zhang, M., Tang, M., Brongersma, M. L., Wang, S. X. 2011; 5 (8): 6449-6457

    Abstract

    We demonstrate top-down synthesis of monodisperse plasmonic nanoparticles designed to contain internal Raman hot spots. Our Raman-active nanoparticles are fabricated using nanoimprint lithography and thin-film deposition and are composed of novel internal structures with sublithographic dimensions: a disk-shaped Ag core, a Petri-dish-shaped SiO(2) base whose inner surface is coated with Ag film, and a sub-10 nm scale circular gap between the core and the base. Confocal Raman measurements and electromagnetic simulations show that Raman hot spots appear at the inside perimeter of individual nanoparticles and serve as the source of a 1000-fold improvement of minimum molecular detection level that enables detection of signals from a few molecules near hot spots. A multimodality version of these nanoparticles, which includes the functionality offered by magnetic multilayers, is also demonstrated. These results illustrate the potential of direct fabrication for creating exotic monodisperse nanoparticles, which combine engineered internal nanostructures and multilayer composite materials, for use in nanoparticle-based molecular imaging and detection.

    View details for DOI 10.1021/nn201649n

    View details for Web of Science ID 000294085400044

    View details for PubMedID 21732686

    View details for PubMedCentralID PMC3160147

  • Silicon nano-well arrays for reliable pattern transfer and locally confined high temperature reactions NANOTECHNOLOGY Wi, J., Wilson, R. J., Lee, D., White, R. M., Wang, S. X. 2011; 22 (30)

    Abstract

    Si nano-well arrays, with precisely controlled undercut Si sidewall profiles and flat bottomed pockets, enable uniform nanoscale pattern transfer from resists to metal deposits without degradation of the initial lithographic resolution, as verified by the formation of arrays of Au nano-dots with 10 nm diameter. An additional functionality of the Si nano-wells as local nano-reactors, where the patterned material is enclosed in a Si pocket during high temperature reaction, is demonstrated by thermally inducing a phase transformation of the as-deposited A1 phase of FePt nano-dots to the high coercivity, chemically ordered L1(0) phase.

    View details for DOI 10.1088/0957-4484/22/30/305304

    View details for Web of Science ID 000292455300006

    View details for PubMedID 21709347

    View details for PubMedCentralID PMC3167870

  • Autoassembly Protein Arrays for Analyzing Antibody Cross-Reactivity NANO LETTERS Gaster, R. S., Hall, D. A., Wang, S. X. 2011; 11 (7): 2579-2583

    Abstract

    We report an autoassembly protein array capable of rapidly screening for aberrant antibody-antigen binding events. Our technique combines magnetic nanoparticle technology with proximity-based, magnetically responsive nanosensors for rapid (under 15 min) and high-density screening of antibody cross-reactivity at sensitivities down to 50 fM in a homogeneous assay. This method will enable the identification of the precise cause of aberrant or cross-reactive binding events in an easy-to-use, rapid, and high-throughput manner.

    View details for DOI 10.1021/nl1026056

    View details for Web of Science ID 000292849400001

    View details for PubMedID 20804215

    View details for PubMedCentralID PMC3136110

  • Fabrication of planar, layered nanoparticles using tri-layer resist templates NANOTECHNOLOGY Hu, W., Zhang, M., Wilson, R. J., Koh, A. L., Wi, J., Tang, M., Sinclair, R., Wang, S. X. 2011; 22 (18)

    Abstract

    A simple and universal pathway to produce free multilayer synthetic nanoparticles is developed based on lithography, vapor phase deposition and a tri-layer resist lift-off and release process. The fabrication method presented in this work is ideal for production of a broad range of nanoparticles, either free in solution or still attached to an intact release layer, with unique magnetic, optical, radioactive, electronic and catalytic properties. Multi-modal capabilities are implicit in the layered architecture. As an example, directly fabricated magnetic nanoparticles are evaluated to illustrate the structural integrity of thin internal multilayers and the nanoparticle stability in aggressive biological environments, which is highly desired for biomedical applications.

    View details for DOI 10.1088/0957-4484/22/18/185302

    View details for Web of Science ID 000288653300005

    View details for PubMedID 21415483

    View details for PubMedCentralID PMC3143003

  • Gradual pressure release for reliable nanoimprint lithography JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B Wi, J., Wilson, R. J., White, R. M., Wang, S. X. 2011; 29 (3)

    View details for DOI 10.1116/1.3574390

    View details for Web of Science ID 000291111300036

  • Quantification of protein interactions and solution transport using high-density GMR sensor arrays NATURE NANOTECHNOLOGY Gaster, R. S., Xu, L., Han, S., Wilson, R. J., Hall, D. A., Osterfeld, S. J., Yu, H., Wang, S. X. 2011; 6 (5): 314-320

    Abstract

    Monitoring the kinetics of protein interactions on a high-density sensor array is vital to drug development and proteomic analysis. Label-free kinetic assays based on surface plasmon resonance are the current gold standard, but they have poor detection limits, suffer from non-specific binding, and are not amenable to high-throughput analyses. Here, we show that magnetically responsive nanosensors that have been scaled to over 100,000 sensors per cm² can be used to measure the binding kinetics of various proteins with high spatial and temporal resolution. We present an analytical model that describes the binding of magnetically labelled antibodies to proteins that are immobilized on the sensor surface. This model is able to quantify the kinetics of antibody-antigen binding at sensitivities as low as 20 zeptomoles of solute.

    View details for DOI 10.1038/NNANO.2011.45

    View details for Web of Science ID 000290301300013

    View details for PubMedID 21478869

    View details for PubMedCentralID PMC3089684

  • Micro-structured ferromagnetic tubes for spin wave excitation JOURNAL OF APPLIED PHYSICS Kozhanov, A., Ouellette, D., Rodwell, M., Allen, S. J., Lee, D. W., Wang, S. X. 2011; 109 (7)

    View details for DOI 10.1063/1.3559475

    View details for Web of Science ID 000289952100198

  • Magnetic, Mechanical, and Optical Characterization of a Magnetic Nanoparticle-Embedded Polymer for Microactuation JOURNAL OF MICROELECTROMECHANICAL SYSTEMS Tsai, K. L., Ziaei-Moayyed, M., Candler, R. N., Hu, W., Brand, V., Klejwa, N., Wang, S. X., Howe, R. T. 2011; 20 (1): 65-72

    View details for DOI 10.1109/JMEMS.2010.2093560

    View details for Web of Science ID 000286934900012

  • nanoLAB: An ultraportable, handheld diagnostic laboratory for global health LAB ON A CHIP Gaster, R. S., Hall, D. A., Wang, S. X. 2011; 11 (5): 950-956

    Abstract

    Driven by scientific progress and economic stimulus, medical diagnostics will move to a stage in which straightforward medical diagnoses are independent of physician visits and large centralized laboratories. The future of basic diagnostic medicine will lie in the hands of private individuals. We have taken significant strides towards achieving this goal by developing an autoassembly assay for disease biomarker detection which obviates the need for washing steps and is run on a handheld sensing platform. By coupling magnetic nanotechnology with an array of magnetically responsive nanosensors, we demonstrate a rapid, multiplex immunoassay that eliminates the need for trained technicians to run molecular diagnostic tests. Furthermore, the platform is battery-powered and ultraportable, allowing the assay to be run anywhere in the world by any individual.

    View details for DOI 10.1039/c0lc00534g

    View details for Web of Science ID 000287409600024

    View details for PubMedID 21264375

  • Effects of Ionizing Radiation on Self-Renewal and Pluripotency of Human Embryonic Stem Cells CANCER RESEARCH Wilson, K. D., Sun, N., Huang, M., Zhang, W. Y., Lee, A. S., Li, Z., Wang, S. X., Wu, J. C. 2010; 70 (13): 5539-5548

    Abstract

    Human embryonic stem cells (hESC) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs, nor has any study assessed their ability to form teratomas, the definitive test of pluripotency. In this study, we use microarrays to analyze the global gene expression changes in hESCs after low-dose (0.4 Gy), medium-dose (2 Gy), and high-dose (4 Gy) irradiation. We identify genes and pathways at each radiation dose that are involved in cell death, p53 signaling, cell cycling, cancer, embryonic and organ development, and others. Using Gene Set Enrichment Analysis, we also show that the expression of a comprehensive set of core embryonic transcription factors is not altered by radiation at any dose. Transplantation of irradiated hESCs to immune-deficient mice results in teratoma formation from hESCs irradiated at all doses, definitive proof of pluripotency. Further, using a bioluminescence imaging technique, we have found that irradiation causes hESCs to initially die after transplantation, but the surviving cells quickly recover by 2 weeks to levels similar to control. To conclude, we show that similar to somatic cells, irradiated hESCs suffer significant death and apoptosis after irradiation. However, they continue to remain pluripotent and are able to form all three embryonic germ layers. Studies such as this will help define the limits for radiation exposure for pregnant women and also radiotracer reporter probes for tracking cellular regenerative therapies.

    View details for DOI 10.1158/0008-5472.CAN-09-4238

    View details for PubMedID 20530673

  • Analysis of Integrated Solenoid Inductor With Closed Magnetic Core IEEE TRANSACTIONS ON MAGNETICS Wright, J. M., Lee, D. W., Mohan, A., Papou, A., Smeys, P., Wang, S. X. 2010; 46 (6): 2387-2390

    View details for DOI 10.1109/TMAG.2010.2044982

    View details for Web of Science ID 000278037800288

  • GMR biosensor arrays: Correction techniques for reproducibility and enhanced sensitivity BIOSENSORS & BIOELECTRONICS Hall, D. A., Gaster, R. S., Osterfeld, S. J., Murmann, B., Wang, S. X. 2010; 25 (9): 2177-2181

    Abstract

    Giant magnetoresistive biosensors possess great potential in biomedical applications for quantitatively detecting magnetically tagged biomolecules. Magnetic sensing does not suffer from the high background levels found in optical sensing modalities such as the enzyme linked immunosorbent assay translating into a technology with higher sensitivity. However, to reveal the full potential of these sensors and compensate for non-idealities such as temperature dependence, digital correction and calibration techniques are not only useful but imperative. Using these calibration techniques to correct for process variations and dynamic changes in the sensing environment (such as temperature and magnetic field), we are able to obtain extremely sensitive and, more importantly, reproducible results for quantifiable biomolecular reorganization. The reproducibility of the system was improved by over 3 x using digital correction techniques and the sensors are made temperature independent by using a novel background correction technique.

    View details for DOI 10.1016/j.bios.2010.01.039

    View details for Web of Science ID 000277930000029

    View details for PubMedID 20219342

    View details for PubMedCentralID PMC2881564

  • GMR biosensor arrays: A system perspective BIOSENSORS & BIOELECTRONICS Hall, D. A., Gaster, R. S., Lin, T., Osterfeld, S. J., Han, S., Murmann, B., Wang, S. X. 2010; 25 (9): 2051-2057

    Abstract

    Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time.

    View details for DOI 10.1016/j.bios.2010.01.038

    View details for Web of Science ID 000277930000009

    View details for PubMedID 20207130

    View details for PubMedCentralID PMC2855856

  • Magnetic Nanotechnology for Biodetection JALA Han, S., Wang, S. 2010; 15 (2): 93-98

    View details for DOI 10.1016/j.jala.2009.10.008

    View details for Web of Science ID 000285163500004

  • Sensitive giant magnetoresistive-based immunoassay for multiplex mycotoxin detection BIOSENSORS & BIOELECTRONICS Mak, A. C., Osterfeld, S. J., Yu, H., Wang, S. X., Davis, R. W., Jejelowo, O. A., Pourmand, N. 2010; 25 (7): 1635-1639

    Abstract

    Rapid and multiplexed measurement is vital in the detection of food-borne pathogens. While highly specific and sensitive, traditional immunochemical assays such as enzyme-linked immunosorbent assays (ELISAs) often require expensive read-out equipment (e.g. fluorescent labels) and lack the capability of multiplex detection. By combining the superior specificity of immunoassays with the sensitivity and simplicity of magnetic detection, we have developed a novel multiplex magnetic nanotag-based detection platform for mycotoxins that functions on a sub-picomolar concentration level. Unlike fluorescent labels, magnetic nanotags (MNTs) can be detected with inexpensive giant magnetoresistive (GMR) sensors such as spin-valve sensors. In the system presented here, each spin-valve sensor has an active area of 90 microm x 90 microm, arranged in an 8 x 8 array. Sample is added to the antibody-immobilized sensor array prior to the addition of the biotinylated detection antibody. The sensor response is recorded in real time upon the addition of streptavidin-linked MNTs on the chip. Here we demonstrate the simultaneous detection of multiple mycotoxins (aflatoxins B(1), zearalenone and HT-2) and show that a detection limit of 50 pg/mL can be achieved.

    View details for DOI 10.1016/j.bios.2009.11.028

    View details for Web of Science ID 000275978700013

    View details for PubMedID 20047828

    View details for PubMedCentralID PMC2947153

  • The influence of Fermi level pinning/depinning on the Schottky barrier height and contact resistance in Ge/CoFeB and Ge/MgO/CoFeB structures APPLIED PHYSICS LETTERS Lee, D., Raghunathan, S., Wilson, R. J., Nikonov, D. E., Saraswat, K., Wang, S. X. 2010; 96 (5)

    View details for DOI 10.1063/1.3285163

    View details for Web of Science ID 000274319500073

  • Portable Biomarker Detection with Magnetic Nanotags. The ... Midwest Symposium on Circuits and Systems conference proceedings : MWSCAS. Midwest Symposium on Circuits and Systems Hall, D. A., Wang, S. X., Murmann, B., Gaster, R. S. 2010: 1779–82

    Abstract

    This paper presents a hand-held, portable biosensor platform for quantitative biomarker measurement. By combining magnetic nanoparticle (MNP) tags with giant magnetoresistive (GMR) spin-valve sensors, the hand-held platform achieves highly sensitive (picomolar) and specific biomarker detection in less than 20 minutes. The rapid analysis and potential low cost make this technology ideal for point-of-care (POC) diagnostics. Furthermore, this platform is able to detect multiple biomarkers simultaneously in a single assay, creating a promising diagnostic tool for a vast number of applications.

    View details for PubMedID 22495252

  • Matrix-insensitive protein assays push the limits of biosensors in medicine NATURE MEDICINE Gaster, R. S., Hall, D. A., Nielsen, C. H., Osterfeld, S. J., Yu, H., Mach, K. E., Wilson, R. J., Murmann, B., Liao, J. C., Gambhir, S. S., Wang, S. X. 2009; 15 (11): 1327-U130

    Abstract

    Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.

    View details for DOI 10.1038/nm.2032

    View details for Web of Science ID 000271543700023

    View details for PubMedID 19820717

  • Small-Resistance and High-Quality-Factor Magnetic Integrated Inductors on PCB IEEE TRANSACTIONS ON ADVANCED PACKAGING Li, L., Lee, D. W., Hwang, K., Min, Y., Hizume, T., Tanaka, M., Mao, M., Schneider, T., Bubber, R., Wang, S. X. 2009; 32 (4): 780-787

    View details for DOI 10.1109/TADVP.2009.2019845

    View details for Web of Science ID 000271435900010

  • Nanosized corners for trapping and detecting magnetic nanoparticles NANOTECHNOLOGY Donolato, M., Gobbi, M., Vavassori, P., Leone, M., Cantoni, M., Metlushko, V., Ilic, B., Zhang, M., Wang, S. X., Bertacco, R. 2009; 20 (38)

    Abstract

    We present a device concept based on controlled micromagnetic configurations in a corner-shaped permalloy nanostructure terminated with two circular disks, specifically designed for the capture and detection of a small number of magnetic beads in suspension. A transverse head-to-head domain wall (TDW) placed at the corner of the structure plays the role of an attracting pole for magnetic beads. The TDW is annihilated in the terminating disks by applying an appropriate magnetic field, whose value is affected by the presence of beads chemically bound to the surface. In the case where the beads are not chemically bound to the surface, the annihilation of the TDW causes their release into the suspension. The variation of the voltage drop across the corner, due to the anisotropic magnetoresistance (AMR) while sweeping the magnetic field, is used to detect the presence of a chemically bound bead. The device response has been characterized by using both synthetic antiferromagnetic nanoparticles (disks of 70 nm diameter and 20 nm height) and magnetic nanobeads, for different thicknesses of the protective capping layer. We demonstrate the detection down to a single nanoparticle, therefore the device holds the potential for the localization and detection of small numbers of molecules immobilized on the particle's functionalized surface.

    View details for DOI 10.1088/0957-4484/20/38/385501

    View details for Web of Science ID 000269356900009

    View details for PubMedID 19713593

  • Visualizing Implanted Tumors in Mice with Magnetic Resonance Imaging Using Magnetotactic Bacteria CLINICAL CANCER RESEARCH Benoit, M. R., Mayer, D., Barak, Y., Chen, I. Y., Hu, W., Cheng, Z., Wang, S. X., Spielman, D. M., Gambhir, S. S., Matin, A. 2009; 15 (16): 5170-5177

    Abstract

    To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (approximately 25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor.We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6.Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.

    View details for DOI 10.1158/1078-0432.CCR-08-3206

    View details for Web of Science ID 000269024900019

    View details for PubMedID 19671860

    View details for PubMedCentralID PMC3409839

  • Dispersion in magnetostatic CoTaZr spin waveguides APPLIED PHYSICS LETTERS Kozhanov, A., Ouellette, D., Griffith, Z., Rodwell, M., Jacob, A. P., Lee, D. W., Wang, S. X., Allen, S. J. 2009; 94 (1)

    View details for DOI 10.1063/1.3063124

    View details for Web of Science ID 000262357800053

  • Protein-Functionalized Synthetic Antiferromagnetic Nanoparticles for Biomolecule Detection and Magnetic Manipulation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Fu, A., Hu, W., Xu, L., Wilson, R. J., Yu, H., Osterfeld, S. J., Gambhir, S. S., Wang, S. X. 2009; 48 (9): 1620-1624

    Abstract

    Direct protein functionalization provides synthetic antiferromagnetic nanoparticles with high chemical specificity and multifunctionality. These nanoparticle-protein conjugates function as improved magnetic labels for biological detection experiments, and exhibit tunable responses to a small external magnetic field gradient, thus allowing the observation of distinctive single nanoparticle motion.

    View details for DOI 10.1002/anie.200803994

    View details for Web of Science ID 000263642300018

    View details for PubMedID 19156803

    View details for PubMedCentralID PMC2665302

  • Formation and properties of magnetic chains for 100 nm nanoparticles used in separations of molecules and cells. Journal of magnetism and magnetic materials Wilson, R. J., Hu, W., Fu, C. W., Koh, A. L., Gaster, R. S., Earhart, C. M., Fu, A., Heilshorn, S. C., Sinclair, R., Wang, S. X. 2009; 321 (10): 1452–58

    Abstract

    Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations of 10(10) per mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immunomagnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.

    View details for PubMedID 20161001

  • Microfabricated magnetic sifter for high-throughput and high-gradient magnetic separation. Journal of magnetism and magnetic materials Earhart, C. M., Wilson, R. J., White, R. L., Pourmand, N., Wang, S. X. 2009; 321 (10): 1436–39

    Abstract

    A microfabricated magnetic sifter has been designed and fabricated for applications in biological sample preparation. The device enables high-throughput, high-gradient magnetic separation of magnetic nanoparticles by utilizing columnar fluid flow through a dense array (~5000/mm(2)) of micropatterned slots in a magnetically soft membrane. The potential of the sifter for separation of magnetic nanoparticles conjugated with capture antibodies is demonstrated through quantitative separation experiments with CD138-labelled MACS nanoparticles. Capture efficiencies ranging from 28-37% and elution efficiencies greater than 73% were measured for a single pass through the sifter.

    View details for PubMedID 20161248

  • MagArray Biochips for Protein and DNA Detection with Magnetic Nanotags: Design, Experiment, and Signal-to-Noise Ratio MICROARRAYS: PREPARATION, MICROFLUIDICS, DETECTION METHODS, AND BIOLOGICAL APPLICATIONS Osterfeld, S. I., Wang, S. X., Dill, K., Liu, R. H., Grodzinski, P. 2009: 299–314

    View details for DOI 10.1007/978-0-387-72719-6_15

    View details for Web of Science ID 000267419200015

  • Multiplex protein assays based on real-time magnetic nanotag sensing PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Osterfeld, S. J., Yu, H., Gaster, R. S., Caramuta, S., Xu, L., Han, S., Hall, D. A., Wilson, R. J., Sun, S., White, R. L., Davis, R. W., Pourmand, N., Wang, S. X. 2008; 105 (52): 20637-20640

    Abstract

    Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.

    View details for DOI 10.1073/pnas.0810822105

    View details for Web of Science ID 000262092800015

    View details for PubMedID 19074273

    View details for PubMedCentralID PMC2602607

  • Determining wave vector and material property from the phase-shift of spin-wave propagation EPL Bao, M., Wong, K., Khitun, A., Lee, J., Hao, Z., Wang, K. L., Lee, D. W., Wang, S. X. 2008; 84 (2)

    View details for DOI 10.1209/0295-5075/84/27009

    View details for Web of Science ID 000263598500034

  • Giant magnetoresistive biochip for DNA detection and HPV genotyping BIOSENSORS & BIOELECTRONICS Xu, L., Yu, H., Akhras, M. S., Han, S., Osterfeld, S., White, R. L., Pourmand, N., Wang, S. X. 2008; 24 (1): 99-103

    Abstract

    A giant magnetoresistive (GMR) biochip based on spin valve sensor array and magnetic nanoparticle labels was developed for inexpensive, sensitive and reliable DNA detection. The DNA targets detected in this experiment were PCR products amplified from Human Papillomavirus (HPV) plasmids. The concentrations of the target DNA after PCR were around 10 nM in most cases, but concentrations of 10 pM were also detectable, which is demonstrated by experiments with synthetic DNA samples. A mild but highly specific surface chemistry was used for probe oligonucleotide immobilization. Double modulation technique was used for signal detection in order to reduce the 1/f noise in the sensor. Twelve assays were performed with an accuracy of approximately 90%. Magnetic signals were consistent with particle coverage data measured with Scanning Electron Microscopy (SEM). More recent research on microfluidics showed the potential of reducing the assay time below one hour. This is the first demonstration of magnetic DNA detection using plasmid-derived samples. This study provides a direct proof that GMR sensors can be used for biomedical applications.

    View details for DOI 10.1016/j.bios.2008.03.030

    View details for Web of Science ID 000259425300015

    View details for PubMedID 18457945

    View details for PubMedCentralID PMC2573902

  • Advances in giant magnetoresistance biosensors with magnetic nanoparticle tags: Review and outlook IEEE TRANSACTIONS ON MAGNETICS Wang, S. X., Li, G. 2008; 44 (7): 1687-1702

    View details for DOI 10.1109/TMAG.2008.920962

    View details for Web of Science ID 000257238200001

  • Nanoscale control of exchange bias with BiFeO3 thin films NANO LETTERS Martin, L. W., Chu, Y., Holcomb, M. B., Huijben, M., Yu, P., Han, S., Lee, D., Wang, S. X., Ramesh, R. 2008; 8 (7): 2050-2055

    Abstract

    We demonstrate a direct correlation between the domain structure of multiferroic BiFeO3 thin films and exchange bias of Co 0.9Fe 0.1/BiFeO3 heterostructures. Two distinct types of interactions - an enhancement of the coercive field ( exchange enhancement) and an enhancement of the coercive field combined with large shifts of the hysteresis loop ( exchange bias) - have been observed in these heterostructures, which depend directly on the type and crystallography of the nanoscale ( approximately 2 nm) domain walls in the BiFeO3 film. We show that the magnitude of the exchange bias interaction scales with the length of 109 degrees ferroelectric domain walls in the BiFeO 3 thin films which have been probed via piezoresponse force microscopy and X-ray magnetic circular dichroism.

    View details for DOI 10.1021/nl801391m

    View details for Web of Science ID 000257504500046

    View details for PubMedID 18547121

  • Electric-field control of local ferromagnetism using a magnetoelectric multiferroic NATURE MATERIALS Chu, Y., Martin, L. W., Holcomb, M. B., Gajek, M., Han, S., He, Q., Balke, N., Yang, C., Lee, D., Hu, W., Zhan, Q., Yang, P., Fraile-Rodriguez, A., Scholl, A., Wang, S. X., Ramesh, R. 2008; 7 (6): 478-482

    Abstract

    Multiferroics are of interest for memory and logic device applications, as the coupling between ferroelectric and magnetic properties enables the dynamic interaction between these order parameters. Here, we report an approach to control and switch local ferromagnetism with an electric field using multiferroics. We use two types of electromagnetic coupling phenomenon that are manifested in heterostructures consisting of a ferromagnet in intimate contact with the multiferroic BiFeO(3). The first is an internal, magnetoelectric coupling between antiferromagnetism and ferroelectricity in the BiFeO(3) film that leads to electric-field control of the antiferromagnetic order. The second is based on exchange interactions at the interface between a ferromagnet (Co(0.9)Fe(0.1)) and the antiferromagnet. We have discovered a one-to-one mapping of the ferroelectric and ferromagnetic domains, mediated by the colinear coupling between the magnetization in the ferromagnet and the projection of the antiferromagnetic order in the multiferroic. Our preliminary experiments reveal the possibility to locally control ferromagnetism with an electric field.

    View details for DOI 10.1038/nmat2184

    View details for Web of Science ID 000256110200022

    View details for PubMedID 18438412

  • High-moment antiferromagnetic nanoparticles with tunable magnetic properties ADVANCED MATERIALS Hu, W., Wilson, R. J., Koh, A., Fu, A., Faranesh, A. Z., Earhart, C. M., Osterfeld, S. J., Han, S., Xu, L., Guccione, S., Sinclair, R., Wang, S. X. 2008; 20 (8): 1479-?

    View details for DOI 10.1002/adma.200703077

    View details for Web of Science ID 000255694200015

  • Inductively coupled circuits with spin wave bus for information processing JOURNAL OF NANOELECTRONICS AND OPTOELECTRONICS Khitun, A., Bao, M., Lee, J., Wang, K. L., Lee, D. W., Wang, S. X., Roshchin, I. V. 2008; 3 (1): 24-34

    View details for DOI 10.1166/jno.2008.003

    View details for Web of Science ID 000255548200005

  • Preparation, structural and magnetic characterization of synthetic anti-ferromagnetic (SAF) nanoparticles PHILOSOPHICAL MAGAZINE Koh, A. L., Hu, W., Wilson, R. J., Wang, S. X., Sinclair, R. 2008; 88 (36): 4225-4241

    View details for DOI 10.1080/14786430802585133

    View details for Web of Science ID 000261804200002

  • Giant Magnetoresistive Sensors for DNA Microarray. IEEE transactions on magnetics Xu, L., Yu, H., Han, S. J., Osterfeld, S., White, R. L., Pourmand, N., Wang, S. X. 2008; 44 (11): 3989–91

    Abstract

    Giant magnetoresistive (GMR) sensors are developed for a DNA microarray. Compared with the conventional fluorescent sensors, GMR sensors are cheaper, more sensitive, can generate fully electronic signals, and can be easily integrated with electronics and microfluidics. The GMR sensor used in this work has a bottom spin valve structure with an MR ratio of 12%. The single-strand target DNA detected has a length of 20 bases. Assays with DNA concentrations down to 10 pM were performed, with a dynamic range of 3 logs. A double modulation technique was used in signal detection to reduce the 1/f noise in the sensor while circumventing electromagnetic interference. The logarithmic relationship between the magnetic signal and the target DNA concentration can be described by the Temkin isotherm. Furthermore, GMR sensors integrated with microfluidics has great potential of improving the sensitivity to 1 pM or below, and the total assay time can be reduced to less than 1 hour.

    View details for PubMedID 20824116

  • Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent. Nanotechnology Lee, H. Y., Lee, S. H., Xu, C., Xie, J., Lee, J. H., Wu, B., Koh, A. L., Wang, X., Sinclair, R., Wang, S. X., Nishimura, D. G., Biswal, S., Sun, S., Cho, S. H., Chen, X. 2008; 19 (16): 165101

    Abstract

    The purpose of this study was to synthesize biocompatible polyvinylpyrrolidone (PVP)-coated iron oxide (PVP-IO) nanoparticles and to evaluate their efficacy as a magnetic resonance imaging (MRI) contrast agent. The PVP-IO nanoparticles were synthesized by a thermal decomposition method and characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and a superconducting quantum interface device (SQUID). The core size of the particles is about 8-10 nm and the overall size is around 20-30 nm. The measured r(2) (reciprocal of T(2) relaxation time) and r2∗ (reciprocal of T2∗ relaxation time) are 141.2 and 338.1 (s mM)(-1), respectively. The particles are highly soluble and stable in various buffers and in serum. The macrophage uptake of PVP-IO is comparable to that of Feridex as measured by a Prussian blue iron stain and phantom study. The signal intensity of a rabbit liver was effectively reduced after intravenous administration of PVP-IO. Therefore PVP-IO nanoparticles are potentially useful for T(2)-weighted MR imaging.

    View details for PubMedID 21394237

  • Room temperature exchange bias and spin valves based on BiFeO3/SrRuO3/SrTiO3/Si (001) heterostructures APPLIED PHYSICS LETTERS Martin, L. W., Chu, Y., Zhan, Q., Ramesh, R., Han, S., Wang, S. X., Warusawithana, M., Schlom, D. G. 2007; 91 (17)

    View details for DOI 10.1063/1.2801695

    View details for Web of Science ID 000250468200064

  • Branch migration displacement assay with automated heuristic analysis for discrete DNA length measurement using DNA microarrays PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Pourmand, N., Caramuta, S., Villablanca, A., Mori, S., Karhanek, M., Wang, S. X., Davis, R. W. 2007; 104 (15): 6146-6151

    Abstract

    The analysis of short tandem repeats (STRs) plays an important role in forensic science, human identification, genetic mapping, and disease diagnostics. Traditional STR analysis utilizes gel- or column-based approaches to analyze DNA repeats. Individual STR alleles are separated and distinguished according to fragment length; thus the assay is generally hampered by its low multiplex capacity. However, use of DNA microarray would employ a simple hybridization and detection for field forensics and biology. Here we demonstrate a rapid, highly sensitive method for STR analysis that utilizes DNA microarray technology. We describe two adaptations to accomplish this: the use of competitive hybridization to remove unpaired ssDNA from an array and the use of neural network classification to automate the analysis. The competitive displacement technique mimics the branch migration process that occurs during DNA recombination. Our technique will facilitate the rapid deduction of identity, length, and number of repeats for the multiple STRs in an unknown DNA sample.

    View details for DOI 10.1073/pnas.0700921104

    View details for Web of Science ID 000245737500012

    View details for PubMedID 17389407

    View details for PubMedCentralID PMC1838402

  • Spin filter based tunnel junctions JOURNAL OF APPLIED PHYSICS Chapline, M. G., Wang, S. X. 2006; 100 (12)

    View details for DOI 10.1063/1.2382720

    View details for Web of Science ID 000243157900058

  • Room-temperature spin filtering in a CoFe2O4/MgAl2O4/Fe3O4 magnetic tunnel barrier PHYSICAL REVIEW B Chapline, M. G., Wang, S. X. 2006; 74 (1)

    View details for DOI 10.1103/PhysRevB.74.014418

    View details for Web of Science ID 000239426400070

  • Spin valve biosensors: Signal dependence on nanoparticle position JOURNAL OF APPLIED PHYSICS Li, G., Sun, S., Wang, S. X. 2006; 99 (8)

    View details for DOI 10.1063/1.2170052

    View details for Web of Science ID 000237404200633

  • Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects NANO LETTERS Cai, W. B., Shin, D. W., Chen, K., Gheysens, O., Cao, Q. Z., Wang, S. X., Gambhir, S. S., Chen, X. Y. 2006; 6 (4): 669-676

    Abstract

    We report the in vivo targeting and imaging of tumor vasculature using arginine-glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD intravenously. The tumor fluorescence intensity reached maximum at 6 h postinjection with good contrast. The results reported here open up new perspectives for integrin-targeted near-infrared optical imaging and may aid in cancer detection and management including imaging-guided surgery.

    View details for DOI 10.1021/nl052405t

    View details for Web of Science ID 000236916200015

    View details for PubMedID 16608262

  • Spin valve sensors for ultrasensitive detection of superparamagnetic nanoparticles for biological applications SENSORS AND ACTUATORS A-PHYSICAL Li, G. X., Sun, S. H., Wilson, R. J., White, R. L., Pourmand, N., Wang, S. X. 2006; 126 (1): 98-106

    Abstract

    We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparamagnetic nanoparticles as potential biomolecular labels in magnetic biodetection technology. We discuss the sensor design and experimentally demonstrate that as few as approximately 23 monodisperse 16-nm superparamagnetic Fe(3)O(4) nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in detection. A patterned self-assembly method of nanoparticles, based on a polymer-mediated process and fine lithography, is developed for the detection. It is found that sensor signal increases linearly with the number of nanoparticles.

    View details for DOI 10.1016/j.sna.2005.10.001

    View details for Web of Science ID 000235103900015

    View details for PubMedCentralID PMC2293286

  • Spin valve sensors for ultrasensitive detection of superparamagnetic nanoparticles for biological applications. Sensors and actuators. A, Physical Li, G., Sun, S., Wilson, R. J., White, R. L., Pourmand, N., Wang, S. X. 2006; 126 (1): 98–106

    Abstract

    We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparamagnetic nanoparticles as potential biomolecular labels in magnetic biodetection technology. We discuss the sensor design and experimentally demonstrate that as few as approximately 23 monodisperse 16-nm superparamagnetic Fe(3)O(4) nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in detection. A patterned self-assembly method of nanoparticles, based on a polymer-mediated process and fine lithography, is developed for the detection. It is found that sensor signal increases linearly with the number of nanoparticles.

    View details for PubMedID 18414592

  • A novel method for STR-based DNA profiling using microarrays JOURNAL OF FORENSIC SCIENCES Kemp, J. T., Davis, R. W., White, R. L., Wang, S. X., Webb, C. D. 2005; 50 (5): 1109-1113

    Abstract

    We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.

    View details for Web of Science ID 000231660300013

    View details for PubMedID 16225215

  • Bio-functionalization of monodisperse magnetic nanoparticles and their use as biomolecular labels in a magnetic tunnel junction based sensor JOURNAL OF PHYSICAL CHEMISTRY B Grancharov, S. G., Zeng, H., Sun, S. H., Wang, S. X., O'Brien, S., Murray, C. B., Kirtley, J. R., Held, G. A. 2005; 109 (26): 13030-13035

    Abstract

    Monodisperse magnetic nanoparticles (NPs) could enable the ultra-sensitive magnetic detection of biological analytes. However, rendering these particles biocompatible has remained a challenge. We report the bio-functionalization and detection of 12-nm manganese ferrite NPs. We have achieved the site-specific binding of biotin-functionalized NPs onto avidin-patterned silicon oxide substrates and DNA-functionalized NPs onto complementary DNA-patterned silicon oxide substrates. Utilizing scanning SQUID microscopy, we show that these substrate-bound NPs retain their magnetic properties. Finally, we demonstrate a novel method of detecting either protein binding or DNA hybridization at room temperature using the NPs and a magnetic tunnel-junction-based biosensor situated in orthogonal magnetic fields.

    View details for DOI 10.1021/jp051098c

    View details for Web of Science ID 000230224700053

    View details for PubMedID 16852617

  • Observation of the Verwey transition in thin magnetite films JOURNAL OF APPLIED PHYSICS Chapline, M. G., Wang, S. X. 2005; 97 (12)

    View details for DOI 10.1063/1.1929092

    View details for Web of Science ID 000230278100070

  • Room-temperature spin coherence in ZnO APPLIED PHYSICS LETTERS Ghosh, S., Sih, V., Lau, W. H., Awschalom, D. D., Bae, S. Y., Wang, S., Vaidya, S., Chapline, G. 2005; 86 (23)

    View details for DOI 10.1063/1.1946204

    View details for Web of Science ID 000230087400037

  • DNA-functionalized MFe2O4 (M = Fe, Co, or Mn) nanoparticles and their hybridization to DNA-functionalized surfaces LANGMUIR Robinson, D. B., Persson, H. H., Zeng, H., Li, G. X., Pourmand, N., Sun, S. H., Wang, S. X. 2005; 21 (7): 3096-3103

    Abstract

    Magnetic MFe2O4 (M = Fe, Co, or Mn) nanoparticles with uniform diameters in the 4-20 nm range and with excellent material properties, reported previously, can be rendered soluble in water or aqueous buffers using a combination of alkylphosphonate surfactants and other surfactants such as ethoxylated fatty alcohols or phospholipids. Surfactant-modified oligonucleotides can be incorporated into the particles' organic shell. The particles can withstand salt concentrations up to 0.3 M, temperatures up to 90 degrees C, and various operations such as concentration to dryness, column or membrane separations, and electrophoresis. The particles can be selectively hybridized to DNA-functionalized gold surfaces with high coverages using a two-story monolayer structure. These particles may find valuable applications involving the magnetic detection of small numbers of biomolecules using spin valves, magnetic tunnel junctions, or other sensors.

    View details for Web of Science ID 000228042400068

    View details for PubMedID 15779990

    View details for PubMedCentralID PMC2924586

  • Growth and characterization of copper nanoclusters embedded in SiC matrix THIN SOLID FILMS Shin, D. W., Wang, S. X., Marshall, A. F., Kimura, W., Dong, C. L., Augustsson, A., Guo, J. H. 2005; 473 (2): 267-271

    View details for DOI 10.1016/j.tsf.2004.07.079

    View details for Web of Science ID 000226169800016

  • Dumbbell-like bifunctional Au-Fe3O4 nanoparticles NANO LETTERS Yu, H., Chen, M., Rice, P. M., Wang, S. X., White, R. L., Sun, S. H. 2005; 5 (2): 379–82

    View details for DOI 10.1021/nl047955q

    View details for Web of Science ID 000227100500034

  • Shape-controlled synthesis and shape-induced texture of MnFe2O4 nanoparticles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Zeng, H., Rice, P. M., Wang, S. X., Sun, S. H. 2004; 126 (37): 11458-11459

    Abstract

    Monodisperse MnFe2O4 nanoparticles with cubelike and polyhedron shapes were synthesized by reaction of Fe(acac)3 and Mn(acac)2 with 1,2-hexadecanediol, oleic acid, and oleylamine. Controlled evaporation of the particle dispersion led to nanoparticle superlattices. The crystal orientation of the particle in the assembly depends on the shape of the particles, with particles in a cubelike shape showing (100) texture and those in the polyhedron shape exhibiting (110) texture.

    View details for DOI 10.1021/ja045911d

    View details for Web of Science ID 000223921800029

    View details for PubMedID 15366890

  • Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Sun, S. H., Zeng, H., Robinson, D. B., Raoux, S., Rice, P. M., Wang, S. X., Li, G. X. 2004; 126 (1): 273-279

    Abstract

    High-temperature solution phase reaction of iron(III) acetylacetonate, Fe(acac)(3), with 1,2-hexadecanediol in the presence of oleic acid and oleylamine leads to monodisperse magnetite (Fe(3)O(4)) nanoparticles. Similarly, reaction of Fe(acac)(3) and Co(acac)(2) or Mn(acac)(2) with the same diol results in monodisperse CoFe(2)O(4) or MnFe(2)O(4) nanoparticles. Particle diameter can be tuned from 3 to 20 nm by varying reaction conditions or by seed-mediated growth. The as-synthesized iron oxide nanoparticles have a cubic spinel structure as characterized by HRTEM, SAED, and XRD. Further, Fe(3)O(4) can be oxidized to Fe(2)O(3), as evidenced by XRD, NEXAFS spectroscopy, and SQUID magnetometry. The hydrophobic nanoparticles can be transformed into hydrophilic ones by adding bipolar surfactants, and aqueous nanoparticle dispersion is readily made. These iron oxide nanoparticles and their dispersions in various media have great potential in magnetic nanodevice and biomagnetic applications.

    View details for DOI 10.1021/ja0380852

    View details for Web of Science ID 000187945400063

    View details for PubMedID 14709092

  • Fe3O4 and its magnetic tunneling junctions grown by ion beam deposition JOURNAL OF APPLIED PHYSICS Aoshima, K., Wang, S. X. 2003; 93 (10): 7954–56

    View details for DOI 10.1063/1.1558633

    View details for Web of Science ID 000182822600105

  • Measurement and analysis of noise sources in giant magnetoresistive sensors up to 6 GHz IEEE TRANSACTIONS ON MAGNETICS Jury, J. C., Klaassen, K. B., van Peppen, J. C., Wang, S. X. 2002; 38 (5): 3545-3555

    View details for DOI 10.1109/TMAG.2002.802706

    View details for Web of Science ID 000178867300022

  • Soft magnetism of Fe-Co-N thin films with a Permalloy underlayer JOURNAL OF APPLIED PHYSICS Sun, N. X., Wang, S. X. 2002; 92 (3): 1477–82

    View details for DOI 10.1063/1.1491017

    View details for Web of Science ID 000176907700049

  • Extending the bandwidth of magnetic tunnel junction sensors by a buffer amplifier IEEE TRANSACTIONS ON MAGNETICS Jury, J. C., Wang, S. X. 2002; 38 (1): 295-297

    View details for Web of Science ID 000174273600015

  • Oxidation kinetics of tunnel barrier and its effect on exchange bias of proximity interface APPLIED PHYSICS LETTERS Bae, S. Y., Shin, K. H., Lee, J. H., Rhie, K. W., Lee, K. I., Ha, J. G., Wang, S. X. 2001; 79 (25): 4130-4132

    View details for Web of Science ID 000172682300020

  • Epitaxial growth of aluminum on permalloy THIN SOLID FILMS Li, Y., Wang, S. X., Khanna, G., Clemens, B. M. 2001; 381 (1): 160-163

    View details for Web of Science ID 000166467800022

  • Spin-dependent tunneling junctions with AlN and AlON barriers APPLIED PHYSICS LETTERS Sharma, M., Nickel, J. H., Anthony, T. C., Wang, S. X. 2000; 77 (14): 2219-2221

    View details for Web of Science ID 000089524900047

  • Sandwich films - Properties of a new soft magnetic material NATURE Wang, S. X., Sun, N. X., Yamaguchi, M., Yabukami, S. 2000; 407 (6801): 150–51

    View details for DOI 10.1038/35025142

    View details for Web of Science ID 000089241000035

  • Magnetic properties, microstructures, and corrosion resistance of high-saturation FeMoN and FeRhN films for recording heads IEEE TRANSACTIONS ON MAGNETICS Wang, S. X., Sin, K., Hong, J., Nguyentran, L. 2000; 36 (2): 513–20

    View details for DOI 10.1109/20.825827

    View details for Web of Science ID 000085790200012

  • Properties of a new soft magnetic material Nature Wang, S. X., Sun, N. X., Yamaguchi, M., Yabukami, S. 2000; 407 (6801): 150–51

    View details for PubMedID 11001044

  • Electronic scattering from Co/Cu interfaces: In situ measurement and comparison with theory PHYSICAL REVIEW B Bailey, W. E., Wang, S. X., Tsymbal, E. Y. 2000; 61 (2): 1330-1335

    View details for Web of Science ID 000085760000074

  • Magnetic properties and high-frequency responses of high moment FeTaN/AlN laminates for high-data-rate magnetic recording IEEE TRANSACTIONS ON MAGNETICS Hong, J. G., Furukawa, A., Sun, N. X., Wang, S. X., Grimes, C. A., Sahu, S. 1999; 35 (5): 2502-2504

    View details for Web of Science ID 000083151100092

  • Determination of barrier oxidation states in spin dependent tunneling structures JOURNAL OF APPLIED PHYSICS Sharma, M., Wang, S. X., Nickel, J. H. 1999; 85 (11): 7803-7806

    View details for Web of Science ID 000080354300043

  • Direct measurement of surface scattering in giant magnetoresistance spin valves JOURNAL OF APPLIED PHYSICS Bailey, W. E., Fery, C., Yamada, K., Wang, S. X. 1999; 85 (10): 7345–48

    View details for DOI 10.1063/1.369360

    View details for Web of Science ID 000080136000050

  • Spin-dependent tunneling junctions with Fe55Ni45 electrodes and in situ resistive measurement of oxide growth APPLIED PHYSICS LETTERS Wee, A. T., Sin, K. S., Wang, S. X. 1999; 74 (17): 2528-2530

    View details for Web of Science ID 000079855900042

  • Inversion of spin polarization and tunneling magnetoresistance in spin-dependent tunneling junctions PHYSICAL REVIEW LETTERS Sharma, M., Wang, S. X., Nickel, J. H. 1999; 82 (3): 616-619

    View details for Web of Science ID 000078059200039

  • Novel sol-gel processing for polycrystalline and epitaxial thin films of La0.67Ca0.33MnO3 with colossal magnetoresistance JOURNAL OF MATERIALS RESEARCH Bae, S. Y., Wang, S. X. 1998; 13 (11): 3234-3240

    View details for Web of Science ID 000076758200029

  • Colossal magnetoresistance in sol-gel derived epitaxial thin film of co-doped La1-xCaxMnOx JOURNAL OF ELECTRONIC MATERIALS Bae, S. Y., Snyder, D. J., Wang, S. X. 1998; 27 (1): 1-7

    View details for Web of Science ID 000071470700001

  • Effect of ion bombardment on the long-range chemical order in FePd films JOURNAL OF APPLIED PHYSICS Surgers, C., Kay, E., Wang, S. X. 1996; 80 (10): 5753–58

    View details for DOI 10.1063/1.363629

    View details for Web of Science ID A1996VU98700031

  • SYNTHESIS, STRUCTURE, AND PROPERTIES OF SR2CUO2CL2 PHYSICAL REVIEW B MILLER, L. L., WANG, X. L., WANG, S. X., STASSIS, C., JOHNSTON, D. C., FABER, J., LOONG, C. K. 1990; 41 (4): 1921–25

    View details for DOI 10.1103/PhysRevB.41.1921

    View details for Web of Science ID A1990CM84700024

  • Large voltage control of magnetic anisotropy in CoFeB/MgO/OX structures at room temperature APL MATERIALS Xue, F., Sato, N., Bi, C., Hu, J., He, J., Wang, S. X. 2019; 7 (10)

    View details for DOI 10.1063/1.5101002

    View details for Web of Science ID 000501309200002

  • Quantification of cDNA on GMR biosensor array towards point-of-care gene expression analysis BIOSENSORS & BIOELECTRONICS Ravi, N., Rizzi, G., Chang, S. E., Cheung, P., Utz, P. J., Wang, S. X. 2019; 130: 338–43

    View details for DOI 10.1016/j.bios.2018.09.050

    View details for Web of Science ID 000461526200036

  • Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors. Theranostics Lee, J. R., Appelmann, I., Miething, C., Shultz, T. O., Ruderman, D., Kim, D., Mallick, P., Lowe, S. W., Wang, S. X. 2018; 8 (5): 1389–98

    Abstract

    Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays.Methods:Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice.Results:The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment.Conclusion:The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.

    View details for PubMedID 29507628

  • An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nature biomedical engineering Vermesh, O., Aalipour, A., Ge, T. J., Saenz, Y., Guo, Y., Alam, I. S., Park, S. M., Adelson, C. N., Mitsutake, Y., Vilches-Moure, J., Godoy, E., Bachmann, M. H., Ooi, C. C., Lyons, J. K., Mueller, K., Arami, H., Green, A., Solomon, E. I., Wang, S. X., Gambhir, S. S. 2018; 2 (9): 696–705

    Abstract

    The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10-80 times the amount of CTCs in a 5-ml blood draw, and 500-5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.

    View details for PubMedID 30505627

  • Novel Method for Magnetic Field Vector Measurement Based on Dual-Axial Tunneling Magnetoresistive Sensors IEEE TRANSACTIONS ON MAGNETICS Zhao, G., Hu, J., Ouyang, Y., Chang, W., Wang, Z., Wang, S. X., He, J., Bi, J. 2017; 53 (8)

    View details for DOI 10.1109/TMAG.2017.2655007

    View details for Web of Science ID 000408121900007

  • Closed-loop model: An optimization of integrated thin-film magnetic devices JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS El-Ghazaly, A., Sato, N., White, R. M., Wang, S. X. 2017; 432: 218-223

    View details for DOI 10.1016/j.jmmm.2017.01.089

    View details for Web of Science ID 000399601600031

  • Exchange-Biased Anisotropic Magnetoresistive Field Sensor IEEE SENSORS JOURNAL Guo, Y., Ouyang, Y., Sato, N., Ooi, C. C., Wang, S. X. 2017; 17 (11): 3309-3315

    View details for DOI 10.1109/JSEN.2017.2695238

    View details for Web of Science ID 000401083200011

  • Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration. Stem cells translational medicine Brett, E., Zielins, E. R., Luan, A., Ooi, C. C., Shailendra, S., Atashroo, D., Menon, S., Blackshear, C., Flacco, J., Quarto, N., Wang, S. X., Longaker, M. T., Wan, D. C. 2017; 6 (1): 151-160

    Abstract

    Clinical translation of cell-based strategies for tissue regeneration remains challenging because survival of implanted cells within hostile, hypoxic wound environments is uncertain. Overexpression of B-cell lymphoma 2 (Bcl-2) has been shown to inhibit apoptosis in implanted cells. The present study describes an "off the shelf" prefabricated scaffold integrated with magnetic nanoparticles (MNPs) used to upregulate Bcl-2 expression in implanted adipose-derived stromal cells for bone regeneration. Iron oxide cores were sequentially coated with branched polyethyleneimine, minicircle plasmid encoding green fluorescent protein and Bcl-2, and poly-β-amino ester. Through in vitro assays, increased osteogenic potential and biological resilience were demonstrated in the magnetofected group over control and nucleofected groups. Similarly, our in vivo calvarial defect study showed that magnetofection had an efficiency rate of 30%, which in turn resulted in significantly more healing compared with control group and nucleofected group. Our novel, prefabricated MNP-integrated scaffold allows for in situ postimplant temporospatial control of cell transfection to augment bone regeneration. Stem Cells Translational Medicine 2017;6:151-160.

    View details for DOI 10.5966/sctm.2016-0051

    View details for PubMedID 28170185

  • Multigene Profiling of Single Circulating Tumor Cells Molecular & Cellular Oncology Park, S., Wong, D., Ooi, C., Nesvet, J., Nair, V. S., Wang, S. X., Gambhir, S. S. 2017; 4 (2): e1289295

    Abstract

    Numerous techniques for isolating circulating tumor cells (CTCs) have been developed. Concurrently, single-cell techniques that can reveal molecular components of CTCs have become widely available. We discuss how the combination of isolation and multigene profiling of single CTCs in our platform can facilitate eventual translation to the clinic.

    View details for DOI 10.1080/23723556.2017.1289295

    View details for PubMedCentralID PMC5383366

  • Hierarchical complexity and the size limits of life Proceedings of the Royal Society B: Biological Sciences Heim, N. A., Payne, J. L., Finnegan, S., Knope, M. L., Kowalewski, M., Lyons, S. K., McShea, D. W., Novack-Gottshall, P. M., Smith, F. A., Wang, S. C. 2017; 284

    Abstract

    Over the past 3.8 billion years, the maximum size of life has increased by approximately 18 orders of magnitude. Much of this increase is associated with two major evolutionary innovations: the evolution of eukaryotes from prokaryotic cells approximately 1.9 billion years ago (Ga), and multicellular life diversifying from unicellular ancestors approximately 0.6 Ga. However, the quantitative relationship between organismal size and structural complexity remains poorly documented. We assessed this relationship using a comprehensive dataset that includes organismal size and level of biological complexity for 11 172 extant genera. We find that the distributions of sizes within complexity levels are unimodal, whereas the aggregate distribution is multimodal. Moreover, both the mean size and the range of size occupied increases with each additional level of complexity. Increases in size range are non-symmetric: the maximum organismal size increases more than the minimum. The majority of the observed increase in organismal size over the history of life on the Earth is accounted for by two discrete jumps in complexity rather than evolutionary trends within levels of complexity. Our results provide quantitative support for an evolutionary expansion away from a minimal size constraint and suggest a fundamental rescaling of the constraints on minimal and maximal size as biological complexity increases.

    View details for DOI 10.1098/rspb.2017.1039

    View details for PubMedCentralID PMC5489738

  • Multilayer anisotropic magnetoresistive angle sensor Sensors and Actuators A: Physical Guo, Y., Deng, Y., Wang, S. X. 2017; 263: 159-165

    View details for DOI 10.1016/j.sna.2017.06.001

  • A Novel High-Performance Energy Harvester Based on Nonlinear Resonance for Scavenging Power-Frequency Magnetic Energy IEEE Transactions on Industrial Electronics Wang, Z., Hu, J., Han, J., Zhao, G., He, J., Wang, S. X. 2017; 64 (8): 6556-6564

    View details for DOI 10.1109/TIE.2017.2682040

  • Stand-Alone Stretchable Absolute Pressure Sensing System for Industrial Applications IEEE Transactions on Industrial Electronics Guo, Y., Schütz, S., Vaghi, A., Li, Y., Guo, Z., Chang, F., Barrettino, D., Wang, S. X. 2017; 64 (11): 8739-8746

    View details for DOI 10.1109/TIE.2017.2701763

  • Electrically Tunable Integrated Thin‐Film Magnetoelectric Resonators Advanced Materials Technologies El-Ghazaly, A., Evans, J. T., Sato, N., Montross, N., Ohldag, H., White, R. M., Wang, S. X. 2017; 2 (8)

    View details for DOI 10.1002/admt.201700062

  • High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays ACS NANO Lee, J., Haddon, D. J., Gupta, N., Price, J. V., Credo, G. M., Diep, V. K., Kim, K., Hall, D. A., Baechler, E. C., Petri, M., Varma, M., Utz, P. J., Wang, S. X. 2016; 10 (12): 10652-10660

    Abstract

    Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid. We have also developed a chemical regeneration scheme to perform multiplex assays with a high level of reproducibility, resulting in greatly reduced experimental costs. In addition, we show that peptides synthesized directly on the nanosensors are approximately two times more sensitive than directly spotted peptides. Reusable peptide nanosensor microarrays enable precise detection of autoantibodies with high resolution and sensitivity and show promise for investigating antibody-mediated immune responses to autoantigens, vaccines, and pathogen-derived antigens as well as other fundamental peptide-protein interactions.

    View details for DOI 10.1021/acsnano.6b03786

    View details for PubMedID 27636738

  • Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors SCIENTIFIC REPORTS Lee, J., Sato, N., Bechstein, D. J., Osterfeld, S. J., Wang, J., Gani, A. W., Hall, D. A., Wang, S. X. 2016; 6

    Abstract

    Giant magnetoresistive (GMR) biosensors consisting of many rectangular stripes are being developed for high sensitivity medical diagnostics of diseases at early stages, but many aspects of the sensing mechanism remain to be clarified. Using e-beam patterned masks on the sensors, we showed that the magnetic nanoparticles with a diameter of 50 nm located between the stripes predominantly determine the sensor signals over those located on the sensor stripes. Based on computational analysis, it was confirmed that the particles in the trench, particularly those near the edges of the stripes, mainly affect the sensor signals due to additional field from the stripe under an applied field. We also demonstrated that the direction of the average magnetic field from the particles that contributes to the signal is indeed the same as that of the applied field, indicating that the particles in the trench are pivotal to produce sensor signal. Importantly, the same detection principle was validated with a duplex protein assay. Also, 8 different types of sensor stripes were fabricated and design parameters were explored. According to the detection principle uncovered, GMR biosensors can be further optimized to improve their sensitivity, which is highly desirable for early diagnosis of diseases.

    View details for DOI 10.1038/srep18692

    View details for Web of Science ID 000368275200001

    View details for PubMedCentralID PMC4700494

  • 45 degrees Induced Magnetic Anisotropy for Isotropic High-Frequency Permeability IEEE TRANSACTIONS ON MAGNETICS Sato, N., El-Ghazaly, A., White, R. M., Wang, S. X. 2015; 51 (11)

    View details for DOI 10.1109/TMAG.2015.2440292

    View details for Web of Science ID 000364770500225

  • Contactless Current Sensors Based on Magnetic Tunnel Junction for Smart Grid Applications Ouyang, Y., He, J., Hu, J., Zhao, G., Wang, Z., Wang, S. X. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2015

    View details for DOI 10.1109/TMAG.2015.2446332

    View details for Web of Science ID 000364770500322

  • Prediction and Optimization of Linearity of MTJ Magnetic Sensors Based on Single-Domain Model Ouyang, Y., He, J., Hu, J., Zhao, G., Wang, Z., Wang, S. X. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2015

    View details for DOI 10.1109/TMAG.2015.2439152

    View details for Web of Science ID 000364770500315

  • Electric Field Sensor Based on Piezoelectric Bending Effect for Wide Range Measurement IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS Xue, F., Hu, J., Wang, S. X., He, J. 2015; 62 (9): 5730-5737

    View details for DOI 10.1109/TIE.2015.2414397

    View details for Web of Science ID 000359560800038

  • High-Density 2D Homo- and Hetero- Plasmonic Dimers with Universal Sub-10-nm Gaps ACS NANO Zhang, M., Large, N., Koh, A. L., Cao, Y., Manjavacas, A., Sinclair, R., Nordlander, P., Wang, S. X. 2015; 9 (9): 9331-9339

    Abstract

    Fabrication of high-density plasmonic dimers on a large (wafer) scale is crucial for applications in surface-enhanced spectroscopy, bio- and molecular sensing, and optoelectronics. Here, we present an experimental approach based on nanoimprint lithography and shadow evaporation that allows for the fabrication of high-density, large-scale homo- (Au-Au and Ag-Ag) and hetero- (Au-Ag) dimer substrates with precise and consistent sub-10-nm gaps. We performed scanning electron, scanning transmission electron, and atomic force microscopy studies along with a complete electron energy-loss spectroscopy (EELS) characterization. We observed distinct plasmonic modes on these dimers, which are well interpreted by finite-difference time-domain (FDTD) and plasmon hybridization calculations.

    View details for DOI 10.1021/acsnano.5b03090

    View details for Web of Science ID 000361935800073

    View details for PubMedID 26202803

  • On the importance of sensor height variation for detection of magnetic labels by magnetoresistive sensors SCIENTIFIC REPORTS Henriksen, A., Wang, S., Hansen, M. 2015; 5: 12282

    Abstract

    Magnetoresistive sensors are widely used for biosensing by detecting the signal from magnetic labels bound to a functionalized area that usually covers the entire sensor structure. Magnetic labels magnetized by a homogeneous applied magnetic field weaken and strengthen the applied field when they are over and outside the sensor area, respectively, and the detailed origin of the sensor signal in experimental studies has not been clarified. We systematically analyze the signal from both a single sensor stripe and an array of sensor stripes as function of the geometrical parameters of the sensor stripes as well as the distribution of magnetic labels over the stripes. We show that the signal from sensor stripes with a uniform protective coating, contrary to conventional wisdom in the field, is usually dominated by the contribution from magnetic labels between the sensor stripes rather than by the labels on top of the sensor stripes because these are at a lower height. We therefore propose a shift of paradigm to maximize the signal due to magnetic labels between sensor stripes. Guidelines for this optimization are provided and illustrated for an experimental case from the literature.

    View details for PubMedID 26195089

  • A Nonintrusive Power Supply Design for Self-Powered Sensor Networks in the Smart Grid by Scavenging Energy From AC Power Line IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS Han, J., Hu, J., Yang, Y., Wang, Z., Wang, S. X., He, J. 2015; 62 (7): 4398-4407

    View details for DOI 10.1109/TIE.2014.2383992

    View details for Web of Science ID 000354945400041

  • Optimum direct current magnetic bias in ferromagnetic phase for improvement of magnetoelectric effect APPLIED PHYSICS LETTERS Xue, F., Hu, J., Wang, S. X., He, J. 2015; 106 (26)

    View details for DOI 10.1063/1.4923417

    View details for Web of Science ID 000357693200031

  • Reduction of magnetic 1/f noise in miniature anisotropic magnetoresistive sensors APPLIED PHYSICS LETTERS Guo, Y., Wang, J., White, R. M., Wang, S. X. 2015; 106 (21)

    View details for DOI 10.1063/1.4921764

    View details for Web of Science ID 000355631400021

  • Increasing ferromagnetic resonance frequency using lamination and shape JOURNAL OF APPLIED PHYSICS El-Ghazaly, A., White, R. M., Wang, S. X. 2015; 117 (17)

    View details for DOI 10.1063/1.4913509

    View details for Web of Science ID 000354984100508

  • Great enhancement of energy harvesting properties of piezoelectric/magnet composites by the employment of magnetic concentrator JOURNAL OF APPLIED PHYSICS Han, J., Hu, J., Wang, S. X., He, J. 2015; 117 (17)

    View details for DOI 10.1063/1.4906964

    View details for Web of Science ID 000354984100005

  • Mobile ions generated by external direct current electric field influence direct current measurement of giant magnetoresistance current sensors JOURNAL OF APPLIED PHYSICS Zhao, G., Hu, J., Ouyang, Y., He, J., Wang, S. X., Yuan, Z. 2015; 117 (17)

    View details for DOI 10.1063/1.4907698

    View details for Web of Science ID 000354984100008

  • Pilot Application of Magnetic Nanoparticle-Based Biosensor for Necrotizing Enterocolitis Journal of Proteomics and Bioinformatics Kim, D., Fu, C., Ling, X. B., Hu, Z., Tao, G., Zhao, Y., Kastenberg, Z. J., Sylvester, K. G., Wang, S. X. 2014

    View details for DOI 10.4172/jpb.S5-002

  • Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation. IEEE transactions on magnetics Ooi, C., Earhart, C. M., Wilson, R. J., Wang, S. X. 2013; 49 (7): 3434–37

    Abstract

    NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen were previously shown to be captured at high efficiencies by a microfabricated magnetic sifter. If fine control and optimization of the magnetic separation process is to be achieved, it is vital to be able to characterize the labeled cells' magnetic moment rapidly. We have thus adapted a rapid prototyping method to obtain the saturation magnetic moment of these cells. This method utilizes a cross-correlation algorithm to analyze the cells' motion in a simple fluidic channel to obtain their magnetophoretic velocity, and is effective even when the magnetic moments of cells are small. This rapid characterization is proven useful in optimizing our microfabricated magnetic sifter procedures for magnetic cell capture.

    View details for PubMedID 24771946

  • GMR Spin-Valve Biosensors HANDBOOK OF SPIN TRANSPORT AND MAGNETISM Hall, D. A., Gaster, R. S., Wang, S. X., Tsymbal, E. Y., Zutic 2012: 715–29

    View details for Web of Science ID 000356247000038

  • High Resolution Crystal Structure of the Methylcobalamin Analogues Ethylcobalamin and Butylcobalamin by X-ray Synchrotron Diffraction INORGANIC CHEMISTRY Hannibal, L., Smith, C. A., Smith, J. A., Axhemi, A., Miller, A., Wang, S., Brasch, N. E., Jacobsen, D. W. 2009; 48 (14): 6615-6622

    Abstract

    The X-ray crystal structures of the methylcobalamin (MeCbl) analogues ethylcobalamin (EtCbl) and butylcobalamin (BuCbl) are reported. The X-ray crystal structures of EtCbl and BuCbl were obtained with some of the lowest crystallographic residuals ever achieved for cobalamins (R = 0.0468 and 0.0438, respectively). The Co-C bond distances for EtCbl and BuCbl are 2.023(2) and 2.028(4) A, whereas the Co-alpha-5,6-dimethylbenzimidazole (Co-N3B) bond distances were 2.232(1) and 2.244(1) A, respectively. Although EtCbl and BuCbl displayed a longer Co-N3B bond than that observed in the naturally occurring methylcobalamin, the orientation of the alpha-5,6-dimethylbenzimidazole moiety with respect to the corrin ring did not vary substantially among the structures. The lengthening of both Co-C and Co-N3B bonds in EtCbl and BuCbl can be attributed to the "inverse" trans influence exerted by the sigma-donating alkyl groups, typically observed in alkylcobalamins. Analysis of the molecular surface maps showed that the alkyl ligands in EtCbl and BuCbl are directed toward the hydrophobic side of the corrin ring. The corrin fold angles in EtCbl and BuCbl were determined to be 14.7 degrees and 13.1 degrees, respectively. A rough correlation exists between the corrin fold angle and the length of the Co-N3B bond, and both alkylcobalamins follow the same trend.

    View details for DOI 10.1021/ic900590p

    View details for Web of Science ID 000268137900042

    View details for PubMedID 19545130

    View details for PubMedCentralID PMC2878369

  • Cryogenic tilt table INTERNATIONAL JOURNAL OF PRECISION ENGINEERING AND MANUFACTURING Ambekar, P. P., Wang, S., Torii, R., DeBra, D. 2009; 10 (3): 37-42

    View details for DOI 10.1007/s12541-009-0045-9

    View details for Web of Science ID 000268009600006

  • Effects of polyhydroxy compounds on beetle antifreeze protein activity BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS Amornwittawat, N., Wang, S., Banatlao, J., Chung, M., Velasco, E., Duman, J. G., Wen, X. 2009; 1794 (2): 341-346

    Abstract

    Antifreeze proteins (AFPs) noncolligatively depress the nonequilibrium freezing point of a solution and produce a difference between the melting and freezing points termed thermal hysteresis (TH). Some low-molecular-mass solutes can affect the TH values. The TH enhancement effects of selected polyhydroxy compounds including polyols and carbohydrates on an AFP from the beetle Dendroides canadensis were systematically investigated using differential scanning calorimetry (DSC). The number of hydroxyl groups dominates the molar enhancement effectiveness of polyhydroxy compounds having one to five hydroxyl groups. However, the above rule does not apply for polyhydroxy compounds having more than five hydroxyl groups. The most efficient polyhydroxy enhancer identified is trehalose. In a combination of enhancers the strongest enhancer plays the major role in determining the TH enhancement. Mechanistic insights into identification of highly efficient AFP enhancers are discussed.

    View details for DOI 10.1016/j.bbapap.2008.10.011

    View details for Web of Science ID 000262952600022

    View details for PubMedID 19038370

  • Gravity Probe B(*) RIVISTA DEL NUOVO CIMENTO Keiser, G. M., Adams, M., BENCZE, W. J., BRUMLEY, R. W., Buchman, S., Clarke, B., Conklin, J., DeBra, D. B., DOLPHIN, M., HIPKINS, D. N., Holmes, T., Everitt, C. W., Goebel, J. H., Gill, D., Green, G. B., Heifetz, M., Kolodziejczak, J., Li, J., Lipa, J., Lockhart, J. M., Mester, J. C., Muhlfelder, B., Ohshima, Y., Parkinson, B. W., Salomon, M., Shestople, P., Silbergleit, A. S., Stahl, K., Taber, M. A., Turneaure, J. P., Wang, S., Worden, P. 2009; 32 (11): 555-589

    View details for DOI 10.1393/ncr/i2009-10049-y

    View details for Web of Science ID 000273677400001

  • Biological Variations in Depression and Anxiety Between East and West CNS NEUROSCIENCE & THERAPEUTICS Chen, P., Wang, S., Poland, R. E., Lin, K. 2009; 15 (3): 283-294

    Abstract

    Ethnicity and culture represent important factors in shaping psychopathology as well as pharmacotherapeutic responses in psychiatric patients. A large body of literature, accumulated over the past several decades, demonstrates that these factors not only determine the metabolism and disposition of medications (pharmacokinetics), but also their interactions with therapeutic targets (pharmacodynamics). This article focuses on the impact of such variations on the diagnosis and treatment of depression and anxiety disorders between East and West. Genes controlling the expression of drug metabolizing enzymes as well as the function of the brain are highly polymorphic, and the patterns and distribution of these polymorphisms are typically divergent across ethnic groups. To the extent that these genetic patterns determine drug response, ethnic variations in these genetic dispositions will lead to differential responses in clinical settings. In addition, the expression of these genes is significantly influenced by environmental factors including diet as well as exposure to other natural products. Superimposed on these biological influences, culturally determined beliefs and behavioral patterns also profoundly influence patients' expectations of treatment response, adherence, and interactions with clinicians. In addition to pharmacotherapeutic responses, emerging data also indicate that significant ethnic variations exist in genetic polymorphisms and neurobiologic correlates (biomarkers) that may be associated with the vulnerability to psychiatric disorders. These considerations argue for the importance of examining biological variations across ethnic groups, especially in the clinical context, in terms of the assessment and treatment of psychiatric patients, and in our understanding of psychiatric phenomenology and nosology.

    View details for DOI 10.1111/j.1755-5949.2009.00093.x

    View details for Web of Science ID 000268790700010

    View details for PubMedID 19691548

  • Genome-wide transcriptome analysis of 150 cell samples INTEGRATIVE BIOLOGY Irimia, D., Mindrinos, M., Russom, A., Xiao, W., Wilhelmy, J., Wang, S., Heath, J. D., Kurn, N., Tompkins, R. G., Davis, R. W., Toner, M. 2009; 1 (1): 99-107

    Abstract

    A major challenge in molecular biology is interrogating the human transcriptome on a genome wide scale when only a limited amount of biological sample is available for analysis. Current methodologies using microarray technologies for simultaneously monitoring mRNA transcription levels require nanogram amounts of total RNA. To overcome the sample size limitation of current technologies, we have developed a method to probe the global gene expression in biological samples as small as 150 cells, or the equivalent of approximately 300 pg total RNA. The new method employs microfluidic devices for the purification of total RNA from mammalian cells and ultra-sensitive whole transcriptome amplification techniques. We verified that the RNA integrity is preserved through the isolation process, accomplished highly reproducible whole transcriptome analysis, and established high correlation between repeated isolations of 150 cells and the same cell culture sample. We validated the technology by demonstrating that the combined microfluidic and amplification protocol is capable of identifying biological pathways perturbed by stimulation, which are consistent with the information recognized in bulk-isolated samples.

    View details for DOI 10.1039/b814329c

    View details for Web of Science ID 000266978200011

    View details for PubMedID 20023796

  • A Prospective Randomized Pilot Study of Site-specific Atlas Incorporation into Target Volume Delineation Instructions in the Cooperative Group Setting: Preliminary Results from a Southwest Oncology Group Pilot using Big Brother 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Fuller, C. D., Duppen, J., Rasch, C. R., Kachnic, L., Wang, S. J., Chang, D., Goodman, K. A., Katz, A. W., OKUNIEFF, P., Thomas, C. R. ELSEVIER SCIENCE INC. 2009: S136–S137

    View details for Web of Science ID 000270573600292

  • Inhibition of Drosophila Wg Signaling Involves Competition between Mad and Armadillo/beta-Catenin for dTcf Binding PLOS ONE Zeng, Y. A., Rahnama, M., Wang, S., Lee, W., Verheyen, E. M. 2008; 3 (12)

    Abstract

    Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor beta (TGFbeta)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector beta-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf.

    View details for DOI 10.1371/journal.pone.0003893

    View details for Web of Science ID 000265455200008

    View details for PubMedID 19065265

    View details for PubMedCentralID PMC2587708

  • Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004 CANCER CAUSES & CONTROL Daniel Carreon, J., Morton, L. M., Devesa, S. S., Clarke, C. A., Gomez, S. L., Glaser, S. L., Sakoda, L. C., Linet, M. S., Wang, S. S. 2008; 19 (10): 1171-1181

    Abstract

    To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups.Incident rates were estimated by age and sex for six Asian ethnic groups--Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese--in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated.During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype.The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.

    View details for DOI 10.1007/s10552-008-9184-z

    View details for Web of Science ID 000260766300017

    View details for PubMedID 18543071

    View details for PubMedCentralID PMC2581633

  • Polycarboxylates enhance beetle antifreeze protein activity BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS Amornwittawat, N., Wang, S., Duman, J. G., Wen, X. 2008; 1784 (12): 1942-1948

    Abstract

    Antifreeze proteins (AFPs) lower the noncolligative freezing point of water in the presence of ice below the ice melting point. The temperature difference between the melting point and the noncolligative freezing point is termed thermal hysteresis (TH). The magnitude of the TH depends on the specific activity and the concentration of AFP, and the concentration of enhancers in the solution. Known enhancers are certain low molecular mass molecules and proteins. Here, we investigated a series of polycarboxylates that enhance the TH activity of an AFP from the beetle Dendroides canadensis (DAFP) using differential scanning calorimetry (DSC). Triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetate, the most efficient enhancer identified in this work, can increase the TH of DAFP by nearly 1.5 fold over than that of the published best enhancer, citrate. The Zn(2+) coordinated carboxylate results in loss of the enhancement ability of the carboxylate on antifreeze activity. There is not an additional increase in TH when a weaker enhancer is added to a stronger enhancer solution. These observations suggest that the more carboxylate groups per enhancer molecule the better the efficiency of the enhancer and that the freedom of motion of these molecules is necessary for them to serve as enhancers for AFP. The hydroxyl groups in the enhancer molecules can also positively affect their TH enhancement efficiency, though not as strongly as carboxylate groups. Mechanisms are discussed.

    View details for DOI 10.1016/j.bbapap.2008.06.003

    View details for Web of Science ID 000261673300007

    View details for PubMedID 18620083

    View details for PubMedCentralID PMC2632549

  • The Bacillus subtilis RNA helicase YxiN is distended in solution BIOPHYSICAL JOURNAL wang, s., Overgaard, M. T., Hu, Y., McKay, D. B. 2008; 94 (1): L1-L3

    Abstract

    The Bacillus subtilis YxiN protein is a modular three-domain RNA helicase of the DEx(D/H)-box protein family. The first two domains form the highly conserved helicase core, and the third domain confers RNA target binding specificity. Small angle x-ray scattering on YxiN and two-domain fragments thereof shows that the protein has a distended structure in solution, in contrast to helicases involved in replication processes. These data are consistent with a chaperone activity in which the carboxy-terminal domain of YxiN tethers the protein to the vicinity of its targets and the helicase core is free to transiently interact with RNA duplexes, possibly to melt out misfolded elements of secondary structure.

    View details for DOI 10.1529/biophysj.107.120709

    View details for Web of Science ID 000251615800001

    View details for PubMedCentralID PMC2134858

  • Strength of coronal mass ejection-driven shocks near the sun and their importance in predicting solar energetic particle events ASTROPHYSICAL JOURNAL Shen, C., Wang, Y., Ye, P., Zhao, X. P., Gui, B., Wang, S. 2007; 670 (1): 849-856

    View details for Web of Science ID 000250965400066

  • Genetic variation and population structure in Native Americans PLOS GENETICS Wang, S., Lewis, C. M., Jakobsson, M., Ramachandran, S., Ray, N., Bedoya, G., Rojas, W., Parra, M. V., Molina, J. A., Gallo, C., Mazzotti, G., Poletti, G., Hill, K., Hurtado, A. M., Labuda, D., Klitz, W., Barrantes, R., Bortolini, M. C., Salzano, F. M., Petzl-Erler, M. L., Tsuneto, L. T., Llop, E., Rothhammer, F., Excoffier, L., Feldman, M. W., Rosenberg, N. A., Ruiz-Linares, A. 2007; 3 (11): 2049-2067

    Abstract

    We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.

    View details for DOI 10.1371/journal.pgen.0030185

    View details for Web of Science ID 000251310200002

    View details for PubMedID 18039031

  • Interleukin-8 modulates growth and invasiveness of estrogen receptor-negative breast cancer cells INTERNATIONAL JOURNAL OF CANCER Yao, C., Lin, Y., Chua, M., Ye, C., Bi, J., Li, W., Zhu, Y., Wang, S. 2007; 121 (9): 1949-1957

    Abstract

    Breast cancer, especially estrogen receptor (ER)-negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER-negative breast cancers express high levels of interleukin-8 (IL-8), whereas their ER-positive counterparts do not. IL-8 is a multi-functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL-8 in ER-negative breast cancer progression by using RNA interference to specifically knockdown IL-8 expression in ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468. In vitro, suppression of IL-8 led to significant reductions in cell invasion (p<0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL-8 significantly reduced the microvessel density (p<0.05), and markedly reduced neutrophil infiltration into the tumors (p<0.05). In contrast to in vitro observations, suppression of IL-8 promoted tumor growth in nude mice (p<0.05). Our results imply that the complex roles of IL-8 in the regulation of ER-negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL-8.

    View details for DOI 10.1002/ijc.22930

    View details for Web of Science ID 000249718100009

    View details for PubMedID 17621625

  • CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells PLOS GENETICS Opavsky, R., Wang, S., Trikha, P., Raval, A., Huang, Y., Wu, Y., Rodriguez, B., Keller, B., Liyanarachchi, S., Wei, G., Davuluri, R. V., Weinstein, M., Felsher, D., Ostrowski, M., Leone, G., Plass, C. 2007; 3 (9): 1757-1769

    Abstract

    Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Global patterns of hypermethylation are tumor-type specific and nonrandom. The biological significance and the underlying mechanisms of tumor-specific aberrant promoter methylation remain unclear, but some evidence suggests that this specificity involves differential sequence susceptibilities, the targeting of DNA methylation activity to specific promoter sequences, or the selection of rare DNA methylation events during disease progression. Using restriction landmark genomic scanning on samples derived from tissue culture and in vivo models of T cell lymphomas, we found that MYC overexpression gave rise to a specific signature of CpG island hypermethylation. This signature reflected gene transcription profiles and was detected only in advanced stages of disease. The further inactivation of the Pten, p53, and E2f2 tumor suppressors in MYC-induced lymphomas resulted in distinct and diagnostic CpG island methylation signatures. Our data suggest that tumor-specific DNA methylation in lymphomas arises as a result of the selection of rare DNA methylation events during the course of tumor development. This selection appears to be driven by the genetic configuration of tumor cells, providing experimental evidence for a causal role of DNA hypermethylation in tumor progression and an explanation for the tremendous epigenetic heterogeneity observed in the evolution of human cancers. The ability to predict genome-wide epigenetic silencing based on relatively few genetic alterations will allow for a more complete classification of tumors and understanding of tumor cell biology.

    View details for DOI 10.1371/journal.pgen.0030167

    View details for Web of Science ID 000249767800018

    View details for PubMedID 17907813

    View details for PubMedCentralID PMC1994712

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