Bio

Bio


Dr. Demirci is currently a Professor at Stanford University School of Medicine, Canary Center Early Cancer Detection. Prior to his Stanford appointment, he was an Associate Professor of Medicine at Brigham and Women's Hospital, Harvard Medical School and at Harvard-MIT Division of Health Sciences and Technology serving at the Division of Biomedical Engineering, Division of Infectious Diseases and Renal Division. He leads a group of 20+ researchers focusing on micro- and nano-scale technologies. He received his B.S. degree in Electrical Engineering in 1999 as a James B. Angell Scholar (summa cum laude) from University of Michigan, Ann Arbor. He received his M.S. degree in 2001 in Electrical Engineering, M.S. degree in Management Science and Engineering in 2005 and Ph.D. in Electrical Engineering in 2005, all from Stanford University.

The Demirci Bio-Acoustic MEMS in Medicine Labs (BAMM) laboratory specializes in applying micro- and nanoscale technologies to problems in medicine at the interface between micro/nanoscale engineering and medicine. We apply innovative technologies to clinical problems. Our major research theme focuses on creating new microfluidic technology platforms targeting broad applications in medicine. In this interdisciplinary space at the convergence of engineering, biology and materials science, our goal is to create novel technologies for disposable point-of-care (POC) diagnostics and monitoring of infectious diseases, cancer and controlling cellular microenvironment in nanoliter droplets for biopreservation and microscale tissue engineering applications. These applications are unified around our expertise to test the limits of cell manipulation by establishing microfluidic platforms to provide solutions to real world problems at the clinic.

Our lab creates technologies to manipulate cells in nanoliter volumes to enable solutions for real world problems in medicine including applications in infectious disease diagnostics and monitoring for global health, cancer early detection, cell encapsulation in nanoliter droplets for cryobiology, and bottom-up tissue engineering. His research interests involve applications of microfluidics and acoustics in medicine, especially: microfluidics for inexpensive, disposable CD4 counts and viral load for HIV in resource-constrained settings for global health problems; 3-D bioprinting and tissue models including 3-D cancer and neural cultures. Dr. Demirci has published over 80 peer reviewed publications in journals including PNAS, Nature Materials, Nature Communications, Advanced Materials, Small, Trends in Biotechnology, Chemical Society Reviews and Lab-chip, over 150 conference abstracts and proceedings, 10+ book chapters, and an edited book. His work was highlighted in Wired Magazine, Nature Photonics, Nature Medicine, MIT Technology Review, Reuters Health News, Science Daily, AIP News, BioTechniques, and Biophotonics. His scientific work has been recognized by numerous national and international awards including the NSF Faculty Early Career Development (CAREER) Award (2012), and the IEEE-EMBS Early Career Achievement Award (2012). He was selected as one of the world’s top 35 young innovators under the age of 35 (TR-35) by the MIT Technology Review. In 2004, he led a team that won the Stanford University Entrepreneur’s Challenge Competition and Global Start-up Competition in Singapore. His work has been translated to start-up companies including DxNow Inc. and KOEK Biotechnology.

Academic Appointments


Honors & Awards


  • Fellow-Elect, American Institute of Medical and Biomedical Engineers (AIMBE) (2016)
  • 2nd Place Student and Investigator Section Oral Presentation, Tissue Engineering and Regenerative Medicine International Society (TERMIS)-Asia Pacific Meeting (2016)
  • StarTURK Award, Assembly of Turkish American Association (2014)
  • Bright Futures Award, Brigham and Women’s Hospital, Brigham Research Institute (2013)
  • Sharktank Competition, American Epilepsy Foundation (2013)
  • Faculty Early Career Development Award, NSF (2012)
  • Early Career Achievement Award, IEEE-EMBS (2012)
  • Partners in Excellence Award, Partners Health Care (2011)
  • Coulter Translational Research Award, Biomedical Engineering Society (BMES) (2011)
  • Engineering in Medicine and Biology Research Award for Translational Research, IEEE-Wyss Institute (2011)
  • Chinese Young Investigator Award, National Science Foundation of China (2010)
  • The Outstanding Young Persons of the World, Junior Chamber International (JCI) (2009)
  • Nano-Biotechnology Award, National Science Council of Turkey and The Turkish Industrialists’ and Businessmen’s Association (2007)
  • TR-35 Award-MIT, MIT Technology Review (2006)
  • Ministry of Education Award, Turkish Ministry of Education (2005)
  • Winner of Accenture Grand Prize, Singapore Business Plan Competition (2004)
  • 1st Place, BASES Entrepreneur’s Challenge Business Plan Competition, Stanford University (2004)
  • Outstanding Paper Award, Transactions on Ultrasonic, Ferroelectrics, and Frequency Control, IEEE (2003)
  • Raymond William Barrow (RWB) Stephens Student Prize of Elsevier Science, Proceedings of Ultrasonic International (2001)
  • Phi Kappa Phi, National Honor Society, University of Michigan (1999)
  • Scholarship for Undergraduate Education, Turkish Ministry of Education (1996)
  • James B. Angell Scholar, University of Michigan (1999)

Boards, Advisory Committees, Professional Organizations


  • Co-founder and Scientific Advisor, DxNow Inc. (2013 - Present)
  • Co-founder and Scientific Advisor, Koek Biotech (2012 - Present)

Professional Education


  • Ph.D., Stanford University, Stanford, CA, Electrical Engineering (2005)
  • M.S., Stanford University, Stanford, CA, Management Science and Engineering (2005)
  • M.S., Stanford University, Stanford, CA, Electrical Engineering (2001)
  • B.S., University of Michigan, Ann Arbor, MI, Electrical Engineering (1999)

Teaching

2016-17 Courses


Publications

All Publications


  • Flexible Substrate-Based Devices for Point-of-Care Diagnostics. Trends in biotechnology Wang, S., Chinnasamy, T., Lifson, M. A., Inci, F., Demirci, U. 2016; 34 (11): 909-921

    Abstract

    Point-of-care (POC) diagnostics play an important role in delivering healthcare, particularly for clinical management and disease surveillance in both developed and developing countries. Currently, the majority of POC diagnostics utilize paper substrates owing to affordability, disposability, and mass production capability. Recently, flexible polymer substrates have been investigated due to their enhanced physicochemical properties, potential to be integrated into wearable devices with wireless communications for personalized health monitoring, and ability to be customized for POC diagnostics. Here, we focus on the latest advances in developing flexible substrate-based diagnostic devices, including paper and polymers, and their clinical applications.

    View details for DOI 10.1016/j.tibtech.2016.05.009

    View details for PubMedID 27344425

  • Microchip-based ultrafast serodiagnostic assay for tuberculosis SCIENTIFIC REPORTS Mani, V., Paleja, B., Larbi, K., Kumar, P., Tay, J. A., Siew, J. Y., Inci, F., Wang, S., Chee, C., Wang, Y. T., Demirci, U., De Libero, G., Singhal, A. 2016; 6

    Abstract

    Access to point-of-care (POC), rapid, inexpensive, sensitive, and instrument-free tests for the diagnosis of tuberculosis (TB) remains a major challenge. Here, we report a simple and low-cost microchip-based TB ELISA (MTBE) platform for the detection of anti-mycobacterial IgG in plasma samples in less than 15 minutes. The MTBE employs a flow-less, magnet-actuated, bead-based ELISA for simultaneous detection of IgG responses against multiple mycobacterial antigens. Anti-trehalose 6,6'-dimycolate (TDM) IgG responses were the strongest predictor for differentiating active tuberculosis (ATB) from healthy controls (HC) and latent tuberculosis infections (LTBI). The TDM-based MTBE demonstrated superior sensitivity compared to sputum microscopy (72% vs. 56%) with 80% and 63% positivity among smear-positive and smear-negative confirmed ATB samples, respectively. Receiver operating characteristic analysis indicated good accuracy for differentiating ATB from HC (AUC = 0.77). Thus, TDM-based MTBE can be potentially used as a screening device for rapid diagnosis of active TB at the POC.

    View details for DOI 10.1038/srep35845

    View details for Web of Science ID 000385927500001

    View details for PubMedID 27775039

  • Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring ADVANCED DRUG DELIVERY REVIEWS Lifson, M. A., Ozen, M. O., Inci, F., Wang, S., Inan, H., Baday, M., Henrich, T. J., Demirci, U. 2016; 103: 90-104

    Abstract

    HIV-1 is a major global epidemic that requires sophisticated clinical management. There have been remarkable efforts to develop new strategies for detecting and treating HIV-1, as it has been challenging to translate them into resource-limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV-1 viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring of antiretroviral therapy, during mother-to-child transmission, and identification of latent HIV-1 reservoirs. In this review, we discuss current challenges in HIV-1 diagnosis and therapy in resource-limited settings and present emerging technologies that aim to address these challenges using innovative solutions.

    View details for DOI 10.1016/j.addr.2016.05.018

    View details for Web of Science ID 000380083700007

    View details for PubMedID 27262924

  • Rapid Assembly of Heterogeneous 3D Cell Microenvironments in a Microgel Array ADVANCED MATERIALS Li, Y., Chen, P., Wang, Y., Yan, S., Feng, X., Du, W., Koehler, S. A., Demirci, U., Liu, B. 2016; 28 (18): 3543-?

    Abstract

    Heterogeneous 3D cell microenvironment arrays are rapidly assembled by combining surface-wettability-guided assembly and microdroplet-array-based operations. This approach enables precise control over individual shapes, sizes, chemical concentrations, cell density, and 3D spatial distribution of multiple components. This technique provides a cost-effective solution to meet the increasing demand of stem cell research, tissue engineering, and drug screening.

    View details for DOI 10.1002/adma.201600247

    View details for Web of Science ID 000376250600016

    View details for PubMedID 26991071

  • Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings. Expert review of molecular diagnostics Wang, S., Lifson, M. A., Inci, F., Liang, L., Sheng, Y., Demirci, U. 2016; 16 (4): 449-459

    Abstract

    The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed.

    View details for DOI 10.1586/14737159.2016.1142877

    View details for PubMedID 26777725

  • Integrating Cell Phone Imaging with Magnetic Levitation (i-LEV) for Label-Free Blood Analysis at the Point-of-Living SMALL Baday, M., Calamak, S., Durmus, N. G., Davis, R. W., Steinmetz, L. M., Demirci, U. 2016; 12 (9): 1222-1229

    Abstract

    There is an emerging need for portable, robust, inexpensive, and easy-to-use disease diagnosis and prognosis monitoring platforms to share health information at the point-of-living, including clinical and home settings. Recent advances in digital health technologies have improved early diagnosis, drug treatment, and personalized medicine. Smartphones with high-resolution cameras and high data processing power enable intriguing biomedical applications when integrated with diagnostic devices. Further, these devices have immense potential to contribute to public health in resource-limited settings where there is a particular need for portable, rapid, label-free, easy-to-use, and affordable biomedical devices to diagnose and continuously monitor patients for precision medicine, especially those suffering from rare diseases, such as sickle cell anemia, thalassemia, and chronic fatigue syndrome. Here, a magnetic levitation-based diagnosis system is presented in which different cell types (i.e., white and red blood cells) are levitated in a magnetic gradient and separated due to their unique densities. Moreover, an easy-to-use, smartphone incorporated levitation system for cell analysis is introduced. Using our portable imaging magnetic levitation (i-LEV) system, it is shown that white and red blood cells can be identified and cell numbers can be quantified without using any labels. In addition, cells levitated in i-LEV can be distinguished at single-cell resolution, potentially enabling diagnosis and monitoring, as well as clinical and research applications.

    View details for DOI 10.1002/smll.201501845

    View details for Web of Science ID 000372008600014

    View details for PubMedID 26523938

  • Towards artificial tissue models: past, present, and future of 3D bioprinting BIOFABRICATION Arslan-Yildiz, A., El Assal, R., Chen, P., Guven, S., Inci, F., Demirci, U. 2016; 8 (1)
  • Engineering long shelf life multilayer biologically active surfaces on microfluidic devices for point of care applications SCIENTIFIC REPORTS Asghar, W., Yuksekkaya, M., Shafiee, H., Zhang, M., Ozen, M. O., Inci, F., Kocakulak, M., Demirci, U. 2016; 6

    Abstract

    Although materials and engineered surfaces are broadly utilized in creating assays and devices with wide applications in diagnostics, preservation of these immuno-functionalized surfaces on microfluidic devices remains a significant challenge to create reliable repeatable assays that would facilitate patient care in resource-constrained settings at the point-of-care (POC), where reliable electricity and refrigeration are lacking. To address this challenge, we present an innovative approach to stabilize surfaces on-chip with multiple layers of immunochemistry. The functionality of microfluidic devices using the presented method is evaluated at room temperature for up to 6-month shelf life. We integrated the preserved microfluidic devices with a lensless complementary metal oxide semiconductor (CMOS) imaging platform to count CD4(+) T cells from a drop of unprocessed whole blood targeting applications at the POC such as HIV management and monitoring. The developed immunochemistry stabilization method can potentially be applied broadly to other diagnostic immuno-assays such as viral load measurements, chemotherapy monitoring, and biomarker detection for cancer patients at the POC.

    View details for DOI 10.1038/srep21163

    View details for Web of Science ID 000370230000001

    View details for PubMedID 26883474

  • Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments ACTA BIOMATERIALIA Namkoong, B., Guven, S., Ramesan, S., Liaudanskaya, V., Abzhanov, A., Demirci, U. 2016; 31: 301-311

    Abstract

    The experimental systems that recapitulate the complexity of native tissues and enable precise control over the microenvironment are becoming essential for the pre-clinical tests of therapeutics and tissue engineering. Here, we described a strategy to develop an in vitro platform to study the developmental biology of craniofacial osteogenesis. In this study, we directly osteo-differentiated cranial neural crest cells (CNCCs) in a 3-D in vitro bioengineered microenvironment. Cells were encapsulated in the gelatin-based photo-crosslinkable hydrogel and cultured up to three weeks. We demonstrated that this platform allows efficient differentiation of p75 positive CNCCs to cells expressing osteogenic markers corresponding to the sequential developmental phases of intramembranous ossification. During the course of culture, we observed a decrease in the expression of early osteogenic marker Runx2, while the other mature osteoblast and osteocyte markers such as Osterix, Osteocalcin, Osteopontin and Bone sialoprotein increased. We analyzed the ossification of the secreted matrix with alkaline phosphatase and quantified the newly secreted hydroxyapatite. The Field Emission Scanning Electron Microscope (FESEM) images of the bioengineered hydrogel constructs revealed the native-like osteocytes, mature osteoblasts, and cranial bone tissue morphologies with canaliculus-like intercellular connections. This platform provides a broadly applicable model system to potentially study diseases involving primarily embryonic craniofacial bone disorders, where direct diagnosis and adequate animal disease models are limited.

    View details for DOI 10.1016/j.actbio.2015.12.004

    View details for Web of Science ID 000370086100027

    View details for PubMedID 26675129

  • Toxicology Study of Single-walled Carbon Nanotubes and Reduced Graphene Oxide in Human Sperm. Scientific reports Asghar, W., Shafiee, H., Velasco, V., Sah, V. R., Guo, S., El Assal, R., Inci, F., Rajagopalan, A., Jahangir, M., Anchan, R. M., Mutter, G. L., Ozkan, M., Ozkan, C. S., Demirci, U. 2016; 6: 30270-?

    Abstract

    Carbon-based nanomaterials such as single-walled carbon nanotubes and reduced graphene oxide are currently being evaluated for biomedical applications including in vivo drug delivery and tumor imaging. Several reports have studied the toxicity of carbon nanomaterials, but their effects on human male reproduction have not been fully examined. Additionally, it is not clear whether the nanomaterial exposure has any effect on sperm sorting procedures used in clinical settings. Here, we show that the presence of functionalized single walled carbon nanotubes (SWCNT-COOH) and reduced graphene oxide at concentrations of 1-25 μg/mL do not affect sperm viability. However, SWCNT-COOH generate significant reactive superoxide species at a higher concentration (25 μg/mL), while reduced graphene oxide does not initiate reactive species in human sperm. Further, we demonstrate that exposure to these nanomaterials does not hinder the sperm sorting process, and microfluidic sorting systems can select the sperm that show low oxidative stress post-exposure.

    View details for DOI 10.1038/srep30270

    View details for PubMedID 27538480

  • Engineering cancer microenvironments for in vitro 3-D tumor models MATERIALS TODAY Asghar, W., El Assal, R., Shafiee, H., Pitteri, S., Paulmurugan, R., Demirci, U. 2015; 18 (10): 539-553
  • Graphene-protein field effect biosensors: glucose sensing MATERIALS TODAY Viswanathan, S., Narayanan, T. N., Aran, K., Fink, K. D., Paredes, J., Ajayan, P. M., Filipek, S., Miszta, P., Tekin, H. C., Inci, F., Demirci, U., Li, P., Bolotin, K. I., Liepmann, D., Renugopalakrishanan, V. 2015; 18 (9): 513-522
  • Deformation of a single mouse oocyte in a constricted microfluidic channel MICROFLUIDICS AND NANOFLUIDICS Luo, Z., Guven, S., Gozen, I., Chen, P., Tasoglu, S., Anchan, R. M., Bai, B., Demirci, U. 2015; 19 (4): 883-890
  • Portable lensless wide-field microscopy imaging platform based on digital inline holography and multi-frame pixel super-resolution LIGHT-SCIENCE & APPLICATIONS Sobieranski, A. C., Inci, F., Tekin, H. C., Yuksekkaya, M., Comunello, E., Cobra, D., von Wangenheim, A., Demirci, U. 2015; 4
  • Biotunable acoustic node assembly of organoids. Advanced healthcare materials Chen, P., Güven, S., Usta, O. B., Yarmush, M. L., Demirci, U. 2015; 4 (13): 1937-1943

    Abstract

    Bioengineering of 3D microtissues from cell spheroids is demonstrated by employing the vibration of acoustic standing waves and its hydrodynamic effect at the bottom of a liquid-carrier chamber. A large number of cell spheroids (>10(4) ) are assembled in seconds into a closely packed structure in a scaffold-free fashion under nodal pattern of the standing waves in a fluidic environment.

    View details for DOI 10.1002/adhm.201500279

    View details for PubMedID 26149464

  • Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics. Proceedings of the National Academy of Sciences of the United States of America Inci, F., Filippini, C., Baday, M., Ozen, M. O., Calamak, S., Durmus, N. G., Wang, S., Hanhauser, E., Hobbs, K. S., Juillard, F., Kuang, P. P., Vetter, M. L., Carocci, M., Yamamoto, H. S., Takagi, Y., Yildiz, U. H., Akin, D., Wesemann, D. R., Singhal, A., Yang, P. L., Nibert, M. L., Fichorova, R. N., Lau, D. T., Henrich, T. J., Kaye, K. M., Schachter, S. C., Kuritzkes, D. R., Steinmetz, L. M., Gambhir, S. S., Davis, R. W., Demirci, U. 2015; 112 (32): E4354-63

    Abstract

    Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

    View details for DOI 10.1073/pnas.1510824112

    View details for PubMedID 26195743

  • Hydrosoluble, UV-crosslinkable and injectable chitosan for patterned cell-laden microgel and rapid transdermal curing hydrogel in vivo ACTA BIOMATERIALIA Li, B., Wang, L., Xu, F., Gang, X., Demirci, U., Wei, D., Li, Y., Feng, Y., Jia, D., Zhou, Y. 2015; 22: 59-69

    Abstract

    Natural and biodegradable chitosan with unique amino groups has found widespread applications in tissue engineering and drug delivery. However, its applications have been limited by the poor solubility of native chitosan in neutral pH solution, which subsequently fails to achieve cell-laden hydrogel at physiological pH. To address this, we incorporated UV crosslinking ability in chitosan, allowing fabrication of patterned cell-laden and rapid transdermal curing hydrogel in vivo. The hydrosoluble, UV crosslinkable and injectable N-methacryloyl chitosan (N-MAC) was synthesized via single-step chemoselective N-acylation reaction, which simultaneously endowed chitosan with well solubility in neutral pH solution, UV crosslinkable ability and injectability. The solubility of N-MAC in neutral pH solution increased 2.21-fold with substitution degree increasing from 10.9% to 28.4%. The N-MAC allowed fabrication of cell-laden microgels with on-demand patterns via photolithography, and the cell viability in N-MAC hydrogel maintained 96.3 ± 1.3% N-MAC allowed rapid transdermal curing hydrogel in vivo within 60s through minimally invasive clinical surgery. Histological analysis revealed that low-dose UV irradiation hardly induced skin injury and acute inflammatory response disappeared after 7 days. N-MAC would allow rapid, robust and cost-effective fabrication of patterned cell-laden polysaccharide microgels with unique amino groups serving as building blocks for tissue engineering and rapid transdermal curing hydrogel in vivo for localized and sustained protein delivery.

    View details for DOI 10.1016/j.actbio.2015.04.026

    View details for Web of Science ID 000357241200007

    View details for PubMedID 25917845

  • Magnetic Levitational Assembly for Living Material Fabrication ADVANCED HEALTHCARE MATERIALS Tasoglu, S., Yu, C. H., Liaudanskaya, V., Guven, S., Migliaresi, C., Demirci, U. 2015; 4 (10): 1469-1476

    Abstract

    Functional living materials with microscale compositional topographies are prevalent in nature. However, the creation of biomaterials composed of living micro building blocks, each programmed by composition, functionality, and shape, is still a challenge. A powerful yet simple approach to create living materials using a levitation-based magnetic method is presented.

    View details for DOI 10.1002/adhm.201500092

    View details for Web of Science ID 000358005500003

    View details for PubMedID 25872008

  • Magnetic levitation of single cells. Proceedings of the National Academy of Sciences of the United States of America Durmus, N. G., Tekin, H. C., Guven, S., Sridhar, K., Arslan Yildiz, A., Calibasi, G., Ghiran, I., Davis, R. W., Steinmetz, L. M., Demirci, U. 2015; 112 (28): E3661-8

    Abstract

    Several cellular events cause permanent or transient changes in inherent magnetic and density properties of cells. Characterizing these changes in cell populations is crucial to understand cellular heterogeneity in cancer, immune response, infectious diseases, drug resistance, and evolution. Although magnetic levitation has previously been used for macroscale objects, its use in life sciences has been hindered by the inability to levitate microscale objects and by the toxicity of metal salts previously applied for levitation. Here, we use magnetic levitation principles for biological characterization and monitoring of cells and cellular events. We demonstrate that each cell type (i.e., cancer, blood, bacteria, and yeast) has a characteristic levitation profile, which we distinguish at an unprecedented resolution of 1 × 10(-4) g⋅mL(-1). We have identified unique differences in levitation and density blueprints between breast, esophageal, colorectal, and nonsmall cell lung cancer cell lines, as well as heterogeneity within these seemingly homogenous cell populations. Furthermore, we demonstrate that changes in cellular density and levitation profiles can be monitored in real time at single-cell resolution, allowing quantification of heterogeneous temporal responses of each cell to environmental stressors. These data establish density as a powerful biomarker for investigating living systems and their responses. Thereby, our method enables rapid, density-based imaging and profiling of single cells with intriguing applications, such as label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including antibiotic or cancer treatment in personalized medicine.

    View details for DOI 10.1073/pnas.1509250112

    View details for PubMedID 26124131

  • Levitational Image Cytometry with Temporal Resolution ADVANCED MATERIALS Tasoglu, S., Khoory, J. A., Tekin, H. C., Thomas, C., Karnoub, A. E., Ghiran, I. C., Demirci, U. 2015; 27 (26): 3901-?

    Abstract

    A simple, yet powerful magnetic-levitation-based device is reported for real-time, label-free separation, as well as high-resolution monitoring of cell populations based on their unique magnetic and density signatures. This method allows a wide variety of cellular processes to be studied, accompanied by transient or permanent changes in cells' fundamental characteristics as a biological material.

    View details for DOI 10.1002/adma.201405660

    View details for Web of Science ID 000357688900007

    View details for PubMedID 26058598

  • Cytometry: Levitational Image Cytometry with Temporal Resolution (Adv. Mater. 26/2015). Advanced materials Tasoglu, S., Khoory, J. A., Tekin, H. C., Thomas, C., Karnoub, A. E., Ghiran, I. C., Demirci, U. 2015; 27 (26): 3900-?

    Abstract

    On page 3901, I. C. Ghiran, U. Demirci, and co-workers design a magnetic-levitation-based device that allows both label-free separation and high-resolution real-time monitoring of cell populations based on their unique magnetic and density signatures. This device can also be utilized to study transient or permanent changes in the fundamental characteristics of cells.

    View details for DOI 10.1002/adma.201570175

    View details for PubMedID 26149363

  • Biomaterials: Magnetic Levitational Assembly for Living Material Fabrication (Adv. Healthcare Mater. 10/2015). Advanced healthcare materials Tasoglu, S., Yu, C. H., Liaudanskaya, V., Guven, S., Migliaresi, C., Demirci, U. 2015; 4 (10): 1420-?

    Abstract

    Functional living materials with microscale compositional topographies are prevalent in nature. However, the creation of biomaterials composed of living micro building blocks, each programmed by composition, functionality, and shape, is still a challenge. On page 1469, S. Tasoglu, U. Demirci, and co-workers present a powerful yet simple approach to create living materials using a levitation-based magnetic method.

    View details for DOI 10.1002/adhm.201570058

    View details for PubMedID 26173421

  • Printed Flexible Plastic Microchip for Viral Load Measurement through Quantitative Detection of Viruses in Plasma and Saliva SCIENTIFIC REPORTS Shafiee, H., Kanakasabapathy, M. K., Juillard, F., Keser, M., Sadasivam, M., Yuksekkaya, M., Hanhauser, E., Henrich, T. J., Kuritzkes, D. R., Kaye, K. M., Demirci, U. 2015; 5

    Abstract

    We report a biosensing platform for viral load measurement through electrical sensing of viruses on a flexible plastic microchip with printed electrodes. Point-of-care (POC) viral load measurement is of paramount importance with significant impact on a broad range of applications, including infectious disease diagnostics and treatment monitoring specifically in resource-constrained settings. Here, we present a broadly applicable and inexpensive biosensing technology for accurate quantification of bioagents, including viruses in biological samples, such as plasma and artificial saliva, at clinically relevant concentrations. Our microchip fabrication is simple and mass-producible as we print microelectrodes on flexible plastic substrates using conductive inks. We evaluated the microchip technology by detecting and quantifying multiple Human Immunodeficiency Virus (HIV) subtypes (A, B, C, D, E, G, and panel), Epstein-Barr Virus (EBV), and Kaposi's Sarcoma-associated Herpes Virus (KSHV) in a fingerprick volume (50 µL) of PBS, plasma, and artificial saliva samples for a broad range of virus concentrations between 10(2) copies/mL and 10(7) copies/mL. We have also evaluated the microchip platform with discarded, de-identified HIV-infected patient samples by comparing our microchip viral load measurement results with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) as the gold standard method using Bland-Altman Analysis.

    View details for DOI 10.1038/srep09919

    View details for Web of Science ID 000355859800001

    View details for PubMedID 26046668

  • Multiscale assembly for tissue engineering and regenerative medicine TRENDS IN BIOTECHNOLOGY Guven, S., Chen, P., Inci, F., Tasoglu, S., Erkmen, B., Demirci, U. 2015; 33 (5): 269-279

    Abstract

    Our understanding of cell biology and its integration with materials science has led to technological innovations in the bioengineering of tissue-mimicking grafts that can be utilized in clinical and pharmaceutical applications. Bioengineering of native-like multiscale building blocks provides refined control over the cellular microenvironment, thus enabling functional tissues. In this review, we focus on assembling building blocks from the biomolecular level to the millimeter scale. We also provide an overview of techniques for assembling molecules, cells, spheroids, and microgels and achieving bottom-up tissue engineering. Additionally, we discuss driving mechanisms for self- and guided assembly to create micro-to-macro scale tissue structures.

    View details for DOI 10.1016/j.tibtech.2015.02.003

    View details for Web of Science ID 000354157900005

  • Portable Microfluidic Integrated Plasmonic Platform for Pathogen Detection SCIENTIFIC REPORTS Tokel, O., Yildiz, U. H., Inci, F., Durmus, N. G., Ekiz, O. O., Turker, B., Cetin, C., Rao, S., Sridhar, K., Natarajan, N., Shafiee, H., Dana, A., Demirci, U. 2015; 5

    Abstract

    Timely detection of infectious agents is critical in early diagnosis and treatment of infectious diseases. Conventional pathogen detection methods, such as enzyme linked immunosorbent assay (ELISA), culturing or polymerase chain reaction (PCR) require long assay times, and complex and expensive instruments, which are not adaptable to point-of-care (POC) needs at resource-constrained as well as primary care settings. Therefore, there is an unmet need to develop simple, rapid, and accurate methods for detection of pathogens at the POC. Here, we present a portable, multiplex, inexpensive microfluidic-integrated surface plasmon resonance (SPR) platform that detects and quantifies bacteria, i.e., Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) rapidly. The platform presented reliable capture and detection of E. coli at concentrations ranging from ~10(5) to 3.2 × 10(7) CFUs/mL in phosphate buffered saline (PBS) and peritoneal dialysis (PD) fluid. The multiplexing and specificity capability of the platform was also tested with S. aureus samples. The presented platform technology could potentially be applicable to capture and detect other pathogens at the POC and primary care settings.

    View details for DOI 10.1038/srep09152

    View details for Web of Science ID 000351699600001

    View details for PubMedID 25801042

  • Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine. Stem cells translational medicine Guven, S., Lindsey, J. S., Poudel, I., Chinthala, S., Nickerson, M. D., Gerami-Naini, B., Gurkan, U. A., Anchan, R. M., Demirci, U. 2015; 4 (3): 261-268

    Abstract

    Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine.

    View details for DOI 10.5966/sctm.2014-0119

    View details for PubMedID 25666845

  • Highlights from the latest articles in advanced biomanufacturing at micro- and nano-scale. Nanomedicine Assal, R. E., Chen, P., Demirci, U. 2015; 10 (3): 347-350

    View details for DOI 10.2217/nnm.14.210

    View details for PubMedID 25707972

  • Advances in Nanotechnology and Microfluidics for Human Papillomavirus Diagnostics PROCEEDINGS OF THE IEEE Tasoglu, S., Tekin, H. C., Inci, F., Knowlton, S., Wang, S., Wang-Johanning, F., Johanning, G., Colevas, D., Demirci, U. 2015; 103 (2): 161-178
  • Emerging Technologies for Point-of-Care Management of HIV Infection ANNUAL REVIEW OF MEDICINE, VOL 66 Shafiee, H., Wang, S., Inci, F., Toy, M., Henrich, T. J., Kuritzkes, D. R., Demirci, U. 2015; 66: 387-405

    Abstract

    The global HIV/AIDS pandemic has resulted in 39 million deaths to date, and there are currently more than 35 million people living with HIV worldwide. Prevention, screening, and treatment strategies have led to major progress in addressing this disease globally. Diagnostics is critical for HIV prevention, screening and disease staging, and monitoring antiretroviral therapy (ART). Currently available diagnostic assays, which include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot (WB), are complex, expensive, and time consuming. These diagnostic technologies are ill suited for use in low- and middle-income countries, where the challenge of the HIV/AIDS pandemic is most severe. Therefore, innovative, inexpensive, disposable, and rapid diagnostic platform technologies are urgently needed. In this review, we discuss challenges associated with HIV management in resource-constrained settings and review the state-of-the-art HIV diagnostic technologies for CD4(+) T lymphocyte count, viral load measurement, and drug resistance testing.

    View details for DOI 10.1146/annurev-med-092112-143017

    View details for Web of Science ID 000348560300026

    View details for PubMedID 25423597

  • Flexible Microwave Antenna Applicator for Chemo-Thermotherapy of the Breast IEEE ANTENNAS AND WIRELESS PROPAGATION LETTERS Asili, M., Chen, P., Hood, A. Z., Purser, A., Hulsey, R., Johnson, L., Ganesan, A. V., Demirci, U., Topsakal, E. 2015; 14: 1778-1781
  • Paper and flexible substrates as materials for biosensing platforms to detect multiple biotargets. Scientific reports Shafiee, H., Asghar, W., Inci, F., Yuksekkaya, M., Jahangir, M., Zhang, M. H., Durmus, N. G., Gurkan, U. A., Kuritzkes, D. R., Demirci, U. 2015; 5: 8719-?

    Abstract

    The need for sensitive, robust, portable, and inexpensive biosensing platforms is of significant interest in clinical applications for disease diagnosis and treatment monitoring at the point-of-care (POC) settings. Rapid, accurate POC diagnostic assays play a crucial role in developing countries, where there are limited laboratory infrastructure, trained personnel, and financial support. However, current diagnostic assays commonly require long assay time, sophisticated infrastructure and expensive reagents that are not compatible with resource-constrained settings. Although paper and flexible material-based platform technologies provide alternative approaches to develop POC diagnostic assays for broad applications in medicine, they have technical challenges integrating to different detection modalities. Here, we address the limited capability of current paper and flexible material-based platforms by integrating cellulose paper and flexible polyester films as diagnostic biosensing materials with various detection modalities through the development and validation of new widely applicable electrical and optical sensing mechanisms using antibodies and peptides. By incorporating these different detection modalities, we present selective and accurate capture and detection of multiple biotargets including viruses (Human Immunodeficieny Virus-1), bacteria (Escherichia coli and Staphylococcus aureus), and cells (CD4(+) T lymphocytes) from fingerprick volume equivalent of multiple biological specimens such as whole blood, plasma, and peritoneal dialysis effluent with clinically relevant detection and sensitivity.

    View details for DOI 10.1038/srep08719

    View details for PubMedID 25743880

  • Recent advances in micro/nanotechnologies for global control of hepatitis B infection BIOTECHNOLOGY ADVANCES Yildiz, U. H., Inci, F., Wang, S., Toy, M., Tekin, H. C., Javaid, A., Lau, D. T., Demirci, U. 2015; 33 (1): 178-190

    Abstract

    The control of hepatitis B virus (HBV) infection is a challenging task, specifically in developing countries there is limited access to diagnostics and antiviral treatment mainly due to high costs and insufficient healthcare infrastructure. Although the current diagnostic technologies can reliably detect HBV, they are relatively laborious, impractical and require expensive resources that are not suitable for resource-limited settings. Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV. Owing to combination of nanomaterials (metal/inorganic nanoparticles, carbon nanotubes, etc.) with microfabrication technologies, utilization of miniaturized sensors detecting HBV and other viruses from ultra-low volume of blood, serum and plasma is realized. The state-of-the-art microfluidic devices with integrated nanotechnologies potentially allow for inexpensive HBV screening at low cost. This review aims to highlight recent advances in nanotechnology and microfabrication processes that are employed for developing point-of-care (POC) HBV assays.

    View details for DOI 10.1016/j.biotechadv.2014.11.003

    View details for Web of Science ID 000351321400013

  • Microchip ELISA Coupled with Cell Phone to Detect Ovarian Cancer HE4 Biomarker in Urine. Methods in molecular biology (Clifton, N.J.) Wang, S., Akbas, R., Demirci, U. 2015; 1256: 111-121

    Abstract

    Ovarian cancer is a leading cause of death from gynecologic cancers in the USA, and early diagnosis can potentially increase 5-year survival rate. Detection of biomarkers derived from hyperplasia of epithelial tissue by enzyme-linked immunosorbent assay (ELISA) proves to be a practical way of early diagnosis of ovarian cancer. However, ELISA is commonly performed in a laboratory setting, and it cannot be used in a clinical setting for on-site consultation. We have shown a microchip ELISA that detects HE4, an ovarian cancer biomarker, from urine using a cell phone integrated with a mobile application for imaging and data analysis. In microchip ELISA, HE4 from urine was first absorbed on the surface; the primary and secondary antibodies were subsequently anchored on the surface via immuno-reaction; and addition of substrate led to color development because of enzymatic labeling. The microchip after color development was imaged using a cell phone, and the color intensity was analyzed by an integrated mobile application. By comparing with an ELISA standard curve, the concentration of HE4 was reported on the cell phone screen. The presented microchip ELISA coupled with a cell phone is portable as opposed to traditional ELISA, and this method can facilitate the detection of ovarian cancer at the point-of-care (POC).

    View details for DOI 10.1007/978-1-4939-2172-0_8

    View details for PubMedID 25626535

  • Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care ADVANCED DRUG DELIVERY REVIEWS Mani, V., Wang, S., Inci, F., De Libero, G., Singhal, A., Demirci, U. 2014; 78: 105-117

    Abstract

    Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care.

    View details for DOI 10.1016/j.addr.2014.05.015

    View details for Web of Science ID 000358460400009

    View details for PubMedID 24882226

  • Two-dimensional numerical study of flow dynamics of a nucleated cell tethered under shear flow CHEMICAL ENGINEERING SCIENCE Luo, Z. Y., He, L., Wang, S. Q., Tasoglu, S., Xu, F., Demirci, U., Bai, B. F. 2014; 119: 236-244
  • Selection of Functional Human Sperm with Higher DNA Integrity and Fewer Reactive Oxygen Species ADVANCED HEALTHCARE MATERIALS Asghar, W., Velasco, V., Kingsley, J. L., Shoukat, M. S., Shafiee, H., Anchan, R. M., Mutter, G. L., Tuezel, E., Demirci, U. 2014; 3 (10): 1671-1679
  • Nanomechanical motion of Escherichia coli adhered to a surface APPLIED PHYSICS LETTERS Lissandrello, C., Inci, F., Francom, M., Paul, M. R., Demirci, U., Ekinci, K. L. 2014; 105 (11)

    View details for DOI 10.1063/1.4895132

    View details for Web of Science ID 000342995800101

  • Microscale Assembly Directed by Liquid-Based Template ADVANCED MATERIALS Chen, P., Luo, Z., Gueven, S., Tasoglu, S., Ganesan, A. V., Weng, A., Demirci, U. 2014; 26 (34): 5936-?
  • Bio-inspired cryo-ink preserves red blood cell phenotype and function during nanoliter vitrification. Advanced materials El Assal, R., Guven, S., Gurkan, U. A., Gozen, I., Shafiee, H., Dalbeyler, S., Abdalla, N., Thomas, G., Fuld, W., Illigens, B. M., Estanislau, J., Khoory, J., Kaufman, R., Zylberberg, C., Lindeman, N., Wen, Q., Ghiran, I., Demirci, U. 2014; 26 (33): 5815-5822

    Abstract

    Current red-blood-cell cryopreservation methods utilize bulk volumes, causing cryo-injury of cells, which results in irreversible disruption of cell morphology, mechanics, and function. An innovative approach to preserve human red-blood-cell morphology, mechanics, and function following vitrification in nanoliter volumes is developed using a novel cryo-ink integrated with a bioprinting approach.

    View details for DOI 10.1002/adma.201400941

    View details for PubMedID 25047246

  • Preserving human cells for regenerative, reproductive, and transfusion medicine. Biotechnology journal Asghar, W., El Assal, R., Shafiee, H., Anchan, R. M., Demirci, U. 2014; 9 (7): 895-903

    Abstract

    Cell cryopreservation maintains cellular life at sub-zero temperatures by slowing down biochemical processes. Various cell types are routinely cryopreserved in modern reproductive, regenerative, and transfusion medicine. Current cell cryopreservation methods involve freezing (slow/rapid) or vitrifying cells in the presence of a cryoprotective agent (CPA). Although these methods are clinically utilized, cryo-injury due to ice crystals, osmotic shock, and CPA toxicity cause loss of cell viability and function. Recent approaches using minimum volume vitrification provide alternatives to the conventional cryopreservation methods. Minimum volume vitrification provides ultra-high cooling and rewarming rates that enable preserving cells without ice crystal formation. Herein, we review recent advances in cell cryopreservation technology and provide examples of techniques that are utilized in oocyte, stem cell, and red blood cell cryopreservation.

    View details for DOI 10.1002/biot.201300074

    View details for PubMedID 24995723

  • Evaluation of Epithelial Chimerism After Bone Marrow Mesenchymal Stromal Cell Infusion in Intestinal Transplant Patients TRANSPLANTATION PROCEEDINGS Kilinc, S., Gurkan, U. A., Guven, S., Koyuncu, G., Tan, S., Karaca, C., Ozdogan, O., Dogan, M., Tugmen, C., Pala, E. E., Bayol, U., Baran, M., Kurtulmus, Y., Pirim, I., Kebapci, E., Demirci, U. 2014; 46 (6): 2125-2132

    Abstract

    Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac puncture and expanded in vitro prior to infusion. Two out of the 3 patients were infused with autologous BMSCs, and small intestine tissue biopsies collected post-operatively were analyzed for epithelial chimerism using XY fluorescent in situ hybridization and short tandem repeat polymerase chain reaction. We observed epithelial chimeric effect in conditions both with and without BMSC infusion. Although our results suggest a higher epithelial chimerism effect with autologous BMSC infusion in I-ITx, the measurements in multiple biopsies at different time points that demonstrate the reproducibility of this finding and its stability or changes in the level over time would be beneficial. These approaches may have potential implications for improved graft survival, lower immunosuppressant doses, superior engraftment of the transplanted tissue, and higher success rates in I-ITx.

    View details for DOI 10.1016/j.transproceed.2014.06.039

    View details for Web of Science ID 000341076800117

    View details for PubMedID 25131122

  • Advances in Plasmonic Technologies for Point of Care Applications CHEMICAL REVIEWS Tokel, O., Inci, F., Demirci, U. 2014; 114 (11): 5728-5752

    View details for DOI 10.1021/cr4000623

    View details for Web of Science ID 000337336500004

  • Guided and magnetic self-assembly of tunable magnetoceptive gels. Nature communications Tasoglu, S., Yu, C. H., Gungordu, H. I., Guven, S., Vural, T., Demirci, U. 2014; 5: 4702-?

    Abstract

    Self-assembly of components into complex functional patterns at microscale is common in nature, and used increasingly in numerous disciplines such as optoelectronics, microfabrication, sensors, tissue engineering and computation. Here, we describe the use of stable radicals to guide the self-assembly of magnetically tunable gels, which we call 'magnetoceptive' materials at the scale of hundreds of microns to a millimeter, each can be programmed by shape and composition, into heterogeneous complex structures. Using paramagnetism of free radicals as a driving mechanism, complex heterogeneous structures are built in the magnetic field generated by permanent magnets. The overall magnetic signature of final structure is erased via an antioxidant vitamin E, subsequent to guided self-assembly. We demonstrate unique capabilities of radicals and antioxidants in fabrication of soft systems with heterogeneity in material properties, such as porosity, elastic modulus and mass density; then in bottom-up tissue engineering and finally, levitational and selective assembly of microcomponents.

    View details for DOI 10.1038/ncomms5702

    View details for PubMedID 25175148

  • Acoustic picoliter droplets for emerging applications in semiconductor industry and biotechnology JOURNAL OF MICROELECTROMECHANICAL SYSTEMS Demirci, U. 2006; 15 (4): 957-966
  • Droplet-based photoresist deposition APPLIED PHYSICS LETTERS Demirci, U. 2006; 88 (14)

    View details for DOI 10.1063/1.2191087

    View details for Web of Science ID 000236612000121

  • Femtoliter to picoliter droplet generation for organic polymer deposition using single reservoir ejector arrays IEEE TRANSACTIONS ON SEMICONDUCTOR MANUFACTURING Demirci, U., Yaralioglu, G. G., Haeggstrom, E., Khuri-Yakub, B. T. 2005; 18 (4): 709-715
  • Picolitre acoustic droplet ejection by ferntosecond laser micromachined multiple-orifice membrane-based 2D ejector arrays ELECTRONICS LETTERS Demirci, U., Ozcan, A. 2005; 41 (22): 1219-1220
  • Picoliter droplets for spinless photoresist deposition REVIEW OF SCIENTIFIC INSTRUMENTS Demirci, U. 2005; 76 (6)

    View details for DOI 10.1063/1.1922867

    View details for Web of Science ID 000229962000094

  • Coherent array imaging using phased subarmys. Part II: Simulations and experimental results IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Johnson, J. A., Oralkan, O., Ergun, S., Demirci, U., Karaman, M., Khuri-Yakub, B. T. 2005; 52 (1): 51-64

    Abstract

    The basic principles and theory of phased subarray (PSA) imaging imaging provides the flexibility of reducing the number of front-end hardware channels between that of classical synthetic aperture (CSA) imaging--which uses only one element per firing event--and full-phased array (FPA) imaging-which uses all elements for each firing. The performance of PSA generally ranges between that obtained by CSA and FPA using the same array, and depends on the amount of hardware complexity reduction. For the work described in this paper, we performed FPA, CSA, and PSA imaging of a resolution phantom using both simulated and experimental data from a 3-MHz, 3.2-cm, 128-element capacitive micromachined ultrasound transducer (CMUT) array. The simulated system point responses in the spatial and frequency domains are presented as a means of studying the effects of signal bandwidth, reconstruction filter size, and subsampling rate on the PSA system performance. The PSA and FPA sector-scanned images were reconstructed using the wideband experimental data with 80% fractional bandwidth, with seven 32-element subarrays used for PSA imaging. The measurements on the experimental sector images indicate that, at the transmit focal zone, the PSA method provides a 10% improvement in the 6-dB lateral resolution, and the axial point resolution of PSA imaging is identical to that of FPA imaging. The signal-to-noise ratio (SNR) of PSA image was 58.3 dB, 4.9 dB below that of the FPA image, and the contrast-to-noise ratio (CNR) is reduced by 10%. The simulated and experimental test results presented in this paper validate theoretical expectations and illustrate the flexibility of PSA imaging as a way to exchange SNR and frame rate for simplified front-end hardware.

    View details for Web of Science ID 000226812800007

    View details for PubMedID 15742562

  • Acoustically actuated flextensional SixNy and single-crystal silicon 2-D micromachined ejector arrays IEEE TRANSACTIONS ON SEMICONDUCTOR MANUFACTURING Demirci, U., Yaralioglu, G. G., Haeggstrom, E., Percin, G., Ergun, S., Khuri-Yakub, B. T. 2004; 17 (4): 517-524
  • Forward-viewing CMUT arrays for medical Imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Demirci, U., Ergun, A. S., Oralkan, O., Karaman, M., Khuri-Yakub, B. T. 2004; 51 (7): 887-895

    Abstract

    This paper reports the design and testing of forward-viewing annular arrays fabricated using capacitive micromachined ultrasonic transducer (CMUT) technology. Recent research studies have shown that CMUTs have broad frequency bandwidth and high-transduction efficiency. One- and two-dimensional CMUT arrays of various sizes already have been fabricated, and their viability for medical imaging applications has been demonstrated. We fabricated 64-element, forward-viewing annular arrays using the standard CMUT fabrication process and carried out experiments to measure the operating frequency, bandwidth, and transmit/receive efficiency of the array elements. The annular array elements, designed for imaging applications in the 20 MHz range, had a resonance frequency of 13.5 MHz in air. The immersion pulse-echo data collected from a plane reflector showed that the devices operate in the 5-26 MHz range with a fractional bandwidth of 135%. The output pressure at the surface of the transducer was measured to be 24 kPa/V. These values translate into a dynamic range of 131.5 dB for 1-V excitation in 1-Hz bandwidth with a commercial low noise receiving circuitry. The designed, forward-viewing annular CMUT array is suitable for mounting on the front surface of a cylindrical catheter probe and can provide Doppler information for measurement of blood flow and guiding information for navigation through blood vessels in intravascular ultrasound imaging.

    View details for Web of Science ID 000222678000018

    View details for PubMedID 15301009

  • Phased subarray imaging for low-cost, wideband coherent array imaging 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Johnson, J. A., Oralkan, O., Ergun, A. S., Demirci, U., Karaman, M., Khuri-Yakub, B. T. 2003: 1875-1878
  • 2D acoustically actuated micromachined droplet ejector array 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Demirci, U., Yaralioglu, G. G., Haeggstrom, E., Percin, G., Khuri-Yakub, B. T. 2003: 1983-1986
  • Capacitive micromachined ultrasonic transducers: Next-generation arrays for acoustic imaging? IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Oralkan, O., Ergun, A. S., Johnson, J. A., Karaman, M., Demirci, U., Kaviani, K., Lee, T. H., Khuri-Yakub, B. T. 2002; 49 (11): 1596-1610

    Abstract

    Piezoelectric materials have dominated the ultrasonic transducer technology. Recently, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as an alternative technology offering advantages such as wide bandwidth, ease of fabricating large arrays, and potential for integration with electronics. The aim of this paper is to demonstrate the viability of CMUTs for ultrasound imaging. We present the first pulse-echo phased array B-scan sector images using a 128-element, one-dimensional (1-D) linear CMUT array. We fabricated 64- and 128-element 1-D CMUT arrays with 100% yield and uniform element response across the arrays. These arrays have been operated in immersion with no failure or degradation in performance over the time. For imaging experiments, we built a resolution test phantom roughly mimicking the attenuation properties of soft tissue. We used a PC-based experimental system, including custom-designed electronic circuits to acquire the complete set of 128 x 128 RF A-scans from all transmit-receive element combinations. We obtained the pulse-echo frequency response by analyzing the echo signals from wire targets. These echo signals presented an 80% fractional bandwidth around 3 MHz, including the effect of attenuation in the propagating medium. We reconstructed the B-scan images with a sector angle of 90 degrees and an image depth of 210 mm through offline processing by using RF beamforming and synthetic phased array approaches. The measured 6-dB lateral and axial resolutions at 135 mm depth were 0.0144 radians and 0.3 mm, respectively. The electronic noise floor of the image was more than 50 dB below the maximum mainlobe magnitude. We also performed preliminary investigations on the effects of crosstalk among array elements on the image quality. In the near field, some artifacts were observable extending out from the array to a depth of 2 cm. A tail also was observed in the point spread function (PSF) in the axial direction, indicating the existence of crosstalk. The relative amplitude of this tail with respect to the mainlobe was less than -20 dB.

    View details for Web of Science ID 000179224100016

    View details for PubMedID 12484483

  • Medical imaging using capacitive micromachined ultrasonic transducer arrays ULTRASONICS Johnson, J., Oralkan, O., Demirci, U., Ergun, S., Karaman, M., Khuri-Yakub, P. 2002; 40 (1-8): 471-476

    Abstract

    We are investigating the use of capacitive micromachined ultrasonic transducers (cMUT's) for use in medical imaging. We propose an ultrasound probe architecture designed to provide volumetric ultrasound imaging from within an endoscope channel. A complete automated experimental system has been implemented for testing the imaging performance of cMUT arrays. This PC-based system includes custom-designed circuit boards, a software interface, and resolution test phantoms. We have already fabricated 1D and 2D cMUT arrays, and tested the pulse-echo imaging characteristics of 1D arrays. Beamforming and image formation algorithms that aim to reduce the complexity of data acquisition hardware are tested via numerical simulations and using real data acquired from our system.

    View details for Web of Science ID 000176648000083

    View details for PubMedID 12159985

  • Broadband capacitive micromachined ultrasonic transducers ranging from 10 kHz to 60 mHz for imaging arrays and more 2002 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Ergun, A. S., Huang, Y., Cheng, C. H., Oralkan, O., Johnson, J., Jagannathan, H., Demirci, U., Yaralioglu, G. G., Karaman, M., Khuri-Yakub, B. T. 2002: 1039-1043
  • Fabrication and characterization of 1-dimensional and 2-dimensional capacitive micromachined ultrasonic transducer (CMUT) arrays for 2-dimensional and volumetric ultrasonic imaging OCEANS 2002 MTS/IEEE CONFERENCE & EXHIBITION, VOLS 1-4, CONFERENCE PROCEEDINGS Ergun, A. S., Cheng, C. H., Demirci, U., Khuri-Yakub, B. T. 2002: 2361-2367
  • An ultrasonic volumetric scanner for image-guided surgery CARS 2001: COMPUTER ASSISTED RADIOLOGY AND SURGERY Johnson, J., Oralkan, O., Kaviani, K., Demirci, U., Karaman, M., Khuri-Yakub, P. 2001; 1230: 187-192
  • Capacitive micromachined ultrasonic transducer arrays for medical imaging: Experimental results 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Demirci, U., Oralkan, O., Johnson, J. A., Ergun, A. S., Karaman, M., Khuri-Yakub, B. T. 2001: 957-960