Bio

Bio


Dr. Fatih Inci is currently working as a Basic Life Science Research Scientist (Academic Staff) at Stanford University School of Medicine, Canary Center at Stanford for Cancer Early Detection. He has been guiding and working with a group of researchers, including postdoctoral fellows, graduate, undergraduate, and high school students, who focus on micro- and nano-technologies for bioengineering and biomedical applications. Dr. Inci received his B.Sc. degree at the Department of Molecular Biology and Genetics in 2007 with magna cum laude honor from Istanbul University (Turkey), and also studied as an Sokrates student at the Department of Biology in University of Groningen (Netherlands) in 2005. He received his Ph.D. degree at the Department of Molecular Biology-Genetics & Biotechnology with summa cum laude honor from Istanbul Technical University (Turkey) in 2013. During his Ph.D. studies, he was also appointed as a visiting scientist in University of New South Wales (Sydney, Australia) and University of Technology Sydney (Australia), as well as working as a research scholar/trainee at Brigham and Women?s Hospital (BWH)-Harvard Medical School, and Harvard-MIT Health Sciences and Technology Division (Boston, MA). Upon the completion of his Ph.D. studies, Dr. Inci worked as a postdoctoral research fellow at BWH-Harvard Medical School (2013-2014) and Stanford University School of Medicine (2014-2015).

Dr. Inci has published his research work in the most prestigious journals, including Proceedings of the National Academy of Sciences of the United States of America (PNAS), ACS Nano, Nature Scientific Reports, Nature Light: Science & Applications, Small, Lab on a chip, Biomacromolecules, Advanced Drug Delivery Reviews, ACS Chemical Reviews, Biotechnology Advances, Annual Review of Medicine, Materials Today, Trends in Biotechnology. Besides his research publications, he has contributed to the publication of 4 book chapters in the world's renowned publishers. His research findings have been presented in national and international conferences, ranging in geography from Barcelona to Osaka, Sydney to Boston, Rio de Janeiro to San Diego and Phoenix to San Francisco. Moreover, he has secured his research findings, technological developments, and scientific discoveries with 6 U.S. patents. Some of them have already been licensed by companies to produce commercial products in the United States, and distributed throughout the world. One such example is his patent in the field of forensics that has been translated into two viable commercial products (CSI-Q and NGDE) produced in the United States by DxNow, Inc.

Dr. Inci?s qualified scientific work has been highlighted and recognized by well-renowned national and international organizations as well as government entities, including National Institute of Health, Nature Medicine, Science AAAS, Popular Science, Newsweek, Boston University, Canary Center-Stanford University, Brigham & Women?s Hospital, A*STAR, Center for Integration of Medicine and Innovative Technology (CIMIT), and Epilepsy Foundation. He has also been awarded with various scholarships and grants from European Molecular Biology Organization-European Science Foundation (EMBO-ESF), American Chemical Society, and Turkey Scientific and Technological Research Society (TUBITAK). He is a professional member at the world?s largest and most prestigious scientific societies, including the American Association for the Advancement of Science (AAAS), Royal Society of Chemistry (RSC), American Association for Cancer Research (AACR), and National Postdoctoral Association (NPA).

Current Role at Stanford


Dr. Fatih Inci?s area of excellence in research is to create micro- and nano-scale platform technologies in the fields of biomedical engineering, biotechnology and medicine by manipulating biomolecules, cells and viruses in small volumes that offers precise solutions for real-world challenges in clinical diagnostics, personalized medicine, early cancer detection, forensic science, and biomarker discovery. By utilizing this interdisciplinary space at the intersection of engineering, biology, chemistry, and material science, he aims to develop innovative, user-friendly, ultra-sensitive and high specific cell manipulation and biosensing platforms for monitoring and analysis of diseases and biomarkers, as well as providing unique solutions to the forensic field. His research interests also focus on many applications of nanoplasmonics, lab-on-a-chip, microfluidics, biosensors, artificial lipid membranes, disease on-chip models, and drug delivery systems. To deploy these applications into medical practice, he presents unique and innovative solutions by employing high-throughput technologies and multiple innovative tools, including localized surface plasmon resonance, surface plasmon resonance spectroscopy, microfluidics, nanomechanical sensors, bioinspired material-based sensors, and quartz crystal microbalance systems.

Honors & Awards


  • Best paper award (co-authored research), XXVII SIBGRAPI Conference on Graphics, Patterns and Images, Rio de Janeiro, Brazil (2014)
  • Honorarium for Publication (along with Utkan Demirci and Onur Tokel), American Chemical Society (2014)
  • New Therapy Commercialization Grants Program (along with Utkan Demirci and Steven Schachter), Epilepsy Foundation (2014)
  • BRIght Future Prize (along with Utkan Demirci and Steven Schachter)., Brigham & Women?s Hospital (Boston, MA) (2013)
  • Biomedical Research Institute Innovation Award (along with Utkan Demirci, Onur Tokel and ShuQi Wang), Brigham & Women?s Hospital (Boston, MA) (2012)
  • Scientific Conference/Travel Grant, European Science Foundation ? European Molecular Biology Organization (2011)
  • Scientific Travel Grant, Istanbul Technical University (Turkey) (2010-2011)
  • Enrolled to Ph.D. Program with undergraduate degree (the first student in the institute), Istanbul Technical University (Turkey) (2007-2013)
  • Ph.D. Fellowship, Turkey Scientific and Technological Research Society (TUBITAK) (2007-2012)
  • Elected as an Erasmus/Socrates Student, University of Groningen (Netherlands) (2005-2006)
  • Scholarship for Undergraduate Students with Honor Degree (only one student per year), Istanbul University (Turkey) (2003-2007)

Education & Certifications


  • Postdoctoral Research Fellow, Stanford University School of Medicine, Radiology Department, Canary Center (Stanford, CA) (2016)
  • Postdoctoral Research Fellow, Brigham and Women?s Hospital, Renal Division, Department of Biomedical Engineering, Harvard Medical School (Boston, MA) (2014)
  • Doctor of Philosophy, Istanbul Technical University, Molecular Biology-Genetics & Biotechnology (Turkey) (2013)
  • Research Scholar/Trainee, Brigham and Women?s Hospital, Renal Division, Department of Biomedical Engineering, Harvard Medical School (Boston, MA) (2012)
  • Visiting Researcher, University of New South Wales, School of Biotechnology and Biomolecular Sciences (Australia) (2010)
  • Visiting Researcher, University of Technology Sydney, Institute for Nanoscale Technology (Australia) (2010)
  • Science Baccalaureate Degree, Istanbul University, Department of Molecular Biology and Genetics (Turkey) (2007)
  • Sokrates Student, University of Groningen, Department of Biology (Netherlands) (2006)

Service, Volunteer and Community Work


  • Session Co-Chair, Global Technology Community (GTC), Point-of-Care Diagnostics Congress (2015)

    Location

    San Diego, CA

Patents


  • "United States Patent Invention No. BWH 21303: Controlled Viable Release of Selectively Captured Label-Free Cells in Microchannels"
  • "United States Patent Invention No. BWH 22611: Methods for Bacteria Detection, Monitoring of Antibiotic Agents, and Energy Harvesting using Micromechanical Devices"
  • "United States Patent Stanford Docket No. 15-315: Quantitative Nanoplasmonic Platform for Multiple Targets"
  • "United States Patent WO/2014/008363: Detection, Capture and Quantification of Biological Moieties from Unprocessed Bodily Fluids using Nanoplasmonic Platform"
  • "United States Patent WO/2016/054295: Systems and Methods for Determining Probative Samples and Isolation and Quantitation of Cells"
  • "United States Patent WO/2016/138255 A1: Portable Lensless Wide-field Microscopy Imaging for Health-Care Applications using Digital In-line Holography and Multi-Frame Pixel Super-Resolution"

Professional

Professional Interests


?Editorial Board Member, Nature Scientific Reports
?Editorial Board Member, Global Journal of Health Science (GJHS)
?Editorial Board Member, SM Journal of Clinical and Medical Imaging
?Editorial Board Member, Radiology ? Open Journal (ROJ)
?Ad hoc Reviewer, Analytical Methods
?Ad hoc Reviewer, Applied Sciences
?Ad hoc Reviewer, Biofabrication
?Ad hoc Reviewer, Biomedical Engineering-Applications: Basis and Communications (BME)
?Ad hoc Reviewer, Chemical Communications
?Ad hoc Reviewer, Expert Review of Molecular Diagnostics
?Ad hoc Reviewer, Global Journal of Health Science (GJHS)
?Ad hoc Reviewer, Infection and Drug Resistance
?Ad hoc Reviewer, International Journal of Biomedical Engineering and Technology
?Ad hoc Reviewer, International Journal of Nanomedicine
?Ad hoc Reviewer, Journal of Molecular Recognition
?Ad hoc Reviewer, Plos One
?Ad hoc Reviewer, RSC Advances

Publications

All Publications


  • Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chemical Society reviews Inan, H., Poyraz, M., Inci, F., Lifson, M. A., Baday, M., Cunningham, B. T., Demirci, U. 2017; 46 (2): 366?88

    Abstract

    Biosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.

    View details for DOI 10.1039/c6cs00206d

    View details for PubMedID 27841420

  • 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

  • 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
  • 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

  • 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

  • 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??g/mL do not affect sperm viability. However, SWCNT-COOH generate significant reactive superoxide species at a higher concentration (25??g/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

  • 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
  • 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
  • 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

  • Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device ((NERD)-R-2) 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-E4363
  • 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

  • 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

    View details for DOI 10.1038/srep08719

    View details for Web of Science ID 000350473100001

  • 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
  • Editorial for Advanced Health Care Technologies Advanced Health Care Technologies Demirci, U., Wang, S., Inci, F. 2015

    View details for DOI 10.2147/AHCT.S58388

  • Detection of Peritonitis in Patients on Peritoneal Dialysis at Home IEEE Pulse Wang, S., Inci, F., Demirci, U. 2015
  • Construction and Characterization of P-Glycoprotein Incorporated Tethered Lipid Bilayers Biochemistry and Biophysics Reports Inci, F., Celik, U., Turken, B., Ozer, O., Kok, F. N. 2015
  • Volume 3: Cell-Encapsulating Hydrogels for Biosensing Gels Handbook - Fundamentals, Properties and Applications Chen, P., Wang, S., Inci, F., Tasoglu, S., Guven, S., Demirci, U. World Scientific. 2015
  • 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

  • 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

  • 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

  • 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

  • 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

  • Nanostructured Optical Photonic Crystal Biosensor for HIV Viral Load Measurement SCIENTIFIC REPORTS Shafiee, H., Lidstone, E. A., Jahangir, M., Inci, F., Hanhauser, E., Henrich, T. J., Kuritzkes, D. R., Cunningham, B. T., Demirci, U. 2014; 4

    Abstract

    Detecting and quantifying biomarkers and viruses in biological samples have broad applications in early disease diagnosis and treatment monitoring. We have demonstrated a label-free optical sensing mechanism using nanostructured photonic crystals (PC) to capture and quantify intact viruses (HIV-1) from biologically relevant samples. The nanostructured surface of the PC biosensor resonantly reflects a narrow wavelength band during illumination with a broadband light source. Surface-adsorbed biotarget induces a shift in the resonant Peak Wavelength Value (PWV) that is detectable with <10 pm wavelength resolution, enabling detection of both biomolecular layers and small number of viruses that sparsely populate the transducer surface. We have successfully captured and detected HIV-1 in serum and phosphate buffered saline (PBS) samples with viral loads ranging from 10(4) to 10(8) copies/mL. The surface density of immobilized biomolecular layers used in the sensor functionalization process, including 3-mercaptopropyltrimethoxysilane (3-MPS), N-gamma-Maleimidobutyryl-oxysuccinimide ester (GMBS), NeutrAvidin, anti-gp120, and bovine serum albumin (BSA) were also quantified by the PC biosensor.

    View details for DOI 10.1038/srep04116

    View details for Web of Science ID 000332014100001

    View details for PubMedID 24576941

  • Portable Digital In-line Holography Platform for Sperm Cell Visualization and Quantification 2014 27TH SIBGRAPI CONFERENCE ON GRAPHICS, PATTERNS AND IMAGES (SIBGRAPI) Sobieranski, A. C., Inci, F., Tekin, H. C., Comunello, E., von Wangenheim, A., Demirci, U. 2014: 274-281
  • Acute On-Chip HIV Detection Through Label-Free Electrical Sensing of Viral Nano-Lysate SMALL Shafiee, H., Jahangir, M., Inci, F., Wang, S., Willenbrecht, R. B., Giguel, F. F., Tsibris, A. M., Kuritzkes, D. R., Demirci, U. 2013; 9 (15): 2553-2563

    Abstract

    Development of portable biosensors has broad applications in environmental monitoring, clinical diagnosis, public health, and homeland security. There is an unmet need for pathogen detection at the point-of-care (POC) using a fast, sensitive, inexpensive, and easy-to-use method that does not require complex infrastructure and well-trained technicians. For instance, detection of Human Immunodeficiency Virus (HIV-1) at acute infection stage has been challenging, since current antibody-based POC technologies are not effective due to low concentration of antibodies. In this study, we demonstrated for the first time a label-free electrical sensing method that can detect lysed viruses, i.e. viral nano-lysate, through impedance analysis, offering an alternative technology to the antibody-based methods such as dipsticks and Enzyme-linked Immunosorbent Assay (ELISA). The presented method is a broadly applicable platform technology that can potentially be adapted to detect multiple pathogens utilizing impedance spectroscopy for other infectious diseases including herpes, influenza, hepatitis, pox, malaria, and tuberculosis. The presented method offers a rapid and portable tool that can be used as a detection technology at the POC in resource-constrained settings, as well as hospital and primary care settings.

    View details for DOI 10.1002/smll.201202195

    View details for Web of Science ID 000327792600013

    View details for PubMedID 23447456

  • Point-of-care assays for tuberculosis: Role of nanotechnology/microfluidics BIOTECHNOLOGY ADVANCES Wang, S., Inci, F., De Libero, G., Singhal, A., Demirci, U. 2013; 31 (4): 438-449

    Abstract

    Tuberculosis (TB) remains one of the most devastating infectious diseases and its eradication is still unattainable given the limitations of current technologies for diagnosis, treatment and prevention. The World Health Organization's goal to eliminate TB globally by 2050 remains an ongoing challenge as delayed diagnosis and misdiagnosis of TB continue to fuel the worldwide epidemic. Despite considerable improvements in diagnostics for the last few decades, a simple and effective point-of-care TB diagnostic test is yet not available. Here, we review the current assays used for TB diagnosis, and highlight the recent advances in nanotechnology and microfluidics that potentially enable new approaches for TB diagnosis in resource-constrained settings.

    View details for DOI 10.1016/j.biotechadv.2013.01.006

    View details for Web of Science ID 000317453600003

    View details for PubMedID 23357365

  • Nanoplasmonic Quantitative Detection of Intact Viruses from Unprocessed Whole Blood ACS NANO Inci, F., Tokel, O., Wang, S., Gurkan, U. A., Tasoglu, S., Kuritzkes, D. R., Demirci, U. 2013; 7 (6): 4733-4745

    Abstract

    Infectious diseases such as HIV and hepatitis B pose an omnipresent threat to global health. Reliable, fast, accurate, and sensitive platforms that can be deployed at the point-of-care (POC) in multiple settings, such as airports and offices, for detection of infectious pathogens are essential for the management of epidemics and possible biological attacks. To the best of our knowledge, no viral load technology adaptable to the POC settings exists today due to critical technical and biological challenges. Here, we present for the first time a broadly applicable technology for quantitative, nanoplasmonic-based intact virus detection at clinically relevant concentrations. The sensing platform is based on unique nanoplasmonic properties of nanoparticles utilizing immobilized antibodies to selectively capture rapidly evolving viral subtypes. We demonstrate the capture, detection, and quantification of multiple HIV subtypes (A, B, C, D, E, G, and subtype panel) with high repeatability, sensitivity, and specificity down to 98 39 copies/mL (i.e., HIV subtype D) using spiked whole blood samples and clinical discarded HIV-infected patient whole blood samples validated by the gold standard, i.e., RT-qPCR. This platform technology offers an assay time of 1 h and 10 min (1 h for capture, 10 min for detection and data analysis). The presented platform is also able to capture intact viruses at high efficiency using immuno-surface chemistry approaches directly from whole blood samples without any sample preprocessing steps such as spin-down or sorting. Evidence is presented showing the system to be accurate, repeatable, and reliable. Additionally, the presented platform technology can be broadly adapted to detect other pathogens having reasonably well-described biomarkers by adapting the surface chemistry. Thus, this broadly applicable detection platform holds great promise to be implemented at POC settings, hospitals, and primary care settings.

    View details for DOI 10.1021/nn3036232

    View details for Web of Science ID 000321093800006

    View details for PubMedID 23688050

  • Acute HIV Detection by Viral Lysate Impedance Spectroscopy on a Microchip IEEE - Solid-State Sensors, Actuators and Microsystems (Transducers & Eurosensors XXVII) Shafiee, H., Jahangir, M., Inci, F., Wang, S., Willenbrecht, R., Giguel, F. F., Kuritzkes, D. R., Demirci, U. 2013
  • Chapter 18: Applications of Quantum Dots for Fluorescence Imaging in Biomedical Research Microfluidic Technologies for Human Health Wang, S., Esfahani, M., Sarenac, D., Cheung, B., Vasudevan, A., Inci, F., Demirci, U. World Scientific. 2013
  • Nanoplasmonic Biosensing Platform for Multiple Pathogen Detection IEEESolid-State Sensors, Actuators and Microsystems (Transducers & Eurosensors XXVII) Inci, F., Tokel, O., Wang, S., Gurkan, U. A., Kuritzkes, D. R., Demirci, U. 2013
  • Well-Defined Cholesterol Polymers with pH-Controlled Membrane Switching Activity BIOMACROMOLECULES Sevimli, S., Inci, F., Zareie, H. M., Bulmus, V. 2012; 13 (10): 3064-3075

    Abstract

    Cholesterol has been used as an effective component of therapeutic delivery systems because of its ability to cross cellular membranes. Considering this, well-defined copolymers of methacrylic acid and cholesteryl methacrylate, poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA), were generated as potential delivery system components for pH-controlled intracellular delivery of therapeutics. Statistical copolymers with varying cholesterol contents (2, 4, and 8 mol %) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the copolymers in aqueous solutions ranged from 5 0.3 to 7 0.4 nm for the copolymers having 2 and 4 mol % CMA and 8 1.1 to 13 1.9 nm for the copolymer having 8 mol % CMA with increasing pH (pH 4.5-7.4). Atomic force microscopy (AFM) analysis revealed that the copolymer having 8 mol % CMA formed supramolecular assemblies while the copolymers having 2 and 4 mol % CMA existed as unimers in aqueous solution. The pH-responsive behavior of the copolymers was investigated via UV-visible spectroscopy revealing phase transitions at pH 3.9 for 2 mol % CMA, pH 4.7 for 4 mol % CMA, and pH 5.4 for 8 mol % CMA. Lipid bilayers and liposomes as models for cellular membranes were generated to probe their interactions with the synthesized copolymers. The interactions were determined in a pH-dependent manner (at pH 5.0 and 7.4) using surface plasmon resonance (SPR) spectroscopy and liposome leakage assay. Both the SPR analyses and liposome leakage assays indicated that the copolymer containing 2 mol % CMA displayed the greatest polymer-lipid interactions at pH 5.0, presenting the highest binding ability to the lipid bilayer surfaces, and also demonstrating the highest membrane destabilization activity. CellTiter-Blue assay showed that the copolymers did not affect the cell viability up to 30 ?M over a period of 72 h.

    View details for DOI 10.1021/bm300846e

    View details for Web of Science ID 000309488600007

    View details for PubMedID 22917061

  • Release of Magnetic Nanoparticles from Cell-Encapsulating Biodegradable Nanobiomaterials ACS NANO Xu, F., Inci, F., Mullick, O., Gurkan, U. A., Sung, Y., Kavaz, D., Li, B., Denkbas, E. B., Demirci, U. 2012; 6 (8): 6640-6649

    Abstract

    The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 0.03 and 0.99 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications.

    View details for DOI 10.1021/nn300902w

    View details for Web of Science ID 000307988900015

    View details for PubMedID 22680777

  • Efficient on-chip isolation of HIV subtypes LAB ON A CHIP Wang, S., Esfahani, M., Gurkan, U. A., Inci, F., Kuritzkes, D. R., Demirci, U. 2012; 12 (8): 1508-1515

    Abstract

    HIV has caused a global pandemic over the last three decades. There is an unmet need to develop point-of-care (POC) viral load diagnostics to initiate and monitor antiretroviral treatment in resource-constrained settings. Particularly, geographical distribution of HIV subtypes poses significant challenges for POC immunoassays. Here, we demonstrated a microfluidic device that can effectively capture various subtypes of HIV particles through anti-gp120 antibodies, which were immobilized on the microchannel surface. We first optimized an antibody immobilization process using fluorescent antibodies, quantum dot staining and AFM studies. The results showed that anti-gp120 antibodies were immobilized on the microchannel surface with an elevated antibody density and uniform antibody orientation using a Protein G-based surface chemistry. Further, RT-qPCR analysis showed that HIV particles of subtypes A, B and C were captured repeatably with high efficiencies of 77.2 13.2%, 82.1 18.8, and 80.9 14.0% from culture supernatant, and 73.2 13.6, 74.4 14.6 and 78.3 13.3% from spiked whole blood at a viral load of 1000 copies per mL, respectively. HIV particles of subtypes A, B and C were captured with high efficiencies of 81.8 9.4%, 72.5 18.7, and 87.8 3.2% from culture supernatant, and 74.6 12.9, 75.5 6.7 and 69.7 9.5% from spiked whole blood at a viral load of 10,000 copies per mL, respectively. The presented immuno-sensing device enables the development of POC on-chip technologies to monitor viral load and guide antiretroviral treatment (ART) in resource-constrained settings.

    View details for DOI 10.1039/c2lc20706k

    View details for Web of Science ID 000301986500016

    View details for PubMedID 22391989

  • Fructose-enhanced reduction of bacterial growth on nanorough surfaces INTERNATIONAL JOURNAL OF NANOMEDICINE Durmus, N. G., Taylor, E. N., Inci, F., Kummer, K. M., Tarquinio, K. M., Webster, T. J. 2012; 7: 537-545

    Abstract

    Patients on mechanical ventilators for extended periods of time often face the risk of developing ventilator-associated pneumonia. During the ventilation process, patients incapable of breathing are intubated with polyvinyl chloride (PVC) endotracheal tubes (ETTs). PVC ETTs provide surfaces where bacteria can attach and proliferate from the contaminated oropharyngeal space to the sterile bronchoalveolar area. To overcome this problem, ETTs can be coated with antimicrobial agents. However, such coatings may easily delaminate during use. Recently, it has been shown that changes in material topography at the nanometer level can provide antibacterial properties. In addition, some metabolites, such as fructose, have been found to increase the efficiency of antibiotics used to treat Staphylococcus aureus (S. aureus) infections. In this study, we combined the antibacterial effect of nanorough ETT topographies with sugar metabolites to decrease bacterial growth and biofilm formation on ETTs. We present for the first time that the presence of fructose on the nanorough surfaces decreases the number of planktonic S. aureus bacteria in the solution and biofilm formation on the surface after 24 hours. We thus envision that this method has the potential to impact the future of surface engineering of biomaterials leading to more successful clinical outcomes in terms of longer ETT lifetimes, minimized infections, and decreased antibiotic usage; all of which can decrease the presence of antibiotic resistant bacteria in the clinical setting.

    View details for DOI 10.2147/IJN.S27957

    View details for Web of Science ID 000302710600001

    View details for PubMedID 22334783

  • Portable microfluidic chip for detection of Escherichia coli in produce and blood INTERNATIONAL JOURNAL OF NANOMEDICINE Wang, S., Inci, F., Chaunzwa, T. L., Ramanujam, A., Vasudevan, A., Subramanian, S., Ip, A. C., Sridharan, B., Gurkan, U. A., Demirci, U. 2012; 7: 2591-2600

    Abstract

    Pathogenic agents can lead to severe clinical outcomes such as food poisoning, infection of open wounds, particularly in burn injuries and sepsis. Rapid detection of these pathogens can monitor these infections in a timely manner improving clinical outcomes. Conventional bacterial detection methods, such as agar plate culture or polymerase chain reaction, are time-consuming and dependent on complex and expensive instruments, which are not suitable for point-of-care (POC) settings. Therefore, there is an unmet need to develop a simple, rapid method for detection of pathogens such as Escherichia coli. Here, we present an immunobased microchip technology that can rapidly detect and quantify bacterial presence in various sources including physiologically relevant buffer solution (phosphate buffered saline [PBS]), blood, milk, and spinach. The microchip showed reliable capture of E. coli in PBS with an efficiency of 71.8% 5% at concentrations ranging from 50 to 4,000 CFUs/mL via lipopolysaccharide binding protein. The limits of detection of the microchip for PBS, blood, milk, and spinach samples were 50, 50, 50, and 500 CFUs/mL, respectively. The presented technology can be broadly applied to other pathogens at the POC, enabling various applications including surveillance of food supply and monitoring of bacteriology in patients with burn wounds.

    View details for DOI 10.2147/IJN.S29629

    View details for Web of Science ID 000304615700001

    View details for PubMedID 22679370

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