Demir Akin, D.V.M., Ph.D.

All Publications

• PpIX-enabled fluorescence-based detection and photodynamic priming of platinum-resistant ovarian cancer cells under fluid shear stress. Photochemistry and photobiology Ruhi, M. K., Rickard, B. P., Overchuk, M., Sinawang, P. D., Stanley, E., Mansi, M., Sierra, R. G., Hayes, B., Tan, X., Akin, D., Chen, B., Demirci, U., Rizvi, I. 2024

  Abstract

  Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

  View details for DOI 10.1111/php.14014

  View details for PubMedID 39189505

• Integrated "lab-on-a-chip" microfluidic systems for isolation, enrichment, and analysis of cancer biomarkers. Lab on a chip Surappa, S., Multani, P., Parlatan, U., Sinawang, P. D., Kaifi, J., Akin, D., Demirci, U. 2023

  Abstract

  The liquid biopsy has garnered considerable attention as a complementary clinical tool for the early detection, molecular characterization and monitoring of cancer over the past decade. In contrast to traditional solid biopsy techniques, liquid biopsy offers a less invasive and safer alternative for routine cancer screening. Recent advances in microfluidic technologies have enabled handling of liquid biopsy-derived biomarkers with high sensitivity, throughput, and convenience. The integration of these multi-functional microfluidic technologies into a 'lab-on-a-chip' offers a powerful solution for processing and analyzing samples on a single platform, thereby reducing the complexity, bio-analyte loss and cross-contamination associated with multiple handling and transfer steps in more conventional benchtop workflows. This review critically addresses recent developments in integrated microfluidic technologies for cancer detection, highlighting isolation, enrichment, and analysis strategies for three important sub-types of cancer biomarkers: circulating tumor cells, circulating tumor DNA and exosomes. We first discuss the unique characteristics and advantages of the various lab-on-a-chip technologies developed to operate on each biomarker subtype. This is then followed by a discussion on the challenges and opportunities in the field of integrated systems for cancer detection. Ultimately, integrated microfluidic platforms form the core of a new class of point-of-care diagnostic tools by virtue of their ease-of-operation, portability and high sensitivity. Widespread availability of such tools could potentially result in more frequent and convenient screening for early signs of cancer at clinical labs or primary care offices.

  View details for DOI 10.1039/d2lc01076c

  View details for PubMedID 37314731

• Systematic Analysis of Tissue-Derived and Biofluid Extracellular Vesicle miRNAs Associated with Prostate Cancer. Advanced biology Larson, J., Ozen, M. O., Kohli, M., Akin, D., Demirci, U. 2023: e2200327

  Abstract

  Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals with prostate cancer (PCa) with cancer-free samples for diagnostic purposes. The aim of this study is to review miRNA signatures to investigate the overlap between miRNAs enriched in PCa tissue and miRNAs enriched in EVs isolated from subjects with PCa biofluids (i.e., urine, serum, and plasma). Signatures dysregulated in EVs from PCa biofluids and tissue are potentially associated with the primary tumor site and might be more indicative of PCa at an early stage. A systematic review of EV-derived miRNAs and a reanalysis of PCa tissue miRNA sequencing data for comparison is presented. Articles in the literature are screened for validated miRNA dysregulation in PCa and compared with TCGA primary PCa tumor data using DESeq2. This resulted in 190 dysregulated miRNAs being identified. Thirty-one eligible studies are identified, indicating 39 dysregulated EV-derived miRNAs. The top ten markers identified as significantly dysregulated in the PCa tissue dataset TCGA (e.g., miR-30b-3p, miR-210-3p, miR-126-3p, and miR-196a-5p) have a significant expression change in EVs with the same directionality in one or several statistically significant results. This analysis highlights several less frequently studied miRNAs in PCa literature.

  View details for DOI 10.1002/adbi.202200327

  View details for PubMedID 37300338

• Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer. Cancers Rickard, B. P., Overchuk, M., Chappell, V. A., Kemal Ruhi, M., Sinawang, P. D., Nguyen Hoang, T. T., Akin, D., Demirci, U., Franco, W., Fenton, S. E., Santos, J. H., Rizvi, I. 2023; 15 (9)

  Abstract

  Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.

  View details for DOI 10.3390/cancers15092564

  View details for PubMedID 37174030

• Programmable Shape Morphing Metasponge ADVANCED INTELLIGENT SYSTEMS Soto, F., Tsui, A., Surappa, S., Ahmed, R., Wang, J., Kilinc, U., Akin, D., Demirci, U. 2023

  View details for DOI 10.1002/aisy.202300043

  View details for Web of Science ID 000974241500001

• Review of HIV Self Testing Technologies and Promising Approaches for the Next Generation. Biosensors Bacon, A., Wang, W., Lee, H., Umrao, S., Sinawang, P. D., Akin, D., Khemtonglang, K., Tan, A., Hirshfield, S., Demirci, U., Wang, X., Cunningham, B. T. 2023; 13 (2)

  Abstract

  The ability to self-test for HIV is vital to preventing transmission, particularly when used in concert with HIV biomedical prevention modalities, such as pre-exposure prophylaxis (PrEP). In this paper, we review recent developments in HIV self-testing and self-sampling methods, and the potential future impact of novel materials and methods that emerged through efforts to develop more effective point-of-care (POC) SARS-CoV-2 diagnostics. We address the gaps in existing HIV self-testing technologies, where improvements in test sensitivity, sample-to-answer time, simplicity, and cost are needed to enhance diagnostic accuracy and widespread accessibility. We discuss potential paths toward the next generation of HIV self-testing through sample collection materials, biosensing assay techniques, and miniaturized instrumentation. We discuss the implications for other applications, such as self-monitoring of HIV viral load and other infectious diseases.

  View details for DOI 10.3390/bios13020298

  View details for PubMedID 36832064

• Label-Free Identification of Exosomes using Raman Spectroscopy and Machine Learning. Small (Weinheim an der Bergstrasse, Germany) Parlatan, U., Ozen, M. O., Kecoglu, I., Koyuncu, B., Torun, H., Khalafkhany, D., Loc, I., Ogut, M. G., Inci, F., Akin, D., Solaroglu, I., Ozoren, N., Unlu, M. B., Demirci, U. 2023: e2205519

  Abstract

  Exosomes, nano-sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface-enhanced Raman spectroscopy (SERS) with machine learning algorithms to employ the classification of EVs derived from five different cell lines to reveal their cellular origins. Using an artificial neural network algorithm, it is shown that the label-free Raman spectroscopy method's prediction ratio correlates with the ratio of HT-1080 exosomes in the mixture. This machine learning-assisted SERS method enables a new direction through label-free investigation of EV preparations by differentiating cancer cell-derived exosomes from those of healthy. This approach will potentially open up new avenues of research for early detection and monitoring of various diseases, including cancer.

  View details for DOI 10.1002/smll.202205519

  View details for PubMedID 36642804

• Large-Scale Functionalized Metasurface-Based SARS-CoV-2 Detection and Quantification. ACS nano Ahmed, R., Guimaraes, C. F., Wang, J., Soto, F., Karim, A. H., Zhang, Z., Reis, R. L., Akin, D., Paulmurugan, R., Demirci, U. 2022

  Abstract

  Plasmonic metasurfaces consist of metal-dielectric interfaces that are excitable at background and leakage resonant modes. The sharp and plasmonic excitation profile of metal-free electrons on metasurfaces at the nanoscale can be used for practical applications in diverse fields, including optoelectronics, energy harvesting, and biosensing. Currently, Fano resonant metasurface fabrication processes for biosensor applications are costly, need clean room access, and involve limited small-scale surface areas that are not easy for accurate sample placement. Here, we leverage the large-scale active area with uniform surface patterns present on optical disc-based metasurfaces as a cost-effective method to excite asymmetric plasmonic modes, enabling tunable optical Fano resonance interfacing with a microfluidic channel for multiple target detection in the visible wavelength range. We engineered plasmonic metasurfaces for biosensing through efficient layer-by-layer surface functionalization toward real-time measurement of target binding at the molecular scale. Further, we demonstrated the quantitative detection of antibodies, proteins, and the whole viral particles of SARS-CoV-2 with a high sensitivity and specificity, even distinguishing it from similar RNA viruses such as influenza and MERS. This cost-effective plasmonic metasurface platform offers a small-scale light-manipulation system, presenting considerable potential for fast, real-time detection of SARS-CoV-2 and pathogens in resource-limited settings.

  View details for DOI 10.1021/acsnano.2c02500

  View details for PubMedID 36125414

• Automated Recognition of Plasmodium falciparum Parasites from Portable Blood Levitation Imaging. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Deshmukh, S. S., Byaruhanga, O., Tumwebaze, P., Akin, D., Greenhouse, B., Egan, E. S., Demirci, U. 2022: e2105396

  Abstract

  In many malaria-endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone-interfaced, battery-operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria-negative and 36 malaria-positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold-standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user-friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource-constrained environments.

  View details for DOI 10.1002/advs.202105396

  View details for PubMedID 35957519

• Engineered living bioassemblies for biomedical and functional material applications. Current opinion in biotechnology Guimaraes, C. F., Soto, F., Wang, J., Akin, D., Reis, R. L., Demirci, U. 2022; 77: 102756

  Abstract

  Recent breakthroughs in biofabrication of bioasemblies, consisting of the engineered structures composed of biological or biosynthetic components into a single construct, have found a wide range of practical applications in medicine and engineering. This review presents an overview of how the bottom-up assembly of living entities could drive advances in medicine, by developing tunable biological models and more precise methods for quantifying biological events. Moreover, we delve into advances beyond biomedical applications, where bioassemblies can be manipulated as functional robots and construction materials. Finally, we address the potential challenges and opportunities in the field of engineering living bioassemblies, toward building new design principles for the next generation of bioengineering applications.

  View details for DOI 10.1016/j.copbio.2022.102756

  View details for PubMedID 35930844

• Volbots: Volvox Microalgae-Based Robots for Multimode Precision Imaging and Therapy ADVANCED FUNCTIONAL MATERIALS Wang, J., Soto, F., Liu, S., Yin, Q., Purcell, E., Zeng, Y., Hsu, E., Akin, D., Sinclair, B., Stoyanova, T., Demirci, U. 2022

  View details for DOI 10.1002/adfm.202201800

  View details for Web of Science ID 000812853500001

• Acoustic Fabrication of Living Cardiomyocyte-based Hybrid Biorobots. ACS nano Wang, J., Soto, F., Ma, P., Ahmed, R., Yang, H., Chen, S., Wang, J., Liu, C., Akin, D., Fu, K., Cao, X., Chen, P., Hsu, E. C., Soh, H. T., Stoyanova, T., Wu, J. C., Demirci, U. 2022

  Abstract

  Organized assemblies of cells have demonstrated promise as bioinspired actuators and devices; still, the fabrication of such "biorobots" has predominantly relied on passive assembly methods that reduce design capabilities. To address this, we have developed a strategy for the rapid formation of functional biorobots composed of live cardiomyocytes. We employ tunable acoustic fields to facilitate the efficient aggregation of millions of cells into high-density macroscopic architectures with directed cell orientation and enhanced cell-cell interaction. These biorobots can perform actuation functions both through naturally occurring contraction-relaxation cycles and through external control with chemical and electrical stimuli. We demonstrate that these biorobots can be used to achieve controlled actuation of a soft skeleton and pumping of microparticles. The biocompatible acoustic assembly strategy described here should prove generally useful for cellular manipulation in the context of tissue engineering, soft robotics, and other applications.

  View details for DOI 10.1021/acsnano.2c01908

  View details for PubMedID 35671037

• Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract ADVANCED INTELLIGENT SYSTEMS Soto, F., Purcell, E., Ozen, M., Sinawang, P., Wang, J., Akin, D., Demirci, U. 2022

  View details for DOI 10.1002/aisy.202200030

  View details for Web of Science ID 000778957300001

• Advanced Point-of-Care Testing Technologies for Human Acute Respiratory Virus Detection. Advanced materials (Deerfield Beach, Fla.) Zhang, Z., Ma, P., Ahmed, R., Wang, J., Akin, D., Soto, F., Liu, B., Li, P., Demirci, U. 2021: e2103646

  Abstract

  The ever-growing global threats to human life caused by the human acute respiratory virus (RV) infections have cost billions of lives, created a significant economic burden, and shaped society for centuries. The timely response to emerging RVs could save human lives and reduce the medical care burden. The development of RV detection technologies is essential for potentially preventing RV pandemic and epidemics. However, commonly used detection technologies lack sensitivity, specificity, and speed, thus often failing to provide the rapid turnaround times. To address this problem, new technologies are devised to address the performance inadequacies of the traditional methods. These emerging technologies offer improvements in convenience, speed, flexibility, and portability of point-of-care test (POCT). Herein, recent developments in POCT are comprehensively reviewed for eight typical acute respiratory viruses. This review discusses the challenges and opportunities of various recognition and detection strategies and discusses these according to their detection principles, including nucleic acid amplification, optical POCT, electrochemistry, lateral flow assays, microfluidics, enzyme-linked immunosorbent assays, and microarrays. The importance of limits of detection, throughput, portability, and specificity when testing clinical samples in resource-limited settings is emphasized. Finally, the evaluation of commercial POCT kits for both essential RV diagnosis and clinical-oriented practices is included.

  View details for DOI 10.1002/adma.202103646

  View details for PubMedID 34623709

• Intracellular detection and communication of a wireless chip in cell. Scientific reports Yang, M. X., Hu, X., Akin, D., Poon, A., Wong, H. P. 2021; 11 (1): 5967

  Abstract

  The rapid growth and development of technology has had significant implications for healthcare, personalized medicine, and our understanding of biology. In this work, we leverage the miniaturization of electronics to realize the first demonstration of wireless detection and communication of an electronic device inside a cell. This is a significant forward step towards a vision of non-invasive, intracellular wireless platforms for single-cell analyses. We demonstrate that a 25 [Formula: see text]m wireless radio frequency identification (RFID) device can not only be taken up by a mammalian cell but can also be detected and specifically identified externally while located intracellularly. The S-parameters and power delivery efficiency of the electronic communication system is quantified before and after immersion in a biological environment; the results show distinct electrical responses for different RFID tags, allowing for classification of cells by examining the electrical output noninvasively. This versatile platform can be adapted for realization of a broad modality of sensors and actuators. This work precedes and facilitates the development of long-term intracellular real-time measurement systems for personalized medicine and furthering our understanding of intrinsic biological behaviors. It helps provide an advanced technique to better assess the long-term evolution of cellular physiology as a result of drug and disease stimuli in a way that is not feasible using current methods.

  View details for DOI 10.1038/s41598-021-85268-5

  View details for PubMedID 33727598

• Progress and challenges in biomarker enrichment for cancer early detection Progress in Biomedical Engineering Sinawang, P., Soto, F., Ozen, M. O., Akin, D., Demirci, U. 2021; 3 (4)

  View details for DOI 10.1088/2516-1091/ac1ea3

• Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial ACS NANO Arami, H., Patel, C. B., Madsen, S. J., Dickinson, P. J., Davis, R. M., Zeng, Y., Sturges, B. K., Woolard, K. D., Habte, F. G., Akin, D., Sinclair, R., Gambhir, S. S. 2019; 13 (3): 2858–69

  View details for DOI 10.1021/acsnano.8b04406

  View details for Web of Science ID 000462950500015

• Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial. ACS nano Arami, H., Patel, C. B., Madsen, S. J., Dickinson, P. J., Davis, R. M., Zeng, Y., Sturges, B. K., Woolard, K. D., Habte, F. G., Akin, D., Sinclair, R., Gambhir, S. S. 2019

  Abstract

  Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

  View details for PubMedID 30714717

• Rapid and specific labeling of single live Mycobacterium tuberculosis with a dual-targeting fluorogenic probe SCIENCE TRANSLATIONAL MEDICINE Cheng, Y., Xie, J., Lee, K., Gaur, R. L., Song, A., Dai, T., Ren, H., Wu, J., Sun, Z., Banaei, N., Akin, D., Rao, J. 2018; 10 (454)

  Abstract

  Tuberculosis (TB) remains a public health crisis and a leading cause of infection-related death globally. Although in high demand, imaging technologies that enable rapid, specific, and nongenetic labeling of live Mycobacterium tuberculosis (Mtb) remain underdeveloped. We report a dual-targeting strategy to develop a small molecular probe (CDG-DNB3) that can fluorescently label single bacilli within 1 hour. CDG-DNB3 fluoresces upon activation of the β-lactamase BlaC, a hydrolase naturally expressed in Mtb, and the fluorescent product is retained through covalent modification of the Mtb essential enzyme decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1). This dual-targeting probe not only discriminates live from dead Bacillus Calmette-Guérin (BCG) but also shows specificity for Mtb over other bacterial species including 43 nontuberculosis mycobacteria (NTM). In addition, CDG-DNB3 can image BCG phagocytosis in real time, as well as Mtb in patients' sputum. Together with a low-cost, self-driven microfluidic chip, we have achieved rapid labeling and automated quantification of live BCG. This labeling approach should find many potential applications for research toward TB pathogenesis, treatment efficacy assessment, and diagnosis.

  View details for PubMedID 30111644

• Internalization of subcellular-scale microfabricated chips by healthy and cancer cells PLOS ONE Parizi, K. B., Akin, D., Wong, H. 2018; 13 (3)

  View details for DOI 10.1371/journal.pone.0194712

  View details for Web of Science ID 000428845900009

• Internalization of subcellular-scale microfabricated chips by healthy and cancer cells. PloS one Parizi, K. B., Akin, D., Wong, H. P. 2018; 13 (3): e0194712

  Abstract

  Continuous monitoring of physiological parameters inside a living cell will lead to major advances in our understanding of biology and complex diseases, such as cancer. It also enables the development of new medical diagnostics and therapeutics. Progress in nanofabrication and wireless communication has opened up the potential of making a wireless chip small enough that it can be wholly inserted into a living cell. To investigate how such chips could be internalized into various types of living single cells and how this process might affect cells' physiology, we designed and fabricated a series of multilayered micron-scale tag structures with different sizes as potential RFID (Radio Frequency IDentification) cell trackers. While the present structures are test structures that do not resonate, the tags that do resonate have similar structure from device fabrication, material properties, and device size point of view. The structures are in four different sizes, the largest with the lateral dimension of 9 mum * 21 mum. The thickness for these structures is kept constant at 1.5 mum. We demonstrate successful delivery of our fabricated chips into various types of living cells, such as melanoma skin cancer, breast cancer, colon cancer and healthy/normal fibroblast skin cells. To our surprise, we observed a remarkable internalization rate difference between each cell type; the uptake rate was faster for more aggressive cancer cells than the normal/healthy cells. Cell viability before and after tag cellular internalization and persistence of the internalized tags have also been recorded over the course of five days of incubation. These results establish the foundations of the possibility of long term, wireless, intracellular physiological signal monitoring.

  View details for PubMedID 29601607

• Micrometer-scale magnetic-resonance-coupled radio-frequency identification and transceivers for wireless sensors in cells Physical Review Applied Hu, X., Aggarwal, K., Yang, M., Parizi, K., Xu, X., Akin, D., Poon, A., Wong, H. 2017

  View details for DOI 10.1103/PhysRevApplied.8.014031

• PCR Amplification and Sequencing Analysis of Full-Length Turkey Coronavirus Spike Gene ANIMAL CORONAVIRUSES Chen, Y., Akin, A., Loa, C., Ababneh, M., Cao, J., Chen, W., Wu, C., Lin, T., Wang, L. 2016: 151-160

  View details for DOI 10.1007/978-1-4939-3414-0_14

  View details for Web of Science ID 000376038100015

• 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

  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 Web of Science ID 000359285100006

  View details for PubMedID 26195743

  View details for PubMedCentralID PMC4538635

• 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

  View details for PubMedCentralID PMC4538635

• Biotargeted nanomedicines for cancer: six tenets before you begin NANOMEDICINE Goldberg, M. S., Hook, S. S., Wang, A. Z., Bulte, J. W., Patri, A. K., Uckun, F. M., Cryns, V. L., Hanes, J., Akin, D., Hall, J. B., Gharkholo, N., Mumper, R. J. 2013; 8 (2): 299-308

  Abstract

  Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the 'magic bullet' that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute's Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice.

  View details for DOI 10.2217/NNM.13.3

  View details for Web of Science ID 000314791200022

  View details for PubMedID 23394158

  View details for PubMedCentralID PMC3643633

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

  Abstract

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

  View details for DOI 10.1021/nn301670a

  View details for Web of Science ID 000307988900039

  View details for PubMedID 22857784

  View details for PubMedCentralID PMC3601027

• Theranostics. NCI Cancer Nanotechnology Plan (2010-2020) Akin D., S.S. Gambhir 2010
• Nanotechnology Research Directions for Societal Needs in 2020. Nanobiosystems, Medicine and Health. M.C. Roco, C.A. Mirkin and M.C. Hersham eds. Mirkin C.A., A. Nel, C. S. Thaxton, B.A. Baird, C. Batt, D. Grainger, S.S.Gambhir, D. Akin, O. Zhou, J.F. Stoddart, T.J. Meade, P. Grodzinski, D. Farrell, H.F. Tibbals, J. De Simone 2010; NSF
• Capture and alignment of phi29 viral particles in sub-40 nanometer porous alumina membranes BIOMEDICAL MICRODEVICES Moon, J., Akin, D., Xuan, Y., Ye, P. D., Guo, P., Bashir, R. 2009; 11 (1): 135-142

  Abstract

  Bacteriophage phi29 virus nanoparticles and its associated DNA packaging nanomotor can provide for novel possibilities towards the development of hybrid bio-nano structures. Towards the goal of interfacing the phi29 viruses and nanomotors with artificial micro and nanostructures, we fabricated nanoporous Anodic Aluminum Oxide (AAO) membranes with pore size of 70 nm and shrunk the pores to sub 40 nm diameter using atomic layer deposition (ALD) of Aluminum Oxide. We were able to capture and align particles in the anodized nanopores using two methods. Firstly, a functionalization and polishing process to chemically attach the particles in the inner surface of the pores was developed. Secondly, centrifugation of the particles was utilized to align them in the pores of the nanoporous membranes. In addition, when a mixture of empty capsids and packaged particles was centrifuged at specific speeds, it was found that the empty capsids deform and pass through 40 nm diameter pores whereas the particles packaged with DNA were mainly retained at the top surface of the nanoporous membranes. Fluorescence microscopy was used to verify the selective filtration of empty capsids through the nanoporous membranes.

  View details for DOI 10.1007/s10544-008-9217-0

  View details for Web of Science ID 000263114000014

  View details for PubMedID 18770041

  View details for PubMedCentralID PMC2728681

• Dielectrophoresis-based cell manipulation using electrodes on a reusable printed circuit board LAB ON A CHIP Park, K., Suk, H., Akin, D., Bashir, R. 2009; 9 (15): 2224-2229

  Abstract

  Particle manipulation based on dielectrophoresis (DEP) can be a versatile and useful tool in lab-on-chip systems for a wide range of cell patterning and tissue engineering applications. Even though there are extensive reports on the use of DEP for cell patterning applications, the development of approaches that make DEP even more affordable and common place is still desirable. In this study, we present the use of interdigitated electrodes on a printed circuit board (PCB) that can be reused to manipulate and position HeLa cells and polystyrene particles over 100 microm thick glass cover slips using DEP. An open-well or a closed microfluidic channel, both made of PDMS, was placed on the glass coverslip, which was then placed directly over the PCB. An AC voltage was applied to the electrodes on the PCB to induce DEP on the particles through the thin glass coverslip. The HeLa cells patterned with DEP were subsequently grown to confirm the lack of any adverse affects from the electric fields. This alternative and reusable platform for DEP particle manipulation can provide a convenient and rapid method for prototyping a DEP-based lab-on-chip system, cost-sensitive lab-on-chip applications, and a wide range of tissue engineering applications.

  View details for DOI 10.1039/b904328d

  View details for Web of Science ID 000268033900015

  View details for PubMedID 19606300

• Real-time detection of airborne viruses on a mass-sensitive device APPLIED PHYSICS LETTERS Lee, J., Jang, J., Akin, D., Savran, C. A., Bashir, R. 2008; 93 (1)

  Abstract

  We present real-time detection of airborne Vaccinia viruses using quartz crystal microbalance (QCM) in an integrated manner. Vaccinia viruses were aerosolized and neutralized using an electrospray aerosol generator, transported into the QCM chamber, and captured by a QCM crystal. The capture of the viruses on the QCM crystal resulted in frequency shifts proportional to the number of viruses. The capture rate varied linearly with the concentration of initial virus suspensions (8.5x10(8)-8.5x10(10) particlesml) at flow rates of 2.0 and 1.1 lmin. This work demonstrates the general potential of mass sensitive detection of nanoscale biological entities in air.

  View details for DOI 10.1063/1.2956679

  View details for Web of Science ID 000258184600069

  View details for PubMedCentralID PMC2682748

• Effects of inlet/outlet configurations on the electrostatic capture of airborne nanoparticles and viruses MEASUREMENT SCIENCE & TECHNOLOGY Jang, J., Akin, D., Bashir, R. 2008; 19 (6)

  Abstract

  Motivated by capture and detection of airborne biological agents in real time with a cantilever biosensor without introducing the agents into liquids, we present the effects of inlet/outlet configurations of a homemade particle collector on the electrostatic capture of airborne 100 nm diameter nanoparticles under swirling gas flows. This particle collector has three different inlet/outlet configurations: forward inlet/outlet (FO), backward inlet/outlet (BO) and straight inlet/outlet (SO) configurations. We also present the electrostatic capture of Vaccinia viruses using the same particle collector and compare these virus measurements with the nanoparticle cases. The most particles were collected in the FO configuration. The numbers of particles captured in the BO and SO configurations were close within their standard deviations. For all the three configurations tested, the number of particles captured in the center electrode C was much smaller than those captured in the other electrodes at a flow rate of 1.1 l min-1 and an applied potential of 2 kV. Using a commercial CFD code FLUENT, we also simulated the effects of the three inlet/outlet configurations on the particle capture in terms of particle trajectories, velocities and travel times. This simulation was in a good agreement with measurements that the FO configuration is the most favorable to particle capture among the tested configurations at a flow rate of 1.1 l min-1. The effects of particle diameters on the capture will also be discussed. This collector can be used for real-time monitoring of bioaerosols along with cantilever biosensors.

  View details for DOI 10.1088/0957-0233/19/6/065204

  View details for Web of Science ID 000256907700014

  View details for PubMedCentralID PMC7115746

• Effects of inlet/outlet configurations on the electrostatic capture of airborne nanoparticles and viruses Measurement Science and Technology Jang J., D. Akin, R. Bashir 2008; 19: 065204-065212
• PCR-based detection in a micro-fabricated platform LAB ON A CHIP Bhattacharya, S., Salamat, S., Morisette, D., Banada, P., Akin, D., Liu, Y., Bhunia, A. K., Ladisch, M., Bashir, R. 2008; 8 (7): 1130-1136

  Abstract

  We present a novel, on-chip system for the electrokinetic capture of bacterial cells and their identification using the polymerase chain reaction (PCR). The system comprises a glass-silicon platform with a set of micro-channels, -chambers, and -electrodes. A platinum thin film resistor, placed in the proximity of the chambers, is used for temperature monitoring. The whole chip assembly is mounted on a Printed Circuit Board (PCB) and wire-bonded to it. The PCB has an embedded heater that is utilized for PCR thermal cycle and is controlled by a Lab-View program. Similar to our previous work, one set of electrodes on the chip inside the bigger chamber (0.6 microl volume) is used for diverting bacterial cells from a flowing stream into to a smaller chamber (0.4 nl volume). A second set of interdigitated electrodes (in smaller chamber) is used to actively trap and concentrate the bacterial cells using dielectrophoresis (DEP). In the presence of the DEP force, with the cells still entrapped in the micro-chamber, PCR mix is injected into the chamber. Subsequently, PCR amplification with SYBR Green detection is used for genetic identification of Listeria monocytogenes V7 cells. The increase in fluorescence is recorded with a photomultiplier tube module mounted over an epifluorescence microscope. This integrated micro-system is capable of genetic amplification and identification of as few as 60 cells of L. monocytogenes V7 in less than 90 min, in 600 nl volume collected from a sample of 10(4) cfu ml(-1). Specificity trials using various concentrations of L. monocytogenes V7, Listeria innocua F4248, and Escherichia coli O157:H7 were carried out successfully using two different primer sets specific for a regulatory gene of L. monocytogenes, prfA and 16S rRNA primer specific for the Listeria spp., and no cross-reactivity was observed.

  View details for DOI 10.1039/b802227e

  View details for Web of Science ID 000257236900020

  View details for PubMedID 18584089

• Real-time detection of air-borne viruses on a mass-sensitive device Applied Physics Letters Lee, J., J. Jang, D. Akin, C.A. Savran, R. Bashir 2008; 93 (1): 13901
• Ultrananocrystalline diamond film as an optimal cell interface for biomedical applications BIOMEDICAL MICRODEVICES Bajaj, P., Akin, D., Gupta, A., Sherman, D., Shi, B., Auciello, O., Bashir, R. 2007; 9 (6): 787-794

  Abstract

  Surfaces of materials that promote cell adhesion, proliferation, and growth are critical for new generation of implantable biomedical devices. These films should be able to coat complex geometrical shapes very conformally, with smooth surfaces to produce hermetic bioinert protective coatings, or to provide surfaces for cell grafting through appropriate functionalization. Upon performing a survey of desirable properties such as chemical inertness, low friction coefficient, high wear resistance, and a high Young's modulus, diamond films emerge as very attractive candidates for coatings for biomedical devices. A promising novel material is ultrananocrystalline diamond (UNCD) in thin film form, since UNCD possesses the desirable properties of diamond and can be deposited as a very smooth, conformal coating using chemical vapor deposition. In this paper, we compared cell adhesion, proliferation, and growth on UNCD films, silicon, and platinum films substrates using different cell lines. Our results showed that UNCD films exhibited superior characteristics including cell number, total cell area, and cell spreading. The results could be attributed to the nanostructured nature or a combination of nanostructure/surface chemistry of UNCD, which provides a high surface energy, hence promoting adhesion between the receptors on the cell surface and the UNCD films.

  View details for DOI 10.1007/s10544-007-9090-2

  View details for Web of Science ID 000250462200002

  View details for PubMedID 17530409

• A cellular Trojan horse for delivery of therapeutic nanoparticles into tumors NANO LETTERS Choi, M., Stanton-Maxey, K. J., Stanley, J. K., Levin, C. S., Bardhan, R., Akin, D., Badve, S., Sturgis, J., Robinson, J. P., Bashir, R., Halas, N. J., Clare, S. E. 2007; 7 (12): 3759-3765

  Abstract

  Destruction of hypoxic regions within tumors, virtually inaccessible to cancer therapies, may well prevent malignant progression. The tumor's recruitment of monocytes into these regions may be exploited for nanoparticle-based delivery. Monocytes containing therapeutic nanoparticles could serve as "Trojan Horses" for nanoparticle transport into these tumor regions. Here we report the demonstration of several key steps toward this therapeutic strategy: phagocytosis of Au nanoshells, and photoinduced cell death of monocytes/macrophages as isolates and within tumor spheroids.

  View details for DOI 10.1021/nl072209h

  View details for Web of Science ID 000251581600037

  View details for PubMedID 17979310

• Electrical capture and lysis of vaccinia virus particles using silicon nano-scale probe array BIOMEDICAL MICRODEVICES Park, K., Akin, D., Bashir, R. 2007; 9 (6): 877-883

  Abstract

  A probe array with nano-scale tips, integrated into a micro-fluidic channel was developed for the capture and lysing of small number of vaccinia virus particles using dielectrophoresis. The nano-scale probe array was fabricated in Silicon on Insulator (SOI) wafers, and sharpened with repeated oxidation steps. The gap between each probe ranged from 100 nm to 1.5 microm depending on fabrication parameters. The probe array was used to capture vaccinia virus using positive dielectrophoresis (DEP) from a flow within the microfluidic channel, and then the same probe array was used to apply high electric field to lyse the virus particles. It was shown that under electric field strengths of about 10(7)V/m, the permeability of ethidium bromide into the vaccinia virus particles was increased. Upon SEM analysis, the particles were found to be damaged and exhibited tubules networks, indicating disintegration of the virus outer layer. In addition, elongated strands of DNA were clearly observed on the chip surface after the application of the high electric field, demonstrating the possibility of electrical lysis of virus particles.

  View details for DOI 10.1007/s10544-007-9101-3

  View details for Web of Science ID 000250462200013

  View details for PubMedID 17610069

• Bacteria-mediated delivery of nanoparticles and cargo into cells NATURE NANOTECHNOLOGY Akin, D., Sturgis, J., Ragheb, K., Sherman, D., Burkholder, K., Robinson, J. P., Bhunia, A. K., Mohammed, S., Bashir, R. 2007; 2 (7): 441-449

  Abstract

  Nanoparticles and bacteria can be used, independently, to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver DNA-based model drug molecules in vivo and in vitro. In our approach, cargo (in this case, a fluorescent or a bioluminescent gene) is loaded onto the nanoparticles, which are carried on the bacteria surface. When incubated with cells, the cargo-carrying bacteria ('microbots') were internalized by the cells, and the genes released from the nanoparticles were expressed in the cells. Mice injected with microbots also successfully expressed the genes as seen by the luminescence in different organs. This new approach may be used to deliver different types of cargo into live animals and a variety of cells in culture without the need for complicated genetic manipulations.

  View details for DOI 10.1038/nnano.2007.149

  View details for Web of Science ID 000248302500016

  View details for PubMedID 18654330

• Solid-state nanopore channels with DNA selectivity NATURE NANOTECHNOLOGY Iqbal, S. M., Akin, D., Bashir, R. 2007; 2 (4): 243-248

  Abstract

  Solid-state nanopores have emerged as possible candidates for next-generation DNA sequencing devices. In such a device, the DNA sequence would be determined by measuring how the forces on the DNA molecules, and also the ion currents through the nanopore, change as the molecules pass through the nanopore. Unlike their biological counterparts, solid-state nanopores have the advantage that they can withstand a wide range of analyte solutions and environments. Here we report solid-state nanopore channels that are selective towards single-stranded DNA (ssDNA). Nanopores functionalized with a 'probe' of hair-pin loop DNA can, under an applied electrical field, selectively transport short lengths of 'target' ssDNA that are complementary to the probe. Even a single base mismatch between the probe and the target results in longer translocation pulses and a significantly reduced number of translocation events. Our single-molecule measurements allow us to measure separately the molecular flux and the pulse duration, providing a tool to gain fundamental insight into the channel-molecule interactions. The results can be explained in the conceptual framework of diffusive molecular transport with particle-channel interactions.

  View details for DOI 10.1038/nnano.2007.78

  View details for Web of Science ID 000245920900016

  View details for PubMedID 18654270

• Biomems and nanotechnology-based approaches for rapid detection of biological entities JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY Bhattacharya, S., Jang, J., Yang, L., Akin, D., Bashir, R. 2007; 15 (1): 1-32

  View details for Web of Science ID 000245613100001

• Capture of airborne nanoparticles in swirling flows using non-uniform electrostatic fields for bio-sensor applications SENSORS AND ACTUATORS B-CHEMICAL Jang, J., Akin, D., Lim, K. S., Broyles, S., Ladisch, M. R., Bashira, R. 2007; 121 (2): 560-566

  View details for DOI 10.1016/j.sub.2006.04.097

  View details for Web of Science ID 000244545100030

• Nanotechnology in Biology and Medicine: Methods, Devices, and Applications. Edited by Tuan Vo-Dinh, Book Review. ChemMedChem Akin D. 2007; 2 (10): 1534-1535
• Biomems and Nanotechnology based approaches for rapid detection of biological entities J. Rapid Methods & Automation in Microbiology Bhattacharya, S., J. Jang, L. Yang, D. Akin, R. Bashir 2007; 15: 1-32
• Capture of airborne nanoparticles in swirling flows using non-uniform electrostatic fields for bio-sensor applications Sensors and Actuators B Jang J., D. Akin, K.S. Lim, S. Broyles, M.R. Ladisch, R. Bashir 2007; 121: 560-566
• Anomalous resonance in a nanomechanical biosensor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Gupta, A. K., Nair, P. R., Akin, D., Ladisch, M. R., Broyles, S., Alam, M. A., Bashir, R. 2006; 103 (36): 13362-13367

  Abstract

  The decrease in resonant frequency (-Deltaomega(r)) of a classical cantilever provides a sensitive measure of the mass of entities attached on its surface. This elementary phenomenon has been the basis of a new class of bio-nanomechanical devices as sensing components of integrated microsystems that can perform rapid, sensitive, and selective detection of biological and biochemical entities. Based on classical analysis, there is a widespread perception that smaller sensors are more sensitive (sensitivity approximately -0.5omega(r)/m(C), where m(C) is the mass of the cantilever), and this notion has motivated scaling of biosensors to nanoscale dimensions. In this work, we show that the response of a nanomechanical biosensor is far more complex than previously anticipated. Indeed, in contrast to classical microscale sensors, the resonant frequencies of the nanosensor may actually decrease or increase after attachment of protein molecules. We demonstrate theoretically and experimentally that the direction of the frequency change arises from a size-specific modification of diffusion and attachment kinetics of biomolecules on the cantilevers. This work may have broad impact on microscale and nanoscale biosensor design, especially when predicting the characteristics of bio-nanoelectromechanical sensors functionalized with biological capture molecules.

  View details for DOI 10.1073/pnas.0602022103

  View details for Web of Science ID 000240512700021

  View details for PubMedID 16938886

  View details for PubMedCentralID PMC1569169

• Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy SENSORS AND ACTUATORS B-CHEMICAL Johnson, L., Gupta, A. T., Ghafoor, A., Akin, D., Bashir, R. 2006; 115 (1): 189-197

  View details for DOI 10.1016/j.snb.2005.08.047

  View details for Web of Science ID 000236929100027

• Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy Sensors and Actuators B Johnson, L., A. Gupta, D. Akin, A. Ghafoor, R. Bashir 2006; 115: 189-197
• Spore detection in air and fluid using micro-cantilever sensors Davila, A. P., Gupta, A., Walter, T., Akin, D., Aronson, A., Bashir, R., Furuya, Y., Su, J., Takeuchi, Varadan, V. K., Ulicny, J. MATERIALS RESEARCH SOC. 2006: 197-+

  View details for Web of Science ID 000237236600027

• Characterization and modeling of a microfluidic dielectrophoresis filter for biological species JOURNAL OF MICROELECTROMECHANICAL SYSTEMS Li, H. B., Zheng, Y. N., Akin, D., Bashir, R. 2005; 14 (1): 103-112

  View details for DOI 10.1109/JMEMS.2004.839124

  View details for Web of Science ID 000226965200012

• Delocalization of vaccinia virus components observed by Atomic Force and Fluorescence Microscopy NanoBiotechnology Ghafoor, A*., D. Akin*, R. Bashir 2005; 4: 337-346
• Mechanical effects of attaching protein layers on nanoscale-thick cantilever beams for resonant detection of virus particles Gupta, A., Akin, D., Bashir, R., IEEE IEEE. 2005: 746-749

  View details for DOI 10.1109/MEMSYS.2005.1454037

  View details for Web of Science ID 000228430000185

• Dielectrophoresis and antibody mediated selective capture of microorganisms in micro-fluidic biochips Li, H., Yang, L., Akin, D., Geng, T., Bhunia, A., Huang, T. T., Ladisch, M., Bashir, R., IEEE IEEE. 2005: 1700-1703

  View details for Web of Science ID 000232189100420

• Characterization and modeling of a microfluidic dielectrophoresis filter for biological species J. Microelectromechanical Systems Li, H., Y. Zheng, D. Akin, R. Bashir 2005; 143: 103-112
• Bacterial delivery of smart nanoparticles-loaded with therapeutic molecules into cancer cells Nanomedicine Akin D., K. Ragheb, J. Sturgis, A.K. Bhunia, J.P. Robinson, R. Bashir 2005; 1: 250
• Detection of bacterial cells and antibodies using surface micromachined thin silicon cantilever resonators JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B Gupta, A., Akin, D., Bashir, R. 2004; 22 (6): 2785-2791

  View details for DOI 10.1116/1.1824047

  View details for Web of Science ID 000226439800041

• Detection of labeled microbial cells using microfluidic biosensor Huang, T., Taylor, D., Sedlak, M., Gregori, G., Akin, D., Bashir, R., Ladisch, M. R., Robinson, P. AMER CHEMICAL SOC. 2004: U123

  View details for Web of Science ID 000223655600557

• Single virus particle mass detection using microresonators with nanoscale thickness APPLIED PHYSICS LETTERS Gupta, A., Akin, D., Bashir, R. 2004; 84 (11): 1976-1978

  View details for DOI 10.1063/1.1667011

  View details for Web of Science ID 000220182600054

• Real-time virus trapping and fluorescent imaging in microfluidic devices NANO LETTERS Akin, D., Li, H. B., Bashir, R. 2004; 4 (2): 257-259

  View details for DOI 10.1021/nl034987p

  View details for Web of Science ID 000188965700013

• Single virus particle mass detection using microresonators with nanoscale thickness Applied Physics Letters Gupta A., D. Akin, R. Bashir 2004; 84: 1976-1978
• BioMEMS to bionanotechnology: state-of-the-art in integrated biochips and future prospects Gupta, A., Li, H., Gomez, R., Chang, W. J., Koo, Y. M., Chang, H., Andreadakis, G., Akin, D., Bashir, R., Islam, M. S., Dutta, A. K. SPIE-INT SOC OPTICAL ENGINEERING. 2004: 340-353

  View details for DOI 10.1117/12.580407

  View details for Web of Science ID 000226789700036

• Real-time virus trapping and fluorescent imaging in micro-fluidic devices Nano Letters Demir Akin, H. Li, R. Bashir 2004; 4: 257-259
• Detection of bacterial cells and antibodies using surface micromachined thin silicon cantilever resonators. J. Vacuum Sci. & Tech. B: Microelectronics and Nanometer Structures Gupta A., D. Akin, R. Bashir 2004; 22: 2785-2791
• Integrated nanoscale silicon sensors using top-down fabrication APPLIED PHYSICS LETTERS Elibol, O. H., Morisette, D., Akin, D., Denton, J. P., Bashir, R. 2003; 83 (22): 4613-4615

  View details for DOI 10.1063/1.1630853

  View details for Web of Science ID 000186787100049

• Poly(dimethylsiloxane) (PDMS) and silicon hybrid biochip for bacterial culture BIOMEDICAL MICRODEVICES Chang, W. J., Akin, D., Sedlak, M., Ladisch, M. R., Bashir, R. 2003; 5 (4): 281-290

  View details for Web of Science ID 000186331900002

• Microfiber assisted fabrication of microfluidic channels using poly(dimethylsiloxane) AICHE JOURNAL Huang, T. T., Chang, W. J., Akin, D., Gomez, R., Bashir, R., Mosier, N., Ladisch, M. R. 2003; 49 (11): 2984-2987

  View details for Web of Science ID 000186664000028

• Investigation of fluid absorption in hybrid poly(dimethylsiloxane) (PDMS)/silicon biochips for long-term cell-incubation applications. Chang, W. J., Gomez, R., Li, H. B., Akin, D., Bashir, R. AMER CHEMICAL SOC. 2003: U364

  View details for Web of Science ID 000187062501811

• Micro-assembly of functionalized particulate monolayer on C-18-derivatized SiO2 surfaces BIOTECHNOLOGY AND BIOENGINEERING Huang, T. T., Geng, T., Akin, D., Chang, W. J., Sturgis, J., Bashir, R., Bhunia, A. K., Robinson, J. P., Ladisch, M. R. 2003; 83 (4): 416-427

  Abstract

  This work describes a simple approach to immobilize functionalized colloidal microstructures onto a C(18)-coated SiO(2) substrate via specific or non-specific bio-mediated interactions. Biotinylated bovine serum albumin pre-adsorbed onto a C(18) surface was used to mediate the surface assembly of streptavidin-coated microbeads (2.8 microm), while a bare C(18) surface was used to immobilize anti-Listeria antibody-coated microbeads (2.8 microm) through hydrophobic interactions. For a C(18) surface pre-adsorbed with bovine serum albumin, hydrophobic polystyrene microbeads (0.8 microm) and positively charged dimethylamino microbeads (0.8 microm) were allowed to self-assemble onto the surface. A monolayer with high surface coverage was observed for both polystyrene and dimethylamino microbeads. The adsorption characteristics of Escherichia coli and Listeria monocytogenes on these microbead-based surfaces were studied using fluorescence microscopy. Both streptavidin microbeads pre-adsorbed with biotinylated anti-Listeria antibody and anti-Listeria antibody-coated microbeads showed specific capture of L. monocytogenes, while polystyrene and dimethylamino microbeads captured both E. coli and L. monocytogenes non-specifically. The preparation of microbead-based surfaces for the construction of microfluidic devices for separation, detection, or analysis of specific biological species is discussed.

  View details for DOI 10.1002/bit.10680

  View details for Web of Science ID 000183993000006

  View details for PubMedID 12800136

• Bio-mediated assembly of functionalized microbeads for capture of microorganisms. Huang, T. T., Geng, T., Akin, D., Chang, W. J., Sturgis, J., Bashir, R., Bhunia, A. K., Robinson, J. P., Ladisch, M. R. AMER CHEMICAL SOC. 2003: U198

  View details for Web of Science ID 000187917800787

• Integrated nanoscale silicon sensors using top-down fabrication Applied Physics Letters Elibol O.H., D. Morisette, D. Akin, J. P. Denton, R. Bashir 2003; 83: 4613-4615
• Poly(dimethylsiloxane) (PDMS) and silicon hybrid biochip for bacterial culture Biomedical Microdevices Chang W.J., D. Akin, R. Bashir 2003; 5: 281-290
• Resonant mass biosensor for ultrasensitive detection of bacterial cells Microfluidics, BioMEMS, and Medical Microsystems, Holger Becker, Peter Woias, Editors Gupta A., D. Akin, R. Bashir 2003; 4982: 21-27
• Interfacing micro/nano technology with life-sciences for detection of cells and microorganisms Bashir, R., Gomez, R., Li, H., Akin, D., Gupta, A., IEEE IEEE. 2003: 157-160

  View details for Web of Science ID 000189347100033

• From BioMEMS to bionanotechnology: Integrated BioChips for the detection of cells and microorganisms Bashir, R., Akin, D., Gomez, R., Li, H., Chang, W. J., Gupta, A., Ozkan, C. S., Santini, J. T., Gao, H., Bao, G. MATERIALS RESEARCH SOCIETY. 2003: 117-124

  View details for Web of Science ID 000187670400017

• A chemical sensor using neurons and a 3-D micro-fluidic chip McNally, H., Kufluoglu, H., Akin, D., Grimmer, J., Walker, J., Shi, R., Borgens, R., Bashir, R., LaVan, D. A., Ayon, A. A., Buchheit, T. E., Madou, M. J. MATERIALS RESEARCH SOCIETY. 2003: 247-252

  View details for Web of Science ID 000183489300038

• Resonant mass biosensor for ultrasensitive detection of bacterial cells Gupta, A., Akin, D., Bashir, R., Becker, H., Woias, P. SPIE-INT SOC OPTICAL ENGINEERING. 2003: 21-27

  View details for DOI 10.1117/12.478147

  View details for Web of Science ID 000181864600006