With my background in medicine, microdevice engineering, and nanotechnology, my strengths lie in developing novel solutions to urgent problems in medicine and cancer research. Having developed a diagnostic microfluidic device at Caltech and initiated a clinical trial to test the device on glioblastoma patients at UCLA, I’m particlularly interested in moving promising technologies past the proof-of-concept phase and into the clinic. My career goals are to continue to work at the interface of medicine and technology as an academic scientist, engineering new wearable and implantable technologies for earlier cancer detection and continuous monitoring.
Honors & Awards
Front cover: Science Translational Medicine (28 February), Science Translational Medicine (2018)
Poster Award - First Prize, Stanford Bio-X Symposium, Stanford, CA (2017)
Oral Presentation Award - Best Talk, SURPAS Postdoc Symposium, Stanford, CA (2016)
Poster Award - First Prize, Canary Early Detection Summit, Palo Alto, CA (2016)
Poster Award - First Prize, IEEE EMBS MIcro/Nanotechnology in Medicine Conference, Waikoloa, HI (2016)
Dean’s Postdoctoral Fellowship, Stanford School of Medicine (2014)
The Gerald S. Levey, M.D., Medical Science Scholarship, UCLA (2011)
Lemelson-MIT Caltech Invention Prize, Caltech, MIT, and Lemelson Program (2009)
Front cover: Nature Biotechnology (16 November), Nature Biotechnology (2008)
Caltech Graduate Research Assistantship, Caltech (2006-2010)
Letter of Distinction: UCLA GI, Endocrine, and Reproductive Health II Bloc, UCLA (2006)
NIH Medical Scientist Training Program, UCLA (2004-2012)
NSF Graduate Fellowship Honorable Mention, NSF (2004)
Departmental Honors, Stanford Chemistry, Stanford (2002)
Advanced Placement Scholar with Distinction, The College Board (1997)
Advanced Placement Scholar with Honor, The College Board (1996)
Boards, Advisory Committees, Professional Organizations
Vice-President, American Medical Association, UCLA Chapter (2004 - 2005)
President, American Medical Association, UCLA Chapter (2005 - 2006)
Ophir Vermesh, Sanjiv Sam Gambhir, Seung-Min Park, Tianjia Jessie Ge, Amin Aalipour. "United States Patent WO2016200900A1 Intravascular Magnetic Wire for Detection, Retrieval or Elimination of Disease Associated Biomarkers and Toxins.", Leland Stanford Junior University, Dec 15, 2016
Ophir Vermesh, Brian KH Yen, James R. Heath. "United States Patent US20090053732A1 Microfluidic Devices, Methods and Systems for Detecting Target Molecules.", California Institute of Technology, Feb 26, 2009
Current Research and Scholarly Interests
My interests lie at the interface of medicine and technology, engineering new wearable and implantable technologies for earlier cancer detection and continuous monitoring. I am particularly interested in moving promising diagnostic technologies past the proof-of-concept phase and into the clinic.
Sanjiv Gambhir, (9/23/2013)
- An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo NATURE BIOMEDICAL ENGINEERING 2018; 2 (9): 696–705
Intraoperative Molecular Imaging in Lung Cancer: The State of the Art and the Future.
Molecular therapy : the journal of the American Society of Gene Therapy
2018; 26 (2): 338–41
View details for PubMedID 29398484
Toward achieving precision health.
Science translational medicine
2018; 10 (430)
Health care systems primarily focus on patients after they present with disease, not before. The emerging field of precision health encourages disease prevention and earlier detection by monitoring health and disease based on an individual's risk. Active participation in health care can be encouraged with continuous health-monitoring devices, providing a higher-resolution picture of human health and disease. However, the development of monitoring technologies must prioritize the collection of actionable data and long-term user engagement.
View details for PubMedID 29491186
The Exosome Total Isolation Chip.
Circulating tumor-derived extracellular vesicles (EVs) have emerged as a promising source for identifying cancer biomarkers for early cancer detection. However, the clinical utility of EVs has thus far been limited by the fact that most EV isolation methods are tedious, nonstandardized, and require bulky instrumentation such as ultracentrifugation (UC). Here, we report a size-based EV isolation tool called ExoTIC (exosome total isolation chip), which is simple, easy-to-use, modular, and facilitates high-yield and high-purity EV isolation from biofluids. ExoTIC achieves an EV yield ∼4-1000-fold higher than that with UC, and EV-derived protein and microRNA levels are well-correlated between the two methods. Moreover, we demonstrate that ExoTIC is a modular platform that can sort a heterogeneous population of cancer cell line EVs based on size. Further, we utilize ExoTIC to isolate EVs from cancer patient clinical samples, including plasma, urine, and lavage, demonstrating the device's broad applicability to cancers and other diseases. Finally, the ability of ExoTIC to efficiently isolate EVs from small sample volumes opens up avenues for preclinical studies in small animal tumor models and for point-of-care EV-based clinical testing from fingerprick quantities (10-100 μL) of blood.
View details for DOI 10.1021/acsnano.7b04878
View details for PubMedID 29090896
- High-Density, Multiplexed Patterning of Cells at Single-Cell Resolution for Tissue Engineering and Other Applications ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2011; 50 (32): 7378-7380
Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood
2008; 26 (12): 1373-1378
As the tissue that contains the largest representation of the human proteome, blood is the most important fluid for clinical diagnostics. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome, the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings.
View details for DOI 10.1038/nbt.1507
View details for Web of Science ID 000261591300023
View details for PubMedID 19029914
View details for PubMedCentralID PMC2775523
- Toward large arrays of multiplex functionalized carbon nanotube sensors for highly sensitive and selective molecular detection NANO LETTERS 2003; 3 (3): 347-351
- Hysteresis caused by water molecules in carbon nanotube field-effect transistors NANO LETTERS 2003; 3 (2): 193-198
Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites.
Proceedings of the National Academy of Sciences of the United States of America
Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1+/CD45- tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/106 cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.
View details for DOI 10.1073/pnas.1914906117
View details for PubMedID 32430322
Photoacoustic clinical imaging.
2019; 14: 77–98
Photoacoustic is an emerging biomedical imaging modality, which allows imaging optical absorbers in the tissue by acoustic detectors (light in - sound out). Such a technique has an immense potential for clinical translation since it allows high resolution, sufficient imaging depth, with diverse endogenous and exogenous contrast, and is free from ionizing radiation. In recent years, tremendous developments in both the instrumentation and imaging agents have been achieved. These opened avenues for clinical imaging of various sites allowed applications such as brain functional imaging, breast cancer screening, diagnosis of psoriasis and skin lesions, biopsy and surgery guidance, the guidance of tumor therapies at the reproductive and urological systems, as well as imaging tumor metastases at the sentinel lymph nodes. Here we survey the various clinical and pre-clinical literature and discuss the potential applications and hurdles that still need to be overcome.
View details for DOI 10.1016/j.pacs.2019.05.001
View details for PubMedID 31293884
- Tracking T Cell Activation By OX40 Immuno-PET: A Novel Strategy for Imaging of Graft Versus Host Disease AMER SOC HEMATOLOGY. 2018
- Positron emission tomography imaging of activated T cells by targeting OX40 reveals spatiotemporal immune dynamics and predicts response to in situ tumor vaccination AMER ASSOC CANCER RESEARCH. 2018
Emerging Intraoperative Imaging Modalities to Improve Surgical Precision.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging
Intraoperative imaging (IOI) is performed to guide delineation and localization of regions of surgical interest. While oncological surgical planning predominantly utilizes x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), intraoperative guidance mainly remains on surgeon interpretation and pathology for confirmation. Over the past decades however, intraoperative guidance has evolved significantly with the emergence of several novel imaging technologies, including fluorescence-, Raman, photoacoustic-, and radio-guided approaches. These modalities have demonstrated the potential to further optimize precision in surgical resection and improve clinical outcomes for patients. Not only can these technologies enhance our understanding of the disease, they can also yield large imaging datasets intraoperatively that can be analyzed by deep learning approaches for more rapid and accurate pathological diagnosis. Unfortunately, many of these novel technologies are still under preclinical or early clinical evaluation. Organizations like the Intra-Operative Imaging Study Group of the European Society for Molecular Imaging (ESMI) support interdisciplinary interactions with the aim to improve technical capabilities in the field, an approach that can succeed only if scientists, engineers, and physicians work closely together with industry and regulatory bodies to resolve roadblocks to clinical translation. In this review, we provide an overview of a variety of novel IOI technologies, discuss their challenges, and present future perspectives on the enormous potential of IOI for oncological surgical navigation.
View details for PubMedID 29916118
PET imaging of OX40+activated T cells predicts therapeutic response in a murine cancer vaccine model
SOC NUCLEAR MEDICINE INC. 2018
View details for Web of Science ID 000467489900074
Imaging activated T cells predicts response to cancer vaccines.
The Journal of clinical investigation
In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemically. In this study, we describe a PET tracer (64Cu-DOTA-AbOX40) that enabled noninvasive and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We report the spatiotemporal dynamics of T cell activation following in situ vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We demonstrate that OX40 imaging was able to predict tumor responses on day 9 after treatment on the basis of tumor tracer uptake on day 2, with greater accuracy than both anatomical and blood-based measurements. These studies provide key insights into global T cell activation following local CpG treatment and indicate that 64Cu-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer immunotherapy strategies.
View details for PubMedID 29596062
Towards clinically translatable in vivo nanodiagnostics
Nature Reviews Materials
View details for DOI 10.1038/natrevmats.2017.14
Molecular profiling of single circulating tumor cells from lung cancer patients
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (52): E8379-E8386
Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.
View details for DOI 10.1073/pnas.1608461113
View details for PubMedID 27956614
Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges.
Nanomedicine : nanotechnology, biology, and medicine
2016; 12 (2): 287-307
Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types.Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome.
View details for DOI 10.1016/j.nano.2015.10.019
View details for PubMedID 26707817
- Gene expression profiling of individual circulating tumor cells from non-small cell lung cancer (NSCLC) patients via integrated nanotechnologies AMER ASSOC CANCER RESEARCH. 2015
Sol-Gel Synthesis and Electrospraying of Biodegradable (P2O5)(55)-(CaO)(30)-(Na2O)(15) Glass Nanospheres as a Transient Contrast Agent for Ultrasound Stem Cell Imaging
2015; 9 (2): 1868-1877
Ultrasound imaging is a powerful tool in medicine because of the millisecond temporal resolution and submillimeter spatial resolution of acoustic imaging. However, the current generation of acoustic contrast agents is primarily limited to vascular targets due to their large size. Nanosize particles have the potential to be used as a contrast agent for ultrasound molecular imaging. Silica-based nanoparticles have shown promise here; however, their slow degradation rate may limit their applications as a contrast agent. Phosphate-based glasses are an attractive alternative with controllable degradation rate and easily metabolized degradation components in the body. In this study, biodegradable P2O5-CaO-Na2O phosphate-based glass nanospheres (PGNs) were synthesized and characterized as contrast agents for ultrasound imaging. The structure of the PGNs was characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), (31)P magic angle spinning nuclear magnetic resonance ((31)P MAS NMR), and Fourier transform infrared (FTIR) spectroscopy. The SEM images indicated a spherical shape with a diameter size range of 200-500 nm. The XRD, (31)P NMR, and FTIR results revealed the amorphous and glassy nature of PGNs that consisted of mainly Q(1) and Q(2) phosphate units. We used this contrast to label mesenchymal stem cells and determined in vitro and in vivo detection limits of 5 and 9 μg/mL, respectively. Cell counts down to 4000 could be measured with ultrasound imaging with no cytoxicity at doses needed for imaging. Importantly, ion-release studies confirmed these PGNs biodegrade into aqueous media with degradation products that can be easily metabolized in the body.
View details for DOI 10.1021/nn506789y
View details for PubMedID 25625373
A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood
LAB ON A CHIP
2010; 10 (22): 3157-3162
We describe an automated, self-powered chip based on lateral flow immunoassay for rapid, quantitative, and multiplex protein detection from pinpricks of whole blood. The device incorporates on-chip purification of blood plasma by employing inertial forces to focus blood cells away from the assay surface, where plasma proteins are captured and detected on antibody "barcode" arrays. Power is supplied from the capillary action of a piece of adsorbent paper, and sequentially drives, over a 40 minute period, the four steps required to capture serum proteins and then develop a multiplex immunoassay. An 11 protein panel is assayed from whole blood, with high sensitivity and high reproducibility. This inexpensive, self-contained, and easy to operate chip provides a useful platform for point-of-care diagnoses, particularly in resource-limited settings.
View details for DOI 10.1039/c0lc00132e
View details for Web of Science ID 000283600900017
View details for PubMedID 20924527
View details for PubMedCentralID PMC3651856
Fast Nonlinear Ion Transport via Field-induced Hydrodynamic Slip in Sub-20-nm Hydrophilic Nanofluidic Transistors
2009; 9 (4): 1315-1319
Electrolyte transport through an array of 20 nm wide, 20 microm long SiO(2) nanofluidic transistors is described. At sufficiently low ionic strength, the Debye screening length exceeds the channel width, and ion transport is limited by the negatively charged channel surfaces. At source-drain biases >5 V, the current exhibits a sharp, nonlinear increase, with a 20-50-fold conductance enhancement. This behavior is attributed to a breakdown of the zero-slip condition. Implications for energy conversion devices are discussed.
View details for DOI 10.1021/nl802931r
View details for Web of Science ID 000265030000006
View details for PubMedID 19265427
Self-powered microfluidic chips for multiplexed protein assays from whole blood
LAB ON A CHIP
2009; 9 (14): 2016-2020
We report herein on a self-powered, self-contained microfluidic-based chip designed to separate plasma from whole blood, and then execute an assay of a multiplexed panel of plasma biomarker proteins. The power source is based upon a chemical reaction that is catalytically triggered by the push of a button on the chip. We demonstrate assays of a dozen blood-based protein biomarkers using this automated, self-contained device. This platform can potentially permit high throughput, accurate, multiplexed blood diagnostic measurements in remote locations and by minimally trained individuals.
View details for DOI 10.1039/b821247c
View details for Web of Science ID 000267572000008
View details for PubMedID 19568669
View details for PubMedCentralID PMC3651861