Steven Yee

All Publications

• Continuous monitoring of blood-interstitial fluid intercompartmental molecular kinetics in freely moving animals. Science advances Chen, Y., Hu, Q., Kwak, J. W., Zakharian, D., Ji, J., Liu, D., Gopalan, D., Lyons, C., Yates, M., Yee, S., Cui, H., Eisenstein, M., Soh, H. T. 2026; 12 (21): eaed1895

  Abstract

  Accurate health monitoring depends on continuous assessment of biochemical markers across multiple body compartments. While blood remains the clinical gold standard, interstitial fluid (ISF) presents a minimally invasive alternative that reflects local tissue physiology, although its biomarker kinetics often differ from blood. It is currently impossible to achieve simultaneous, continuous monitoring of both compartments, limiting insight into their dynamic relationship. To address this, we present BICEP (blood-ISF continuous-sensing electrochemical probe), a wireless electrochemical platform for continuous dual-compartment monitoring of analytes in blood and ISF. The BICEP system incorporates microfabricated soft sensors with biofouling-resistant aptamer interfaces, paired with a wearable potentiostat for remote configuration and readout. Using this system, we continuously tracked kanamycin signal in both anesthetized and freely moving rats, revealing distinct kinetic profiles and individualized temporal delays between blood and ISF signals. These findings confirm that ISF is not merely a proxy for blood but exhibits unique molecular kinetics influenced by individual variability and physiological state. This platform advances personalized health monitoring by providing integrated, dynamic correlation of blood and ISF biomarkers, deepening understanding of their physiological interplay under real-life conditions and paving the way for broader use of wearable ISF-based biosensors.

  View details for DOI 10.1126/sciadv.aed1895

  View details for PubMedID 42160425

  View details for PubMedCentralID PMC13189097

• Direct Optical Detection of Factor Xa Activity in Minimally Processed Whole Blood. ACS sensors Cartwright, A. P., Wollant, B. C., York, E. S., Zheng, L., Yee, S., Chau, H. C., Batsuli, G., Soh, H. T. 2025

  Abstract

  The ability to measure factor Xa activity directly in whole blood samples offers a path toward point-of-care monitoring and personalized anticoagulant dosage, potentially reducing bleeding risk and other anticoagulant-associated complications. We present a strategy to enable direct optical detection of factor Xa in minimally processed whole blood samples. Our strategy relies on a custom FRET-pair labeled DNA-peptide substrate, allowing FRET ratio to be monitored as an indicator of factor Xa activity. Substrates are tethered to a tapered-fiber sensor to allow evanescent detection of fluorescence directly at the sensor surface, minimizing background media interference and enabling detection directly in blood samples. After characterizing the custom substrate and demonstrating the correlation of fiber-based measurements to an existing chromogenic assay, we demonstrate the detection of endogenous factor Xa activity in >85% whole blood. Finally, we demonstrate the detection of therapeutic concentrations of enoxaparin, a widely used anticoagulant, directly in 90% whole blood in less than an hour and correlate these measurements to activated partial thromboplastin time (aPTT) testing. Together, these results indicate a promising strategy to achieve point-of-care factor Xa detection, enabling personalized anticoagulant treatment and reducing adverse outcomes.

  View details for DOI 10.1021/acssensors.5c00430

  View details for PubMedID 40163026

• Rapid, Sensitive Detection of Protein Biomarkers in Minimally-Processed Blood Products with a Monolithic Sandwich Immunoassay Reagent. Advanced materials (Deerfield Beach, Fla.) Maganzini, N., Reschke, A., Cartwright, A. P., Gidi, Y., Thompson, I. A., Yee, S., Hariri, A., Dory, C., Rosenberg-Hasson, Y., Pan, J., Eisenstein, M., Vuckovic, J., Cornell, T. T., Soh, H. T. 2025: e2412613

  Abstract

  For more than fifty years, the enzyme-linked immunosorbent assay (ELISA) serves as the gold standard for protein biomarker detection. However, conventional ELISA requires considerable sample preparation including reagent addition, incubation, and washing steps, limiting its usefulness at the point-of-care. In this work, the "instant ELISA" (fluorophore-linked immunosorbent assay) biosensor that can measure protein biomarkers in the picomolar range within 15min in undiluted plasma or serum with no sample preparation is described. The sensor leverages a synthetic reagent termed the "monolithic dual-antibody clamp" (MDAC) which preserves the specificity, sensitivity, and generalizability of an ELISA, but produces a fluorescence signal as two surface-tethered antibodies form a "sandwich" by binding to two distinct epitopes on the target. As exemplars, picomolar quantification of tumor necrosis factor alpha (TNFalpha) and monocyte chemotactic protein (MCP)-1, the latter of which is a useful prognostic indicator of cytokine release syndrome in patient plasma samples during chimeric antigen receptor T cell therapy are demonstrated.

  View details for DOI 10.1002/adma.202412613

  View details for PubMedID 39910829

• Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media. Advanced materials (Deerfield Beach, Fla.) Hariri, A. A., Cartwright, A. P., Dory, C., Gidi, Y., Yee, S., Thompson, I. A., Fu, K., Yang, K., Wu, D., Maganzini, N., Feagin, T., Young, B. E., Afshar, B. H., Eisenstein, M., Digonnet, M., Vuckovic, J., Soh, H. T. 2023: e2304410

  Abstract

  Aptamers are a promising class of affinity reagents because signal transduction mechanisms can be built into the reagent, so that they can directly produce a physically measurable output signal upon target binding. However, endowing the signal transduction functionality into an aptamer remains a trial-and-error process that can compromise its affinity or specificity and typically requires knowledge of the ligand binding domain or its structure. In this work, we describe a design architecture that can convert an existing aptamer into a "reversible aptamer-switch" whose kinetic and thermodynamic properties can be tuned without a priori knowledge of the ligand binding domain or its structure. Finally, by combining these aptamer-switches with evanescent-field based optical detection hardware that rejects sample autofluorescence, we demonstrate the first optical biosensor system that can continuously measure multiple biomarkers (dopamine and cortisol) in complex samples (artificial cerebrospinal fluid and undiluted plasma) with second-scale time resolution at physiologically relevant concentration ranges. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/adma.202304410

  View details for PubMedID 37975267

• Optically Powered Milli-Scale Robot System for Nanoliter Fluid Delivery Based on Diamagnetic Levitation IEEE TRANSACTIONS ON MAGNETICS Beauchamp, M., Yee, S., O'Carroll, I., Chapman, E., ElBidweihy, H. 2023; 59 (11)

  View details for DOI 10.1109/TMAG.2023.3281968

  View details for Web of Science ID 001099797000043

• An antibody-based molecular switch for continuous small-molecule biosensing. Science advances Thompson, I. A., Saunders, J., Zheng, L., Hariri, A. A., Maganzini, N., Cartwright, A. P., Pan, J., Yee, S., Dory, C., Eisenstein, M., Vuckovic, J., Soh, H. T. 2023; 9 (38): eadh4978

  Abstract

  We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive "antibody-switches" that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample preparation-free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nanomolar to 3.3 millimolar. Last, we integrated this switch with a fiber optic sensor to achieve continuous sensing of cortisol in a buffer and blood with <5-min time resolution. We believe that this modular sensor design can enable continuous biosensor development for many biomarkers.

  View details for DOI 10.1126/sciadv.adh4978

  View details for PubMedID 37738337

• Y-Z cut lithium niobate longitudinal piezoelectric resonant photoelastic modulator OPTICS EXPRESS Atalar, O., Yee, S., Safavi-Naeini, A., Arbabian, A. 2022; 30 (26): 47103-47114

  Abstract

  The capability to modulate the intensity of an optical beam has scientific and practical significance. In this work, we demonstrate Y-Z cut lithium niobate acousto-optic modulators with record-high modulation efficiency, requiring only 1.5 W/cm2 for 100% modulation at 7 MHz. These modulators use a simple fabrication process; coating the top and bottom surfaces of a thin lithium niobate wafer with transparent electrodes. The fundamental shear acoustic mode of the wafer is excited through the transparent electrodes by applying voltage with frequency corresponding to the resonant frequency of this mode, confining an acoustic standing wave to the electrode region. Polarization of light propagating through this region is modulated at the applied frequency. Polarization modulation is converted to intensity modulation by placing the modulator between polarizers. To showcase an important application space for this modulator, we integrate it with a standard image sensor and demonstrate 4 megapixel time-of-flight imaging.

  View details for DOI 10.1364/OE.476970

  View details for Web of Science ID 000914755600002

  View details for PubMedID 36558647

• Self-Powered High Energy Laser Detectors via Thermoelectric Generators Seymour, M., Yee, S., Nelson, C., Jenkins, B., ElBidweihy, H., Joyce, P., Brownell, C., Mechtel, D. edited by Balaya, P., Dutta, A. K., Xu, S. SPIE-INT SOC OPTICAL ENGINEERING. 2021

  View details for DOI 10.1117/12.2587812

  View details for Web of Science ID 000696727700006

• Photothermal actuation of levitated pyrolytic graphite revised APL Materials Yee, S., Oney, L., Cosby, T., Durkin, D. P., ElBidweihy, H. 2021; 9

  View details for DOI 10.1063/5.0061390

• High-energy laser detection through thermoelectric generators OPTICAL ENGINEERING Merkel, J., Yee, S., Nelson, C., Jenkins, R., ElBidweihy, H., Joyce, P., Brownell, C., Mechtel, D. 2020; 59 (11)

  View details for DOI 10.1117/1.OE.59.11.117105

  View details for Web of Science ID 000597284800035

• Autonomous Microrobotic Manipulation Using Visual Servo Control MICROMACHINES Feemster, M., Piepmeier, J. A., Biggs, H., Yee, S., ElBidweihy, H., Firebaugh, S. L. 2020; 11 (2)

  Abstract

  This describes the application of a visual servo control method to the microrobotic manipulation of polymer beads on a two-dimensional fluid interface. A microrobot, actuated through magnetic fields, is utilized to manipulate a non-magnetic polymer bead into a desired position. The controller utilizes multiple modes of robot actuation to address the different stages of the task. A filtering strategy employed in separation mode allows the robot to spiral from the manipuland in a fashion that promotes the manipulation positioning objective. Experiments demonstrate that our multiphase controller can be used to direct a microrobot to position a manipuland to within an average positional error of approximately 8 pixels (64 µm) over numerous trials.

  View details for DOI 10.3390/mi11020132

  View details for Web of Science ID 000520181500021

  View details for PubMedID 31991607

  View details for PubMedCentralID PMC7074596

• Optical control and manipulation of diamagnetically levitated pyrolytic graphite AIP ADVANCES Young, J., Biggs, H., Yee, S., ElBidweihy, H. 2019; 9 (12)

  View details for DOI 10.1063/1.5129886

  View details for Web of Science ID 000505567500001

• Optomechanical Actuation of Diamagnetically Levitated Pyrolytic Graphite IEEE TRANSACTIONS ON MAGNETICS Ewall-Wice, M., Yee, S., DeLawder, K., Montgomery, S. R., Joyce, P. J., Brownell, C., ElBidweihy, H. 2019; 55 (7)

  View details for DOI 10.1109/TMAG.2019.2892332

  View details for Web of Science ID 000472626900001

• A Miniature Reconfigurable Circularly Polarized Antenna Using Liquid Microswitches Yee, S., Weinstein, D., Fiering, J., White, D., Duwel, A., IEEE IEEE. 2015

  View details for Web of Science ID 000380567600022

• Microstrip Antenna Tuning using Variable Reactive Microelectromechanical Systems Yee, S. C., Anderson, C. R., Charles, H. K., Firebaugh, S. L., Mechtel, D. M., IEEE IEEE. 2011: 1828-1833

  View details for Web of Science ID 000302341400281