From single molecules to biomedical applications

Research

Revealing biology with light.
Building tools for better measurement.

We develop optical biosensors, bioanalytical methods, and instrumentation to study molecular and cellular activity, measure interactions relevant to drug discovery, and address unmet diagnostic needs. Our research connects advances in imaging with practical biomedical applications.

01

Research thrust

Plasmonic and evanescent imaging of molecular and cellular activities

How can we observe individual proteins and cellular processes without fluorescent labels? We develop microscopes that turn small changes in scattered light and surface interactions into quantitative measurements.

Overview of plasmonic scattering microscopy connecting the optical setup to single-protein detection, digital binding kinetics, protein oscillators, cell-released proteins, local heating, exosome quantification, cell mechanics, and cellular dynamics.

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Plasmonic imaging across biological scales. Our microscopy toolkit connects single-protein detection and molecular binding measurements with studies of cellular activity, secreted proteins, exosomes, and cell mechanics.

Author-provided overview artwork for Zhang, P., Zhou, X. & Wang, S. (2023), Chemistry–Methods, e202200066. Original composition retained; resized for display.

Single-protein characterization

We combine evanescent imaging with single-protein oscillators to measure protein size, charge, mobility, and binding. These measurements help distinguish individual molecules and reveal variation that ensemble methods can miss. Recent work applies this approach to therapeutic antibody aggregation and quality assessment.

Dynamic cellular activity

Our plasmonic imaging platforms investigate electrical signals, cell-released protein complexes, and mechanical activity at the single-cell level. Plasmonic cell force microscopy maps cell force dynamics without labels, while plasmonic thermal microscopy enables rapid temperature control for studying temperature-sensitive ion channels.

02

Research thrust

Label-free quantification of molecular interactions

How strongly does a molecule bind, and how quickly does it attach and release? We develop optical methods to answer these questions for proteins, small molecules, and membrane receptors, with an emphasis on preserving their biological environment.

Binding kinetics on individual cells

We use plasmonic scattering microscopy to study membrane-protein binding directly on cells. Resolving individual cells reveals differences in binding behavior that are hidden in population averages. Our ongoing work aims to increase throughput for drug screening and studies of cellular heterogeneity.

Virion-display nano-oscillator arrays

In collaboration with researchers at Johns Hopkins University, we display human membrane proteins in viral envelopes tethered to sensor chips. Tracking their electrically driven oscillations reveals ligand binding without extracting and reconstituting the membrane proteins. DNA barcoding extends this approach toward multiplexed measurements of small-molecule binding kinetics.

DNA-barcoded virion–gold nanoparticle nano-oscillators tethered to a gold sensor surface, with electron microscopy and plasmonic images illustrating electrical-field-driven oscillation.

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Multiplexed binding measurements with virion nano-oscillators. Membrane proteins displayed on virions are coupled to gold nanoparticles and tethered to a sensor surface. Plasmonic imaging tracks their electrically driven motion, while DNA barcodes identify different sensors for parallel binding measurements.

TOC / graphical abstract from Cao, S.-H. et al. (2025), Angewandte Chemie International Edition 64, e202506464. Original image retained; resized for display.

03

Research thrust

Optical imaging-based medical diagnostic technologies

How can optical measurements help address unmet clinical needs? Working with clinical, microbiology, and industry collaborators, we develop imaging platforms and assays for faster bacterial testing, sensitive blood biomarker detection, and cell therapy monitoring.

Rapid antimicrobial susceptibility testing workflow: patient sample, large-volume video microscopy of bacteria, machine learning analysis, and an example pathogen identification and antibiotic susceptibility report.

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Rapid antimicrobial susceptibility testing. Large-volume video microscopy records individual bacteria in a patient sample. Machine learning analyzes the images to support pathogen identification and antibiotic susceptibility testing. The report shown is an illustrative example.

Antimicrobial susceptibility testing

Large-volume scattering imaging tracks individual bacteria and their responses to antibiotics. Combined with machine learning, the approach supports rapid phenotypic testing. We have evaluated prototypes using urinary tract infection samples and are extending the technology to tuberculosis drug susceptibility testing.

Blood biomarkers at the point of care

We develop digital immunoassays that count individual molecules or nanoparticles to detect low concentrations of cardiac biomarkers in small blood samples. With Mayo Clinic collaborators, we are advancing microfluidic assays and portable prototypes toward clinical validation.

Monitoring CAR T-cell therapy

We are developing optical methods to quantify circulating CAR T-cells and, in related ongoing work, therapy-associated cytokines. Our 2026 proof-of-concept study combines selective cell capture with machine learning-assisted imaging to detect CAR T-cells in spiked whole blood, providing a foundation for further development and clinical evaluation.