# Plasmonic Scattering Microscopy for high-throughput in-situ quantification of molecular binding kinetics on single cells

> **NIH NIH R42** · BIOSENSING INSTRUMENT, INC. · 2024 · $295,561

## Abstract

SUMMARY
 Membrane proteins play key roles in many cellular functions and are the largest class of drug targets.
Measuring the molecular interactions of membrane proteins are critical for understanding protein functions,
discovering biomarkers, and developing drugs. Most popular methods for measuring membrane protein
interaction kinetics involves extraction, purification, stabilization of the membrane protein in an artificial lipid
environment, which is not only labor intensive but may also introduce bias and costly missteps due to the loss of
the heterogeneous native cellular microenvironment. Therefore, an in situ detection technique that enables
sensitive measurement of native receptor behavior at single cell and population level is critical to expediting drug
development.
 We propose to develop Plasmonic Scattering Microscopy (PSM) as a breakthrough technology for high
throughput label-free quantification of membrane protein binding interaction kinetics on single cells. PSM
advances the field of biomarker discovery and drug development by enabling high throughput real-time functional
study of drug candidate interactions with cell membrane receptors in their native microenvironments.
 Surface plasmon resonance microscopy (SPRM) is the current state-of-the-are for studying label-free binding
kinetics. PSM is a breakthrough advancement of SPR-based sensing. Rather than measuring changes in sensor
reflectivity, PSM innovatively measures changes in plasmonic scattering. This novel approach enables
quantitative real-time measurement of label-free molecular binding kinetics on single cells in high throughput but
avoids the major drawbacks of reflection-based imaging known to plague traditional SPR-based approaches.
 Unlike SPRM, PSM exhibits several distinct technological advances, including a ~5 times greater signal to
noise ratio, ~10 times greater field of view, ~5 times greater resolution, ~50 times higher throughput, enhanced
sensitivity and data quality that avoids interferences from secondary reflection and near-field diffraction events,
and the capability of simultaneous fluorescence imaging for orthogonal validation.
 In this fast-track STTR project, Biosensing Instrument Inc. (BI) will work with the inventor of PSM technology
at Arizona State University to develop a commercial prototype multi-functional PSM instrument that can perform
PSM and fluorescence imaging. We will also collaborate with potential customers in biomedical research and
pharmaceutical industries to validate PSM performance and develop key applications.
 This project addresses the significant unmet need for acquiring more native biorelevant data sooner in the
early-stage drug development process, thereby mitigating costly missteps and false leads. PSM technology
enables sensitive label-free kinetic quantification of membrane protein behavior in their native cellular
microenvironment with high throughput while also permitting simultaneous fluorescence validation. PSM
addre...

## Key facts

- **NIH application ID:** 11008269
- **Project number:** 1R42GM154550-01A1
- **Recipient organization:** BIOSENSING INSTRUMENT, INC.
- **Principal Investigator:** Nguyen Ly
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $295,561
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008269

## Citation

> US National Institutes of Health, RePORTER application 11008269, Plasmonic Scattering Microscopy for high-throughput in-situ quantification of molecular binding kinetics on single cells (1R42GM154550-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11008269. Licensed CC0.

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