权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Critical angle reflection imaging for label-free quantification of molecular interactions

用于分子相互作用无标记定量的临界角反射成像

基本信息

批准号：
10596659
负责人：
Nguyen Ly
金额：
$ 83.24万
依托单位：
BIOSENSING INSTRUMENT, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10596659
关键词：
Acceleration Address Arizona Binding Binding Proteins Biological Assay Biological Models Biomedical Research Biosensing Techniques Cell physiology Cell surface Cells Chemistry Collaborations Consumption Coupled Detection Drug Industry Drug Screening Drug Targeting Environment Exhibits Feedback Film Fluorescence Glass Gold Hela Cells Image Imaging Device Imaging technology Immobilization In Situ Kinetics Label Lectin Ligands Light Lighting Lipids Mainstreaming Measurement Measures Membrane Glycoproteins Membrane Proteins Methods Molecular Multiparametric Analysis Optics Performance Pharmaceutical Preparations Phase Play Proteins Records Refractive Indices Resolution Small Business Technology Transfer Research Surface Surface Plasmon Resonance System Technology Testing Time United States National Institutes of Health Universities Validation Wheat Germ Agglutinins Work absorption aqueous biomarker discovery biomarker validation commercial prototype commercialization cost detection sensitivity disease diagnosis drug candidate drug development fluorescence imaging imaging capabilities imaging system improved instrument interest prevent protein function prototype sensor small molecule success temporal measurement usability

项目摘要

TITLE: Critical angle reflection imaging (CARi) for label-free quantification of molecular interactions SUMMARY Measuring molecular interactions of proteins are critical for understanding protein functions and cellular processes, for discovery and validating biomarkers, and for developing and screening drugs. In particular, membrane proteins play key roles in many cellular functions and are the largest class of drug targets. Most popular methods for measuring membrane protein interaction kinetics involves extraction and purification of membrane proteins and stabilizing the proteins in an artificial lipid environment, which is not only time consuming and labor intensive, but also may introduce bias due to the loss of the native cellular microenvironment. We proposed to develop critical angle reflection imaging (CARi) as a breakthrough technology for in-situ cell- based studies of membrane protein binding interaction kinetics to advance the field of biomarker discovery and drug development. CARi builds upon surface plasmon resonance imaging (SPRi), acquiring many of its unique advantages, but overcoming many of its limitations. CARi uses an optical configuration similar to SPRi that measures light reflected from below the sensing surface, which is sensitive to molecular bindings induced refractive index changes above the sensing surface. This enables CARi to detect molecular interaction label- free and in real-time. However, unlike SPRi, CARi exhibits several distinct technological advances, including a ~10 times greater sensitivity, ~100 times greater vertical detection range for measuring entire cell surfaces, simultaneous fluorescence compatibility for orthogonal validation, broader wavelength of light selection, convenient use of glass-based surface chemistries, and simple low-cost glass sensor chips. In this fast-track STTR project, Biosensing Instrument Inc. (BI) will work with the inventor of CARi technology at Arizona State University to develop a commercial prototype multi-functional CARi instrument that can perform CARi, SPRi, and fluorescence imaging. We will also collaborate with potential customers in biomedical research and pharmaceutical industries to validate CARi performance and develop key applications. The success of this project will enable ultra-high sensitivity for label-free kinetic quantification of small molecule interactions on membrane proteins with single-cell resolution and permit simultaneous fluorescence imaging for orthogonal validation. This powerful capability of label-free in-situ cell-based kinetic binding analysis is greatly needed for expediting biomarker discovery, disease diagnosis and drug screening.

标题: