Phenotypic assay for drug discovery and personalized medicine based on real-time vibrational spectroscopy enhanced by plasmonic metasurfaces

基于等离子体超表面增强的实时振动光谱的药物发现和个性化医疗表型测定

• 批准号: 10025960
• 负责人: Gennady Shvets
• 金额: $ 59.87万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10025960
• 关键词: Address; Affect; Apoptosis; Binding; Biochemical; Biochemical Process; Biological Assay; Cancer cell line; Cell Line; Cell physiology; Cell-Matrix Junction; Cells; Cellular Assay; Cellular Membrane; Chemicals; Cholesterol; Classification; Clinical; Colon Carcinoma; Complex; Consumption; Cytoskeletal Modeling; Cytoskeleton; Data; Data Analyses; Development; Devices; Drug resistance; EGF gene; Elements; Epidermal Growth Factor Receptor; Family; Fingerprint; Fourier Transform; Geometry; Goals; Gold; Growth Factor; Heterogeneity; Hour; Kinetics; Label; Lasers; Libraries; Light; Lighting; Lipids; Machine Learning; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Microscope; Modeling; Molecular; Molecular Target; Morphology; Nature; Noise; Optics; Patients; Pharmaceutical Preparations; Pharmacologic Actions; Pharmacology; Phenotype; Process; Proteins; Protocols documentation; Receptor Signaling; Research; Resolution; Scanning; Screening for cancer; Signal Pathway; Signal Transduction; Skin Cancer; Source; Spectrum Analysis; Speed; Supervision; Techniques; Testing; Time; anti-cancer; assay development; base; cancer cell; cancer heterogeneity; cytotoxic; design; detector; drug discovery; drug testing; electric impedance; improved; indexing; infrared spectroscopy; inhibitor/antagonist; kinase inhibitor; metallicity; novel; optical spectra; overexpression; personalized medicine; plasmonics; polypeptide; precision drugs; programs; quantum; response; temporal measurement; therapeutic target; time use; vector; vibration

Abstract The goal of this research is to develop a new spectroscopic technique – Time-dependent Infrared Reflection Spectroscopy Assay (TIRSA) – that will enable us to measure the real-time spectral response of a cell to various pharmacological compounds. The uniqueness of TIRSA is that it exploits infrared-reflective plasmonic (gold) metasurfaces to detect, as a function of time, biochemical changes in close proximity of cellular membranes, as well as cytoskeleton reorganization occurring. The optical spectra obtained over the course of several hours after administering the drug will be used to identify its effects on signaling pathways without any labels because vibrational fingerprints of biomolecules are the natural labels. Unlike time-consuming cytotoxic assays, the TIRSA can be potentially as short as several hours, thereby addressing one of the most serious deficiencies of phenotypic assays: their low throughput. Powerful techniques of machine learning (ML) will be used to process the enormous amount of biochemical information obtained by TIRSA, and to conduct supervised and unsupervised data analysis that will be based on large libraries of spectral cellular responses to single-target chemical compounds such as kinase inhibitors and others. New laser-based hardware for TIRSA will enable high sensitivity, time and space resolution.

抽象的 这项研究的目标是开发一种新的光谱技术——时间相关红外反射 光谱测定 (TIRSA) – 这将使我们能够测量细胞的实时光谱响应 各种药理化合物。 TIRSA 的独特之处在于它利用红外反射等离子体 （金）超表面检测作为时间函数的细胞附近的生化变化 膜以及细胞骨架重组发生。过程中获得的光谱 给药后几个小时将用于确定其对信号通路的影响，而无需任何 标签，因为生物分子的振动指纹是天然标签。与耗时的细胞毒性不同 TIRSA 检测的时间可能短至几个小时，从而解决了最严重的问题之一 表型测定的缺陷：通量低。强大的机器学习 (ML) 技术将 用于处理TIRSA获得的大量生化信息，并进行 基于大型光谱细胞反应库的监督和非监督数据分析 单一目标化合物，如激酶抑制剂等。新的基于激光的硬件 TIRSA 将实现高灵敏度、时间和空间分辨率。

项目成果

Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells.

• DOI: 10.3390/cells11101600
• 发表时间: 2022-05-10
• 期刊: Cells
• 影响因子: 6

Monitoring the effects of chemical stimuli on live cells with metasurface-enhanced infrared reflection spectroscopy.

• DOI: 10.1039/d1lc00580d
• 发表时间: 2021-10-12
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Huang SH;Li J;Fan Z;Delgado R;Shvets G
• 通讯作者: Shvets G

Metasurface-Enhanced Infrared Spectroscopy: An Abundance of Materials and Functionalities.

超表面增强红外光谱：丰富的材料和功能。

• DOI: 10.1002/adma.202110163
• 发表时间: 2023
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: John-Herpin,Aurelian;Tittl,Andreas;Kühner,Lucca;Richter,Felix;Huang,StevenH;Shvets,Gennady;Oh,Sang-Hyun;Altug,Hatice
• 通讯作者: Altug,Hatice