EAGER: A Novel Lab-on-Chip with Optical Micro-Stretch Assembly for Characterization of Stretch-Activated Cell Electrophysiology

EAGER：一种具有光学微拉伸组件的新型芯片实验室，用于表征拉伸激活细胞电生理学

• 批准号: 1647800
• 负责人: Makarand Deo
• 金额: $ 30万
• 依托单位: Norfolk State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1647800&HistoricalAwards=false
• 关键词: EAGER; Novel; Lab; Chip; Optical

The National Science Foundation uses the Early-concept Grants for Exploratory Research (EAGER) funding mechanism to support exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches. This EAGER project was awarded as a result of the invitation in the Dear Colleague Letter NSF 16-080 to proposers from Historically Black Colleges and Universities to submit proposals that would strengthen research capacity of faculty at the institution. The project at Norfolk State University aims use a novel optical non-contact cell stretching method to create a controlled stretch in biological cells. Accordingly, the project outcome can unveil mechanisms governing heart electrical abnormalities via modeling and relate the electrophysiological measurements to mechanical stretching by enabling reproducible stretch conditions in vitro to mechanistically characterize various human disorders including heart failure. Excitable biological cells, such as heart cells, exhibit mechano-electric sensitivity by which their electrical behavior is modulated by mechanical stimuli or stretch. This is especially critical in chronic diseases such as heart failure where increased stress may induce life-threatening abnormalities, called arrhythmias. Specialized stretch-activated ion channels in cells are thought to be responsible for this phenomenon. However, these channels are not well characterized, partly due to a lack of efficient cell stretching and simultaneous electrical recording techniques. In this project, a novel optical non-contact stretching method, using counter-propagating laser beams, is proposed which is capable of producing a controlled stretch in biological cells in the most realistic condition. A microfluidic platform for performing automated, high throughput electrophysiological recordings from cells will be designed. Tightly focused laser beams will be used to stretch the cells while simultaneously performing the patch clamp recordings. The proposed optofluidic chip will be used to systematically characterize the stretch-activated ion channels in cardiac cells. The experiments combined with advanced computer-based modeling will provide useful insights into the mechanisms of arrhythmias in heart failure conditions. The cell-stretching technique could be extended to study several other diseases such as cancer, brain tumors, Parkinson disease and even plant disorders. This EAGER project is funded by the Engineering Directorate.

美国国家科学基金会使用探索性研究早期概念赠款（EAGER）资助机制，以支持未经测试但可能具有变革性的研究想法或方法的早期阶段的探索性工作。EAGER项目是由于在亲爱的同事信NSF 16-080中邀请来自历史上黑人学院和大学的提议者提交提案，以加强该机构教师的研究能力而获得的。诺福克州立大学的这个项目旨在使用一种新的光学非接触细胞拉伸方法来在生物细胞中产生受控的拉伸。因此，该项目成果可以通过建模揭示控制心脏电异常的机制，并通过使体外可再现的拉伸条件能够机械地表征包括心力衰竭在内的各种人类疾病，将电生理测量与机械拉伸联系起来。可兴奋的生物细胞，如心脏细胞，表现出机械-电敏感性，通过这种敏感性，它们的电行为受到机械刺激或拉伸的调节。这在慢性疾病中尤其重要，如心力衰竭，其中增加的压力可能会诱发危及生命的异常，称为心律失常。细胞中专门的拉伸激活离子通道被认为是造成这种现象的原因。然而，这些通道没有得到很好的表征，部分原因是缺乏有效的细胞拉伸和同步电记录技术。在这个项目中，提出了一种新的光学非接触式拉伸方法，使用反向传播的激光束，这是能够在最现实的条件下在生物细胞中产生受控的拉伸。将设计用于执行自动化的、高通量的细胞电生理记录的微流体平台。将使用紧密聚焦的激光束来拉伸细胞，同时进行膜片钳记录。所提出的光流控芯片将用于系统地表征心肌细胞中的牵张激活离子通道。结合先进的计算机建模的实验将提供有用的见解心律失常的机制，在心力衰竭的条件。细胞拉伸技术可以扩展到研究其他几种疾病，如癌症，脑瘤，帕金森病，甚至植物疾病。EAGER项目由工程局资助。

项目成果

Non-contact trapping and stretching of biological cells using dual-beam optical stretcher on microfluidic platform

微流控平台上双光束光学拉伸器对生物细胞的非接触捕获和拉伸

• DOI: 10.1117/12.2514299
• 发表时间: 2019
• 期刊: Health Monitoring of Structural and Biological Systems XIII
• 作者: Dong, Aotuo;Uppalapati, Balaadithya;Islam, Md. Shariful;Gibbs, Brandon;Kamatchi, Ganesan;Albin, Sacharia;Deo, Makarand;Fromme, Paul;Su, Zhongqing
• 通讯作者: Su, Zhongqing

Accurate Estimation of Refractive Indices of Organic Microparticles in Dual-Beam Optical Trap

• DOI: 10.1109/embc44109.2020.9176338
• 发表时间: 2020-07
• 期刊: 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC)
• 作者: Aotuo Dong;M. Islam;S. Albin;M. Deo