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

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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.