MRI: Development of an Instrument for Single Cell Electrical Stimulation and Analysis

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Understanding how the smallest organism unit, a single cell, responds to electrical stimulations is vital for developing precision electrical stimulation treatments for tissue repair, inventing novel conductive biomaterials for tissue regeneration, and identifying new sensitive biomarkers for cancer therapy. Researchers at University of Akron through the Major Research Instrument (MRI) program are working on developing a new instrument to discover and interpret specific responses of single cells to defined electrical stimulations. By integrating the advances in microfluidics and bio-nanotechnology, the instrument will have the following unique capabilities and significances: a) precise delivery of controlled electrical stimulation to single cells, b) collection and analysis of multiple types of molecules secreted by cells, c) direct assessment of resultant single cell responses without the interfering signals from surrounding cells, tissues or substances, and d) "touch free" cell manipulation during the stimulation procedure, avoiding enzymatic, physical treatment of cells. With these unique capabilities, this instrument will advance basic understanding of how cells sense, function, proliferate, and communicate in response to electrical stimulations, which will undoubtedly have transformative impacts on tissue engineering, regenerative medicine, cancer biology, biomaterials and biomimetic devices. The instrument will serve as a major research facility that will build new research and training capacities for faculty members and students at University of Akron, especially for the university's newly created Biomimicry Research and Innovation Center and Integrated Bioscience Ph.D. Program, and benefit bioscience researchers from other research institutes, industry and government laboratories in Akron-Cleveland area. The design concept and the instrument will also provide excellent training opportunities for graduate, undergraduate and K-12 students via course development, University of Akron's "Increasing Diversity in Engineering Academics", and "Women in Engineering" programs. Deciphering and manipulation of specific responses of single cells to definable electrical stimulations is urgently needed to advance current cell research. However, to date a universal instrument is unavailable than can precisely deliver various electrical stimulation to individual cells, collect and analyze secreted molecules by cells. This NSF project aims to develop a new instrument that will enable cracking the bioelectrical code of single cells of any type, building new research capacities for single cell level manipulation and characterization. To achieve the desired functions and specifications, the instrument will consist of 1) a standing surface acoustic wave (SSAW) cell focuser in which single cells will be focused in the centerline of microchannels, 2) an array of microelectrodes in a serpentine microchannel to apply controlled electrical stimulations to single cells in a continuous flow, 3) an array of cell culture chambers to culture the stimulated cells, and form target molecule-microparticle aggregates, and 4) a resistive pulse sensor array to measure the aggregates and determine multiple type of molecule concentrations in cell secretome. Ultimately, the above four major parts will be integrated into a compact yet powerful new instrument for cell research. The new instrument will directly impact the advanced researches on 1) Cardiac repair and regeneration, 2) Neural tissue engineering, 3) Electrical stimulation assisted wound healing and 4) Conductive biomaterials for nerve regeneration.