Single-Cell Iterative Mechano-Electrical Properties Analyzer

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Proposal Number: 1403304P.I.: Agah, MasoudInstitution: Virginia Polytechnic Institute and State UniversityTitle: Single-Cell Iterative Mechano-Electrical Properties AnalyzerA research team of engineers and life scientists will coordinate efforts to micro-engineer a new microfluidic biosensing platform called the iterative mechano-electrical properties (iMEP) analyzer. This sensor will simultaneously capture electronic records of biomechanical and bioelectrical properties of cells. The iMEP analyzer provides instrumentation to analyze biophysical properties that can be used to compare biophysical properties of cells with diverse functions such as neurons and bones, biophysical changes in developmental cell lineages, biophysical responses to hormones and drugs, as well as biophysical changes in diseased cells. In the future this technology may enable novel ways for diagnosing cancer and screening drugs.Technical AbstractThe objective of this research is to develop a lab-on-a-chip sensor that analyzes the bioelectro-mechanical properties of living cells. This single-cell analyzer characterizes the biophysical properties of cells including electrical and mechanical as they undergo dynamic changes in their microenvironment and quantifies the biophysical differences between normal and malignant human breast cells. As cells travel through narrow channels in the chip, they undergo alternative deformation (compression) and mechanical relaxation, the rates and intensities of which are modulated by controlling the channel dimensions. Embedded electrodes link cell biomechanical events to real-time, continuous monitoring of cell electrical properties (bioimpedance). Simultaneously, quantitative cell mechanical deformation information is recorded using video microscopy and a high speed camera; when coupled with fluorescent tagging techniques, dynamic changes in intracellular signaling molecules can also be captured by high speed video microscopy. The research represents a significant advance in achieving a device for diagnosing cancer at the single cell level in order to find this disease at its earliest and most manageable stage, and for ascertaining drug-responsiveness of individual cells. This is a research direction that will contribute significantly to the revolution in medicine to provide individualized diagnostic and prognostic decisions for cancer patients. Support for this project will also enhance the educational development of students, from high school through graduate school, allowing them at a young age to gain an appreciation of the power of merging engineering and biological technologies. It is important to convey to the next generation of scientists that biology is engineered and that engineering can be used to dissect biology.This award is being made jointly by two Programs- (1) Nano-Biosensing, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate), and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).