Single-Cell Iterative Mechano-Electrical Properties Analyzer

提案号：1403304pi标题：单细胞迭代机电特性分析仪一个由工程师和生命科学家组成的研究团队将协调努力，对一种名为迭代机电特性（iMEP）分析仪的新型微流体生物传感平台进行微工程设计。该传感器将同时捕获细胞的生物力学和生物电特性的电子记录。iMEP分析仪提供了分析生物物理特性的仪器，可用于比较具有不同功能的细胞（如神经元和骨骼）的生物物理特性，发育细胞系的生物物理变化，对激素和药物的生物物理反应，以及病变细胞的生物物理变化。在未来，这项技术可能会为癌症诊断和药物筛选提供新的方法。技术摘要：本研究的目的是开发一种芯片实验室传感器，用于分析活细胞的生物机电特性。这种单细胞分析仪表征细胞的生物物理特性，包括电学和力学，因为它们在微环境中经历动态变化，并量化正常和恶性人类乳腺细胞之间的生物物理差异。当细胞通过芯片中的狭窄通道时，它们会经历变形（压缩）和机械松弛，其速率和强度可通过控制通道尺寸来调节。嵌入式电极将细胞生物力学事件与细胞电学特性（生物阻抗）的实时、连续监测联系起来。同时，利用视频显微镜和高速摄像机记录细胞的定量力学变形信息；当与荧光标记技术相结合时，细胞内信号分子的动态变化也可以通过高速视频显微镜捕捉到。这项研究代表了在单细胞水平上诊断癌症的一个重大进步，以便在最早和最易控制的阶段发现这种疾病，并确定单个细胞的药物反应性。这是一个研究方向，将为医学革命做出重大贡献，为癌症患者提供个性化的诊断和预后决定。对这个项目的支持也将促进学生的教育发展，从高中到研究生院，让他们在年轻的时候就能体会到工程和生物技术结合的力量。重要的是要向下一代科学家传达生物学是工程的，工程可以用来解剖生物学。该奖项由两个项目联合颁发——(1)化学、生物工程、环境和运输系统部门（工程局）的纳米生物传感，以及(2)生物基础设施部门（生物科学局）的生物研究仪器开发。

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).