Models and ultra-sensitive apparatus for electronic single cell analysis

电池是动态电子材料，其响应于环境压力而改变电子状态。已经有许多证据表明，细胞表现出与重要的生理变化相一致的介电变化，如干细胞的分化、癌细胞中多药耐药性（MDR）的发展和程序性细胞死亡（凋亡）。介电响应的单细胞测量可以识别介电亚群和这些亚群的时间变化，这是普通的散装探针不可能的。拟议的研究计划将得出定量模型的电子和生理变化之间的关系，在细胞中，也产生仪器与上级能力，以检测这些介电变化的单细胞。这项工作将集中在使用介电泳（DEP）的流动系统，使细胞从水库的分析区域，使大量的细胞在一个合理的时间范围内分析实用。与G. Bridges我开发了一种基于流动的单细胞DEP分析仪器。它可以通过检测细胞内钾离子浓度下降引起的修饰极化来检测细胞凋亡。利用微波干涉仪差示检测技术，建立了中国人卵巢细胞（CHO）凋亡的DEP细胞仪。

Cells are dynamic electronic materials that change electronic state in response to environmental pressures. There have been many demonstrations that cells exhibit dielectric changes that coincide with important physiological changes such as the differentiation of stem cells, the development of multi drug resistance (MDR) in cancer cells, and programmed cell death (apoptosis). Single cell measurements of the dielectric response can identify dielectric sub-populations and temporal changes to these sub-populations that are not possible with common bulk probes. The proposed research program will derive quantitative models of the relationship between electronic and physiological changes in cells and also to produce instrumentation with superior ability to detect these dielectric changes in single cells. The work will focus on the use of dielectrophoresis (DEP) in a flow system that bring cells from a reservoir to the analysis region, making the analysis of a large number of cells practical in a reasonable time frame. In collaboration with G. Bridges I have developed a flow based single cell DEP analysis instrument. It can detect apoptosis by sensing the modified polarization that results from a drop in intracellular potassium, concentrations. Using a microwave interferometer in a differential detection approach, this DEP cytometer detected apoptosis in Chinese Hamster Ovary (CHO) cells.