Multi-frequency impedance sensor for cell analysis

描述(由申请人提供)：单个细胞的宽带阻抗分析产生关于细胞大小、活力、形态和内部结构的丰富信息。细胞的介电特性，包括膜电导率、细胞质电导率和膜电容，可以从多频阻抗数据中得到，并用于区分和计数混合样品中的细胞群体。此外，阻抗分析可以用来推断细胞分化、细胞凋亡的开始，或由于毒物暴露而引起的细胞变化。我们已经建立了一种原理验证粒子分析系统，当单个细胞通过集成到微流控流动通道中的传感器时，该系统可以在多个频率下测量它们的阻抗特性。本提案中所述工作的目标是改进我们目前的粒子阻抗分析仪，以产生用于细胞分析的高通量、多用途单元。具体地说，将开发一种基于相对低成本的离散元件的可扩展阻抗测量电路，以允许在三个频率下进行粒子阻抗谱。将开发一种更简单的阻抗传感器通道的制造方法，以产生信用卡大小的、可能是一次性的微流体装置。传感器通道盒和阻抗传感电子设备将被集成在一起，所产生的原型设备将用于表征培养细胞和血细胞亚群的介电特性。该项目的长期目标是实现一种廉价、可商业化的手持式多频粒子阻抗传感器，可用于许多细胞分析应用，包括组织培养、药物研发、护理点诊断以及其他科学和工业需求。

DESCRIPTION (provided by applicant): Broadband impedance analysis of individual cells yields a wealth of information about cell size, viability, morphology and interior structure. Cell dielectric properties including membrane conductivity, cytoplasmic conductivity, and membrane capacitance can be derived from multi-frequency impedance data and used to differentiate and enumerate cell populations in a mixed sample. Additionally, impedance analysis can be used to deduce cell differentiation, the onset of apoptosis, or cellular changes due to toxicant exposure. We have built a proof-of-principle particle analysis system that measures the impedance characteristics of individual cells at multiple frequencies as they pass through a sensor incorporated into a microfluidic flow channel. The goal of the effort described in this proposal is to improve our current particle impedance analyzer to yield a high-throughput, multipurpose unit for cell analysis. Specifically, a scalable impedance measurement circuit based on relatively low cost discrete components will be developed to allow for particle impedance spectroscopy at three frequencies. A more facile fabrication method for the impedance sensor channel will be developed to yield a credit-card sized, potentially disposable microfluidic device. The sensor channel cartridge and impedance sensing electronics will be integrated and the resulting prototype device used to characterize the dielectric properties of cultured cells and blood cell subpopulations. The long-term goal of this project is to realize an inexpensive, commercializable, hand-held multi-frequency particle impedance sensor that can be used for many cell analysis applications, including tissue culture, drug discovery, point-of-care diagnostics, and other scientific and industrial needs.