Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing
Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing
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DOI：
10.1039/b103933b
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发表时间：
2001-01-01
期刊：
影响因子：
6.1
通讯作者：
Renaud, P
中科院分区：
文献类型：
--
作者：
Gawad, S;Schild, L;Renaud, P
一种新的细胞学工具，基于微库尔特粒子计数器(CPC)原理，旨在血液学、肿瘤学或毒理学中用于细胞计数和分离的诊断应用。该设备测量单个细胞或颗粒的光谱阻抗，允许在单个细胞的基础上筛选超过100个样本S(-1)。该分析仪旨在驱动产生后续细胞分离的分选致动器。尺寸缩小和功能集成是实现精确测量和高吞吐量的关键。通过三维有限元模拟，比较了不同电极几何形状对电池参数估计的影响。该装置基于玻璃-聚酰亚胺微流控芯片，具有集成的通道和电极，在待研究颗粒的长度范围内(1-20微米)微制造。层流液体带着悬浮颗粒通过测量区域。每个颗粒的阻抗信号由一对微电极记录，以介质周围的电池为基准。微机械芯片和处理电路允许在从100 kHz到15 MHz的多个频率下同时进行阻抗测量。在这篇文章中，我们描述了作为完整细胞分选设备的第一个组成部分的芯片上流式细胞仪的微制造和特性。然后我们讨论信号调节技术，最后对不同大小和类型的细胞和颗粒进行阻抗测量，以演示混合样本中亚群的分化。
A new cytological tool, based on the micro Coulter particle counter (CPC) principle, aimed at diagnostic applications for cell counting and separation in haematology, oncology or toxicology is described. The device measures the spectral impedance of individual cells or particles and allows screening rates over 100 samples s(-1) on a single-cell basis. This analyzer is intended to drive a sorting actuator producing a subsequent cell separation. Size reduction and integration of functions are essential in achieving precise measurements and high throughput. 3D finite element simulations are presented to compare various electrode geometries and their influence on cell parameters estimation. The device is based on a glass-polyimide microfluidic chip with integrated channels and electrodes microfabricated at the length scale of the particles to be investigated (1-20 mum). A laminar liquid flow carries the suspended particles through the measurement area. Each particle's impedance signal is recorded by a differential pair of microelectrodes using the cell surrounding media as a reference. The micromachined chip and processing electronic circuit allow simultaneous impedance measurements at multiple frequencies, ranging from 100 kHz to 15 MHz. In this paper, we describe the microfabrication and characterisation of an on-chip flow-cytometer as the first building block of a complete cell-sorting device. We then discuss the signal conditioning technique and finally impedance measurements of cells and particles of different sizes and types to demonstrate the differentiation of subpopulations in a mixed sample.