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      Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization

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          Abstract

          This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications.

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          Microfluidics: Fluid physics at the nanoliter scale

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            Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing.

            A new cytological tool, based on the microCoulter particle counter (microCPC) 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 microm). 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.
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              Blood-on-a-chip.

              Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                29 April 2015
                May 2015
                : 16
                : 5
                : 9804-9830
                Affiliations
                [1 ]State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190, China; E-Mails: chenjian@ 123456mail.ie.ac.cn (J.C.); xuechengcheng13@ 123456mails.ucas.ac.cn (C.X.); zhaoyang110@ 123456mails.ucas.ac.cn (Y.Z.); dychen@ 123456mail.ie.ac.cn (D.C.)
                [2 ]Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: mhwu@ 123456mail.cgu.edu.tw (M.-H.W.); jbwang@ 123456mail.ie.ac.cn (J.W.); Tel.: +886-3-211-8800 (ext 3599) (M.-H.W.); Fax: +886-3-211-8668 (M.-H.W.); Tel./Fax: +86-10-5888-7191 (J.W.).
                Article
                ijms-16-09804
                10.3390/ijms16059804
                4463619
                25938973
                6b5692d8-9e8d-4839-b745-c5e538de6e6a
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 December 2014
                : 20 April 2015
                Categories
                Review

                Molecular biology
                microfluidics,single-cell electrical property analysis,impedance flow cytometry,high throughput

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