Digital signal processing methods for impedance microfluidic cytometry

Impedance microfluidic cytometry is a noninvasive, label-free technology that can characterize the dielectric properties of single particles (beads/cells) at high speed. In this paper we show how digital signal processing methods are applied to the impedance signals for noise removal and signal recovery in an impedance microfluidic cytometry. Two methods are used; correlation to identify typical signals from a particle and for a noisier environment, an adaptive filter is used to remove noise. The benefits of adaptive filtering are demonstrated quantitatively from the correlation coefficient and signal-to-noise ratio. Finally, the adaptive filtering method is compared to the Savitzky–Golay filtering method.

Single cell analysis requires precise manipulation and characterization to be performed in micro scale devices using Lab-on-a-Chip (LOC) technology. Dielectric or impedance spectroscopy has been used to discriminate cells on the basis of size and dielectric properties. Characterization of the dielectric properties of particles can be performed in two ways, using AC electrokinetic techniques (Morgan and Green 2003) or electrical impedance methods (Morgan et al. 2007). Impedance spectroscopy has been implemented on a microfluidic chip, providing a high speed method of characterising the dielectric properties of different micron-sized particles. The first cytometer capable of measuring the electrical properties of a single particle was developed by Coulter (1956). The device measured the DC resistance (or low frequency impedance) between two electrically isolated fluid-filled chambers as particles passed through a small connecting orifice. For a fixed sized orifice, the change in electrical current is used to count and size the cells. Single particle impedance measurement can be categorized as stationary or dynamic (flow-cytometry) measurements. Recently, Cho et al. (2006) fabricated twin microcantilever arrays in microchannels for measuring the impedance of normal and abnormal red blood cells. Malleo et al. (2007) developed a microfluidic chip to hydrodynamically capture single cells and analyse the kinetics of cell response to Streptolysin-O. Jang and Wang (2007) fabricated a polydimethylsiloxane (PDMS) channel with pillars to capture a single cell and measured the impedance. Wang et al. (2008) used a metal oxide semiconductor field effect transistor (MOSFET) to detect the resistive pulse induced by CD4+ T-lymphocytes in a PDMS channel.

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