High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences

Sun, Tao; Holmes, David; Gawad, Shady; Green, Nicolas G.; Morgan, Hywel

doi:10.1039/b703546b

Cited by 108 publications

(79 citation statements)

References 32 publications

(60 reference statements)

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“…We have used these modeling methods to validate the experimental data and probed the dielectric properties of the measured biological cells. 30,[33][34][35] In this paper, the impedance analysis is performed in the static case -the cell is locating in the center, between the two electrodes and also the dynamic case -the cell is moving along the channel. The validations of using these methods are verified by the comparisons between each other.…”

Section: Resultsmentioning

confidence: 99%

Analytical and Numerical Modeling Methods for Impedance Analysis of Single Cells on-Chip

Sun

Green

Morgan

2008

NANO

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Electrical impedance spectroscopy (EIS) is a noninvasive method for characterizing the dielectric properties of biological particles. The technique can differentiate between cell types and provide information on cell properties through measurement of the permittivity and conductivity of the cell membrane and cytoplasm. In terms of lab-on-a-chip (LOC) technology, cells pass sequentially through the microfluidic channel at high speed and are analyzed individually, rather than as traditionally done on a mixture of particles in suspension. This paper describes the analytical and numerical modeling methods for EIS of single cell analysis in a microfluidic cytometer. The presented modeling methods include Maxwell's mixture theory, equivalent circuit model and finite element method. The difference and advantages of these methods have been discussed. The modeling work has covered the static case -an immobilized cell in suspension and the dynamic case -a moving cell in the channel.

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Section: Resultsmentioning

confidence: 99%

Analytical and Numerical Modeling Methods for Impedance Analysis of Single Cells on-Chip

Sun

Green

Morgan

2008

NANO

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“…In contrast to measurements of single cells at discrete frequencies, Morgan et al have developed a method for broad band multifrequency analysis of cells using pseudorandom signal generated by a maximum length sequence (MLS) system (76)(77)(78)(79)(80). This method permits the characterization of cells within 1 ms at 512 discrete frequencies ranging from 976 Hz to 500 kHz.…”

Section: Single Cell Dielectric Spectroscopy: Multifrequency Analysismentioning

confidence: 99%

Microfluidic impedance‐based flow cytometry

Berardino²,

et al. 2010

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Microfabricated flow cytometers can detect, count, and analyze cells or particles using microfluidics and electronics to give impedance-based characterization. Such systems are being developed to provide simple, low-cost, label-free, and portable solutions for cell analysis. Recent work using microfabricated systems has demonstrated the capability to analyze micro-organisms, erythrocytes, leukocytes, and animal and human cell lines. Multifrequency impedance measurements can give multiparametric, high-content data that can be used to distinguish cell types. New combinations of microfluidic sample handling design and microscale flow phenomena have been used to focus and position cells within the channel for improved sensitivity. Robust designs will enable focusing at high flowrates while reducing requirements for control over multiple sample and sheath flows. Although microfluidic impedance-based flow cytometers have not yet or may never reach the extremely high throughput of conventional flow cytometers, the advantages of portability, simplicity, and ability to analyze single cells in small populations are, nevertheless, where chip-based cytometry can make a large impact. ' 2010International Society for Advancement of Cytometry Key terms microfluidics; impedance characterization; label free; single cell analysis; hydrodynamic focusing; sorting MICROFLUIDIC flow cytometers can bring many advantages to the field of flow cytometry (FCM). Compared to typical flow cytometry channel sizes, the miniaturized dimensions permit microfluidic systems to analyze single cells, to identify cellular variability in gene expression, or drug response within a cell population. Chipbased cytometers can have lower size and costs than conventional benchtop instruments, and may be portable. Today, the developmental aim for microfluidic systems is to reach the same sensitivity and capability for multiparametric analyses as delivered by conventional flow cytometers. Many efforts have been made to improve existing devices and to create new miniaturized high-end instruments. Microfluidic chips can incorporate on-chip cell preparation, cell culture, lysis, and modules for optical, electrophoretic, or genomic analysis (1). They are also suitable for analysis of cells in suspension as well as adherent cells.Miniaturized cytometry devices will have high impact in the development of point-of-care devices in developing countries. Accurate CD4 1 T-cell counts are used to monitor human immunodeficiency virus (HIV)-infected patients, and various thresholds of the number of CD4 1 T lymphocytes per ll of whole blood are used to start antiretroviral therapy (2-5). A simple, single-purpose CD4 cell counting device, which does not require standard laboratory equipment or trained laboratory personnel, could help some of the 33 million HIV-infected people worldwide monitor the stage of infection (6)(7)(8). In this application, increased analysis throughput is a secondary concern compared to increased sensitivity and specificity. Portable, miniatu...

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“…However, the filtered signal has noise with a pseudo-periodic sinusoidal form (see Fig. 5a, b in Sun et al 2007c). The degree of noise reduction and signal enhancement depends on the order of the polynomial and the length of the filter.…”

Section: Savitzky-golay Filteringmentioning

confidence: 99%

Digital signal processing methods for impedance microfluidic cytometry

Sun

Berkel

Green

et al. 2008

Microfluid Nanofluid

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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.

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High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences

Cited by 108 publications

References 32 publications

Analytical and Numerical Modeling Methods for Impedance Analysis of Single Cells on-Chip

Analytical and Numerical Modeling Methods for Impedance Analysis of Single Cells on-Chip

Microfluidic impedance‐based flow cytometry

Digital signal processing methods for impedance microfluidic cytometry

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