A Simple and Robust Event-Detection Algorithm for Single-Cell Impedance Cytometry

Abstract

Abstract-Microfluidic impedance cytometry is emerging as a powerful label-free technique for the characterization of single biological cells. In order to increase the sensitivity and the specificity of the technique, suited digital signal processing methods are required to extract meaningful information from measured impedance data.In this work, a simple and robust event-detection algorithm for impedance cytometry is presented. Since a differential measuring scheme is generally adopted, the signal recorded when a cell passes through the sensing region of the device exhibits a typical odd-symmetric pattern. This feature is exploited twice by the proposed algorithm: first, a preliminary segmentation, based on the correlation of the data stream with the simplest oddsymmetric template, is performed; then, the quality of detected events is established by evaluating their E2O index, that is, a measure of the ratio between their even and odd parts.A thorough performance analysis is reported, showing the robustness of the algorithm with respect to parameter choice and noise level. In terms of sensitivity and positive predictive value, an overall performance of 94.9% and 98.5%, respectively, was achieved on two datasets relevant to microfluidic chips with very different characteristics, considering three noise levels.The present algorithm can foster the role of impedance cytometry in single-cell analysis, which is the new frontier in "Omics".

Coplanar electrode microfluidic chip enabling accurate sheathless impedance cytometry

“…A stimulation frequency of 1 MHz was used for the bead suspension, 32 whereas yeast measurements were performed at 0.5 MHz. 4,7,8,43 Event detection in the data stream was performed with an algorithm reported previously, 44 and a simple Matlab script was used for event fitting and feature extraction. With the present flow rate and sample concentration, a theoretical throughput of 166 events per second was computed.…”

Advances in High-Resolution Microscale Impedance Sensors

“…Despite the vast literature (reviewed in [37] up to 2010), single-cell IFC has not yet reached the same maturity and diffusion of ECIS. From the analysis of recent advances in the field of single-cell detection [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59], the following trends can be highlighted. (1) Smarter and more robust event detection algorithms are emerging.…”

“…(1) Smarter and more robust event detection algorithms are emerging. Instead of simply fixing a threshold on the impedance value exceeded by the resistive pulse for each passage, digital segmentation and autocorrelation leveraging the odd symmetry of differential pulses can be used [44], as well as multielectrode structures that, while increasing the input capacitance and the measurement time, produce specific signatures, whose shape can be better identified against noise [45] or improved electrode layout [46]. (2) Combination of IFC with dielectrophoresis (DEP) is increasing for sorting [47], trapping [48], orienting [49], and sensing [50].…”

Simulation and performance analysis of a novel high-accuracy sheathless microfluidic impedance cytometer with coplanar electrode layout

“…The synthetic data streams were processed with an in-house software toolbox. First, event detection in the data stream was performed using the algorithm described in [25]. With the present flow rate and sample concentration, a theoretical throughput of 166 events per second was computed.…”