Performance-enhanced clogging-free viscous sheath constriction impedance flow cytometry

Zhu, Junwen; Feng, Yongxiang; Chai, Huichao; Liang, Fei; Cheng, Zhen; Wang, Wenhui

doi:10.1039/d3lc00178d

Cited by 6 publications

(4 citation statements)

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“…Comparing to the above separation methods, emerging microfluidic techniques offer a promising solution with unique advantages. [8][9][10][11] Among these, dielectrophoresis (DEP), as a typical electrodynamic method, is an attractive technique for bioparticle manipulation, and can achieve label-free, well-controllable, low-damage, and low-cost separation of bioparticles based on size and dielectric properties. [12,13] With these capabilities, DEP has demonstrated a broad range of applications over the last few decades in bioparticle manipulation such as cancer cells, [14,15] blood cells, [16,17] bacteria, [18,19] proteins, [20,21] etc.…”

Section: Introductionmentioning

confidence: 99%

Capillarity Enabled Large‐Array Liquid Metal Electrodes for Compact and High‐Throughput Dielectrophoretic Microfluidics

Chai,

Zhu,

Feng

et al. 2024

Advanced Materials

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Dielectrophoresis (DEP) particle separation has label‐free, well‐controllable, and low‐damage merits. Sidewall microelectrodes made of liquid metal alloy (LMA) inherits the additional advantage of thick electrodes to generate impactful DEP force. However, existing LMA electrode‐based devices lack the ability to integrate large‐array electrodes in a compact footprint, severely limiting flow rate and thus throughput. Herein, a facile and versatile method is proposed to integrate high‐density thick LMA electrodes in microfluidic devices, taking advantage of the passive control ability of capillary burst valves (CBVs). CBVs with carefully designed burst pressures are co‐designed in microfluidic channels, allowing self‐assembly of LMA electrode array through simple hand‐push injection. The arrayed electrode configuration brings the accumulative DEP deflection effect. Specifically, we demonstrate to fabricate 5000 pairs of sidewall electrodes in a compact chip to achieve 10 times higher throughput in DEP deflection. We applied the 5000‐electrode‐pair device to successfully separate the mixed sample of human peripheral blood mononuclear cells (PBMCs) and A549 cells with the flow rate of 70 µL min−1. It is envisioned that this work can greatly facilitate LMA electrode array fabrication and offer a robust and versatile platform for DEP separation applications.This article is protected by copyright. All rights reserved

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Section: Introductionmentioning

confidence: 99%

Capillarity Enabled Large‐Array Liquid Metal Electrodes for Compact and High‐Throughput Dielectrophoretic Microfluidics

Chai,

Zhu,

Feng

et al. 2024

Advanced Materials

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“…It is crucial to achieve sensitive and accurate cell detection results in MIC [9]. Various optimization techniques have been developed to enhance the performance of MIC platforms for bio-particle event detection, including improving the electrode layout [10][11][12][13], channel design [14][15][16][17], and data processing algorithms [18,19]. These optimizations aim to reduce the baseline noise, decrease the coefficient of variation (CV) of events, increase the signal-tonoise ratio (SNR) of particle events, and improve the detection capability of the MIC system.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Microfluidic Impedance Cytometry by Bypass Electrode Layout Design

Wu,

Zhang,

et al. 2024

Biosensors

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Microfluidic impedance cytometry (MIC) has emerged as a popular technique for single-cell analysis. Traditional MIC electrode designs consist of a pair of (or three) working electrodes, and their detection performance needs further improvements for microorganisms. In this study, we designed an 8-electrode MIC device in which the center pair was defined as the working electrode, and the connection status of bypass electrodes could be changed. This allowed us to compare the performance of layouts with no bypasses and those with floating or grounding electrodes by simulation and experiment. The results of detecting Φ 5 μm beads revealed that both the grounding and the floating electrode outperformed the no bypass electrode, and the grounding electrode demonstrated the best signal-to-noise ratio (SNR), coefficient of variation (CV), and detection sensitivity. Furthermore, the effects of different bypass grounding areas (numbers of grounding electrodes) were investigated. Finally, particles passing at high horizontal positions can be detected, and Φ 1 μm beads can be measured in a wide channel (150 μm) using a fully grounding electrode, with the sensitivity of bead volume detection reaching 0.00097%. This provides a general MIC electrode optimization technology for detecting smaller particles, even macromolecular proteins, viruses, and exosomes in the future.

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“…15 IFC recently has received vigorous advances in sensing sensitivity, multimode (e.g., mechanical and electrical), and throughput. 16 Thus, it has been applied to various kinds of cells as a useful tool in analyzing various cell populations, 17 quantifying subpopulations from heterogeneous samples, 18,19 characterizing deformation of size, 20 or multiparametric mechanophenotyping 21 at the single cell level. Among them, many studies utilize phenomenological parameters 22,23 (e.g., opacity, impedance amplitude, and phase) to characterize the electrical properties, however, these parameters are highly dependent on the measurement platform and the results may not be compared across different platforms.…”

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confidence: 99%

“…In IFC, electrical characterization of single cells is performed by applying an AC voltage to patterned electrodes in a microchannel and measuring the frequency-dependent instantaneous impedance change caused by the transiting cell . IFC recently has received vigorous advances in sensing sensitivity, multimode (e.g., mechanical and electrical), and throughput . Thus, it has been applied to various kinds of cells as a useful tool in analyzing various cell populations, quantifying subpopulations from heterogeneous samples, , characterizing deformation of size, or multiparametric mechanophenotyping at the single cell level.…”

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confidence: 99%

Evaluating the Accuracy of Impedance Flow Cytometry with Cell-Sized Liposomes

et al. 2023

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Electrical properties of single cells are important label-free biomarkers of disease and immunity. At present, impedance flow cytometry (IFC) provides important means for high throughput characterization of single-cell electrical properties. However, the accuracy of the spherical single-shell electrical model widely used in IFC has not been well evaluated due to the lack of reliable and reproducible single-shell model particles with true-value electrical parameters as benchmarks. Herein, a method is proposed to evaluate the accuracy of the single-cell electrical model with cell-sized unilamellar liposomes synthesized through double emulsion droplet microfluidics. The influence of three key dimension parameters (i.e., the measurement channel width w, height h, and electrode gap g) in the single-cell electrical model were evaluated through experiment. It was found that the relative error of the electrical intrinsic parameters measured by IFC is less than 10% when the size of the sensing zone is close to the measured particles. It further reveals that h has the greatest influence on the measurement accuracy, and the maximum relative error can reach ∼30%. Error caused by g is slightly larger than w. This provides a solid guideline for the design of IFC measurement system. It is envisioned that this method can advance further improvement of IFC and accurate electrical characterization of single cells.

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Performance-enhanced clogging-free viscous sheath constriction impedance flow cytometry

Abstract: As label-free and high-throughput single cell analysis platform, impedance flow cytometry (IFC) suffers from clogging caused by narrow microchannel as mechanical constriction (MC). Current sheath constriction (SC) solutions lack systematic...

Cited by 6 publications

References 53 publications

Capillarity Enabled Large‐Array Liquid Metal Electrodes for Compact and High‐Throughput Dielectrophoretic Microfluidics

Capillarity Enabled Large‐Array Liquid Metal Electrodes for Compact and High‐Throughput Dielectrophoretic Microfluidics

Optimizing Microfluidic Impedance Cytometry by Bypass Electrode Layout Design

Evaluating the Accuracy of Impedance Flow Cytometry with Cell-Sized Liposomes

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