Self-aligned sequential lateral field non-uniformities over channel depth for high throughput dielectrophoretic cell deflection

Huang, Xuhai; Torres‐Castro, Karina; Varhue, Walter; Salahi, Armita; Ahmed, Rasin; Honrado, Carlos; Brown, Audrey C.; Guler, Jennifer L.

doi:10.1039/d0lc01211d

Cited by 25 publications

(29 citation statements)

References 54 publications

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“…It is noteworthy that the current device lacks a tangential flow after the buffer swap stage to focus the cells with respect to the field nonuniformity for enabling sequential DEP deflection. Hence, the nDEP and pDEP deflection are not as clearly apparent as in our prior work [37] that used focusing flows, but lacked the buffer swap stage. Nevertheless, based on crossover frequency measurements on RBCs after the reported on‐chip buffer swap, we confirm that the computed membrane capacitance of 11.25 mF/m 2 (see Supporting Information S5 and S6) is close to that of prior work [40].…”

Section: Resultsmentioning

confidence: 67%

“…Based on this, red blood cells (RBCs) in the input sample (3.3 × 10 8 cells/ml) are transferred from a media of 1× PBS at ∼15 000 µS/cm conductivity to a buffer with a media conductivity of ∼175 µS/cm and the collected sample exhibits minimal dilution (10 8 cells/ml). In this manner, the media conductivity and flow rate of the collected sample are validated to support in‐line negative dielectrophoresis (nDEP) at 30 kHz and positive dielectrophoresis (pDEP) at 1 MHz, by using a set of sequential field nonuniformities in the downstream microchannel for flowthrough DEP [37]. Based on this platform, we envision the ability for on‐chip automation [38] and integration of sample preparation in‐line with DEP sorting to reduce user intervention and stress on cells, as well as for monitoring of cell media properties, as well as their numbers, velocity, viability, and position in the microchannel, as may be required for tailoring DEP separations for different degrees of cellular heterogeneity within the biological sample of interest.…”

Section: Introductionmentioning

confidence: 99%

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On‐chip microfluidic buffer swap of biological samples in‐line with downstream dielectrophoresis

et al. 2022

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Microfluidic cell enrichment by dielectrophoresis, based on biophysical and electrophysiology phenotypes, requires that cells be resuspended from their physiological media into a lower conductivity buffer for enhancing force fields and enabling the dielectric contrast needed for separation. To ensure that sensitive cells are not subject to centrifugation for resuspension and spend minimal time outside of their culture media, we present an on‐chip microfluidic strategy for swapping cells into media tailored for dielectrophoresis. This strategy transfers cells from physiological media into a 100‐fold lower conductivity media by using tangential flows of low media conductivity at 200‐fold higher flow rate versus sample flow to promote ion diffusion over the length of a straight channel architecture that maintains laminarity of the flow‐focused sample and minimizes cell dispersion across streamlines. Serpentine channels are used downstream from the flow‐focusing region to modulate hydrodynamic resistance of the central sample outlet versus flanking outlets that remove excess buffer, so that cell streamlines are collected in the exchanged buffer with minimal dilution in cell numbers and at flow rates that support dielectrophoresis. We envision integration of this on‐chip sample preparation platform prior to or post‐dielectrophoresis, in‐line with on‐chip monitoring of the outlet sample for metrics of media conductivity, cell velocity, cell viability, cell position, and collected cell numbers, so that the cell flow rate and streamlines can be tailored for enabling dielectrophoretic separations from heterogeneous samples.

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Section: Resultsmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

On‐chip microfluidic buffer swap of biological samples in‐line with downstream dielectrophoresis

et al. 2022

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“…The field of non-uniformity production geometries can be categorized into two main groups. Electrode-based planar geometries, which are highly effective for field coupling but extend over a limited height of the channel; or insulator based geometries that extend over the whole channel depth, but show weak field coupling because the electrodes are distant from the field non-uniformities [52][53][54][55]. Most of the signal-based methods introduced here rely on the former group.…”

Section: Integration Of Microelectrodesmentioning

confidence: 99%

“…Various 3D metal electrode patterning methods have been utilized to boost the electric field extent across the channel height [61] while maintaining the high coupling of the field. However, the fabrication of these geometries has various challenges, including the need for labour-intensive interlayer alignment and highly specialized deposition techniques accessible only in limited facilities [55]. A new approach for 3D metal geometries facile fabrication in the microchannel relies on the co-fabrication of adjoining electrodes and channels [62].…”

Section: Integration Of Microelectrodesmentioning

confidence: 99%

“…In this method, the liquid metal alloy solidifies in the electrode channel at room temperature [63]. The main advantage of this method is creating patterned metal sidewall electrodes across the entire device height, needless to alignment between the metal electrodes and microchannel layer [55]. Besides, this method can prevent contact between the electrodes and cells.…”

Section: Integration Of Microelectrodesmentioning

confidence: 99%

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Signal-Based Methods in Dielectrophoresis for Cell Separation

Farasat¹,

Ronizi²,

Bakhshi³

et al. 2022

Preprint

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Separation and detection of cells and particles in a suspension are essential for various applications, including biomedical investigations and clinical diagnostics. Microfluidics realizes the miniaturization of analytical devices by controlling the motion of a small volume of fluids in microchannels and microchambers. Accordingly, microfluidic devices have been widely used in particle/ cell manipulation processes. Different microfluidic methods for particle separation include dielectrophoretic, magnetic, optical, acoustic, hydrodynamic, and chemical techniques. Dielectrophoresis (DEP) is a method for manipulating polarizable particles’ trajectories in non-uniform electric fields using unique dielectric characteristics. It provides several advantages for dealing with neutral bioparticles owing to its sensitivity, selectivity, and noninvasive nature. This review provides a detailed study on the signal-based DEP methods that use the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation. Rather than employing complex channels or time-consuming fabrication procedures, these methods realize sorting and detecting the cells/particles by modifying the signal parameters while using a simple device. In addition, these methods can significantly impact clinical diagnostics by making low-cost and rapid separation possible.

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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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Self-aligned sequential lateral field non-uniformities over channel depth for high throughput dielectrophoretic cell deflection

Abstract: Self-aligned sequential lateral field non-uniformities extending uniformly over the sample channel depth are fabricated using a single lithography step for enabling phenotype-specific dielectrophoretic separation of cells.

Cited by 25 publications

References 54 publications

On‐chip microfluidic buffer swap of biological samples in‐line with downstream dielectrophoresis

On‐chip microfluidic buffer swap of biological samples in‐line with downstream dielectrophoresis

Signal-Based Methods in Dielectrophoresis for Cell Separation

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

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