Target cell concentration using dielectrophoresis (DEP)
Inventors
O'Halloran, Jonathan • MURTON, Heather • Osborne, Stephen • Boada, Eduardo • Salmon, Jonathan
Assignees
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Publication Number
US-10710075-B2
Publication Date
2020-07-14
Expiration Date
Abstract
Methods and devices for concentrating target cells using dielectrophoresis (DEP) are disclosed. The method allows relatively high throughput of sample through a microfluidic device in order to allow rapid capture of target cells even when they are present in low concentrations within the sample. The method utilizes multiple chambers through which samples will flow, the chambers arranged such that the first capture area has a larger area and faster flow rate than a second chamber, the second chamber being positioned downstream of the first capture area and being smaller with a slower flow rate to further concentrate the material captured in the first capture area.
Core Innovation
The invention relates to concentrating target particles in a sample using a microfluidic device that includes at least a first capture area and a second capture area downstream in fluid communication. Each capture area contains a plurality of electrodes arranged such that a sample flowing through the capture area flows over the electrodes, and the first capture area has a larger volume than the second capture area.
A sample is introduced into the first capture area and flowed through the first capture area at a first flow rate while the first plurality of electrodes is activated to trap target particles. The first plurality of electrodes is then deactivated to release trapped target particles, providing an enriched sample comprising target particles at a second concentration greater than the first concentration.
The enriched sample is then introduced into the second capture area and flowed through the second capture area at a second flow rate lower than the first flow rate, while the second plurality of electrodes is activated to trap target particles. The microfluidic device includes at least one inlet divided into multiple channels, each channel being of smaller circumference than the at least one inlet, and a control module sequentially activates and deactivates the first plurality of electrodes and subsequently activates the second plurality of electrodes.
Claims Coverage
The document provides two independent claims. They cover a two-stage downstream capture architecture with electrode activation/deactivation for reversible trapping and enrichment, together with a microfluidic inlet/channel configuration and a lower second-stage flow rate.
Two downstream electrode capture areas with releasable trapping and enrichment
A microfluidic device comprising at least one first capture area with a first plurality of electrodes for selectively and releasably capturing target particles, and a second capture area downstream of the first capture area and of smaller volume, with a second plurality of electrodes for selectively and releasably capturing target particles; introducing a sample into the first capture area, activating the first plurality to trap, deactivating the first plurality to release trapped target particles to provide an enriched sample with a second concentration greater than the first concentration, then introducing the enriched sample to the second capture area and activating the second plurality to trap target particles.
Inlet divided into smaller-circumference channels for sample flow over electrodes
The microfluidic device includes at least one inlet divided into multiple channels, wherein each channel is of smaller circumference than the at least one inlet, with sample flowing through the first capture area over the first plurality of electrodes and sample flowing through the second capture area over the second plurality of electrodes.
Flow-rate hierarchy using lower flow in the second capture area
Flow the sample comprising target particles through the first capture area at a first flow rate, then flow the enriched sample through the second capture area at a second flow rate lower than the first flow rate, while providing the second plurality of electrodes in an activated state to trap the target particles.
Sequential electrode activation and control of lower second-stage flow
A microfluidic device for concentrating target particles comprising a control module configured to sequentially activate and deactivate the first plurality of electrodes and subsequently activate the second plurality of electrodes, and a flow controller configured to control a flow rate through the second capture area to be lower than a flow rate through the first capture area.
Overall, the independent claims cover a two-stage microfluidic concentration approach using activated and deactivated electrode pluralities in a first and downstream second capture area to release an enriched sample for further trapping, together with inlet/channel division and a flow-rate hierarchy coordinated by a control module and flow controller.
Stated Advantages
Provides an enriched sample comprising target particles at a second concentration greater than the first concentration.
Enables trapping of target particles in the second capture area after first-stage release and enriched-sample introduction.
Documented Applications
Concentrating target particles in a sample, including target cells, using a microfluidic device.
Nucleic acid extraction and/or amplification after the enriched sample is introduced into a second area and flowed through that area.
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