Target cell concentration using dielectrophoresis (DEP)

Inventors

O'Halloran, Jonathan • MURTON, Heather • Osborne, Stephen • Boada, Eduardo • Salmon, Jonathan

Assignees

QuantumDx Group Ltd

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Publication Number

US-11850593-B2

Patent

Publication Date

2023-12-26

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 provides a microfluidic device for concentrating target cells or target particles using di-electrophoresis (DEP). The device includes a first capture area with a plurality of electrodes tuned to trap target cells using DEP when activated and to release the target cells when de-activated, with a waste area downstream of the first capture area in fluid communication with the first capture area.

Downstream of the first capture area, a second capture area in fluid communication with the first area receives the released, enriched sample. The second capture area has a smaller volume than the first capture area and includes a plurality of electrodes tuned to trap target cells using DEP, with one or more flow regulators adapted to ensure that the volumetric flow rate through the second capture area is lower than the volumetric flow rate through the first capture area.

When the first plurality of electrodes are activated, the device directs sample out from the first capture area to the waste area, while trapping occurs in the first capture area. When the first plurality of electrodes are de-activated, trapped target cells are released and the sample flows out from the first capture area to the second capture area, enabling a two-stage concentration followed by further trapping in the smaller second capture area under a lower volumetric flow rate.

The disclosed embodiments further include dividing an inlet of the first capture area into multiple channels, bifurcated inlet channels forming parallel smaller-circumference channels, optional buffer/media exchange introduced by a control module when electrodes are de-activated, waste routing depending on electrode activation state, and optional inclusion of an optical detection device for detecting signals from the second area.

Claims Coverage

The independent claims are directed to a microfluidic device with two staged DEP capture areas and conditional waste or enriched-sample routing with flow-rate control, and to a method implementing that two-stage trapping and release workflow. Across the independent claims, there are four main inventive features.

Two-stage DEP capture with sequential areas of different volume

A second capture area downstream of the first capture area, the second capture area being of a smaller volume than the first capture area and comprising a plurality of electrodes tuned to trap target cells using di-electrophoresis (DEP), with a sample flowing over the electrodes.

First capture electrodes configured for DEP trapping and release

A first capture area comprising a plurality of electrodes tuned to trap the target cells using di-electrophoresis (DEP) when activated, and to release the target cells when de-activated, with a sample flowing over the electrodes.

Waste area downstream of the first capture area

A waste area downstream of the first capture area and in fluid communication with the first capture area, such that when the electrodes tuned to trap target cells using di-electrophoresis (DEP) in the first capture area are activated, sample flows out from the first capture area to the waste area.

Electrode-activation dependent routing plus flow-rate hierarchy to the second area

When the electrodes tuned to trap target cells using di-electrophoresis (DEP) in the first capture area are de-activated, sample flows out from the first capture area to the second capture area, and one or more flow regulators ensure that the volumetric flow rate of sample travelling through the second capture area is lower than the volumetric flow rate of sample travelling through the first capture area.

The independent claims cover a DEP-based microfluidic concentration architecture with electrode-state-controlled routing, a smaller downstream second capture area for further trapping, and flow regulators that maintain a lower volumetric flow rate through the second capture area. Dependent claims add optional channelization of the first capture area, optional buffer/media exchange tied to electrode deactivation, and optional optical detection of signals from the second area.

Stated Advantages

Documented Applications

Not explicitly described in patent.

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