Microfluidic device with dialysis section having stomata tapering counter to flow direction

Abstract

A microfluidic device for removing cell debris from a biological sample, the microfluidic device having a dialysis section with a large constituent channel and a small constituent channel, and a series of stoma for fluid communication between the large constituent channel and the small constituent channel, the large constituent channel having an upstream end for receiving the biological sample, the biological sample being a liquid carrying a mixture of cell debris and target molecules, the small constituent channel having a downstream end for connection to a hybridization section with an array of probes for reaction with the target molecules to form probe-target complexes, wherein, each of the stoma is tapered in a counter-flow direction such that each have a small opening to the large constituent channel and a large opening to the small constituent channel, the small openings being sized to allow the target molecules to flow into the small constituent channel but retain the cell debris larger than a threshold size in the large constituent channel.

Description

FIELD OF THE INVENTION[0001]The present invention relates to diagnostic devices that use microsystems technologies (MST). In particular, the invention relates to microfluidic and biochemical processing and analysis for molecular diagnostics.CO-PENDING APPLICATIONS[0002]The following applications have been filed by the Applicant which relate to the present application:GBS001USGBS002USGBS003USGBS005USGBS006USGSR001USGSR002USGAS001USGAS002USGAS003USGAS004USGAS006USGAS007USGAS008USGAS009USGAS010USGAS012USGAS013USGAS014USGAS015USGAS016USGAS017USGAS018USGAS019USGAS020USGAS021USGAS022USGAS023USGAS024USGAS025USGAS026USGAS027USGAS028USGAS030USGAS031USGAS032USGAS033USGAS034USGAS035USGAS036USGAS037USGAS038USGAS039USGAS040USGAS041USGAS042USGAS043USGAS044USGAS045USGAS046USGAS047USGAS048USGAS049USGAS050USGAS054USGAS055USGAS056USGAS057USGAS058USGAS059USGAS060USGAS061USGAS062USGAS063USGAS065USGAS066USGAS067USGAS068USGAS069USGAS070USGAS080USGAS081USGAS082USGAS083USGAS084USGAS085USGAS086USGAS087USGAS...

AI Technical Summary

Benefits of technology

[0088]The easily usable, mass-producible, and inexpensive microfluidic device accepts a biochemical sample, uses a dialysis section for separating the sample constituents of different dimensions, and separately processes the sample constituents separated based on their dimensions.

[0089]The dialysis section directly selects the component of the sample which contains the target, removing unwanted components of the processed mixture which may interfere with later detection of the target, inhibit later analytical steps, or might clog the chambers or connections within the microfluidic device and degrade operation. The dialysis section functionality also extracts additional information from the sample and increases the sensitivity, signal-to-noise ratio, and dynamic range of the assay system.

[0090]The dialysis section being integral to the device, provides for the low system component-count and simple manufacturing procedures, leading into an inexpensive assay system. Also the dialysis section being fabricated via only surface-micromachining, provides for the simple and inexpensive manufacturing procedures, leading into the further reduction of assay system costs.

[0113]The easily usable, mass-producible, and inexpensive microfluidic device accepts a biochemical sample, uses a dialysis section for separating the sample constituents of different dimensions, and separately processes the sample constituents separated based on their dimensions.

[0114]The dialysis section directly selects the component of the sample which contains the target, removing unwanted components of the processed mixture which may interfere with later detection of the target, inhibit later analytical steps, or might clog the chambers or connections within the microfluidic device and degrade operation. The dialysis section functionality also extracts additional information from the sample and increases the sensitivity, signal-to-noise ratio, and dynamic range of the assay system. The dialysis section incorporates stomata based on trapezoidal planform pillars; this aspect of the design reduces, for a given lithographic space width, the stomata's dimensions as required for many applications.

[0115]The dialysis section being integral to the device, provides for the low system component-count and simple manufacturing procedures, leading into an inexpensive assay system. Also the dialysis section being fabricated via only surface-micromachining, provides for the simple and inexpensive manufacturing procedures, leading into the further reduction of assay system costs.

Problems solved by technology

Insufficient stringency can result in a high degree of nonspecific binding.

Excessive stringency can lead to a failure of appropriate binding, which results in diminished sensitivity.

Despite the advantages that molecular diagnostic tests offer, the growth of this type of testing in the clinical laboratory has been slower than expected and remains a minor part of the practice of laboratory medicine.

This is primarily due to the complexity and costs associated with nucleic acid testing compared with tests based on methods not involving nucleic acids.

However, controlling fluid flow through the LOC device, adding reagents, controlling reaction conditions and so on necessitate bulky external plumbing and electronics.

Connecting a LOC device to these external devices effectively restricts the use of LOC devices for molecular diagnostics to the laboratory setting.

The cost of the external equipment and complexity of its operation precludes LOC-based molecular diagnostics as a practical option for point-of-care settings.

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