Loc device for pathogen detection, genetic analysis and proteomic analysis with dialysis, chemical lysis, incubation and tandem nucleic acid amplification

Abstract

A lab-on-a-chip (LOC) device for pathogen detection, genetic analysis and proteomic analysis of a biological sample, the LOC device having an inlet for receiving the sample, a supporting substrate, a leukocyte dialysis section for dividing the sample into a leukocyte stream, and a pathogen and erythrocyte stream containing cells and sample constituents smaller than a first size threshold, a pathogen dialysis section for dividing the pathogen and erythrocyte stream into an erythrocyte stream and a pathogen stream containing cells and sample constituents smaller than a second size threshold, a leukocyte lysis section downstream of the leukocyte dialysis section for lysing the leukocytes with a lysis reagent to release genetic material and proteins therein, a leukocyte incubation section downstream of the leukocyte lysis section for enzymatic reaction of the genetic material with enzymes, a pathogen lysis section downstream of the pathogen dialysis section for lysing the pathogens with a lysis reagent to release genetic material and proteins therein, a pathogen incubation section downstream of the pathogen lysis section for enzymatic reaction of the genetic material with enzymes, an erythrocyte lysis section downstream of the pathogen dialysis section for lysing the erythrocytes with a lysis reagent to release proteins therein, a first leukocyte nucleic acid amplification section downstream of the leukocyte incubation section for amplifying nucleic acid sequences, a second leukocyte nucleic acid amplification section downstream of the first leukocyte nucleic acid amplification section for amplifying nucleic acid sequences, a first pathogen nucleic acid amplification section downstream of the pathogen incubation section for amplifying nucleic acid sequences, and, a second pathogen nucleic acid amplification section downstream of the first pathogen nucleic acid amplification for amplifying nucleic acid sequences, wherein, the leukocyte dialysis section, the pathogen dialysis section, the leukocyte lysis section, the pathogen lysis section, the leukocyte incubation section, the pathogen incubation section, the first and second leukocyte nucleic acid amplification sections and the first and second pathogen nucleic acid amplification sections are all supported on the supporting substrate.

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

[0065]Molecular diagnostic systems based on microfluidic technologies provide the means to automate and speed up molecular diagnostic assays. The quicker detection times are primarily due to the extremely low volumes involved, automation, and the low-overhead inbuilt cascading of the diagnostic process steps within a microfluidic device. Volumes in the nanoliter and microliter scale also reduce reagent consumption and cost. Lab-on-a-chip (LOC) devices are a common form of microfluidic device. LOC devices have MST structures within a MST layer for fluid processing integrated onto a single supporting substrate (usually silico...

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 ba...

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