Loc device for electrochemiluminescent detection of target nucleic acid sequences with calibrated photodetection of probes in hybridization array

Abstract

A lab-on-a-chip (LOC) device for detecting target nucleic acid sequences in a fluid, the LOC device having electrochemiluminescent (ECL) probes for detecting the target nucleic acid sequences, each of the probes having an ECL luminophore for emitting photons when in an excited state, a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, electrodes for receiving an electrical pulse to excite the ECL luminophores, detection photodiodes for exposure to the photons emitted by the ECL luminophores, and, at least one calibration photodiode for exposure to ambient light, wherein during use, a difference between the output from any of the detection photodiode and the output from the calibration photodiode is compared to a predetermined threshold difference such that output differences greater than the predetermined threshold indicate the target is present.

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

[0091]The hybridization array provides for analysis of the targets via hybridization, with the calibration photosensor improving the reliability, sensitivity, and dynamic range of the analytical outcomes.

[0092]The electrochemiluminescence-based assay target detection obviates any need, of the assay system, for an excitation light source, excitation optics, and optical filter elements, in turn, providing for a more compact and more inexpensive assay system. The absence of the requirement for the rejection of any excitation light also simplifies the detector circuitry, making the assay system even more inexpensive.

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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