William Marsh Rice University

Baylor College of Medicine

Robert F Curl

Michael L Metzker

Carter Kittrell

Graham B I Scott

Gerard Wysocki

Frank K Tittel

Anatoliy A Kosterev

The present invention provides a technology called Pulse-Multiline Excitation or PME. This technology provides a novel approach to fluorescence detection with application for high-throughput identification of informative SNPs, which could lead to more accurate diagnosis of inherited disease, better prognosis of risk susceptibilities, or identification of sporadic mutations. The PME technology has two main advantages that significantly increase fluorescence sensitivity: (1) optimal excitation of all fluorophores in the genomic assay and (2) 'color-blind' detection, which collects considerably more light than standard wavelength resolved detection. Successful implementation of the PME technology will have broad application for routine usage in clinical diagnostics, forensics, and general sequencing methodologies and will have the capability, flexibility, and portability of targeted sequence variation assays for a large majority of the population.

Pulsed-multiline excitation for color-blind fluorescence detection

Novel methods and laser spectroscopic systems for accurately measuring the concentration of compounds are disclosed herein. The disclosed methods utilize a modulation cancellation technique resulting in a significantly increase in the sensitivity and accuracy of laser spectroscopic measurements. In general, the methods and systems utilize modulation phase-shifting and amplitude attenuation to cancel the signals detected from at least two modulated light beams. Thus, any signal detected will be directly proportional to the concentration measurement.

Modulation cancellation method in laser spectroscopy

A widely tunable, mode-hop-free semiconductor laser operating in the mid-IR comprises a QCL laser chip having an effective QCL cavity length, a diffraction grating defining a grating angle and an external cavity length with respect to said chip, and means for controlling the QCL cavity length, the external cavity length, and the grating angle. The laser of claimwherein said chip may be tuned over a range of frequencies even in the absence of an anti-reflective coating. The diffraction grating is controllably pivotable and translatable relative to said chip and the effective QCL cavity length can be adjusted by varying the injection current to the chip. The laser can be used for high resolution spectroscopic applications and multi species trace-gas detection. Mode-hopping is avoided by controlling the effective QCL cavity length, the external cavity length, and the grating angle so as to replicate a virtual pivot point.

Piezo activated mode tracking system for widely tunable mode-hop-free external cavity mid-IR semiconductor lasers

The present invention provides a technology called Pulse-Multiline Excitation or PME. This technology provides a novel approach to fluorescence detection with application for high-throughput identification of informative SNPs, which could lead to more accurate diagnosis of inherited disease, better prognosis of risk susceptibilities, or identification of sporadic mutations. The PME technology has two main advantages that significantly increase fluorescence sensitivity: (1) optimal excitation of all fluorophores in the genomic assay and (2) 'color-blind' detection, which collects considerably more light than standard wavelength resolved detection. This technology differs significantly from the current state-of-the-art DNA sequencing instrumentation, which features single source excitation and color dispersion for DNA sequence identification. Successful implementation of the PME technology will have broad application for routine usage in clinical diagnostics, forensics, and general sequencing methodologies and will have the capability, flexibility, and portability of targeted sequence variation assays for a large majority of the population.

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Houston, TX, United States of America

Robert F Curl