Abstract: The present invention relates, e.g., to a method for determining the size distribution of DNA molecules in a sample comprising cell-free nucleic acid, comprising labeling the DNA with a fluorescent dye in a stoichiometric manner, subjecting the DNA to molecular spectroscopy (e.g., cylindrical illumination confocal spectroscopy), analyzing suitable fluorescent burst parameters of the labeled DNA, and conducting single molecule DNA integrity analysis of the labeled DNA molecules in the sample. In one embodiment of the invention, the method is used as a diagnostic method for detecting cancer.

Abstract: A microfluidic system includes a microfluidic cartridge and an electromagnetic droplet actuator arranged proximate the microfluidic cartridge. The microfluidic cartridge includes a plurality of droplet wells with topological barrier structures between adjacent wells. The topological barrier structures are configured to allow magnetic particles and material attached to the magnetic particles to pass between adjacent wells while confining droplets within respective wells. The electromagnetic droplet actuator includes a plurality of electromagnetic components arranged to provide an electronically selectable magnetic field pattern to actuate movement of a plurality of magnetic particles when contained within at least one droplet in at least one of the plurality of droplet wells.

Abstract: A microfluidic device for a confocal fluorescence detection system has an input channel defined by a body of the microfluidic device, a sample concentration section defined by the body of the microfluidic device and in fluid connection with the input channel, a mixing section defined by the body of the microfluidic device and in fluid connection with the concentration section, and a detection region that is at least partially transparent to illumination light of the confocal fluorescence detection system and at least partially transparent to fluorescent light when emitted from a sample under observation as the sample flows through the detection region.

Abstract: A method of using a fluidic device includes providing a fluidic chip having a plurality of surface energy traps; depositing at least one fluid droplet on the fluidic chip, the fluid droplet including magnetic particles suspended therein; and moving at least a portion of the at least one fluid droplet across a surface of the fluidic chip by altering a magnetic interaction applied to the magnetic particles such that the at least one fluid droplet interacts with at least one of the plurality of surface energy traps.

Abstract: A system for producing microbeads includes a microfluidic device defining a supply channel and a shearing channel, a microbead precursor material disposed in the supply channel, a carrier fluid disposed in the shearing channel, and a pressure distribution system fluidly connected to each of the supply channel and the shearing channel to control at least relative pressures of the microbead precursor material and the carrier fluid. The supply channel includes a check valve adapted to be subjected to a bias pressure that is sufficient to close the check valve to flow of microbead precursor material when a supply pressure of the microbead precursor material is below a threshold pressure and is open to flow of the microbead precursor material when the supply pressure of the microbead precursor material is greater than the threshold pressure.

Abstract: A fluidic cartridge for biochemical assays includes a cartridge body defining a first droplet region and a second droplet region with a droplet restraining barrier therebetween. The droplet restraining barrier has a gap between the first and the second droplet regions. The fluidic cartridge also includes a first droplet dispensed in the first droplet region. The first droplet includes a plurality of magnetic particles dispersed therein. The fluidic cartridge also includes a second droplet disposed in the second droplet region. The plurality of magnetic particles are sufficiently small to be drawn through the gap between the first and second droplet regions when compelled by an applied magnetic field, and the first droplet is restrained by the restraining barrier while the plurality of magnetic particles are drawn through the gap. A biochemical assay system includes a stage adapted to receive a fluidic cartridge, and a magnetic control assembly that includes a magnet.

Abstract: A cylindrical illumination confocal spectroscopy system has a fluidic device having a fluid channel defined therein, an objective lens unit arranged proximate the fluidic device, an illumination system in optical communication with the objective lens unit to provide light to illuminate a sample through the objective lens unit, and a detection system in optical communication with the objective lens unit to receive at least a portion of light that passes through the objective lens unit from the sample. The illumination system includes a beam-shaping lens unit constructed and arranged to provide a substantially planar illumination beam that subtends across, and is longer than, a lateral dimension of the fluid channel.

Abstract: The present invention relates, e.g., to a method for detecting a nucleic acid molecule of interest in a sample comprising cell-free nucleic acids, comprising fluorescently labeling the nucleic acid molecule of interest, by specifically binding a fluorescently labeled nanosensor or probe to the nucleic acid of interest, or by enzymatically incorporating a fluorescent probe or dye into the nucleic acid of interest, illuminating the fluorescently labeled nucleic acid molecule, causing it to emit fluorescent light, and measuring the level of fluorescence by single molecule spectroscopy, wherein the detection of a fluorescent signal is indicative of the presence of the nucleic acid of interest in the sample.

Abstract: A microfluidic device for a confocal fluorescence detection system has an input channel defined by a body of the microfluidic device, a sample concentration section defined by the body of the microfluidic device and in fluid connection with the input channel, a mixing section defined by the body of the microfluidic device and in fluid connection with the concentration section, and a detection region that is at least partially transparent to illumination light of the confocal fluorescence detection system and at least partially transparent to fluorescent light when emitted from a sample under observation as the sample flows through the detection region.

Abstract: The present invention relates, e.g., to a method for determining the size distribution of DNA molecules in a sample comprising cell-free nucleic acid, comprising labeling the DNA with a fluorescent dye in a stoichiometric manner, subjecting the DNA to molecular spectroscopy (e.g., cylindrical illumination confocal spectroscopy), analyzing suitable fluorescent burst parameters of the labeled DNA, and conducting single molecule DNA integrity analysis of the labeled DNA molecules in the sample. In one embodiment of the invention, the method is used as a diagnostic method for detecting cancer.

Abstract: The present invention features methods and compositions for methylation detection, as well as a novel method for polynucleotide extraction and sodium bisulfite treatment.

Abstract: The present invention relates to methods, kits and devices with multiple open reaction chambers having multiple pre-deposited primer compositions, and a basic sample loading mechanism that utilizes an immiscible companion fluid for preparing and performing multiple Polymerase Chain Reactions

Abstract: A cylindrical illumination confocal spectroscopy system has a fluidic device having a fluid channel defined therein, an objective lens unit arranged proximate the fluidic device, an illumination system in optical communication with the objective lens unit to provide light to illuminate a sample through the objective lens unit, and a detection system in optical communication with the objective lens unit to receive at least a portion of light that passes through the objective lens unit from the sample. The illumination system includes a beam-shaping lens unit constructed and arranged to provide a substantially planar illumination beam that subtends across, and is longer than, a lateral dimension of the fluid channel, the substantially planar illumination beam having a diffraction limited thickness in a direction substantially orthogonal to the lateral dimension of the fluid channel.

Abstract: A method and system for specifically detecting perfectly matched probe-target hybrids by annealing a hairpin-based probe to a nucleic acid target under conditions favoring the formation of perfectly matched targets over mismatched targets, and electrochemically detecting the annealed probe. Sensitivity of detection can be enhanced by catalyzed reporter deposition of probe signal prior to electrochemical detection. Specificity can be enhanced by including hairpin-based competitor probes in the annealing step. The detection assay is particularly applicable to typing single nucleotide polymorphisms by DNA sandwich hybridization.

Abstract: The invention disclosed herein provides biosensors and methods which increase the sensitivity of assays of optically labelled molecules fluorescently tagged polypeptides and polynucleotides while decreasing the sample volume required for detection. By integrating reflective sidewalls into the receptacles used in such assays, the signal-to-noise ratio of the optical signal is increased significantly. Typically the receptacles are microchannels. In addition, the geometry of the receptacles can be controlled to further optimize the signal-to-noise ratio of the optical signal. The invention disclosed herein further provides methods and devices involving integrated electronics, wherein an element such as a diode, a transistor, an integrated circuit etc., is integrated with a bio-reactor/channel in order to facilitate the detection or fabrication of bio-materials.

Abstract: The invention disclosed herein provides biosensors and methods which increase the sensitivity of assays of optically labelled molecules fluorescently tagged polypeptides and polynucleotides while decreasing the sample volume required for detection. By integrating reflective sidewalls into the receptacles used in such assays, the signal-to-noise ratio of the optical signal is increased significantly. Typically the receptacles are microchannels. In addition, the geometry of the receptacles can be controlled C to further optimize the signal-to-noise ratio of the optical signal. The invention disclosed herein further provides methods and devices involving integrated electronics, wherein an element such as a diode, a transistor, an integrated circuit etc., is integrated with a bioreactor/channel in order to facilitate the detection or fabrication of bio-materials.

Abstract: A method and system for specifically detecting perfectly matched probe-target hybrids by annealing a hairpin-based probe to a nucleic acid target under conditions favoring the formation of perfectly matched targets over mismatched targets, and electrochemically detecting the annealed probe. Sensitivity of detection can be enhanced by catalyzed reporter deposition of probe signal prior to electrochemical detection. Specificity can be enhanced by including hairpin-based competitor probes in the annealing step. The detection assay is particularly applicable to typing single nucleotide polymorphisms by DNA sandwich hybridization.

Abstract: A method is disclosed for generating a model for predicting standard cycle time for a semiconductor process stage. A generic cycle time model is created based on Little's formula and Kingman's equation. Past cycle times as related to equipment utilization is used to generate a regression curve. The regression curve is then used to determine the coefficients of the generic cycle time model. Then, the standard cycle time of a stage for a future upcoming cycle is determined by using the cycle time model.