Abstract: Methods and microfluidic circuitry for inline injection of nucleic acids for capillary electrophoresis analysis are provided. According to various embodiments, microfabricated structures including affinity-based capture matrixes inline with separation channels are provided. The affinity-based capture matrixes provide inline sample plug formation and injection into a capillary electrophoresis channel. Also provided are methods and apparatuses for a microbead-based inline injection system for DNA sequencing.

Abstract: Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Abstract: An electrochemical detector including side channels associated with a separation channel of a sample component separation apparatus is provided. The side channels of the detector, in one configuration, provide a sheath-flow for an analyte exiting the separation channel which directs the analyte to the electrically developed electrochemical detector.

Abstract: An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000 base pairs of raw sequence data per hour.

Abstract: Sample component separation apparatus and methods are described. An exemplary sample component separation apparatus includes a separation channel having a turn portion configured to reduce band-broadening caused by passage of a sample through the turn portion. To reduce band broadening caused by passage of a sample through a turn portion, the turn portion may be constructed and arranged to have a sample transport characteristic that is different from the corresponding sample transport characteristic of a substantially straight portion of the separation channel. For example, the turn portion may be configured with an effective channel width that is smaller than the effective channel widths of the substantially straight portion of the separation channel.

Abstract: A miniaturized optical excitation and detector system is described for detecting fluorescently labeled analytes in electrophoretic microchips and microarrays. The system uses miniature integrated components, light collection, optical fluorescence filtering, and an amorphous a-Si:H detector for detection. The collection of light is accomplished with proximity gathering and/or a micro-lens system. Optical filtering is accomplished by integrated optical filters. Detection is accomplished utilizing a-Si:H detectors.

Abstract: Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Abstract: A capillary array electrophoresis (CAE) micro-plate with an array of separation channels connected to an array of sample reservoirs on the plate. The sample reservoirs are organized into one or more sample injectors. One or more waste reservoirs are provided to collect wastes from reservoirs in each of the sample injectors. Additionally, a cathode reservoir is also multiplexed with one or more separation channels. To complete the electrical path, an anode reservoir which is common to some or all separation channels is also provided on the micro-plate. Moreover, the channel layout keeps the distance from the anode to each of the cathodes approximately constant.

Abstract: A miniaturized optical excitation and detector system is described for detecting fluorescently labeled analytes in electrophoretic microchips and microarrays. The system uses miniature integrated components, light collection, optical fluorescence filtering, and an amorphous a-Si:H detector for detection. The collection of light is accomplished with proximity gathering and/or a micro-lens system. Optical filtering is accomplished by integrated optical filters. Detection is accomplished utilizing a-Si:H detectors.

Abstract: A microfabricated liquid sample loading system comprising a first plate having an array of microfabricated holes passing therethrough; a second plate positioned against the first plate, the second plate having an array of microfabricated holes passing therethrough; and a plurality of microfabricated channels disposed on a surface of at least one of the first or second plates, the microfabricated channels connecting the array of microfabricated holes in the first plate with the array of microfabricated holes in the second plate.

Abstract: An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000 base pairs of raw sequence data per hour.

Abstract: The present invention provides methods and kits for identifying nucleotides at a variant site in a target molecule by forming fluorescence resonance energy transfer labeled product. The location and type of fluorescent labels in the labeled product provide strong signals and relatively high spectral purity that facilitate detection. Utilizing various secondary labels and different combinations of acceptor and donor labels, certain methods permit multiple analyses to be conducted simultaneously and at high throughput. The methods can be used in a variety of applications such as analyzing point mutations and single nucleotide polymorphisms (SNPs). In addition, the methods have utility in other applications in which specific sequence information is of value, including detection of pathogens, paternity disputes, prenatal testing and forensic analysis.

Abstract: An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000 base pairs of raw sequence data per hour.

Abstract: Novel fluorescent labeling techniques and fluorescent labels are provided, employing high affinity non-covalently binding and intercalating fluorescent dyes and dsDNA. The dyes find application to provide highly sensitive labeling of nucleic acids in electrophoretic gels and as pre-prepared labels for binding to a wide variety of specific binding pair members. The DNA-dye fluorescer complex can be used for labels in diagnostic assays, detection of specific nucleic acid sequences, and the like.

Abstract: A miniature device has a body including one, two or more reaction chambers. The reaction chambers are constructed for one or more of the following: sample acquisition, preparation or analysis. Preferably, a sample preparation reaction includes nucleic acid extraction, amplification, nucleic acid fragmentation, labeling, extension or a transcription.

Abstract: A fully integrated monolithic small volume PCR-CE device in glass, or the like materials, is fabricated using thin film metal heaters and thermocouples to thermally cycle sub-microliter PCR volumes. Successful amplification of a PCR fragment is demonstrated on a PCR-CE chip. The process utilizes a linear polyacrylamide surface coating coupled with addition of BSA to the amplification buffer was necessary to obtain amplification efficiencies comparable to a positive control. The micro-reactor reduced significantly the time required for amplification and the reaction volume was in the sub-microliter regime. Likewise addressed are the known problems connected with reliable microfabrication of metal coatings and the insulating layers required to shield these layers from the PCR reaction mix, and the longstanding unresolved issue of exposed metal regions in the PCR-CE chip resulting in electrolysis of water and bubble formation whenever a voltage is applied.

Abstract: This invention relates to a microfabricated capillary electrophoresis chip for detecting multiple redox-active labels simultaneously using a matrix coding scheme and to a method of selectively labeling analytes for simultaneous electrochemical detection of multiple label-analyte conjugates after electrophoretic or chromatographic separation.

Abstract: The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, nucleic acid fragmentation and the like.

Abstract: Novel fluorescent labeling techniques and fluorescent labels are provided, employing high affinity non-covalently binding and intercalating fluorescent dyes and dsDNA. The dyes find application to provide highly sensitive labeling of nucleic acids in electrophoretic gels and as pre-prepared labels for binding to a wide variety of specific binding pair members. The DNA-dye fluorescer complex can be used for labels in diagnostic assays, detection of specific nucleic acid sequences, and the like.

Abstract: A Monster Capillary Array Electrophoresis scanner measures four-color electropherograms from over a thousand capillary electrophoretic separations in parallel. The system consists of a two-dimensional confocal rotary scanner and a four-color detection unit.