Abstract: Techniques for controlling analytical instruments are provided. A sequence of steps can be utilized to specify wells of a microfluidic device, mobility to be applied to fluid in the wells, and the duration to apply the mobility. For example, fluids can be sequentially run past down a main channel to a detection zone of the microfluidic device in order to analyze the fluids. In order to increase the efficiency of the analysis, fluids can be processed in parallel by running one fluid down the main channel while another fluid is loaded to the main channel.

Abstract: Methods, systems, kits for carrying out a wide variety of different assays that comprise providing a first reagent mixture which comprises a first reagent having a fluorescent label. A second reagent is introduced into the first reagent mixture to produce a second reagent mixture, where the second reagent reacts with the first reagent to produce a fluorescently labeled product having a substantially different charge than the first reagent. A polyion is introduced into at least one of the first and second reagent mixtures, and the fluorescent polarization in the second reagent mixture relative to the first reagent mixture is determined, this fluorescent polarization being indicative of the rate or extent of the reaction.

Abstract: Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3?-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Microfluidic devices, including particle arrays, are used in the sequencing methods.

Abstract: The present invention is directed to a method for determining the molecular weight and diffusivity of a sample solute by providing a plus shaped microchannel network on a microfluidic chip, having at least four microchannels intersecting at a cross point; flowing a sample stream comprising a sample solute of unknown diffusivity and a blank stream from separate microchannels through the cross point and out to separate microchannels; creating a sample curve measuring the concentration of the sample solute that diffuses from the sample stream to the blank stream at the cross point while altering the flowrate of one of the blank stream or the sample stream; and determining a diffusion coefficient of the sample solute by extrapolating data from similar curves of at least two solutes having known molecular weights and/or diffusion coefficients created under similar conditions as those generated by the sample solute.

Abstract: The present invention generally provides improved methods of fabricating polymeric microfluidic devices that incorporate microscale fluidic structures, whereby the fabrication process does not substantially distort or deform such structures. The methods of the invention generally provide enhanced bonding processes for mating and bonding substrate layers to define the microscale channel networks therebetween.

Abstract: Methods and devices for delivering fluids into microfluidic device body structures are described. The methods and devices include the use of fluid manifolds that are integrated or interchangeable with device body structures. Methods of fabricating manifolds are also provided.

Abstract: The invention provides methods and apparatuses that allow a protein sample to undergo reduction, alkylation, and digestion in a continuous flow process carried out within a microfluidic device. Methods and apparatuses in accordance with the invention can be employed as part of an automated proteomics analysis carried out in an integrated proteomics system.

Abstract: Embodiments of the invention comprise microfluidic devices, instrumentation interfacing with those devices, processes for fabricating that device, and methods of employing that device to perform PCR amplification. Embodiments of the invention are also compatible with quantitative Polymerase Chain Reaction (“qPCR”) processes. Microfluidic devices in accordance with the invention may contain a plurality of parallel processing channels. Fully independent reactions can take place in each of the plurality of parallel processing channels. The availability of independent processing channels allows a microfluidic device in accordance with the invention to be used in a number of ways. For example, separate samples could be processed in each of the independent processing channels. Alternatively, different loci on a single sample could be processed in multiple processing channels.

Abstract: Methods, systems, kits for carrying out a wide variety of different assays that comprise providing a first reagent mixture which comprises a first reagent having a fluorescent label. A second reagent is introduced into the first reagent mixture to produce a second reagent mixture, where the second reagent reacts with the first reagent to produce a fluorescently labeled product having a substantially different charge than the first reagent. A polyion is introduced into at least one of the first and second reagent mixtures, and the fluorescent polarization in the second reagent mixture relative to the first reagent mixture is determined, this fluorescent polarization being indicative of the rate or extent of the reaction.

Abstract: An optical detection system for a microfluidic device and a dry-focus microfluidic device compatible with the compact optical detection system are described. The system includes an LED; means for collimating light emitted by the LED; an aspherical, fused-silica objective lens; means for directing the collimated light through the objective onto a microfluidic device; and means for detecting a fluorescent signal emitted from the microfluidic device. The working distance between the objective and the device allows light from an external LED or laser to be brought in along a diagonal path to illuminate the microfluidic device. The dry-focus microfluidic device includes multiple channels and multiple closed optical alignment marks having curved walls. At least one of the channels is positioned between at least two of the marks. The marks are illuminated for alignment and focusing purposes by light brought in on a diagonal path from an external white LED.

Abstract: Methods and systems of monitoring reactions, e.g., assays, that filter out background signal from substrate, in detecting the product. The methods and systems controllably move detectable reaction product from a first location to a second location at which the product is detected while controllably moving potentially interfering substrate materials away from or not toward the second location. Controllable movement of the different species is accomplished through the controlled combination of bulk fluid flow and differential electrophoresis of substrate and product to move the product, but not the substrate past the detection region.

Abstract: Methods and apparatuses for priming sample substrates such as DNA sipper chips are disclosed. According to one aspect of the present invention, a priming system that is suitable for priming a substrate which has a plurality of wells and at least one channel includes a base unit and a top unit. The base unit is arranged to accommodate, or support, the substrate. The top unit, which is substantially physically separate from the base unit, fits over the substrate when the substrate is held by the base unit. The top unit includes an adapter portion that interfaces with the substrate. Included in the adapter portion is a first cavity that is used to facilitate pressurizing a first well of the substrate when the adapter portion is interfaced with the substrate such that the first cavity is aligned with the first well.

Abstract: A method for detecting one or more components of interest in a fluid-borne sample in a microchannel of a microfluidic device includes flowing the fluid-borne sample, in which the one or more components of interest are bound to a first labeled component binding moiety to form a first labeled complex, through a binding channel region of the microchannel. The binding channel region includes a second component-binding moiety reversibly bound to a wall surface of the binding channel region. At least a portion of the one or more components of interest is bound to the second component-binding moiety to form a second labeled complex. The second labeled complex is released from the binding channel region and flowed through a detection channel region of the microchannel, where the second labeled complex is detected.

Abstract: Methods for chromatographically separating materials, including the separation of materials in kinase or phosphatase assays, in microfluidic devices under positive or negative fluid pressure. Devices and integrated systems for performing chromatographic separations are also provided.

Abstract: Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3?-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Microfluidic devices, including particle arrays, are used in the sequencing methods.

Abstract: Methods and systems that employ hybrid fluid flow profiles for optimized movement of materials through channel networks. These systems employ hybrid pressure-based and electrokinetic based flow systems for moving materials through interconnected channel networks while maintaining interconnection among the various channel segments. In particular, the invention is generally directed to channel networks where flow in a first channel segment is driven by pressure flow with its consequent parabolic flow profile, while flow in an interconnected channel segment is dominated by electrokinetic flow with its consequent plug flow profile. The invention also provides channel networks wherein fluid flow in channel segments is driven by both pressure and electric field and the multiple species contained in a fluid plug are separated (and can be concentrated) by altering the applied pressure and electric fields in the various channel segments of the channel networks.

Abstract: The present invention is directed to a method for determining the molecular weight and diffusivity of a sample solute by providing a plus shaped microchannel network on a microfluidic chip, having at least four microchannels intersecting at a cross point; flowing a sample stream comprising a sample solute of unknown diffusivity and a blank stream from separate microchannels through the cross point and out to separate microchannels; creating a sample curve measuring the concentration of the sample solute that diffuses from the sample stream to the blank stream at the cross point while altering the flowrate of one of the blank stream or the sample stream; and determining a diffusion coefficient of the sample solute by extrapolating data from similar curves of at least two solutes having known molecular weights and/or diffusion coefficients created under similar conditions as those generated by the sample solute.

Abstract: A microfluidic system and method for employing it to control fluid temperatures of fluids residing within microchannels of a microfluidic device. The microfluidic device is provided with a top layer and a bottom layer and microchannels configured therebetween. Temperature of the fluid within the microchannels is controlled in various ways including the use of electrical resistive heating elements and by providing zones located in contact with the top and bottom layers of the microfluidic device for circulating heat transfer of fluid therein.

Abstract: A priming unit for a microfluidics device contains a pressurization unit and pressure and temperature detectors as part of a feedback loop that controls the pressure applied by the pressurization unit and the time during which the pressure is applied. This control feature is particularly useful in controlling the exposure time of the microchannels to dyes in the priming liquids since certain dyes tend to adhere to the walls of the channels and produce non-uniform results.

Abstract: The present invention is an automated microfluidic chip processing apparatus that includes a deck for holding at least one microfluidic chip and capable of being accessed by a liquid handling system, a fluid control system, and a detection system, wherein a chip handling device transports the chip from the deck to the fluid control system and the detection system. The present invention also includes a chip for use with an automated microfluidic chip processing apparatus, and a method for processing a microfluidic chip using such an apparatus.