Abstract: Substrates comprising dual functional polymer layered surfaces and the preparation thereof by using UV nano-imprinting processes are disclosed. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Abstract: A method of detecting nucleic acids with an amplified signal utilizes first and second amplification nanoparticles.

Abstract: A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.

Abstract: In one aspect, a microfluidic device for multiple reactions is provided, which comprises a reaction channel comprising multiple reaction chambers connected to a closed chamber or an elastic balloon outside of the microfluidic device, wherein a wall of the closed chamber is an elastic membrane; and a control channel comprising an elastic side wall, wherein the intersections between the side wall of the control channel with the reaction channel form multiple pneumatic microvalves. In another aspect, a method for conducting multiple reactions using the microfluidic device is provided, which comprises: a) filling the reaction chambers with a sample; and b) applying pressure to the control channel to expand the elastic side wall of the control channel, wherein the expanded elastic side wall forms a pneumatic microvalve that separates the reaction chambers.

Abstract: The purpose of the present invention is to provide a single cell analysis device in which the improvement of the nucleic acid capturing efficiency and the improvement of the cell capturing efficiency are both achieved and a highly accurate single cell analysis data is thereby obtained. The present invention relates to an improvement of a cell analysis device including a two-dimensional array chip having a plurality of cell capture parts capable of capturing a single cell in each of the capture parts, and nucleic acid capture parts corresponding to the respective cell capture parts, the nucleic acid capture parts being capable of capturing a nucleic acid extracted from the cell captured by the cell capture part.

Abstract: An analyte in a liquid sample is detected using a capacitive sensor having electrodes and a sensor surface, and a signal processor. The sample is dried to reduce its liquid content, and capacitive measurements are made after the drying and preferably also before the drying. The sample may include particles, and the analyte is part of or attached to the particles, and the particles provide a major part of the capacitance change compared to absence of particles. In another example the particles are degenerative and form an integral mass upon application of heat, enhancing the extent of capacitance change.

Abstract: Methods of detecting target nucleic acid is a sample are described. A first probe is attached to first beads, and the first beads are placed in the sample so that any target nucleic acid attaches to the first probe. A second probe also attaches to the target nucleic acid so that any of the target nucleic acid links or “tethers” the first and second probes. A capacitive sensor detects capacitance of the beads and processes capacitance data to quantify target nucleic acid presence in the sample. The second probe may be immobilised on the sensor surface. Alternatively the second beads are introduced into the sample with the second probe attached, and the extent of tethering of the first beads to the second beads is indicative of the extent of target NA present.

Abstract: This disclosure relates DNA based movement of objects. In certain embodiments, particles, pairs of particles, or a rods are conjugated with single stranded DNA that hybridizes to a single stranded RNA that is conjugated to a substrate. When the DNA particle, pair of particles, or rod interacts with the surface RNA in the presence of an endonuclease, such as RNase H and the DNA hybridizes to the RNA, then the particle, pair of particle, or rod moves along the surface. The complementarity of the DNA and RNA affect the velocity.

Abstract: Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.

Abstract: A method for in-line measurement of the quality of a microarray are disclosed and the method includes the following steps. A solid substrate is provided, and the solid substrate includes a plurality of areas in an array. At least one biomarker is in-situ synthesized on at least one of the plurality of areas by a plurality of synthesis steps. After performing at least one of the plurality of synthesis step, a check step is immediately performed on a semi-product of the at least one biomarker by an atomic force microscope to obtain an in-line measurement result. The quality of the semi-product of the at least one biomarker is determined based on the in-line measurement result.

Abstract: Devices having nanochannels suitable for confinement and alignment of DNA molecules, as well as methods of fabricating the same and methods of using the same for DNA analysis, are provided. A device can include a dynamically-controlled, unified microchannel-nanochannel platform suitable for confinement and alignment of DNA molecules. The nanochannels can be reversibly formed within nanoslits formed in a deformable substrate or base layer.

Abstract: The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in an active loading of molecules and complexes into reaction sites with improved efficiency over loading by passive diffusion methods alone.

Abstract: Some embodiments described herein relate to a substrate comprising a silane functionalized surface for reversibly immobilizing a biological molecule of interest, such as oligonucleotides, polynucleotides, or protein. Methods for immobilizing the biological molecule and the use in DNA sequencing and other diagnostic applications are also disclosed.

Abstract: A composition includes a nanopore including first and second sides and an aperture, nucleotides each including an elongated tag, and a first polynucleotide that is complementary to a second polynucleotide. A polymerase can be disposed adjacent to the first side of the nanopore and configured to add nucleotides to the first polynucleotide based on a sequence of the second polynucleotide. A permanent tether can include a head region anchored to the polymerase, a tail region, and an elongated body disposed therebetween that occurs in the aperture of the nanopore. A first moiety can be disposed on the elongated body that binds to the elongated tag of a first nucleotide upon which the polymerase is acting. A reporter region can be disposed on the elongated body that indicates when the first nucleotide is complementary or is not complementary to a next nucleotide in the sequence of the second polynucleotide.

Abstract: Disclosed are methods and compositions for detection and amplification of nucleic acids, wherein two DNA strands hybridized to an RNA strand are ligated. In one aspect, the disclosed methods include removal of an energy source, such as ATP, upon charging a ligase to form an enzyme-AMP intermediate, and then adding substrate, which results in one complete round of RNA-templated DNA ligation. In another aspect, the ligation reaction is accomplished by use of a mixture of at least two different ligase enzymes. The disclosed methods and compositions for RNA-templated DNA ligation may be particularly useful for detection of RNA sequence variants, for example RNA splice variants, and for quantitative expression analysis.

Abstract: In one aspect, methods are described herein for the selective detection and quantitative analysis of biological molecule compositions. A method described herein comprises providing a mixture comprising biological molecules, such as DNA, RNA or proteins, complexed with a translocating agent, such as another DNA or protein, and non-complexed biological molecules. The mixture is contacted with a membrane comprising at least one nanopore and an electric field is applied across the nanopore to selectively translocate the biological molecules complexed with the translocating agent through the at least one nanopore. Concentration of the complexed biological molecules is determined based on the translocation rate of said molecules.

Abstract: In one aspect, methods of sensing are described herein. In some embodiments, such a method comprises disposing a population of luminescent species in a test sample, exposing the test sample to electromagnetic radiation having a wavelength corresponding to an excitation wavelength of the luminescent species, detecting light emitted by the luminescent species within a detection region of the test sample, and correlating the light emitted by the luminescent species within the detection region to a presence or absence of an analyte within the test sample. The luminescent species, in a non-aggregated state, exhibits luminescence blinking and, in an aggregated state, does not exhibit luminescence blinking. Additionally, correlating the light emitted by the luminescent species to the presence or absence of the analyte comprises determining whether the light emitted by the luminescent species within the detection region is blinking luminescence or non-blinking luminescence.

Abstract: Methods and systems for processing polynucleotides (e.g., DNA) are disclosed. A processing region includes one or more surfaces (e.g., particle surfaces) modified with ligands that retain polynucleotides under a first set of conditions (e.g., temperature and pH) and release the polynucleotides under a second set of conditions (e.g., higher temperature and/or more basic pH). The processing region can be used to, for example, concentrate polynucleotides of a sample and/or separate inhibitors of amplification reactions from the polynucleotides. Microfluidic devices with a processing region are disclosed.

Abstract: Apparatus and methods for using a flow cell array are provided herein. A method includes delivering multiple items of chemical matter independently to multiple reaction sites of a flow cell array across multiple distinct instances of time; imaging multiple parallel chemical reactions at the multiple reaction sites of the flow cell array; and recording an emission from each of the multiple chemical reactions site.

Abstract: A method and a device are provided for facilitating the disaggregation of a plurality of solid phase substrate as the plurality of solid phase substrate are transferred from a first location to a second location. A plurality of solid phase substrate are deposited at the first location and a plurality of particles are added to the plurality of solid phase substrate. A force is generated to draw the plurality of solid phase substrate from the first location to a second location. The plurality of particles causes clumps of the plurality of solid phase substrate to break apart as the plurality of solid phase substrate are moved in response to the force.