Abstract: Apparatus and methods for using a flow cell array are provided herein. A method includes determining placement of multiple reaction site openings, wherein each reaction site opening is connected to a first sub-surface channel; connecting the first sub-surface channel to two or more additional sub-surface channels by multiple vias; and providing a material for multiple reaction sites, wherein an overlap of the multiple reaction site openings and the material delineate the multiple reaction sites.

Abstract: Devices and methods generate an ordered restriction map of genomic DNA extracted from whole cells, nuclei, whole chromosomes, or other sources of long DNA molecules. The devices have a fluidic microchannel that merges into a reaction nanochannel that merges into a detection nanochannel at an interface where the nanochannel diameter decreases in size by between 50% to 99%. Intact molecules of DNA are transported to the reaction nanochannel and then fragmented in the reaction nanochannel using restriction endonuclease enzymes. The reaction nanochannel is sized and configured so that the fragments stay in an original order until they are injected into the detection nanochannel. Signal at one or more locations along the detection nanochannel is detected to map fragments in the order they occur along a long DNA molecule.

Abstract: Methods and systems are provided for characterizing responses of a ligand-functionalized surface, which rely on dispensing a segmented liquid flow including liquid sequences, each including: an analyte segment including biomolecules of analyte; a spacer segment; and a wash segment including a washing liquid, whereby spacer segments separate wash segments from analyte segments in the dispensed segmented liquid flow. A measurement cycle is performed for each of the liquid sequences of the segmented liquid flow being dispensed. A measurement cycle includes: ejecting an analyte segment of each liquid sequence toward the ligand-functionalized surface and extracting, from each liquid sequence, a spacer segment succeeding the analyte segment as the latter is being ejected; ejecting a wash segment succeeding the extracted spacer segment in each liquid sequence to flush unbound and/or weakly bound biomolecules of analytes from the surface; and reading out a signal of bound biomolecules of analytes on the surface.

Abstract: Provided herein is technology relating to depositing and/or placing a macromolecule at a desired site for an assay and particularly, but not exclusively, to methods and systems for transporting a macromolecule such as a protein, a nucleic acid, or a protein:nucleic acid complex to an assay site, such as the bottom of a nanopore, a nanowell, or a zero mode waveguide.

Abstract: In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and an enzyme molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the enzyme. In various examples, the enzyme is a polymerase. The circuit may further comprise molecular arms used to wire the enzyme to the electrodes. In various embodiments, the circuit functions as a sensor, wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as substrates interact with the enzyme.

Abstract: Microfluidic devices are provided for trapping, isolating, and processing single cells. The microfluidic devices include a cell capture chamber having a cell funnel positioned within the cell capture chamber to direct a cell passing through the cell capture chamber towards one or more a cell traps positioned downstream of the funnel to receive a cell flowing. The devices may further include auxiliary chambers integrated with the cell capture chamber for subsequent processing and assaying of the contents of a captured cell. Methods for cell capture and preparation are also provided that include flowing cells through a chamber, funneling the cells towards a cell trap, capturing a predefined number of the cells within the trap, interrupting the flow of cells, flowing a wash solution through the chamber to remove contaminants from the chamber, and sealing the predefined number of cells in the chamber.

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: 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: A microclinical analyzer usable for analysis of one or more bio-objects, each bio-object including an organ or a group of cells includes a fluidic network having a plurality of fluidic switches, a plurality of fluidic paths in fluid communication with the plurality of fluidic switches, and one or more on-chip pumps coupled to corresponding fluidic paths; a sensor array coupled to the fluidic network; and a microcontroller for individually controlling the plurality of fluidic switches and the one or more on-chip pumps of the fluidic network as so to operably and selectively deliver an effluent of at least one bio-object to the sensor array for detecting properties of the effluent, or to a predetermined outlet destination.

Abstract: A biological and chemical sample processing device that b. comprises a high pressure-resistant, shallow and wide area microfluidic chamber having at least one wall formed by a detachable slide containing samples such as immobilized entities, biological samples or molecules, c. comprises an arrangement of microfluidic access holes for injecting to and collecting fluid form said chamber, d. is interfaced with inlet ports and microfluidic channels which are formed external to the chamber, e. is configured so that the slide may be brought into contact with the device to form the said chamber, f. is adapted to deliver and to transport fluidic substances and reagents inside said chamber in a fast manner, preferably within less than 15 seconds, and in a regular or uniform way owing to said arrangement of microfluidic access holes.

Abstract: Disclosed is a chip.

Abstract: Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed.

Abstract: The present disclosure provides, among other things, systems for nucleic acid amplification. Provided systems for nucleic acid amplification substantially irreversibly seal the contents of a nucleic acid amplification reaction vessel. Provided systems reduce amplification contamination, for example amplification carryover contamination. Provided systems reduce amplification of spurious nucleic acids or amplification products. The present disclosure also provides methods of amplifying nucleic acids. The present disclosure also provides methods of amplifying nucleic acids using provided systems. Provided systems and methods are useful for nucleic acid amplification.

Abstract: A method for producing silicate-containing magnetic particles having a closed and tight silicate layer and high purity. In addition, the novel method prevents an uncontrolled formation of aggregates and clusters of silicates on the magnetite surface, thereby having a positive influence on the properties and biological applications. The method enables depletion of nanoparticulate solid substance particles on the basis of a fractionated centrifugation. The silicate-coated magnetic particles exhibit optimized magnetization and suspension behavior as well as advantageous run-off behavior from plastic surfaces. These highly pure magnetic particles coated with silicon dioxide are preferably used for isolating nucleic acids from cell and tissue samples, whereby the separating out from a sample matrix ensues by means of magnetic fields.

Abstract: The present invention provides a label-free sensing chip for identifying a chemical substance, comprising: (a) a transparent substrate comprising a base and first periodic ridges; and (b) a metal layer covering said transparent substrate, comprising second periodic ridges and third periodic ridges, in which said second periodic ridges has a height equal to or greater than the height of the first periodic ridges, and each ridge of the second periodic ridges fits into the space between each ridge of the first periodic ridges, and said third periodic ridges correspondingly located on said first periodic ridges. The present invention also provides a method for identifying a chemical substance by using the foresaid label-free sensing chip.

Abstract: Compositions, systems, and methods for detecting events are provided. A composition can include a nanopore including a first side, a second side, and an aperture extending through the first and second sides; and a permanent tether including head and tail regions and an elongated body disposed therebetween. The head region can be anchored to or adjacent to the first or second side of the nanopore. The elongated body including a reporter region can be movable within the aperture responsive to a first event occurring adjacent to the first side of the nanopore. For example, the reporter region is translationally movable toward the first side responsive to the first event, then toward the second side, then toward the first side responsive to a second event. The first event can include adding a first nucleotide to a polynucleotide. The second event can include adding a second nucleotide to the polynucleotide.

Abstract: Techniques, apparatus and systems are described for performing label-free monitoring of processes. In one aspect, a label-free monitoring system includes an array of label-free optical sensors to detect an optical signal in response to synthesis of one or more target genetic structures. Each label-free optical sensor is functionalized with a respective target genetic structure. The system also includes a fluid flow control module that includes fluid receiving units to provide paths for different fluids to flow into the fluid flow control module and at least one switch connected to the fluid receiving units to selectively switch among the fluid receiving units to receive a select sequence of the fluids through the fluid receiving units. The select sequence of the fluids includes at least a dNTP or base.

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: Disclosed are a biochip capable of detecting and analyzing multivalent bindings between target protein and binding mediator from monovalent bindings and a method for manufacturing the same. A biochip according to an embodiment comprises: a hydrogel functional layer on which a binding mediator is formed and of which physical properties are changed by a reaction between target protein to be introduced and the binding mediator; and a transducer configured to deliver a displacement signal corresponding to a change in the physical properties of the hydrogel functional layer to an analysis instrument, wherein the reaction is multivalent bindings between the target protein and the binding mediator, and de-swelling occurs in at least a portion of the hydrogel functional layer by the multivalent bindings.

Abstract: The invention relates to an automated method for high-throughput DNA sequencing from high density DNA arrays by (a) initiating a first sequencing reaction on a first high density DNA array; and imaging said first high density DNA array using a detector, and (b) initiating a first sequencing reaction on a second high density DNA array; and imaging said second high density DNA array using the detector, wherein the first sequencing reaction in (a) is initiated before the first sequencing reaction in (b) is initiated such that the sequencing reactions in (a) and (b) are staggered. By using asynchronous sequencing reactions and imaging two separate arrays using one detector, imaging can be carried out on one array while sequencing reactions are carried out on one the other, substrate, the other substrate is imaged, reducing the idle time of the imaging system.