A biochip for the integration of all steps in a complex process from the insertion of a sample to the generation of a result, performed without operator intervention includes microfluidic and macrofluidic features that are acted on by instrument subsystems in a series of scripted processing steps. Methods for fabricating these complex biochips of high feature density by injection molding are also provided.

A method of synthesizing an oligonucleotide using a nanofluidic device including a plurality of nanopore channels, a plurality of electrodes, and an electrolyte solution, includes coupling a primer to an inner wall of a nanopore channel of the plurality of nanopore channels, the primer having a protecting group. The method also includes applying a voltage to an electrode of the plurality of electrodes that corresponds to the nanopore channel to produce an acid from the electrolyte solution at the electrode. The electrode includes an anode and a cathode disposed at opposite sides of the nanopore channel. The method further includes the acid removing the protecting group from the primer. Moreover, the method includes coupling a nucleotide to the primer with the protecting group removed to form an intermediate product. In addition, the method includes repeating the steps on the intermediate product until the oligonucleotide is synthesized.

The present invention discloses an electrophoretic chip comprising: (a) a non-conductive substrate designed to support elements of said electrophoretic chip; (b) an electrode structure for conducting current through said electrophoretic chip, printed on said non-conductive substrate and comprising a counter electrode and at least one working electrode, each electrode comprising a conductive low-resistance ink layer printed on the non-conductive substrate, and a carbon ink layer printed on top of and fully or partially covering said conductive low-resistance ink layer; (c) a dielectric ink insulator layer placed on top of, and covering, said electrode structure, said dielectric ink insulator layer having at least one opening above the counter electrode and at least one opening above said at least one working electrode, thereby forming at least one addressable location; and (d) a molecule capturing matrix spotted on and covering said at least one addressable location, thereby creating at least one microgel region.

Methods of detecting the presence of toxins in a sample using electrophoretic separations and of performing electrophoretic separation of complex samples are provided. The method of detecting the presence of toxins includes reacting a sample and a substrate with a signaling enzyme which converts the substrate to the product in a reaction medium, introducing a run buffer into a separation channel having an inlet end, selectively introducing at least one of the substrate and the product of the reaction medium into the inlet end of the separation channel, electrophoretically separating the substrate and the product, and determining the rate of conversion of the substrate to the product, wherein a change in the rate of conversion is indicative of the presence of toxins. The method of performing electrophoretic separations of complex samples having charged particulates and oppositely charged analytes comprising introducing a run buffer into a separation channel having an inlet end, selectively introducing the oppositely charged analytes in the complex sample into the separation channel, and electrophoretically separating the charged particulates and the oppositely charged analytes. Additionally, a device for varying with respect to time the bulk flow of a fluid in a separation channel of an electrophoretic device having a buffer reservoir in fluid contact with the separation channel is provided. The device includes a pressure sensor in fluid contact with a buffer reservoir, a high pressure reservoir in selective fluidic communication with the buffer reservoir, a low pressure reservoir in selective fluidic communication with the buffer reservoir and in fluidic communication with the high pressure reservoir, and a pumping device for pumping a gas from the low pressure reservoir to the high pressure reservoir.

Methods are provided for separating magnetically responsive beads from a droplet in a droplet actuator. Droplet operations electrodes and a magnet are arranged in a droplet actuator to manipulate a bead-containing droplet and position it relative to a magnetic field region that attracts the magnetically responsive beads. The droplet operations electrodes are operated to control the droplet shape and transport it away from the magnetic field region to form a concentration of beads in the droplet. The continued transport of the droplet away from the magnetic field causes the concentration of beads to break away from the droplet to yield a small, concentrated bead-containing droplet immobilized by the magnet.

A particle analysis device includes a liquid space adapted to store a liquid; a chip disposed above the liquid space, the chip having a connection pore extending vertically and communicating with the liquid space; an upper hole disposed above the chip, the upper hole extending vertically and communicating with the connection pore; a first electrode adapted to apply an electric potential to a liquid in the upper hole; and a second electrode adapted to apply an electric potential to the liquid in the liquid space. The upper hole having a diameter that is equal to or greater than the maximum width of the connection pore, and the entirety of the connection pore falling within the range of the upper hole.

Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Methods, systems and devices that allow independently applied pressures to a BGE reservoir and a sample reservoir for pressure-driven injection that can inject a discrete sample plug into a separation channel that does not require voltage applied to the sample reservoir and can allow for in-channel focusing methods to be used. The methods, systems and devices are particularly suitable for use with a mass spectrometer.

Embodiments include systems, apparatuses, and methods to efficiently separate analytes in a sample and elute fractions of the separated analytes. In some embodiments, a method includes introducing a sample in a capillary with a first end ionically coupled to a first running buffer and a second end ionically coupled to a second running buffer to form a pH gradient. The method includes applying a voltage between the first running buffer and the second running buffer, to separate a plurality of analytes in the sample. The method includes disposing the second end of the capillary in a collection well including a chemical mobilizer and applying a voltage to elute one or more analytes from the plurality of analytes in the sample, that have been separated, into the collection well. Embodiments include detection methods to monitor separation of analytes, mobilization of analytes, and/or elution of fractions containing analytes.

A diagnostic system detects and/or measures hemoglobin variants in blood of subject, such as HbA1c, to determine blood glucose concentration in the subject.