The present invention concerns a method of sequencing immobilized polynucleotides in which beads which are tethered to the solid support are used as labels to identify bases within the polynucleotides. The beads carry sets of probes or bases which can bind to the polynucleotide allowing identification of the target base(s). Identification of the base(s) is achieved through sequential application of different cleavage means specific to different probes/bases carried on the beads. Also provided is an apparatus for performing the method and a kit comprising the apparatus and other components necessary for performing the method.

The present invention concerns a method of sequencing immobilized polynucleotides in which beads which are tethered to the solid support are used as labels to identify bases within the polynucleotides. The beads carry sets of probes or bases which can bind to the polynucleotide allowing identification of the target base(s). Identification of the base(s) is achieved through sequential application of different cleavage means specific to different probes/bases carried on the beads. Also provided is an apparatus for performing the method and a kit comprising the apparatus and other components necessary for performing the method.

An apparatus includes a flow cell body, a plurality of electrodes, an integrated circuit, and an imaging assembly. The flow cell body defines one or more flow channels and a plurality of wells. Each flow channel is configured to receive a flow of fluid. Each well is fluidically coupled with the corresponding flow channel. Each well is configured to contain at least one polynucleotide. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are operable to effect writing of polynucleotides in the corresponding wells. The integrated circuit is operable to drive selective deposition or activation of selected nucleotides to attach to polynucleotides in the wells to thereby generate polynucleotides representing machine-written data in the wells. The imaging assembly is operable to capture images indicative of one or more nucleotides in a polynucleotide.

An apparatus includes a flow cell body, a plurality of electrodes, an integrated circuit, and an imaging assembly. The flow cell body defines one or more flow channels and a plurality of wells. Each flow channel is configured to receive a flow of fluid. Each well is fluidically coupled with the corresponding flow channel. Each well is configured to contain at least one polynucleotide. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are operable to effect writing of polynucleotides in the corresponding wells. The integrated circuit is operable to drive selective deposition or activation of selected nucleotides to attach to polynucleotides in the wells to thereby generate polynucleotides representing machine-written data in the wells. The imaging assembly is operable to capture images indicative of one or more nucleotides in a polynucleotide.

A DNA sequencing device and related methods, wherein the device includes a substrate, a nanochannel formed in the substrate, a first electrode positioned on a first side of the nanochannel, and a second electrode. The second electrode is positioned on a second side of the nanochannel opposite the first electrode and is spaced apart from the first electrode to form an electrode gap that is exposed in the nanochannel. At least a portion of first electrode is movable relative to the second electrode to decrease a size of the electrode gap.

A DNA sequencing device and related methods, wherein the device includes a substrate, a nanochannel formed in the substrate, a first electrode positioned on a first side of the nanochannel, and a second electrode. The second electrode is positioned on a second side of the nanochannel opposite the first electrode and is spaced apart from the first electrode to form an electrode gap that is exposed in the nanochannel. At least a portion of first electrode is movable relative to the second electrode to decrease a size of the electrode gap.

Methods, systems, and devices for sampling/isolating material from cells. An exemplary system may comprise a chip including an electrode array of sampling electrodes arranged along a surface of the chip. A cell-receiving area may be located adjacent the surface of the chip. The system also may comprise a tag array of tags supported by the chip and aligned with the electrode array. Each tag of the tag array may include an identifier that is unique to the tag within the tag array. Each tag may be configured to bind nucleic acids, or a capturing agent distinct from the tag may be aligned with each sampling electrode of the electrode array to capture a protein or other analyte of interest. The system further may comprise a control circuit configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode.

Methods, systems, and devices for sampling/isolating material from cells. An exemplary system may comprise a chip including an electrode array of sampling electrodes arranged along a surface of the chip. A cell-receiving area may be located adjacent the surface of the chip. The system also may comprise a tag array of tags supported by the chip and aligned with the electrode array. Each tag of the tag array may include an identifier that is unique to the tag within the tag array. Each tag may be configured to bind nucleic acids, or a capturing agent distinct from the tag may be aligned with each sampling electrode of the electrode array to capture a protein or other analyte of interest. The system further may comprise a control circuit configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode.

A method of determining the result of an assay in a microfluidic device includes the steps of: dispensing a sample droplet onto a first portion of an electrode array of the microfluidic device; dispensing a reagent droplet onto a second portion of the electrode array of the microfluidic device; controlling actuation voltages applied to the electrode array to mix the sample droplet and the reagent droplet into a product droplet; sensing a dynamic property of the product droplet; and determining an assay of the sample droplet based on the sensed dynamic property. The dynamic property is a physical property of the product droplet that influences a transport property of the product droplet on the electrode array. Example dynamic properties of the product droplet include the moveable state, split-able state, and viscosity based on droplet properties. The method may be used to perform an amoebocyte lysate (LAL) assay.

A method of determining the result of an assay in a microfluidic device includes the steps of: dispensing a sample droplet onto a first portion of an electrode array of the microfluidic device; dispensing a reagent droplet onto a second portion of the electrode array of the microfluidic device; controlling actuation voltages applied to the electrode array to mix the sample droplet and the reagent droplet into a product droplet; sensing a dynamic property of the product droplet; and determining an assay of the sample droplet based on the sensed dynamic property. The dynamic property is a physical property of the product droplet that influences a transport property of the product droplet on the electrode array. Example dynamic properties of the product droplet include the moveable state, split-able state, and viscosity based on droplet properties. The method may be used to perform an amoebocyte lysate (LAL) assay.