The present disclosure relates to a device, system and method for sensing functional motions of a single protein molecule via direct attachment of one or more electrodes to the molecule. The present disclosure also relates to an array, a system comprising an array and method for sequencing a biopolymer using an array.

The present disclosure relates to a device, system and method for sensing functional motions of a single protein molecule via direct attachment of one or more electrodes to the molecule. The present disclosure also relates to an array, a system comprising an array and method for sequencing a biopolymer using an array.

The present disclosure relates to systems, devices, and methods for nucleic acid sequencing including polynucleotide strands having a nucleotide(s) modified with a redox label(s) attached thereto or capable of receiving the modified nucleotide(s) with a redox label(s) attached thereto. The systems, devices, and methods include a dielectric member with an attached translocating protein positioned between oxidizing and reducing electrodes. The oxidizing and reducing electrodes generate an electrical field extending to a reaction area where the translocation of the polynucleotide strand through the protein occurs such the modified nucleotide(s) with redox label(s) attached thereto are identified by changes in current flow in the oxidizing and reducing electrodes, wherein the changes identify electron transfer from the reducing electrode, to redox label, and to oxidizing electrode when the modified nucleotide with a redox label covalently bonded to the nucleoside base of the modified nucleotide of the polynucleotide strand is at the reaction area.

The present disclosure relates to systems, devices, and methods for nucleic acid sequencing including polynucleotide strands having a nucleotide(s) modified with a redox label(s) attached thereto or capable of receiving the modified nucleotide(s) with a redox label(s) attached thereto. The systems, devices, and methods include a dielectric member with an attached translocating protein positioned between oxidizing and reducing electrodes. The oxidizing and reducing electrodes generate an electrical field extending to a reaction area where the translocation of the polynucleotide strand through the protein occurs such the modified nucleotide(s) with redox label(s) attached thereto are identified by changes in current flow in the oxidizing and reducing electrodes, wherein the changes identify electron transfer from the reducing electrode, to redox label, and to oxidizing electrode when the modified nucleotide with a redox label covalently bonded to the nucleoside base of the modified nucleotide of the polynucleotide strand is at the reaction area.

Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

Provided herein, in some embodiments, are methods of purifying a nucleic acid preparation. The methods may comprise contacting a nucleic acid preparation comprising messenger ribonucleic acid with an RNase III enzyme that is immobilized on a solid support and binds to double-stranded RNA contaminants.

Provided herein, in some embodiments, are methods of purifying a nucleic acid preparation. The methods may comprise contacting a nucleic acid preparation comprising messenger ribonucleic acid with an RNase III enzyme that is immobilized on a solid support and binds to double-stranded RNA contaminants.

The present disclosure relates, according to some embodiments, to methods for preparing a library for sequencing. For example, a method may comprise (a) in a coupled reaction, (i) contacting a population of nucleic acid fragments with a tailing enzyme to produce tailed fragments, and (ii) ligating to the tailed fragments a sequencing adapter with a ligase to produce adapter-tagged fragments; and/or separating adapter-tagged fragments from the tailing enzyme and the ligase to produce separated adapter-tagged fragments and, optionally, separated tailing enzyme and/or separated ligase. In some embodiments, a tailing enzyme and/or a ligase used in library preparation may be immobilized enzymes.

The present disclosure relates, according to some embodiments, to methods for preparing a library for sequencing. For example, a method may comprise (a) in a coupled reaction, (i) contacting a population of nucleic acid fragments with a tailing enzyme to produce tailed fragments, and (ii) ligating to the tailed fragments a sequencing adapter with a ligase to produce adapter-tagged fragments; and/or separating adapter-tagged fragments from the tailing enzyme and the ligase to produce separated adapter-tagged fragments and, optionally, separated tailing enzyme and/or separated ligase. In some embodiments, a tailing enzyme and/or a ligase used in library preparation may be immobilized enzymes.