Abstract: The present disclosure relates to tagged nucleoside-5?-oligophosphates having a positively charged polymer tag structure and components thereof. Such nucleoside-5?-oligophosphates are useful, for example, in nanopore-based sequencing-by-synthesis applications. Also disclosed herein are nanopore constructs engineered to have additional negatively-charged moieties in the channel of the nanopore. Such nanopores can be useful, for example, for providing a repellant force against template and/or primer nucleic acids inserting into the pore during a nucleic sequence-by-synthesis process. The tagged nucleoside-5?-oligophosphates and nanopores disclosed herein can be used together to provide nanopore-based nucleic acid sequencing-by-synthesis systems and processes having reduced background tag levels and improved throughput.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: This application discloses compositions comprising primer compounds that reduce or block deleterious threading into a nanopore of nucleic acid strands displaced by a nanopore-linked polymerase, for example during the use of a nanopore device for nucleic acid sequencing. Also disclosed are methods for using the compositions to reduce deleterious threading events during nanopore-based nucleic acid detection techniques, such as nanopore sequencing.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: The disclosure relates to tagged nucleoside compounds comprising a nucleotide polyphosphate covalently attached to a tag, wherein the compound is a polymerase substrate and the polymer moiety is capable of entering a nanopore linked to the polymerase and thereby altering the flow of ions through the nanopore. The disclosure also provides methods for preparing the tagged nucleoside compounds and for their use as tags in nanopore-based nucleic acid detection and sequencing.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5?-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

Abstract: Intermediates and methods for forming activated metal complexes bound to surfaces on oxide layers, immobilizing beads to the modified surface and articles produced thereby are described. Hydroxyl groups on the oxide surfaces are reacted with a metal reagent complex of the formula Y(L-Pol)m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a methoxyethanol, a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a plurality of functional groups that are reactive with or that form complexes with Y.

Abstract: Intermediates and methods for forming passivated surfaces on oxide layers and articles produced thereby are described. Hydroxyl or hydroxide groups on the oxide surfaces are reacted with a metal reagent of the formula Y(L-Pol)m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a polyvalent reagent comprising a passivating moiety and a plurality of functional groups that are reactive with or that form complexes with Y. The passivating agent can also include a functional group such as biotin to provide surfaces with a desired functionality. The passivated surfaces exhibit minimal binding to bio-molecules and can be used in single-molecule detection schemes.

Abstract: Intermediates and methods for forming passivated surfaces on oxide layers and articles produced thereby are described. Hydroxyl or hydroxide groups on the oxide surfaces are reacted with a metal reagent of the formula Y(L-Pol)m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a polyvalent reagent comprising a passivating moiety and a plurality of functional groups that are reactive with or that form complexes with Y. The passivating agent can also include a functional group such as biotin to provide surfaces with a desired functionality. The passivated surfaces exhibit minimal binding to bio-molecules and can be used in single-molecule detection schemes.

Abstract: Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.

Abstract: Intermediates and methods for forming activated metal complexes bound to surfaces on oxide layers, immobilizing beads to the modified surface and articles produced thereby are described. Hydroxyl groups on the oxide surfaces are reacted with a metal reagent complex of the formula Y(L-Pol)m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a methoxyethanol, a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a plurality of functional groups that are reactive with or that form complexes with Y.

Abstract: Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.