Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

The present disclosure provides a composition with ultra sensitivity for detection of nucleic acid and the method of use thereof. The composition comprises a target probe capable of hybridizing to a target nucleic acid, at least one first bridge probe, at least one second bridge probe, and a label probe. The target probe includes a pre-bridge region having a first tail nucleotide sequence. The first bridge probe includes sequentially a first head region having a first head nucleotide sequence, a first gap region having a gap nucleotide sequence, and a first tail region having the first tail nucleotide sequence. The second bridge probe includes sequentially a second head region having a second head nucleotide sequence complementary to the first head nucleotide sequence, a second gap region having the gap nucleotide sequence, and a second tail region having a second tail nucleotide sequence complementary to the first tail nucleotide sequence. The label probe is capable of hybridizing to the first and the second gap nucleotide region.

The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.

Methods, systems and programing for substance detection with a magnetic sensor are presented. In one example, a magnetic sensor having one or more layers is formed on a base for sensing a magnetic field created by magnetic particles present in proximity to the magnetic sensor. A first end of each of a first set of strands is immobilized with respect to the magnetic sensor. A magnetic particle is attached to a second end of each of the first set of strands so that when a material containing a substance is in contact with the base, the substance causes at least some of the first set of strands to break resulting in that the magnetic particle attached to the second end of each of the at least some of the first set of strands is no longer in proximity to the magnetic sensor.

This disclosure relates to a biosensor for detecting a target analyte in a sample comprising: a double-stranded oligonucleotide comprising an overhang on a first strand of the oligonucleotide, and a second strand of the oligonucleotide that is a reporter moiety comprising a detectable label; a first detection probe comprising a recognition moiety and a junction forming moiety, wherein the junction forming moiety comprises a first portion capable of binding by complementarity to the overhang of the first strand of the double-stranded oligonucleotide; a second detection probe comprising a recognition moiety and a junction forming moiety, wherein the junction forming moiety comprises a first portion capable of binding by complementarity to an internal segment of the first strand of the double-stranded oligonucleotide; and a capture probe functionalized on an electrode, wherein the capture probe comprises an immobilized strand attached to the electrode. Methods and uses thereof are also disclosed herein.

This disclosure relates to a biosensor for detecting a target analyte in a sample comprising: a double-stranded oligonucleotide comprising an overhang on a first strand of the oligonucleotide, and a second strand of the oligonucleotide that is a reporter moiety comprising a detectable label; a first detection probe comprising a recognition moiety and a junction forming moiety, wherein the junction forming moiety comprises a first portion capable of binding by complementarity to the overhang of the first strand of the double-stranded oligonucleotide; a second detection probe comprising a recognition moiety and a junction forming moiety, wherein the junction forming moiety comprises a first portion capable of binding by complementarity to an internal segment of the first strand of the double-stranded oligonucleotide; and a capture probe functionalized on an electrode, wherein the capture probe comprises an immobilized strand attached to the electrode. Methods and uses thereof are also disclosed herein.

Provided herein are reagents, compositions, and methods for sequencing nucleic acids. Among the reagents disclosed are nucleotides labeled with cleavable linkers. Certain linkers are configured to undergo immolation reactions following cleavage, which can generate scars with enhanced properties for nucleic acid sequencing and synthesis. The present disclosure also provides reagents, compositions, and methods for capping scars generated through linker cleavage, which can alter scar properties, and in some cases can increase the rate and accuracy of nucleotide incorporations during polymerization.