Provided are methods and systems for reducing the time needed for sequencing nucleic acids. The approach relies on detecting formation of nucleotide-specific ternary complexes comprising a polymerase (e.g., a DNA polymerizing enzyme), a primed template nucleic acid molecule, and a nucleotide complementary to the templated base of the primed template nucleic acid. The methods and systems facilitate determination of the next correct nucleotide, as well as the subsequent next correct nucleotide from a cycle of examining four different nucleotides without requiring chemical incorporation of any nucleotide into the primer.

Provided are methods and systems for reducing the time needed for sequencing nucleic acids. The approach relies on detecting formation of nucleotide-specific ternary complexes comprising a polymerase (e.g., a DNA polymerizing enzyme), a primed template nucleic acid molecule, and a nucleotide complementary to the templated base of the primed template nucleic acid. The methods and systems facilitate determination of the next correct nucleotide, as well as the subsequent next correct nucleotide from a cycle of examining four different nucleotides without requiring chemical incorporation of any nucleotide into the primer.

A method for determining the sequence of a polynucleotide is described. The method comprises detecting in a sequencing reaction the incorporation of a first, second, third, or fourth nucleotide using first and second excitation wavelengths and a photodetector having a detection window comprising a range of wavelengths.

A method for determining the sequence of a polynucleotide is described. The method comprises detecting in a sequencing reaction the incorporation of a first, second, third, or fourth nucleotide using first and second excitation wavelengths and a photodetector having a detection window comprising a range of wavelengths.

Embodiments of the present disclosure relate to methods, kits and compositions for two-channel nuclei acid sequencing using blue and violet light excitation (e.g., lasers at 450-460 nm and 400-405 nm respectively). In particular, the nucleotides may be directly labeled with a blue dye, a violet dye, or both a blue dye and a violet dye. Alternatively, one or more nucleotides for incorporation may be unlabeled and affinity reagents containing a blue dye, a violet dye, or both a blue dye and a violet dye may be used to bind specifically to each type of nucleotides incorporated.

Embodiments of the present disclosure relate to methods, kits and compositions for two-channel nuclei acid sequencing using blue and violet light excitation (e.g., lasers at 450-460 nm and 400-405 nm respectively). In particular, the nucleotides may be directly labeled with a blue dye, a violet dye, or both a blue dye and a violet dye. Alternatively, one or more nucleotides for incorporation may be unlabeled and affinity reagents containing a blue dye, a violet dye, or both a blue dye and a violet dye may be used to bind specifically to each type of nucleotides incorporated.

The present disclosure provides techniques for improving the rate and efficiency of charge transfer within an integrated circuit configured to receive incident photons. Some aspects of the present disclosure relate to integrated circuits that are configured to induce one or more intrinsic electric fields that increase the rate and efficiency of charge transfer within the integrated circuits. Some aspects of the present disclosure relate to integrated circuits configured to induce a charge carrier depletion in the photodetection region(s) of the integrated circuits. In some embodiments, the charge carrier depletion in the photodetection region(s) may be intrinsic, in that the depletion is induced even in the absence of external electric fields applied to the integrated circuit. Some aspects of the present disclosure relate to processes for operating and/or manufacturing integrated devices as described herein.

The present disclosure provides techniques for improving the rate and efficiency of charge transfer within an integrated circuit configured to receive incident photons. Some aspects of the present disclosure relate to integrated circuits that are configured to induce one or more intrinsic electric fields that increase the rate and efficiency of charge transfer within the integrated circuits. Some aspects of the present disclosure relate to integrated circuits configured to induce a charge carrier depletion in the photodetection region(s) of the integrated circuits. In some embodiments, the charge carrier depletion in the photodetection region(s) may be intrinsic, in that the depletion is induced even in the absence of external electric fields applied to the integrated circuit. Some aspects of the present disclosure relate to processes for operating and/or manufacturing integrated devices as described herein.

Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.

Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.