Quantum-Si Incorporated

Described herein are techniques for detecting amino acid variants in peptides using data from a sequencing device. Sequencing data is generated from traces of light pulses output by the sequencing device from detecting light emissions by fluorescently tagged N-terminal amino acid (NAA) recognizers during sequencing of at least one peptide. The sequencing data comprising light pulse durations and inter-pulse durations between successive light pulses. The techniques generate read(s) each comprising a sequence of recognition segments indicating time periods in which fluorescently tagged NAA recognizers were binding to particular NAAs of the peptide, assign fluorescently tagged NAA recognizers to recognition segments, align read(s) to reference peptide sequences to obtain peptide alignments, and detect amino acid variants using the peptide alignments.

Methods of sequencing molecules based on luminescence lifetimes and/or intensities are provided. In some aspects, methods of sequencing nucleic acids involve determining the luminescence lifetimes, and optionally luminescence intensities, of a series of luminescently labeled nucleotides incorporated during a nucleic acid sequencing reaction.

Aspects of the present disclosure provide improved fluorescence imaging techniques suitable for fluorescence-based analysis (e.g., sequencing) of an excited sample. Some aspects relate to directing an imaging aperture of a fluorescence imaging device towards a sample well region and capturing an image of the sample well region. Some aspects relate to selecting a sample well region and capturing an image of the selected sample well region. Some aspects relate to, during at least a portion of performing a controlled cleavage of a terminal amino acid in a first sample well, capturing a fluorescence image of a second sample well. Some aspects relate to setting a duration of imaging by and/or a location of an imaging aperture of a fluorescence imaging device. In some embodiments, aspects of the present disclosure provide for faster, less expensive, and/or greater control over fluorescence imaging and analysis of a sample.

Compositions useful for the detection of single molecules in a sample are provided. In some aspects, the disclosure provides a nucleic acid connected to a nucleotide and two or more luminescent labels. In some embodiments, the nucleic acids described herein comprise one or more structural features that provide enhanced fluorescence intensity. In some aspects, methods of sequencing using the labeled nucleotides of the disclosure are provided.

Aspects of the application provide methods of identifying and sequencing proteins, polypeptides, and amino acids, and compositions useful for the same. In some aspects, the application provides methods of obtaining data during a degradation process of a polypeptide, and outputting a sequence representative of the polypeptide. In some aspects, the application provides amino acid recognition molecules comprising a shielding element that enhances photostability in polypeptide sequencing reactions.

Compositions useful for the detection of single molecules in a sample are provided. In some aspects, the disclosure provides a nucleotide connected to a nucleic acid comprising a FRET label comprising at least three luminescent molecules. In some embodiments, the nucleic acids described herein comprise one or more structural features that provide enhanced fluorescence intensity. In some aspects, methods of sequencing using the labeled nucleotides of the disclosure are provided.

Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region and a drain region electrically coupled to the photodetection region, and the photodetection region may be configured to induce an intrinsic electric field in a direction from the photodetection region to the drain region(s). In some embodiments, a charge storage region and the drain region may be positioned on a same side of the photodetection region. In some embodiments, at least one drain layer may be configured to receive incident photons and/or charge carriers via the photodetection region. In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in the plurality of pixels.

Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.

The present disclosure relates to methods and compositions for protein identification via peptide barcodes.

Provided herein are compounds of Formulae (I), (II), (III), and (III-d). Also provided herein are methods of preparation of Formulae (I), (II), and (III-d). Further provided herein are methods of functionalizing or sequencing a peptide by reaction of compounds of Formula (III-d) with peptidases.