Granted Patent
B2
US 12,655,467 · App. 18/611,338 · Granted Jun 16, 2026
Methods for nucleic acid sequencing
Inventors:
Jonathan M. Rothberg (Miami Beach, FL); Jeremy Lackey (Foster City, CA); Brian Reed (Madison, CT); Xinghua Shi (Madison, CT); Haidong Huang (Madison, CT)
Assignee:
Quantum-Si Incorporated
C12Q1/6818C12Q1/6869C12Q1/6874G01N21/6408G01N21/6428G01N21/6454G01N21/648G01N2021/6419G01N2021/6421G01N2021/6439G01N2201/06113G01N2201/0697
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Abstract
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.
Claims (17)
1 . A method of identifying a single molecule, the method comprising:
exposing the single molecule to a plurality of luminescently labeled molecules;
determining at least a luminescent lifetime of one or more luminescently labeled molecules during an interaction of at least one of the plurality of luminescently labeled molecules with the single molecule or with a complex comprising the single molecule; and
identifying the single molecule based at least in part on the luminescent lifetime of the one or more luminescently labeled molecules;
wherein the single molecule is a protein or a peptide.
2 . The method of claim 1 , further comprising directing a series of pulses of one or more excitation energies towards a vicinity of the single molecule.
3 . The method of claim 2 , wherein each of the series of pulses comprises a single excitation energy.
4 . The method of claim 2 , wherein a first portion of the series of pulses comprises a first excitation energy and a second portion of the plurality of pulses comprises a second excitation energy.
5 . The method of claim 2 , wherein the series of pulses is delivered at an average frequency of between about 10 MHz and about 100 MHz or between about 100 MHz and about 1 GHz.
6 . The method of claim 2 , wherein the series of pulses is delivered at an average frequency of between about 50 MHz and about 200 MHz.
7 . The method of claim 1 , further comprising detecting a plurality of emitted photons from the one or more luminescently labeled molecules.
8 . The method of claim 1 , wherein determining at least a luminescent lifetime further comprises determining a luminescent intensity or a luminescent wavelength of one or more luminescently labeled molecules, and wherein identifying the single molecule based at least in part on the luminescent lifetime further comprises identifying the single molecule based on the luminescent intensity or the luminescent wavelength of the one or more luminescently labeled molecules.
9 . The method of claim 1 , further comprising recording for each of a plurality of emitted photons from the one or more luminescently labeled molecules a time duration between detection of the emitted photon and a prior delivered excitation energy.
10 . The method of claim 1 , wherein the single molecule is immobilized on a solid support.
11 . The method of claim 10 , wherein the solid support comprises a bottom surface of a sample well.
12 . The method of claim 8 , wherein the luminescent lifetime is determined by measuring a distribution of emission events over time, and wherein the luminescent intensity is determined by measuring an amount of emission events across the distribution.
13 . The method of claim 1 , wherein the at least one of the plurality of luminescently labeled molecules is a series of luminescently labeled amino acid monomers.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 26, 2024
From: ROTHBERG, JONATHAN M.; LACKEY, JEREMY; REED, BRIAN; SHI, XINGHUA; HUANG, HAIDONG
To: QUANTUM-SI INCORPORATED
Reel/Frame 068708/0679 →
Continuity (10)
Provisional Application
62164464
· May 20, 2015
Provisional Application
62164482
· May 20, 2015
Provisional Application
62164506
· May 20, 2015
Provisional Application
62164485
· May 20, 2015
Provisional Application
62035258
· Aug 8, 2014
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