Patents by Inventor Billy Tsz Cheong Lau
Billy Tsz Cheong Lau has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11661597Abstract: A population of nucleic acid adaptors is provided. In some embodiments, the population contains at least 50,000 different molecular barcode sequences, where the barcode sequences are double-stranded and at least 90% of the barcode sequences have an edit distance of at least 2. In certain cases, the adaptor may have an end in which the top and bottom strands are not complementary (i.e., may be in the form of a Y-adaptor). In some embodiments and depending on the how the adaptor is going to be employed, the other end of the adaptor may have a ligatable end or may be a transposon end sequence.Type: GrantFiled: April 13, 2016Date of Patent: May 30, 2023Assignee: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITYInventors: Billy Tsz Cheong Lau, Hanlee P. Ji
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Publication number: 20230032847Abstract: Provided herein is a method for sample analysis. In some embodiments, the method may involve: (a) incubating a nucleic acid sample with a terminal transferase and a cyclooctene-functionalized nucleotide to produced cyclooctene-functionalized nucleic acid molecules; (b) tethering the cyclooctene-functionalized nucleic acid molecules to a tetrazine-functionalized support via an Alder cycloaddition reaction; (c) performing at least two separate primer extension reactions using the tethered nucleic acid molecules as a template to produce multiple distinct sets of primer extension products; (d) separately analyzing the sets of primer extension products using different methods to produce multiple data sets; and (e) integrating the data sets.Type: ApplicationFiled: January 4, 2021Publication date: February 2, 2023Inventors: Hanlee P. Ji, Billy Tsz Cheong Lau
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Publication number: 20210048426Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.Type: ApplicationFiled: April 2, 2020Publication date: February 18, 2021Applicant: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Kee-Hyun PAIK, Henrik H.J. PERSSON, Billy Tsz Cheong LAU, Hanlee P. JI, Robert W. DUTTON, Yang LIU, Ronald W. DAVIS
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Publication number: 20200017902Abstract: Methods and reagents for performing digital PCR for detection and quantification of mutant alleles and copy number variation are disclosed. In particular, the invention relates to methods using a nonspecific DNA-binding dye, which produces a fluorescent signal that increases in intensity according to the number of base-pairs present in the PCR amplicon product. The method utilizes mutant-specific and wild-type-specific primers having non-complementary “tail” sequences of different lengths. Accordingly, the amplicons for the wild-type and mutant alleles differ in length and can be distinguished based on the difference in the intensities of their fluorescent signals. The methods of the invention can be used to detect rare genetic events, including single nucleotide mutations, alterations of copy number, and deletions or insertions of nucleotides.Type: ApplicationFiled: September 18, 2019Publication date: January 16, 2020Inventors: Hanlee P. Ji, Billy Tsz Cheong Lau, Laura Miotke
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Patent number: 10465238Abstract: Methods and reagents for performing digital PCR for detection and quantification of mutant alleles and copy number variation are disclosed. In particular, the invention relates to methods using a nonspecific DNA-binding dye, which produces a fluorescent signal that increases in intensity according to the number of base-pairs present in the PCR amplicon product. The method utilizes mutant-specific and wild-type-specific primers having non-complementary “tail” sequences of different lengths. Accordingly, the amplicons for the wild-type and mutant alleles differ in length and can be distinguished based on the difference in the intensities of their fluorescent signals. The methods of the invention can be used to detect rare genetic events, including single nucleotide mutations, alterations of copy number, and deletions or insertions of nucleotides.Type: GrantFiled: December 16, 2014Date of Patent: November 5, 2019Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Hanlee P. Ji, Billy Tsz Cheong Lau, Laura Miotke
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Patent number: 10465241Abstract: A method for analyzing short tandem repeats (STRs) is described herein. In some embodiments, the method comprises: separately digesting two portions of a genomic sample at sites that are upstream and downstream of an STR; fragmenting those products; ligating adaptors to the fragmentation products; selectively amplifying part of the top strand but not the bottom strand of the ligation products derived from the first portion, and part of the bottom strand but not the top strand of the ligation products derived from the second portion; sequencing at least some of the amplification products to produce a plurality of top strand reads and a plurality of bottom strand reads; and counting the number of STR repeats in a sequence read. A kit for performing the method is also provided.Type: GrantFiled: June 8, 2016Date of Patent: November 5, 2019Assignee: THE BOARD OF TRUSTEES OF THE LELEAND STANFORD JUNIOR UNIVERSITYInventors: Giwon Shin, Billy Tsz Cheong Lau, HoJoon Lee, Hanlee P. Ji
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Publication number: 20180100145Abstract: A population of nucleic acid adaptors is provided. In some embodiments, the population contains at least 50,000 different molecular barcode sequences, where the barcode sequences are double-stranded and at least 90% of the barcode sequences have an edit distance of at least 2. In certain cases, the adaptor may have an end in which the top and bottom strands are not complementary (i.e., may be in the form of a Y-adaptor). In some embodiments and depending on the how the adaptor is going to be employed, the other end of the adaptor may have a ligatable end or may be a transposon end sequence.Type: ApplicationFiled: April 13, 2016Publication date: April 12, 2018Inventors: Billy Tsz Cheong Lau, Hanlee P. Ji
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Patent number: 9689027Abstract: Provided herein is a method for sample analysis. In some embodiments, the method may involve: a) enzymatically attaching a reactive group to nucleic acid molecules in a sample; b) covalently reacting the reactive group with surface exposed reactive sites on a porous support, thereby covalently tethering the nucleic acid molecules to the porous support; c) performing a primer extension reaction using the tethered nucleic acid molecules as a template to produce primer extension products; and d) eluting the primer extension products from the porous support, while leaving the tethered nucleic acid molecules tethered to the porous support.Type: GrantFiled: November 5, 2014Date of Patent: June 27, 2017Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Anna McGinty Cushing, Billy Tsz Cheong Lau, Hanlee P. Ji
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Publication number: 20170097332Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.Type: ApplicationFiled: December 16, 2016Publication date: April 6, 2017Applicant: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Kee-Hyun PAIK, Henrik H.J. PERSSON, Billy Tsz Cheong LAU, Hanlee P. JI, Robert W. DUTTON, Yang LIU, Ronald W. DAVIS
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Publication number: 20160362751Abstract: A method for analyzing short tandem repeats (STRs) is described herein. In some embodiments, the method comprises: separately digesting two portions of a genomic sample at sites that are upstream and downstream of an STR; fragmenting those products; ligating adaptors to the fragmentation products; selectively amplifying part of the top strand but not the bottom strand of the ligation products derived from the first portion, and part of the bottom strand but not the top strand of the ligation products derived from the second portion; sequencing at least some of the amplification products to produce a plurality of top strand reads and a plurality of bottom strand reads; and counting the number of STR repeats in a sequence read. A kit for performing the method is also provided.Type: ApplicationFiled: June 8, 2016Publication date: December 15, 2016Inventors: Giwon Shin, Billy Tsz Cheong Lau, HoJoon Lee, Hanlee P. Ji
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Publication number: 20160304936Abstract: Methods and reagents for performing digital PCR for detection and quantification of mutant alleles and copy number variation are disclosed. In particular, the invention relates to methods using a nonspecific DNA-binding dye, which produces a fluorescent signal that increases in intensity according to the number of base-pairs present in the PCR amplicon product. The method utilizes mutant-specific and wild-type-specific primers having non-complementary “tail” sequences of different lengths. Accordingly, the amplicons for the wild-type and mutant alleles differ in length and can be distinguished based on the difference in the intensities of their fluorescent signals. The methods of the invention can be used to detect rare genetic events, including single nucleotide mutations, alterations of copy number, and deletions or insertions of nucleotides.Type: ApplicationFiled: December 16, 2014Publication date: October 20, 2016Inventors: Hanlee P. JI, Billy Tsz Cheong LAU, Laura MIOTKE
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Publication number: 20160003798Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.Type: ApplicationFiled: June 19, 2015Publication date: January 7, 2016Inventors: Kee-Hyun Paik, Henrik H.J. Persson, Billy Tsz Cheong Lau, Hanlee P. Ji, Robert W. Dutton, Yang Liu, Ronald W. Davis
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Publication number: 20150140553Abstract: Provided herein is a method for sample analysis. In some embodiments, the method may involve: a) enzymatically attaching a reactive group to nucleic acid molecules in a sample; b) covalently reacting the reactive group with surface exposed reactive sites on a porous support, thereby covalently tethering the nucleic acid molecules to the porous support; c) performing a primer extension reaction using the tethered nucleic acid molecules as a template to produce primer extension products; and d) eluting the primer extension products from the porous support, while leaving the tethered nucleic acid molecules tethered to the porous support.Type: ApplicationFiled: November 5, 2014Publication date: May 21, 2015Inventors: Anna McGinty Cushing, Billy Tsz Cheong Lau, Hanlee P. Ji