US 12,204,142 B2
Arrays of integrated analytical devices and methods for production
Ravi Saxena, Millbrae, CA (US); Michael Tzu Ru, San Mateo, CA (US); Takashi Whitney Orimoto, Sunnyvale, CA (US); Annette Grot, Cupertino, CA (US); Mathieu Foquet, Newark, CA (US); and Hou-Pu Chou, Sunnyvale, CA (US)
Assigned to PACIFIC BIOSCIENCES OF CALIFORNIA, INC., Menlo Park, CA (US)
Filed by Pacific Biosciences of California, Inc., Menlo Park, CA (US)
Filed on Sep. 4, 2020, as Appl. No. 17/012,966.
Application 17/012,966 is a continuation of application No. 16/430,134, filed on Jun. 3, 2019, granted, now 10,768,362.
Application 16/430,134 is a continuation of application No. 15/953,792, filed on Apr. 16, 2018, granted, now 10,310,178, issued on Jun. 4, 2019.
Application 15/953,792 is a continuation of application No. 15/600,668, filed on May 19, 2017, granted, now 9,946,017, issued on Apr. 17, 2018.
Application 15/600,668 is a continuation of application No. 15/158,756, filed on May 19, 2016, granted, now 9,658,161, issued on May 23, 2017.
Application 15/158,756 is a continuation of application No. 13/920,037, filed on Jun. 17, 2013, granted, now 9,372,308, issued on Jun. 21, 2016.
Claims priority of provisional application 61/660,776, filed on Jun. 17, 2012.
Prior Publication US 2021/0124115 A1, Apr. 29, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. G02B 6/12 (2006.01); B29D 11/00 (2006.01); B29D 17/00 (2006.01); C12Q 1/6869 (2018.01); G01N 21/64 (2006.01); G02B 5/18 (2006.01); G02B 6/02 (2006.01); G02B 6/124 (2006.01); G02B 6/136 (2006.01); B29L 11/00 (2006.01); G01N 21/77 (2006.01)
CPC G02B 6/12004 (2013.01) [B29D 11/0073 (2013.01); B29D 17/007 (2013.01); C12Q 1/6869 (2013.01); G01N 21/6454 (2013.01); G01N 21/648 (2013.01); G02B 5/189 (2013.01); G02B 6/02123 (2013.01); G02B 6/12002 (2013.01); G02B 6/124 (2013.01); G02B 6/136 (2013.01); B29L 2011/005 (2013.01); B29L 2011/0066 (2013.01); B29L 2011/0075 (2013.01); G01N 2021/6467 (2013.01); G01N 2021/6471 (2013.01); G01N 2021/6478 (2013.01); G01N 2021/7713 (2013.01); G01N 2201/0873 (2013.01); G02B 2006/12038 (2013.01); G02B 2006/12109 (2013.01)] 19 Claims
 
1. A method of nucleic acid sequencing comprising the steps of:
providing an array of integrated analytical devices, wherein at least one integrated analytical device in the array of integrated analytical devices comprises a nucleic acid template/polymerase primer complex immobilized within an optically confined region, a plurality of fluorescently labeled nucleotides in fluid contact with the nucleic acid template/polymerase primer complex, and a single detector element optically coupled to the optically confined region, wherein the optically confined region is in a nanowell that is illuminated by an optical excitation waveguide, and wherein at least two fluorescently labeled nucleotides of the plurality of fluorescently labeled nucleotides emit fluorescence of different intensities at an emission wavelength;
illuminating the optically confined region with an excitation wavelength;
measuring a fluorescent signal from the optically confined region at the single detector element; and
identifying at least one of the at least two fluorescently labeled nucleotides by an intensity of the measured fluorescent signal at the emission wavelength.