US 11,718,870 B2
Tunneling junctions for sequencing
Yann Astier, Livermore, CA (US); Juraj Topolancik, Redwood City, CA (US); Hannes Kuchelmeister, Munich (DE); Frank Bergmann, Iffeldorf (DE); Dieter Heindl, Munich (DE); and Nikolaus Klaus-Peter Stengele, Pleiskirchen (DE)
Assigned to Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
Filed by Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
Filed on Jun. 19, 2019, as Appl. No. 16/445,635.
Claims priority of provisional application 62/688,257, filed on Jun. 21, 2018.
Prior Publication US 2019/0390267 A1, Dec. 26, 2019
Int. Cl. C12Q 1/6869 (2018.01); C12Q 1/6876 (2018.01); G01N 15/10 (2006.01)
CPC C12Q 1/6869 (2013.01) [C12Q 1/6876 (2013.01); G01N 15/1031 (2013.01); G01N 15/1056 (2013.01); C12Q 2525/117 (2013.01); C12Q 2535/122 (2013.01); C12Q 2563/113 (2013.01); C12Q 2563/116 (2013.01); C12Q 2563/155 (2013.01); C12Q 2565/607 (2013.01)] 43 Claims
 
1. A method of determining a sequence of a nucleic acid using a sequencing device, the method comprising:
adding a set of nucleotides to the sequencing device, wherein:
each nucleotide of the set of nucleotides is attached to a label compound comprising a moiety,
the sequencing device comprises a tunneling junction, and
the tunneling junction comprises a first conductor and a second conductor separated by an insulating layer, wherein:
the thickness of the insulating layer separating the first conductor and the second conductor is greater than the size of each moiety of each nucleotide of the set of nucleotides,
the first conductor comprises a first ferromagnetic material, and
the second conductor comprises a second ferromagnetic material;
elongating a nascent strand using a polymerase attached to the tunneling junction and connected to a template parent strand to be sequenced, wherein the elongating includes the polymerase incorporating a first nucleotide of the set of nucleotides into the nascent strand via hybridization to the template parent strand;
measuring a value of an electrical characteristic or a magnetic characteristic through the first conductor, a first moiety of a first label compound attached to the first nucleotide, and the second conductor; and
detecting the first nucleotide as being hybridized to the template parent strand using the value of the electrical characteristic or the magnetic characteristic.