US 12,234,502 B2
Oligonucleotide assembly using pH based electrode controlled hybridization
Yuan-Jyue Chen, Seattle, WA (US); Bichlien Hoang Nguyen, Seattle, WA (US); Karin Strauss, Seattle, WA (US); and Jake Allen Smith, Seattle, WA (US)
Assigned to Microsoft Technology Licensing, LLC, Redmond, WA (US)
Filed by MICROSOFT TECHNOLOGY LICENSING, LLC, Redmond, WA (US)
Filed on Jun. 3, 2021, as Appl. No. 17/338,012.
Prior Publication US 2022/0389483 A1, Dec. 8, 2022
Int. Cl. C12Q 1/6809 (2018.01); C12Q 1/6837 (2018.01); G01N 15/1433 (2024.01)
CPC C12Q 1/6809 (2013.01) [C12Q 1/6837 (2013.01); G01N 15/1433 (2024.01)] 20 Claims
 
1. A method of selectively assembling oligonucleotides on a microelectrode array coated with a plurality of anchor sequences, the method comprising:
introducing multiple copies of a first oligonucleotide complex having two sticky ends and encoding a first arbitrary value into a solution in a reaction chamber containing the microelectrode array;
incubating the multiple copies of the first oligonucleotide complex with the microelectrode array so that the multiple copies of the first oligonucleotide complex hybridize to the anchor sequences;
inhibiting hybridization of a first subset of the multiple copies of the first oligonucleotide complex through changing local pH by activating a first subset of electrodes on the microelectrode array such that double-stranded oligonucleotides de-hybridize at the first subset of electrodes but not at other locations on the surface of the microelectrode array; and
closing nicks between ones of the multiple copies of the first oligonucleotide complex that remain hybridized to the anchor sequences thereby forming assembled oligonucleotides.