	US 12,226,747 B2
	Methods and systems for monitoring solid-phase stepwise oligonucleotide synthesis
Paul Dentinger, Sunol, CA (US)
Assigned to CENTRILLION TECHNOLOGY HOLDINGS CORPORATION, Grand Cayman (KY)
Appl. No. 17/058,287
Filed by CENTRILLION TECHNOLOGY HOLDINGS CORPORATION, Grand Cayman (KY)
PCT Filed May 29, 2019, PCT No. PCT/US2019/034471 § 371(c)(1), (2) Date Nov. 24, 2020, PCT Pub. No. WO2019/232101, PCT Pub. Date Dec. 5, 2019.
Claims priority of provisional application 62/677,187, filed on May 29, 2018.
Prior Publication US 2021/0197164 A1, Jul. 1, 2021
Int. Cl. B01J 19/00 (2006.01); G01N 21/21 (2006.01)

CPC B01J 19/0046 (2013.01) [G01N 21/211 (2013.01); B01J 2219/00529 (2013.01); B01J 2219/00608 (2013.01); B01J 2219/00612 (2013.01); B01J 2219/00659 (2013.01); B01J 2219/00675 (2013.01); B01J 2219/00693 (2013.01); B01J 2219/00702 (2013.01); B01J 2219/00722 (2013.01)]

17 Claims

1. A method of monitoring a solid-phase reaction on a surface of a substrate, comprising:

(a) taking a first measurement of a property of the surface at a plurality of positions on the surface before a first reaction on the surface;

(b) taking a second measurement of the property of the surface at the plurality of positions on the surface after the first reaction on the surface; and

(c) determining a first quality of the first reaction on the surface based on the first measurement and the second measurement,

wherein the first measurement and the second measurement are measured by an ellipsometer, and

wherein the first quality of the first reaction is (1) yield of the first reaction at each of the plurality of the positions, (2) uniformity of the first reaction at each of the plurality of the positions, (3) whether the first reaction provides the correct product at each of the plurality of the positions, or (4) whether the first reaction is conducted at each of the plurality of the positions.