IP Library › Granted Patent US 12,252,745
Granted Patent B2
US 12,252,745 · App. 18/759,368 · Granted Mar 18, 2025

Detection and digital quantitation of multiple targets

Inventors: Eleen Yee Lam Shum (San Carlos, CA); Hei Mun Christina Fan (Palo Alto, CA); Stephen P. A. Fodor (Palo Alto, CA); Haeun Grace Lee (Palo Alto, CA)
Assignee: ENUMERIX, INC.
C12Q1/6876G01N21/6428G01N33/542C12Q2600/156C12Q2600/16G01N2021/6439
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Quick Facts
Patent No.
US 12,252,745
App. No.
18/759,368
Filed
Jun 28, 2024
Granted
Mar 18, 2025
Kind
B2
Art Unit
1683
USPC
435/6.11
Abstract

This disclosure provides for devices, methods, and systems for performing a non-invasive prenatal testing (NIPT) digital assay upon generating at least a large number of counts per chromosome for a set of chromosomes present in a sample, where performing the NIPT digital assay can include: distributing nucleic acids of the sample and materials for an amplification reaction across a plurality of partitions; amplifying the nucleic acids with the materials, within the plurality of partitions; and generating counts per chromosome upon detecting signals from the plurality of partitions. The inventions enable processing of samples for NIPT digital analyses and/or other digital analyses involving other loci of interest, with unprecedented partitioning, reaction, readout, and analytical performance.

Claims (23)

1. A method for performing a non-invasive prenatal testing (NIPT) digital assay, the method comprising:

(a) obtaining a nucleic acid sample comprising a plurality of target nucleic acid molecules, wherein said plurality of target nucleic acid molecules comprises sequences associated with a plurality of chromosomes;

(b) generating a plurality of partitions, wherein said plurality of partitions comprises at least 9 million partitions, and wherein each partition of said plurality of partitions comprises:

(i) materials for an amplification reaction; and

(ii) less than or equal to one target nucleic acid molecule of said plurality of target nucleic acid molecules, wherein each target nucleic acid molecule comprises a sequence corresponding to a chromosome;

(c) amplifying said plurality of target nucleic acid molecules within said plurality of partitions; and

(d) detecting signals from said plurality of partitions, thereby generating counts corresponding to said plurality of chromosomes, wherein at least 150,000 counts are generated for each chromosome of said plurality of chromosomes.

2. The method of claim 1 , wherein less than 6% of nucleic acid molecules of said nucleic acid sample are of fetal origin.

3. The method of claim 1 , wherein said plurality of chromosomes comprises chromosome 21.

4. The method of claim 1 , wherein said plurality of chromosomes comprises chromosome 18.

5. The method of claim 1 , wherein said plurality of chromosomes comprises chromosome 13.

6. The method of claim 1 , wherein said materials for an amplification reaction comprise primers configured to amplify at least 70 loci of a chromosome of said plurality of chromosomes.

7. The method of claim 1 , wherein said plurality of target nucleic acid molecules comprise at least 210 different target loci.

8. The method of claim 1 , wherein said nucleic acid sample comprises nucleic acid molecules extracted from plasma.

9. The method of claim 1 , wherein less than 15% of partitions of said plurality of partitions comprise one target nucleic acid molecule.

10. The method of claim 9 , wherein less than 10% of partitions of said plurality of partitions comprise one target nucleic acid molecule.

11. The method of claim 1 , wherein (b) comprises centrifuging said nucleic acid sample through a substrate having a distribution of holes.

12. The method of claim 1 , wherein said plurality of partitions is contained within a collecting container and wherein (d) comprises scanning a set of cross sections of a collecting container containing the plurality of partitions.

13. The method of claim 1 , wherein (c) and (d) is completed within a duration of no more than 3 hours.

14. The method of claim 1 , wherein said plurality of partitions comprises at least 25 million partitions.

15. The method of claim 1 , wherein (d) comprises generating at least 200,000 counts per chromosome for each of the plurality of chromosomes.

16. The method of claim 1 , wherein said plurality of chromosomes comprises chromosome X.

17. The method of claim 1 , wherein said plurality of chromosomes comprises chromosome Y.

Assignments (1)
CHANGE OF NAME Recorded Apr 4, 2025
From: ENUMERIX, INC.
To: COUNTABLE LABS, INC.
Reel/Frame 070746/0051 →
Continuity (4)
Continuation In Part 17939774 · Sep 7, 2022
Continuation PCTUS2022042385 · Sep 1, 2022
Provisional Application 63240164 · Sep 2, 2021
Related Publication 20240352523A1 · Oct 24, 2024
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