IP Library › Granted Patent US 11,359,244
Granted Patent B2
US 11,359,244 · App. 16/887,679 · Granted Jun 14, 2022

Characterization of molecules in nanofluidics

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Quick Facts
Patent No.
US 11,359,244
App. No.
16/887,679
Filed
May 29, 2020
Granted
Jun 14, 2022
Kind
B2
Art Unit
1634
USPC
435/6.1
Abstract

Methods are provided for detecting and quantitating molecules using fluidics. In preferred embodiments, the methods comprise analyzing blood to detect the presence of circulating DNA or cells from a fetus or tumor.

Claims (13)

1. A method of characterizing a sample comprising polynucleotide sequences, the method comprising:

labeling a plurality of sequence-specific locations on a polynucleotide sequence of a sample molecule of less than 550 nucleotides in length;

linearizing at least a portion of the sample molecule in a fluidic nanochannel, wherein the fluidic nanochannel has a length of at least 10 nm and a cross-sectional diameter of less than 5000 nm;

quantifying a signal from the labels on the sample molecule;

comparing a quantity of the signal from the sample molecule to a quantity of signal from a reference molecule of less than 550 nucleotides in length, so as to compare coverage depth of polynucleotide sequences of the sample molecule to coverage depth of polynucleotide sequences of the reference molecule; and

determining a presence or absence of a genetic abnormality in the sample molecule when the coverage depth of the sample molecule differs from the coverage depth of the reference molecule.

2. The method of claim 1 , wherein the sample comprises circulating fetal cells.

3. The method of claim 1 , further comprising generating a histogram distribution to reflect coverage depth for the sample.

4. The method of claim 1 , wherein the sample molecule and the reference molecule are from different tissues of the same organism.

5. The method of claim 1 , wherein the sample molecule is derived from maternal blood, and wherein the reference molecule is derived from a maternal sample other than blood.

6. The method of claim 1 , wherein the quantity of signal from the reference molecule comprises an electronically or optically stored value or set of values.

7. The method of claim 1 , wherein the genetic abnormality comprises at least one of a translocation, addition, amplification, transversion, inversion, aneuploidy, polyploidy, monosomy, trisomy, trisomy 21, trisomy 13, trisomy 14, trisomy 15, trisomy 16, trisomy 18, trisomy 22, triploidy, tetraploidy, and sex chromosome aneuploidy.

8. The method of claim 1 , wherein the fluidic nanochannel has a length of at least 10 nm and a cross-sectional diameter of less than 1000 nm.