Detection of nucleic acid sequences using deterministic lateral displacement arrays

Patent metadata

Field	Value
Publication number	US-11149298-B2
Application number	US-201816007347-A
Country	US
Kind code	B2
Filing date	Jun 13, 2018
Priority date	Jun 13, 2018
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

Techniques regarding detecting one or more defined nucleic acid sequences are provided. For example, one or more embodiments described herein can comprise a method, which can comprise adding a molecular probe to a sample fluid comprising a first deoxyribonucleic acid segment and a second deoxyribonucleic acid segment. The molecular probe can have an affinity to bond to a defined nucleic acid sequence. The method can also comprise separating, via a nanoscale deterministic lateral displacement array, the first deoxyribonucleic acid segment from the second deoxyribonucleic acid segment based on a size of the first deoxyribonucleic acid segment.

First claim

What is claimed is:

1. A method, comprising:
forming a sample fluid by adding a molecular probe to a fluid comprising a first deoxyribonucleic acid segment and a second deoxyribonucleic acid segment, wherein the molecular probe has an affinity to bond to a defined nucleic acid sequence;
supplying the sample fluid to a nanoscale deterministic lateral displacement array;
separating, via the nanoscale deterministic lateral displacement array, the first deoxyribonucleic acid segment from the second deoxyribonucleic acid segment based on a size of the first deoxyribonucleic acid segment; and
determining whether the first deoxyribonucleic acid segment comprises the defined nucleic acid sequence by detecting a flow path of the molecular probe in the nanoscale deterministic lateral displacement array, wherein a size of the molecular probe is less than a critical diameter of the nanoscale deterministic lateral displacement array, and wherein a size of the first deoxyribonucleic acid segment is greater than or equal to the critical diameter.

2. The method of claim 1 , wherein the forming the sample fluid comprises annealing the molecular probe and the fluid to facilitate a chemical reaction between the molecular probe and one of the first deoxyribonucleic acid segment and the second deoxyribonucleic acid segment.

3. The method of claim 2 , further comprising:
detecting, by a sensor, a location of the molecular probe.

4. The method of claim 3 , wherein a system operatively coupled to a processor performs the detecting based on the location.

5. The method of claim 1 , wherein the first deoxyribonucleic acid segment comprises the defined nucleic acid sequence, wherein the forming the sample fluid further comprises covalently bonding the molecular probe to the first deoxyribonucleic acid segment, and wherein the separating further comprises separating the molecular probe from the second deoxyribonucleic acid segment.

6. The method of claim 1 , wherein the separating further comprises separating the molecular probe from the first deoxyribonucleic acid segment.

7. The method of claim 1 , wherein the first deoxyribonucleic acid segment is larger than the second deoxyribonucleic acid segment.

8. The method of claim 1 , wherein the nanoscale deterministic lateral displacement array comprises a first output region and a second output region, wherein the separating comprises guiding a molecule to the first output region, wherein a molecular size of the molecule is less than a predefined threshold, wherein the separating further comprises displacing the first deoxyribonucleic acid segment to the second output region, and wherein a molecular size of the first deoxyribonucleic acid segment is greater than or equal to the predefined threshold.

9. The method of claim 8 , wherein the molecule is selected from a group consisting of the second deoxyribonucleic acid segment and the molecular probe.

10. The method of claim 9 , wherein the separating comprises guiding both the second deoxyribonucleic acid segment and the molecular probe to the first output region.

11. The method of claim 1 , wherein the molecular probe comprises an identifier selected from a group consisting of a fluorescent tag and a magnetic bead.

12. A method, comprising:
forming a sample fluid by annealing a fluid comprising a probe molecule, a first deoxyribonucleic acid segment, and a second deoxyribonucleic acid segment, wherein the probe molecule bonds to the first deoxyribonucleic acid segment based on the first deoxyribonucleic acid segment comprising a defined nucleic acid sequence;
suppling the sample fluid to a nanoscale deterministic lateral displacement array;
separating, via the nanoscale deterministic lateral displacement array, the first deoxyribonucleic acid segment from the second deoxyribonucleic acid segment based on a size of the first deoxyribonucleic acid segment; and
determining whether the first deoxyribonucleic acid segment comprises the defined nucleic acid sequence by detecting a flow path of the probe molecule through the nanoscale deterministic lateral displacement array, wherein a size of the probe molecule is less than a critical diameter of the nanoscale deterministic lateral displacement array, and wherein a size of the first deoxyribonucleic acid segment is greater than or equal to the critical diameter.

13. The method of claim 12 , wherein the first deoxyribonucleic acid segment is displaced laterally away from a flow path of the second deoxyribonucleic acid segment.

14. The method of claim 12 , wherein the probe molecule covalently bonds to the defined nucleic acid sequence.

15. The method of claim 14 , wherein the first deoxyribonucleic acid segment and the probe molecule are displaced laterally away from a flow path of the second deoxyribonucleic acid segment.

16. The method of claim 14 , wherein the first deoxyribonucleic acid segment is displaced laterally away from a flow path of the second deoxyribonucleic acid segment and the probe molecule.

17. A method, comprising:
forming a sample fluid by adding a molecular probe to a fluid comprising a deoxyribonucleic acid segment, wherein the molecular probe has an affinity to bond to a defined nucleic acid sequence;
supplying the sample fluid to a nanoscale deterministic lateral displacement array;
displacing, via nanoscale deterministic lateral displacement array comprised within a microfluidic channel, the deoxyribonucleic acid segment towards a collection region of the microfluidic channel, wherein the nanoscale deterministic lateral displacement array displaces a molecule having a size greater than a defined threshold, and wherein a size of the molecular probe is less than the defined threshold; and
determining whether the deoxyribonucleic acid segment comprises the defined nucleic acid sequence by detecting a flow path of the molecular probe through the nanoscale deterministic lateral displacement array, wherein a size of the molecular probe is less than a critical diameter of the nanoscale deterministic lateral displacement array, and wherein a size of the deoxyribonucleic acid segment is greater than or equal to the critical diameter.

18. The method of claim 17 , wherein the deoxyribonucleic acid segment comprises the defined nucleic acid sequence, wherein the forming the sample fluid comprises bonding the molecular probe to the deoxyribonucleic acid segment, wherein the displacing comprises displacing the molecular probe towards the collection region, and wherein the deoxyribonucleic acid segment is determined to comprise the defined nucleic acid sequence based on the flow path of the molecular probe entering the collection region.

19. The method of claim 17 , wherein the displacing further comprises displacing the deoxyribonucleic acid segment from the molecular probe.

20. The method of claim 17 , wherein the deoxyribonucleic acid segment is larger than the defined threshold.

Assignees

• IBM

Inventors

• Gifford Stacey
• Kim Sung-Cheol
• Smith Joshua T
• Wunsch Benjamin

Classifications

• C12Q1/6823 Primary

  Release of bound markers · CPC title

• B01L2400/086

  using baffles or other fixed flow obstructions · CPC title

• C12Q1/6806

  Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) · CPC title

• C12Q1/6813 Primary

  Hybridisation assays · CPC title

• C12Q1/6825

  Nucleic acid detection involving sensors · CPC title