Spin relaxometry based molecular sequencing

• US 10,281,550 B2
• Filed: 11/14/2016
• Issued: 05/07/2019
• Est. Priority Date: 11/14/2016
• Status: Active Grant

• Current Assignee: Lockheed Martin Corporation (Martin Marietta Corporation)
• Original Assignee: Lockheed Martin Corporation (Martin Marietta Corporation)
• Inventors: Sinton, Steven W., Bedworth, Peter V., Swett, Jacob Louis
• Primary Examiner(s): Bhat, Narayan K
• Application Number:
  US15/350,303
• Publication Number:
  US 20180136301A1
• Time in Patent Office: 904 Days
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/116 electrical properties of nucleic acids, e.g. impedance, conductivity or resistance
• CPC Class Codes: C12Q 2563/137 Metal/ion, e.g. metal label
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: C12Q 2565/633 NMR
• CPC Class Codes: G01N 24/10 by using electron paramagnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01R 33/1269 of molecules labeled with magnetic beads magnetic particles for bio assay G01N33/54326
• CPC Class Codes: G01R 33/60 using electron paramagnetic resonance G01R33/24, G01R33/62 take precedence

Abstract

A method and system for detecting a target molecule. The method includes allowing a fluid containing the target molecule to pass by a complementary moiety attached to a paramagnetic ion so as to cause the complementary moiety and the paramagnetic ion to change a position. A magnetic effect change caused by the change in position of the paramagnetic ion is detected. The target molecule is identified based on the identity of the complementary moiety and the detected magnetic effect change.

Claims

1. A method for detecting a target molecule comprising:

allowing a fluid containing the target molecule to pass by a complementary moiety attached to a paramagnetic ion so as to cause the complementary moiety and the paramagnetic ion to change a position;

detecting a magnetic effect change caused by the change in position of the paramagnetic ion comprising detecting a change in spin relaxation of an electron spin center; and

identifying the target molecule based on the identity of the complementary moiety and the detected magnetic effect change.

2. The method of claim 1, wherein the electron spin center comprises one or more of diamond nitrogen vacancy (DNV) centers, defect centers in silicon carbide, or defect centers in silicon.

3. The method of claim 1, wherein the detecting a magnetic effect change comprises detecting a change in photoluminescence from the electron spin center.

4. The method of claim 1, wherein the detecting a magnetic effect change is performed by detecting a change in an electrical read out.

5. The method of claim 1, wherein the magnetic effect change is detected based on the fluid containing the target molecule passing through a pore of a substrate.

6. The method of claim 5, further comprising:

detecting a change in ionic current as the target molecule is in the pore, wherein the identifying the target molecule is further based on the detected change in the ionic current.

7. The method of claim 5, wherein substrate comprises diamond, and the electron spin center comprises one or more diamond nitrogen vacancy (DNV) centers.

8. The method of claim 7, wherein substrate comprises DNV centers arranged in a band surrounding the pore.

9. The method of claim 5, wherein paramagnetic ion is attached to an inner surface of the pore via a ligand attachment of the paramagnetic ion.

10. The method of claim 1, wherein the paramagnetic ion is attached to the complementary molecule.

11. The method of claim 1, wherein the paramagnetic ion is one of Gd3+, another Lathanide series ion, or Manganese.

12. The method of claim 1, wherein the target molecule is part of a DNA molecule.

13. The method of claim 1, wherein the identifying the target molecule is further based on a second effect detecting technique other than the magnetic effect change.

14. A method for detecting target moieties of a target molecule comprising:

allowing a fluid containing the target molecule to pass by a plurality of complementary moieties, each of the plurality of complementary moieties attached to a different respective paramagnetic ion and specific to a respective of the target moieties, so as to cause a respective complementary moiety and paramagnetic ion to change a position;

detecting a magnetic effect change caused by the change in position of a respective of the paramagnetic ions for each of the plurality of target moieties comprising detecting a change in spin relaxation of an electron spin center; and

identifying the target moieties based on the identities of the complementary moieties and the detected magnetic effect changes.

15. The method of claim 14, wherein the electron spin center comprises one or more diamond nitrogen vacancy (DNV) centers, defect centers in silicon carbide, or defect centers in silicon.

16. The method of claim 14, wherein the detecting a magnetic effect change is performed by detecting a change in an electrical read out.

17. The method of claim 14, wherein for each of the plurality of target moieties, the magnetic effect change is detected based on the fluid containing the target molecule passing through a pore of a substrate.

18. The method of claim 17, further comprising:

detecting a change in ionic current as the target molecule is in the pore, wherein the identifying the target moieties is further based on the detected change in the ionic current.

19. The method of claim 17, wherein substrate comprises diamond, and the electron spin centers each comprises one or more diamond nitrogen vacancy (DNV) centers.

20. The method of claim 14, wherein the target molecule is a DNA molecule and the target moieties are part of the DNA molecule.

21. The method of claim 14, wherein the identifying the target moieties are further based on a second effect detecting technique other than the magnetic effect change.

22. A system for detecting a target molecule comprising:

a substrate comprising an electron spin center;

a complementary moiety attached to a paramagnetic ion, which is attached to the substrate;

a magnetic effect detector arranged to detect a magnetic effect change of the electron spin center caused by a change in position of the paramagnetic ion due to the target molecule passing by the complementary moiety; and

a processor configured to identify the target molecule based on the identity of the complementary moiety and the detected magnetic effect change.

23. The system of claim 22, wherein the magnetic effect detector comprises:

a light source arranged to direct excitation light onto the electron spin center; and

a light detector arranged to receive photoluminescence light from the electron spin center based on the excitation light.

24. The system of claim 22, wherein the electron spin center comprises one or more diamond nitrogen vacancy (DNV) centers.

25. The system of claim 22, wherein the substrate comprises a pore, the complementary moiety attached to an inner surface of the pore.

26. The system of claim 22, wherein the substrate comprises diamond, and the electron spin center comprises one or more diamond nitrogen vacancy (DNV) centers.

27. The system of claim 25, wherein the substrate comprises diamond nitrogen vacancy (DNV) centers arranged in a band surrounding the pore.

28. The system of claim 25, wherein paramagnetic ion is attached to an inner surface of the pore via a ligand attachment of the paramagnetic ion.

29. A system for detecting target moieties of a target molecule comprising:

a substrate comprising a plurality of electron spin centers;

a plurality of complementary moieties attached to respective of a plurality of paramagnetic ions, which are attached to the substrate, each of the plurality of complementary moieties attached to a different respective paramagnetic ion and specific to a respective of the target moieties;

a magnetic effect detector arranged to detect, for each of the target moieties, a magnetic effect change of a respective electron spin center caused by a change in position of a respective of the paramagnetic ions due to the target moieties passing by a respective of the complementary moieties; and

a processor configured to identify the target moieties based on the identities of the complementary moieties and detected magnetic effect changes.

30. The system of claim 29, wherein the magnetic effect detector comprises:

a light source arranged to direct excitation light onto one of the electron spin centers; and

a light detector arranged to receive photoluminescence light from the one of the electron spin centers based on the excitation light.

31. The system of claim 29, wherein the electron spin centers each comprise one or more diamond nitrogen vacancy (DNV) centers, defect centers in silicon carbide, or defect centers in silicon.

32. The system of claim 29, wherein the substrate comprises a pore, the complementary moieties attached to an inner surface of the pore.

33. The system of claim 29, wherein the substrate comprises diamond, and the electron spin centers comprises diamond nitrogen vacancy (DNV) centers.

34. The system of claim 33, wherein the substrate comprises diamond nitrogen vacancy (DNV) centers arranged in a band surrounding the pore.

35. The system of claim 32, wherein paramagnetic ions are attached to an inner surface of the pore via ligand attachments of the paramagnetic ions.

36. A method for detecting target moieties of a target molecule comprising:

allowing a fluid containing the target molecule to pass by a plurality of complementary moieties, each of the plurality of target moieties attached to a different respective paramagnetic ion and specific to a respective of the complementary moieties, so as to cause a respective target moiety and paramagnetic ion to change a position;

detecting a magnetic effect change caused by the change in position of a respective of the paramagnetic ions for each of the plurality of target moieties comprising detecting a change in spin relaxation of an electron spin center; and

identifying the target moieties based on the identities of the complementary moieties and the detected magnetic effect changes.