IP Library › Granted Patent US 9,310,378
Granted Patent B2
US 9,310,378 · App. 12/986,975 · Granted Apr 12, 2016

Compositions and processes for improved mass spectrometry analysis

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Quick Facts
Patent No.
US 9,310,378
App. No.
12/986,975
Filed
Jan 7, 2011
Granted
Apr 12, 2016
Kind
B2
Art Unit
1634
USPC
435/6.1
Abstract

The invention provides a novel additive for improved analysis by mass spectrometry. More specifically, ascorbic acid has been found to reduce or eliminate the presence of adducts commonly present in mass spectra. The improved processes and compositions of the invention allow for increased accuracy, sensitivity and throughput for samples analyzed by mass spectrometry.

Claims (54)

1. A Matrix-Assisted Laser Desorption/Ionization mass spectrometry substrate, comprising a support that includes an array of spots, some or all of which spots comprise:

(i) a matrix material for Matrix-Assisted Laser Desorption/Ionization mass spectrometry of nucleic acids, wherein the matrix material is selected from among 3-hydroxypicolinic acid, di-ammoniumcitrate or a mixture of 3-hydroxypicolinic acid and di-ammoniumcitrate and;

(ii) an additive that comprises ascorbic acid, or a salt, tautomer or analog thereof, in an amount that reduces the amount of an adduct formed under Matrix-Assisted Laser Desorption/Ionization mass spectrometry conditions, wherein the analog of ascorbic acid is according to the following formula:

wherein:

R 1 and R 2 independently are OH, halogen, R 3 , OR 3 , azido, cyano, CH 2 R 3 , CHR 3 R 4 , SR 3 , NR 3 R 4 ; and

R 3 and R 4 independently are H, alkyl, acetylene or cyano, or an optionally substituted aryl carbocyclic ring, aryl heterocyclic ring, non-aryl carbocyclic ring or non-aryl heterocyclic ring.

2. The substrate of claim 1 , wherein each spot is about 200 micrometers to about 1 millimeter in diameter.

3. The substrate of claim 1 , wherein a center-to-center distance between spots is about 2.25 millimeters.

4. The substrate of claim 1 , wherein a center-to-center distance between spots is about 1.125 millimeters.

5. The substrate of claim 1 , wherein each spot is of a thickness of about 10 micrometers to about 100 micrometers.

6. The substrate of claim 1 , wherein the additive consists essentially of ascorbic acid, or a salt, tautomer or analog thereof.

7. The substrate of claim 6 , wherein the additive consists of ascorbic acid, or a salt, tautomer or analog thereof.

8. The substrate of claim 6 , wherein the additive consists essentially of ascorbic acid.

9. The substrate of claim 8 , wherein the additive consists of ascorbic acid.

10. The substrate of claim 1 , wherein the additive further comprises ammonium oxalate.

11. The substrate of claim 1 , wherein some or all of the spots include an analyte, wherein the analyte is a nucleic acid.

12. The substrate of claim 11 , wherein the nucleic acid is deoxyribonucleic acid.

13. The substrate of claim 11 , wherein the nucleic acid is ribonucleic acid.

14. The substrate of claim 1 , wherein the additive comprises about 5 mM to about 50 mM ascorbic acid, or a salt, tautomer or analog thereof.

15. The substrate of claim 1 , wherein the additive comprises about 5 mM to about 50 mM ascorbic acid.

16. The substrate of claim 1 , wherein the matrix material comprises 3-hydroxy picolinic acid.

17. The substrate of claim 1 , wherein the mass spectrometry matrix comprises di-ammonium citrate.

18. The substrate of claim 1 , wherein the support is selected from the group consisting of a bead, chip, capillary, plate, membrane, wafer, comb, pin, a wafer with pits, an array of pits or nanoliter wells, and substantially flat surface.

19. The substrate of claim 18 , wherein the support is a silicon wafer.

20. The substrate of claim 18 , wherein the support is a substantially flat surface with hydrophobic regions surrounding hydrophilic loci, some or all of which loci contain a spot.

21. A mass spectrometry system, comprising a mass spectrometer for performing Matrix-Assisted Laser Desorption/Ionization Time-of-Flight mass spectrometry and a Matrix-Assisted Laser Desorption/Ionization mass spectrometry substrate, which substrate comprises a support that includes an array of spots, some or all of which spots comprise:

(i) a matrix material for Matrix-Assisted Laser Desorption/Ionization mass spectrometry of nucleic acids, wherein the matrix material is selected from among 3-hydroxypicolinic acid, di-ammoniumcitrate or a mixture of 3-hydroxypicolinic acid and di-ammoniumcitrate; and

(ii) an additive that comprises ascorbic acid, or a salt, tautomer or analog thereof, in an amount that reduces the amount of an adduct formed under Matrix-Assisted Laser Desorption/Ionization mass spectrometry conditions, wherein the analog of ascorbic acid is according to the following formula:

wherein:

R 1 and R 2 independently are OH, halogen, R 3 , OR 3 , azido, cyano, CH 2 R 3 , CHR 3 R 4 , SR 3 , NR 3 R 4 ; and

R 3 and R 4 independently are H, alkyl, acetylene or cyano, or an optionally substituted aryl carbocyclic ring, aryl heterocyclic ring, non-aryl carbocyclic ring or non-aryl heterocyclic ring.

22. The system of claim 21 , wherein each spot is about 200 micrometers to about 1 millimeter in diameter.

23. The system of claim 21 , wherein a center-to-center distance between spots is about 2.25 millimeters.

24. The system of claim 21 , wherein a center-to-center distance between spots is about 1.125 millimeters.

25. The system of claim 21 , wherein each spot is of a thickness of about 10 micrometers to about 100 micrometers.

26. The system of claim 21 , wherein the additive consists essentially of ascorbic acid, or a salt, tautomer or analog thereof.

27. The system of claim 26 , wherein the additive consists of ascorbic acid, or a salt, tautomer or analog thereof.

28. The system of claim 26 , wherein the additive consists essentially of ascorbic acid.

29. The system of claim 28 , wherein the additive consists of ascorbic acid.

30. The system of claim 21 , wherein the additive further comprises ammonium oxalate.

31. The system of claim 21 , wherein some or all of the spots include an analyte, wherein the analyte is a nucleic acid.

32. The system of claim 31 , wherein the nucleic acid is deoxyribonucleic acid.

33. The system of claim 31 , wherein the nucleic acid is ribonucleic acid.

34. The system of claim 21 , wherein the additive comprises about 5 mM to about 50 mM ascorbic acid, or a salt, tautomer or analog thereof.

35. The system of claim 21 , wherein the additive comprises about 5 mM to about 50 mM ascorbic acid.

36. The system of claim 21 , wherein the mass spectrometry matrix comprises 3-hydroxy picolinic acid.

37. The system of claim 21 , wherein the mass spectrometry matrix comprises di-ammonium citrate.

38. The system of claim 21 , wherein the support is selected from the group consisting of a bead, chip, capillary, plate, membrane, wafer, comb, pin, a wafer with pits, an array of pits or nanoliter wells, and substantially flat surface.

39. The system of claim 38 , wherein the support is a silicon wafer.

40. The system of claim 38 , wherein the support is a substantially flat surface with hydrophobic regions surrounding hydrophilic loci, some or all of which loci contain a spot.

41. The substrate of claim 16 , wherein the additive further comprises ammonium oxalate.

42. The system of claim 36 , wherein the additive further comprises ammonium oxalate.

43. The substrate of claim 1 , wherein the mass spectrometry matrix comprises a mixture of 3-hydroxy picolinic acid and di-ammonium citrate.

44. The system of claim 21 , wherein the mass spectrometry matrix comprises a mixture of 3-hydroxy picolinic acid and di-ammonium citrate.