IP Library Granted Patent US 12,077,819
Granted Patent B2
US 12,077,819 · App. 16/404,582 · Granted Sep 3, 2024

Compositions and processes for improved mass spectrometry analysis

Inventor: Thomas Becker (La Jolla, CA)
Assignee: AGENA BIOSCIENCE, INC.
C12Q1/6872G01N33/6848G01N33/6851Y10T436/143333Y10T436/24Y10T436/25125
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Quick Facts
Patent No.
US 12,077,819
App. No.
16/404,582
Granted
Sep 3, 2024
Kind
B2
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 (24)

1. A substrate for mass spectrometry, comprising target sites, wherein more than one of the target sites comprise a matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry and an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog thereof, wherein the molar ratio of the adduct-reducing additive to the matrix material is about 1:20, about 1:19, about 1:18, about 1:17, about 1:16, about 1:15, about 1:14, about 1:13 or about 1:12.

2. The substrate of claim 1 , wherein the target sites comprising the matrix material and the adduct-reducing additive comprise one or more of a well, pit, pin, tower, bead, and a physical barrier positioned on the surface of the substrate.

3. The substrate of claim 1 , wherein the adduct-reducing additive comprises ascorbic acid.

4. The substrate of claim 1 , wherein the molar ratio of the adduct-reducing additive to the matrix material is about 1:15.

5. The substrate of claim 1 , wherein the matrix material comprises 3-hydroxypicolinic acid, di-ammoniumcitrate, 2,5-dihydroxybenzoic acid, Alpha-cyano-4-hydroxycinnamic acid, 2,4,6-trihydroxyacetophenone, T-2-(3-(4-t-Butyl-phenyl)-2-methyl-2-propenylidene)malononitrile, dithranol, sinapic acid, trans-3-indoleacrylic acid, or 2-(4-hydroxyphenylazo)benzoic acid.

6. The substrate of claim 1 , wherein the substrate comprises silica or silicon dioxide.

7. The substrate of claim 1 , wherein the matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry comprises 3-hydroxypicolinic acid.

8. The substrate of claim 1 , wherein all of the target sites comprise a matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry and an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog thereof.

9. The substrate of claim 1 , wherein the analog of ascorbic acid comprises the 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 1 and R 2 are not both OH; 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.

10. The substrate of claim 1 , wherein the target sites comprising the matrix material and the adduct-reducing additive, further comprise ammonium oxalate.

11. The substrate of claim 3 , wherein the target sites comprising the matrix material and the adduct-reducing additive, further comprise ammonium oxalate.

12. The substrate of claim 11 , wherein the matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry comprises 3-hydroxypicolinic acid.

13. The substrate of claim 1 , wherein the adduct-reducing additive comprises about 5 mM to about 50 mM ascorbic acid.

14. The substrate of claim 2 , wherein the target sites comprising the matrix material and the adduct-reducing additive are hydrophilic, and the substrate is hydrophobic.

15. The substrate of claim 1 , which consists essentially of a matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry and an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog thereof.

16. The substrate of claim 1 , which consists of a matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry and an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog thereof.

17. The substrate of claim 7 , wherein the target sites comprising the matrix material and the adduct-reducing additive, further comprise di-ammonium citrate as an additive.

18. The substrate of claim 1 , wherein the matrix material and the adduct-reducing additive is in a solid form of a dried solution containing the matrix and the adduct-reducing additive.

19. The substrate of claim 18 , wherein the solid form of the dried solution comprises crystals.

20. The substrate of claim 1 , wherein the substrate is contained in a sealed package.

21. The substrate of claim 20 , wherein the sealed package limits or eliminates exposure of the substrate to light or UV radiation.

Assignments (4)
SECURITY INTEREST Recorded Dec 10, 2021
From: AGENA BIOSCIENCE, INC.
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 058358/0661 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2019
From: SEQUENOM, INC.
To: BIOSCIENCES ACQUISITION COMPANY
Reel/Frame 049115/0049 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2019
From: BECKER, THOMAS
To: SEQUENOM, INC.
Reel/Frame 049115/0224 →
CHANGE OF NAME Recorded May 8, 2019
From: BIOSCIENCES ACQUISITION COMPANY
To: AGENA BIOSCIENCE, INC.
Reel/Frame 049116/0001 →
Continuity (5)
Continuation 15840432 · Dec 13, 2017
Continuation 15065739 · Mar 9, 2016
Continuation 12986975 · Jan 7, 2011
Continuation 12014671 · Jan 15, 2008
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