MEASURING CONCENTRATION OF ANALYTES IN LIQUID SAMPLES USING SURFACE-ENHANCED RAMAN SPECTROSCOPY

• US 20170074799A1
• Filed: 09/16/2016
• Published: 03/16/2017
• Est. Priority Date: 09/16/2015
• Status: Active Grant

• Current Assignee: OndaVia, Inc.
• Original Assignee: OndaVia, Inc.
• Inventors: PETERMAN, Mark Charles, ARIZA, Carlos Atico, KLEINMAN, Samuel Louis, BENHABIB, Merwan
• Granted Patent: US 9,863,924 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: G01N 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G01N 33/18 Water
• CPC Class Codes: G01N 33/182 Specific anions in water

Abstract

A hand-held microfluidic testing device is provided that includes a housing having a cartridge receiving port and a cartridge for input to the cartridge receiving port. An optical detection system in the housing is capable of providing an illuminated electric field useful for Raman spectroscopy. The cartridge may have a sample well. The sample well is loaded with a mixture of water containing the analyte, Raman-scattering nanoparticles and a calibration solution. The calibration solution contains an analogue of the analyte differing in its Raman response, for example an isotope of the analyte. Optionally, a chemical compound capable of increasing interaction between the analyte and the nanoparticles may be added.

Claims

1. A method of measuring the amount of an analyte in water, the method comprising the steps of:

obtaining a sample of water of known volume containing an analyte;

mixing a known amount of an isotopologue with the sample;

mixing Raman-scattering nanoparticles with the sample;

producing a Raman spectrum of the mixture; and

,

performing a ratiometric analysis of peaks or bands within the Raman spectrum corresponding to the analyte and the isotopologue within the Raman spectrum to quantify the analyte.

2. The method of claim 1 wherein the analyte is a molecular anion and the isotopologue is a molecular anion with all oxygen atoms substituted with ¹⁸O.

3. The method of claim 2 further comprising adding an amine to the mixture and adjusting the pH to 5.0 or less.

4. The method of claim 1 wherein the analyte is selenate and the isotopologue is a sulfate isotopologue or a selenate isotopologue containing four atoms of ¹⁸O.

5. The method of claim 4 comprising adding cysteamine or cystamine to the mixture.

6. The method of claim 1 wherein the analyte is perchlorate or chromate and the isotopologue is a heavy-oxygen isotopologue of perchlorate.

7. The method of claim 6 wherein comprising adding a thiol compound to the mixture and adjusting the pH of the mixture to 1.8-3.0.

8. The method of claim 1 wherein the analyte is a molecular cation and comprising adding an anionic compound, such as 3-mercaptopropionic acid, to the mixture.

9. The method of claim 1 comprising a step of pre-treating the mixture after adding the isotopologue but before producing the Raman spectrum.

10. The method of claim 1 wherein the pre-treating step comprises removing anions from the mixture.

11. The method of claim 1 wherein the analyte is an amine and the isotopologue is an amine with one or more hydrogen atoms replaced with deuterium.

12. The method of claim 11 comprising adjusting the pH of the mixture to a pH at least one more, or at least 2 more, than the pKa of the analyte.

13. The method of claim 11 wherein the analyte is MEA and the isotopologue is an MEA isotopologue.

14. The method of claim 11 wherein the analyte is methylamine and the isotopologue is methylamine-d₃.

15. The method of claim 11 wherein the analyte is diethanolamine and the isotopologue is diethanolamine-d₈.

16. The method of claim 11 wherein the analyte is a triazine-based compounds, for example MEA-triazine or dithiazine, and the isotopologue is ethanolamine-d₄ or a triazine isotopologue.

17. The method of claim 11 wherein the analytes are ethanolamine and methylamine and the isotopolgues are ethanolamine-d₄ and methylamine-d₃.

24. The method of claim 1 comprising adding one or more chemical compounds selected from the group consisting of thiols, amines, silanes, polymeric particles, metallic particles, crown esters, cysteamine, cystamine, diethylaminethanethiol, mercaptopropionic acid, 1-propanethiol, octanethiol, octyldecanethiol, polystyrene, iron, and silica.

25. The method of claim 1 wherein said analyte is an amine.

26. The method of claim 1 wherein said analyte is an anion.

27. The method of claim 1 wherein said Raman-enhancing substrate is comprised of gold or silver particles.

28. The method of claim 27 wherein said nanoparticles are 10 to 200 nm in diameter.

18. A method of measuring the amount of an analyte in water, the method comprising the steps of:

obtaining a sample of water of known volume containing an analyte;

reacting the analyte with a compound to consume the compound or produce a second compound;

mixing a known amount of an isotopologue with the reaction product;

mixing Raman-scattering nanoparticles with the reaction product;

producing a Raman spectrum of the mixture; and

,

performing a ratiometric analysis of peaks or bands within the Raman spectrum corresponding to the compound or second compound or both and the isotopologue within the Raman spectrum to quantify the analyte.

19. The method of claim 18 wherein the compound or second compound is an amine and further comprising adding an isotopologue of an amine to the mixture.

20. The method of claim 19 comprising reacting a gem-halogenated compound such as trichloroethylene, a trihalomethane, chloroform, or a haloacetic acid with pyridine or a pyridine derivative such as nicotinamide, for example at a pH of 12-13.

21. The method of claim 20 wherein the isotopologue is pyridine-d₅ or an isotopologue of a pyridine derivative.

22. The method of claim 18 comprising reacting an aldehyde such as formaldehyde with cysteamine or cystamine to create a to create a thiazolidine.

23. The method of claim 22 comprising adding a cysteamine isotopologue, cystamine isotopologue or a thiazolidine isotopologue to the mixture.