Mass-spectrometer systems and methods

• US 10,067,140 B2
• Filed: 11/15/2016
• Issued: 09/04/2018
• Est. Priority Date: 01/10/2014
• Status: Active Grant

• Current Assignee: PureHoney Technologies, Inc.
• Original Assignee: PureHoney Technologies, Inc.
• Inventors: Ozbal, Can
• Primary Examiner(s): SOUW, BERNARD E
• Application Number:
  US15/352,066
• Publication Number:
  US 20170059580A1
• Time in Patent Office: 658 Days
• Field of Search: 250281, 250282, 250288, 250428, 250430, 250432 PD, 250526, 600309, 600317, 600321, 604 65- 67, 604323, 604335, 604504, 422131, 422140, 422141, 422500, 422504, 422505, 422509, 422513, 422527, 422534, 422537, 422554, 422 56
• CPC Class Codes: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 2001/4088 filtration
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: G01N 33/9446 Antibacterials
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K

Abstract

Embodiments of the present disclosure present novel systems, devices and methods for an automated biological sample analysis using mass-spectrometry. The time from sample introduction to the reporting of data, in some embodiments, takes a relatively short amount of time (e.g., several minutes). In some embodiments, a biological sample to be analyzed is a blood sample. For many applications, only a single drop of blood may be sufficient. Through the use of a mixture of standards with unique molecular mass, a quantitative analysis of the target analyte can be performed in a single MS run (for example), eliminating the need to create and analyze standard curves. One advantage of such embodiments may be that the system, devices, and methods can eliminate the need for batch creation since the requirement to amortize the time and effort of creating and analyzing standard curves can be eliminated.

Claims

1. A system for determining the concentration of an analyte of interest in a bodily fluid, the system comprising:

a fluid pumping system comprising at least one positive pressure pump;

a sample preparation portion comprising a single-use, disposable cartridge comprising;

a solid residue of a plurality of internal standards within a sample introduction port, the plurality of internal standards comprising a plurality of stable isotopes of the analyte of interest or a plurality of chemically derivatized analyte samples, each of the plurality of internal standards being at different, known concentrations;

a filtration region;

a chromatography region; and

an outlet port configured to be in fluid communication with a mass spectrometer;

a sample analysis portion comprising the mass spectrometer, wherein the mass spectrometer produces a spectra for the analyte of interest in a sample of a bodily fluid, and at least one of the plurality of internal standards in a single spectral measurement; and

at least one processor having operational thereon computer instructions for at least controlling operation of the system, creating a standard curve of the spectra, and determining a concentration of the analyte of interest contained in the bodily fluid sample based upon the standard curve, and reporting the at least one analyte concentration.

2. The system of claim 1, wherein fluid pumping system comprises a first pump and a second pump and at least one valve for directing fluid flow, and wherein the at least one valve comprises a multi-port valve.

3. The system of claim 2, wherein the multi-port valve includes a selector configured to select at least one pair of ports for fluid communication there-between.

4. The system of claim 3, wherein the multi-port valve comprises at least 6 ports designated respectively as ports 1 through 6.

5. The system of claim 4, wherein upon the selector being in a first position, ports 1 and 2 are in fluid communication, ports 3 and 4 are in fluid communication, and ports 5 and 6 are in fluid communication.

6. The system of claim 5, wherein upon the selector being in a second position, ports 2 and 3 are in fluid communication, ports 4 and 5 are in fluid communication, and ports 6 and 1 are in fluid communication.

7. The system according to claim 3, wherein at least one position of the selector is configured for loading and washing position of the bodily fluid sample.

8. The system according to claim 3, wherein at least one position of the selector is configured for an elution of the bodily fluid sample.

9. The system of claim 4, wherein port 1 is connected to the first pump and port 2 is connected to the sample introduction port.

10. The system of claim 4, wherein port 3 is connected to the second pump and port 4 is connected to the mass spectrometer.

11. The system of claim 4, wherein port 5 is connected to is connected to the outlet of the cartridge and port 6 is connected to a waste tank.

12. The system of claim 4, wherein port 1 is connected to the first pump and port 2 is connected to the sample introduction port, port 3 is connected to the second pump and port 4 is connected to the mass spectrometer, port 5 is connected to is connected to the outlet of the cartridge and port 6 is connected to a waste tank.

13. The system of claim 3, wherein the multi-port valve comprises at least 3 ports designated respectively as ports 1 through 3.

14. The system of claim 13, wherein upon the selector being in a first position, ports 2 and 3 are in fluid communication.

15. The system of claim 14, wherein upon the selector being in a second position, ports 1 and 3 are in fluid communication.

16. The system according to claim 14, wherein the first position is configured for loading and washing position of the bodily fluid sample.

17. The system according to claim 15, wherein the second position of the selector is configured for elution and mass-spectrometric analysis of the bodily fluid sample.

18. The system of claim 13, wherein port 1 is connected to the mass spectrometer.

19. The system of claim 13, wherein port 2 is connected to a waste tank.

20. The system of claim 13, wherein port 3 is connected to is connected to the outlet of the cartridge.