Collection probe and methods for the use thereof

• US 10,643,832 B2
• Filed: 08/31/2017
• Issued: 05/05/2020
• Est. Priority Date: 09/02/2016
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Eberlin, Livia Schiavinato, Milner, Thomas, Zhang, Jialing, Lin, John, Rector, John, Katta, Nitesh, Zahedivash, Aydin
• Primary Examiner(s): McCormack, Jason L
• Application Number:
  US15/692,167
• Publication Number:
  US 20180158661A1
• Time in Patent Office: 978 Days
• Field of Search: 250281, 250282, 250288
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: G01N 1/02 Devices for withdrawing samples sampling of foundation soil E02D1/04; collecting or conveying radioactive samples G01T7/00, e.g. G01T7/02, G01T7/08
• CPC Class Codes: G01N 2001/028 Sampling from a surface, swabbing, vaporising
• CPC Class Codes: G01N 2001/4061 Solvent extraction
• CPC Class Codes: G01N 2560/00 Chemical aspects of mass spectrometric analysis of biological material
• CPC Class Codes: G01N 30/72 Mass spectrometers mass spectrometers per se H01J49/00
• CPC Class Codes: G01N 33/487 of liquid biological material
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: H01J 49/0031 Step by step routines describing the use of the apparatus H01J49/0081 takes precedence
• CPC Class Codes: H01J 49/04 Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
• CPC Class Codes: H01J 49/0431 for liquid samples interfaces to liquid chromatographs G01N30/7233
• CPC Class Codes: H01J 49/0459 for solid samples

Abstract

Method and devices are provided for assessing tissue samples from a plurality of tissue sites in a subject using molecular analysis. In certain aspects, devices of the embodiments allow for the collection of liquid tissue samples and delivery of the samples for mass spectrometry analysis.

Claims

1. A method for assessing tissue samples in a living subject comprising:

(a) applying a fixed or discrete volume of a solvent to a tissue site in the living subject, using a probe that is structurally separate from, and in fluid contact with the tissue site and wherein the fixed or discrete volume of the solvent is not applied as a desorption electrospray ionization (DESI)-spray;

(b) collecting the applied solvent with the probe to obtain a liquid sample; and

(c) subjecting the liquid sample to mass spectrometry analysis.

2. The method of claim 1, wherein the fixed or discrete volume of a solvent is applied as a droplet.

3. The method of claim 1, wherein the fixed or discrete volume of a solvent is applied using a mechanical pump to move the solvent through a solvent conduit.

4. The method of claim 1, wherein collecting the applied solvent comprises applying a negative pressure to pull the liquid sample into a collection conduit and/or applying a gas pressure to push the liquid sample into a collection conduit.

5. The method of claim 4, wherein the solvent is applied through a solvent conduit that is separate from the collection conduit.

6. The method of claim 5, wherein the gas pressure is applied through a gas conduit that is separate from the solvent conduit and the collection conduit.

7. The method of claim 1, wherein the fixed or discrete volume of solvent is between 0.1 and 100 microliters.

8. The method of claim 1, wherein the applied solvent is collected between 0.1 and 30 seconds after the applying step.

9. The method of claim 1, wherein the tissue site is an internal tissue site in the living subject.

10. The method of claim 1, further comprising collecting a plurality of liquid samples from a plurality of tissue sites.

11. The method of claim 10, wherein the probe is washed between collecting respective liquid samples from the plurality of tissue sites.

12. The method of claim 10, wherein the probe is disposable and is changed between collecting respective liquid samples from the plurality of tissue sites.

13. The method of claim 10, wherein the probe comprises a collection tip, and the method further comprises:

ejecting the collection tip from the probe after the respective liquid samples are collected.

14. The method of claim 10, wherein the plurality of tissue sites surrounds a section of tissue that has been surgically resected.

15. The method of claim 1, further comprising:

(d) characterizing the liquid sample based on the mass spectrometry analysis.

16. The method of claim 15, wherein characterizing the liquid sample comprises determining a tissue type of the tissue site.

17. The method of claim 16, wherein determining the tissue type comprises identifying a diseased tissue.

18. The method of claim 17, wherein the diseased tissue comprise cancer cells.

19. The method of claim 17, wherein the diseased tissue comprise lung, breast, ovarian or thyroid cancer cells.

20. The method of claim 1, wherein the probe comprises:

a reservoir, a first conduit, a second conduit and a third conduit, wherein;

the reservoir is in fluid communication with the first conduit, the second conduit and the third conduit;

the first conduit is in fluid communication with a chamber comprising the solvent;

the second conduit is in fluid communication with a gas supply; and

the third conduit is in fluid communication with a mass spectrometer.

21. The method of claim 1, wherein the solvent is sterile.

22. The method of claim 1, wherein the solvent is water.

23. The method of claim 1, wherein the probe is in contact with the tissue site when the fixed or discrete volume of the solvent is applied to the tissue site.

24. The method of claim 1, wherein the probe is flushed after the obtaining the liquid sample.

25. The method of claim 1, wherein the reservoir has a volume between 1 and 500 microliters.

26. A method for obtaining a mass spectrometry profile for a tissue site in a living subject comprising:

(a) using a probe that is structurally separate from, and in fluid contact with, the tissue site to apply a discrete volume of a solvent to the tissue site in the living subject and wherein the discrete volume of the solvent is not applied as a desorption electrospray ionization (DESI)-spray;

(b) using the probe to collect the applied solvent to obtain a liquid sample; and

(c) subjecting the liquid sample to mass spectrometry analysis.