Probe for extraction of molecules of interest from a sample

• US 9,870,907 B2
• Filed: 06/12/2015
• Issued: 01/16/2018
• Est. Priority Date: 03/11/2002
• Status: Expired due to Term

• Current Assignee: JP Scientific Limited
• Original Assignee: JP Scientific Limited
• Inventors: Pawliszyn, Janusz B., Gomez Rios, German Augusto
• Primary Examiner(s): Stoffa, Wyatt
• Application Number:
  US14/738,678
• Publication Number:
  US 20150318158A1
• Time in Patent Office: 949 Days
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: B01J 20/286 Phases chemically bonded to a substrate, e.g. to silica or to polymers
• CPC Class Codes: B01J 20/287 Non-polar phases; Reversed phases
• CPC Class Codes: G01N 1/405 by adsorption or absorption
• CPC Class Codes: G01N 2030/009 Extraction
• CPC Class Codes: G01N 2030/062 extracting sample from raw material
• CPC Class Codes: G01N 2560/00 Chemical aspects of mass spectrometric analysis of biological material
• CPC Class Codes: G01N 33/50 Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: H01J 49/0031 Step by step routines describing the use of the apparatus H01J49/0081 takes precedence
• CPC Class Codes: H01J 49/10 Ion sources; Ion guns
• CPC Class Codes: H01J 49/26 Mass spectrometers or separator tubes
• CPC Class Codes: Y10T 428/2933 Coated or with bond, impregnation or core

Abstract

The present disclosure describes a device for generating ionized molecules for analysis in a mass spectrometer. The device includes: a mesh substrate coated with an extraction phase, the extraction phase comprising a polymer that absorbs a molecule of interest from a matrix, or a polymer and solid phase microextraction (SPME) particles having pores dimensioned to absorb a molecule of interest from a matrix, where the mesh substrate has a sufficiently open structure to allow fluid to flow through the mesh substrate; and a solid substrate connected to the mesh substrate to provide stability to the coated mesh substrate. Mass spectrometry systems that include such a device are also described. Methods of analyzing an analyte previously extracted from a matrix onto the device are also described.

Claims

1. A device for generating ionized molecules for analysis in a mass spectrometer, the device comprising:

a mesh substrate coated with an extraction phase of substantially uniform thickness that is from about 0.2 μ

m to about 50 μ

m, the extraction phase comprising;

a polymer that absorbs a molecule of interest from a matrix, or

a polymer and solid phase microextraction (SPME) particles having pores dimensioned to adsorb a molecule of interest from a matrix,

wherein the coated mesh substrate has a sufficiently open structure to allow fluid to flow through the coated mesh substrate; and

a solid substrate connected to the mesh substrate to provide stability to the coated mesh substrate.

2. The device according to claim 1, wherein the mesh substrate comprises a plurality of connected or impregnated wires, filaments or strings.

3. The device according to claim 2, wherein the plurality of connected or impregnated wires, filaments or strings have a diameter from 50 micrometers to 0.5 millimeters.

4. The device according to claim 2, wherein the plurality of connected or impregnated wires, filaments or strings comprise a metal, a metal alloy, or a polymer substrate.

5. The device according to claim 4, wherein the metal, metal alloy, or polymer substrate is:

stainless steel, nitinol, nickel, titanium, aluminum, brass, iron, bronze, or polybutylene terephthalate.

6. The device according to claim 1, wherein the mesh substrate has an open area of at least 20%.

7. The device according to claim 1, wherein the extraction phase has a thickness sufficient to include one or two layers of particles.

8. The device according to claim 1, wherein the extraction phase is loaded with an internal standard.

9. The device according to claim 1, wherein the solid substrate comprises a metal, a metal alloy, or a polymer.

10. The device according to claim 9, wherein the solid substrate comprises stainless steel, titanium, a nickel-titanium alloy, nitinol, polybutylene terephthalate, or a 3-D printed polymer.

11. The device according to claim 1, wherein the solid substrate comprises a metal or a metal alloy and the coated mesh substrate is welded to the solid substrate.

12. The device according to claim 2, wherein the plurality of connected or impregnated wires, filaments or strings are in a grid configuration.

13. The device according to claim 6, wherein the mesh substrate has an open area of from about 50% to about 60%.

14. A mass spectrometry system comprising:

a source of a heated gas, or a heated and metastable gas;

an inlet for a mass spectrometer;

a nozzle fluidly connected to the source of the heated gas, or heated and metastable gas for directing a flow of the heated gas, or heated and metastable gas to the inlet; and

a device according to claim 1 positioned coaxial to, and at about a 0°

angle from, the nozzle and the mass spectrometer inlet;

wherein the nozzle is positioned to direct the heated gas, or heated and metastable gas through the coated mesh substrate of the device to desorb and ionize at least a portion of compounds sorbed on the coated mesh substrate, and wherein the inlet is positioned to collect and transport at least a portion of the desorbed and ionized compound to the mass spectrometer for analysis.

15. A method for analyzing an analyte previously extracted from a matrix onto a device according to claim 1, the method comprising:

flowing a heated gas, a metastable gas, or a heated and metastable gas through the coated mesh substrate to desorb and ionize the analyte sorbed on the coated mesh substrate;

transporting the desorbed and ionized analyte to a mass spectrometer; and

analyzing the ionized analyte by mass spectrometry.

16. The method according to claim 15, further comprising rinsing the coated mesh substrate with a rinsing solution at least once before flowing the heated gas, metastable gas, or heated and metastable gas through the coated mesh substrate.

17. The method according to claim 15, wherein the desorbing is performed along the coated mesh substrate to characterize a distribution gradient of analytes along the coated mesh substrate.

18. A method for measuring or identifying one or more component of interest in a sample, said method comprising the steps of:

positioning a device according to claim 1 in the sample;

adsorbing the one or more component of interest onto the extraction phase;

removing the device from the sample; and

exposing the device to sufficient energy to desorb and ionize the one or more component of interest, resulting in ionization and desorption of the one or more component of interest from the extraction phase into a mass spectrometer for measurement or identification.

19. The method according to claim 18, wherein exposing the device to sufficient energy to desorb and ionize the one or more component of interest comprises exposing the mesh substrate to a laser or a hot carrier gas.

20. A holder positioning one or more devices according to claim 1 between a nozzle that is fluidly connected to a source of a heated gas, a metastable gas, or a heated and metastable gas, and an inlet for a mass spectrometer so that ionized molecules desorbed from the coated mesh substrate are transported to the mass spectrometer, the holder comprising:

connectors for each of the one or more devices, each of the connectors releasably securing one of the devices.

21. The holder according to claim 20, wherein the holder is sized and shaped to simultaneously hold up to twelve devices according to claim 1, and is sized and shaped to be fitted on an automated electrical actuator that positions the coated mesh substrate between the nozzle and the inlet for the mass spectrometer.