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EP-4741827-A2 - DESORPTION ELECTROSPRAY IONISATION MASS SPECTROMETRY ("DESI-MS") AND DESORPTION ELECTROFLOW FOCUSING IONISATION ("DEFFI-MS") ANALYSIS OF BIOLOGICAL SAMPLES ON SWABS

EP4741827A2EP 4741827 A2EP4741827 A2EP 4741827A2EP-4741827-A2

Abstract

A method is disclosed comprising providing a biological sample on a swab 900, directing a spray of charged droplets onto a surface of the swab 900 in order to generate a plurality of analyte ions, and analysing the analyte ions.

Inventors

  • TAKÁTS, Zoltán
  • SZALAY, Dániel
  • RICHARDSON, KEITH GEORGE
  • Bennett, Philip Robert
  • MacIntyre, David Alan
  • Pruski, Pamela
  • JONES, EMRYS
  • LANGRIDGE, JAMES IAN
  • MORRIS, Michael Raymond
  • KARANCSI, Tamás
  • PRINGLE, STEVEN DEREK
  • BALOG, Júlia
  • SIMON, Dániel
  • GÖDÖRHÁZY, Lajos

Assignees

  • Micromass UK Limited

Dates

Publication Date
20260513
Application Date
20160307

Claims (15)

  1. A method comprising: providing a sample on a swab; wetting said swab with a first liquid; contacting said wetted swab with one or more electrodes in order to generate an aerosol, smoke or vapour; generating a plurality of analyte ions from said aerosol, smoke or vapour; and analysing said analyte ions.
  2. A method as claimed in claim 1, wherein said first liquid comprises water.
  3. A method as claimed in claim 1 or 2, further comprising directing or aspirating at least some of said aerosol, smoke or vapour into a vacuum chamber of a mass spectrometer and/or ion mobility spectrometer and causing at least some of said aerosol, smoke or vapour to impact upon a collision surface in order to form analyte ions.
  4. A method as claimed in claim 3, further comprising mixing said aerosol, smoke or vapour with a matrix prior to causing said aerosol, smoke or vapour to impact upon said collision surface.
  5. A method as claimed in any preceding claim, further comprising applying an AC or RF voltage to said one or more electrodes in order to generate said aerosol, smoke or vapour.
  6. A method as claimed in any preceding claim, wherein said one or more electrodes comprise a rapid evaporation ionisation mass spectrometry ("REIMS") device.
  7. A method as claimed in any preceding claim, wherein analysing analyte ions comprises: (i) mass analysing and/or ion mobility analysing said analyte ions and/or ions derived from said analyte ions; and/or (ii) determining the ion mobility, collision cross section or interaction cross section of said analyte ions and/or ions derived from said analyte ions.
  8. Apparatus comprising: one or more electrodes arranged and adapted to contact a sample on a swab which has been wetted with a first liquid so as to generate an aerosol, smoke or vapour; a device which is arranged and adapted to generate a plurality of analyte ions from said aerosol, smoke or vapour; and an analyser for analysing said analyte ions.
  9. Apparatus as claimed in claim 9, wherein said first liquid comprises water.
  10. Apparatus as claimed in claim 8 or 9, further comprising a device for directing or aspirating at least some of said aerosol, smoke or vapour into a vacuum chamber of a mass spectrometer and/or ion mobility spectrometer and a collision surface, wherein said apparatus is arranged and adapted to cause at least some of said aerosol, smoke or vapour to impact upon said collision surface in order to generate said analyte ions.
  11. Apparatus as claimed in claim 10, further comprising a device for mixing said aerosol, smoke or vapour with a matrix prior to causing said aerosol, smoke or vapour to impact upon said collision surface.
  12. Apparatus as claimed in any of claims 8-11, further comprising a device arranged and adapted to apply an AC or RF voltage to said one or more electrodes in order to generate said aerosol, smoke or vapour.
  13. Apparatus as claimed in any of claims 8-12, wherein said one or more electrodes comprise a rapid evaporation ionisation mass spectrometry ("REIMS") device.
  14. Apparatus as claimed in any of claims 8-13, further comprising: (i) a mass analyser or filter and/or ion mobility analyser for mass analysing and/or ion mobility analysing analyte ions and/or ions derived from said analyte ions; and/or (ii) an ion mobility device for determining the ion mobility, collision cross section or interaction cross section of analyte ions and/or ions derived from said analyte ions.
  15. A mass spectrometer and/or ion mobility spectrometer comprising apparatus as claimed in any of claims 8-14.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority from and the benefit of United Kingdom patent application No. 1503876.3 filed on 6 March 2015, United Kingdom patent application No. 1503864.9 filed on 6 March 2015, United Kingdom patent application No. 1518369.2 filed on 16 October 2015, United Kingdom patent application No. 1503877.1 filed on 6 March 2015, United Kingdom patent application No. 1503867.2 filed on 6 March 2015, United Kingdom patent application No. 1503863.1 filed on 6 March 2015, United Kingdom patent application No. 1503878.9 filed on 6 March 2015, United Kingdom patent application No. 1503879.7 filed on 6 March 2015 and United Kingdom patent application No. 1516003.9 filed on 9 September 2015. The entire contents of these applications are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates generally to mass spectrometers and in particular to the analysis of material by ambient ionisation ion sources including rapid evaporative ionisation mass spectrometry ("REIMS") ion sources and the analysis of material by desorption electrospray ionisation ("DESI") mass spectrometry. Various embodiments relate to the use of mass spectrometers in diagnostic methods. Various embodiments are contemplated wherein analyte ions generated by an ambient ionisation ion source are then subjected either to: (i) mass analysis by a mass analyser such as a quadrupole mass analyser or a Time of Flight mass analyser; (ii) ion mobility analysis (IMS) and/or differential ion mobility analysis (DMA) and/or Field Asymmetric Ion Mobility Spectrometry (FAIMS) analysis; and/or (iii) a combination of firstly ion mobility analysis (IMS) and/or differential ion mobility analysis (DMA) and/or Field Asymmetric Ion Mobility Spectrometry (FAIMS) analysis followed by secondly mass analysis by a mass analyser such as a quadrupole mass analyser or a Time of Flight mass analyser (or vice versa). Various embodiments also relate to an ion mobility spectrometer and/or mass analyser and a method of ion mobility spectrometry and/or method of mass analysis. BACKGROUND The mucosal membrane is a protective layer responsible for trapping pathogens in the human body. The mucosal membrane is an easily accessible and highly clinically relevant sample to diagnose pathogenic and cancerous associated diseases. It is known to use medical swabs as a standard collection device for mucosal membranes. Conventionally, the swab is placed into a sterile tube containing a buffer solution for storage and then the tube is sent to a laboratory for analysis. A laboratory receiving the tube will wipe the smear content across a culture medium such as an agar plate. The culture medium is then incubated to allow organisms present on the swab to grow. Microbial identification may then be performed, e.g., under a microscope. Any organisms present in the sample may also be identified by 16S gene-sequencing and/or by using matrix-assisted laser desorption ionisation ("MALDI") mass spectrometry and then comparing the mass spectra with a commercial available database. Although easy to handle, the current approach to the analysis of medical swabs for diagnostic purposes is culture-dependent and involves a time consuming and costly workflow. Diagnosis of diseases, such as infections or dysbiosis, and appropriate treatment is therefore associated with considerable delay. Furthermore, around 95% of bacteria cannot be cultured for analysis. It is therefore desired to provide an improved method for mucosal analysis, e.g., diagnosis. SUMMARY According to an aspect there is provided a method comprising: providing a sample on a swab;directing a spray of electrically charged droplets onto a surface of the swab in order to generate a plurality of analyte ions; andanalysing the analyte ions. Desorption electrospray ionisation ("DESI") is an ambient ionisation method that involves directing a spray of (primary) electrically charged droplets onto a surface. The electrospray mist is pneumatically directed at the sample where subsequent splashed (secondary) droplets carry desorbed ionised analytes. After ionisation, the resulting ions travel through air and pass into an atmospheric pressure interface of a mass spectrometer. Desorption electrospray ionisation ("DESI") is a technique that allows for ambient ionisation of a trace sample at atmospheric pressure with no sample preparation being required. A "swab" in accordance with various embodiments is intended to be understood as comprising a "standard medical swab" i.e. a swab that is designed for sampling biological samples such as mucosal membranes. For example, the term "standard medical swab" should be understood as covering a "cotton bud" (British) or a "cotton swab" (American) i.e. a small wad of cotton wrapped around one or both ends of a tube. The tube may be made from plastic, rolled paper or wood. StableFlex (RTM) fibre cores are known and comprise a 80 µm fused silica co