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US 12,555,763 B2Granted
Tissue analysis
AssigneeMicromass UK Limited
InventorsEmrys Jones, Richard Chapman, Steven Derek Pringle, Michael Raymond Morris
Life of this patent
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Abstract
Disclosed herein is a method of analysing a tissue sample. The method comprises identifying one or more regions of interest within the tissue sample based on a tissue stain that has been applied to the tissue sample. Analyte material is then generated from the one or more regions of interest identified based on the tissue stain using a direct surface sampling probe (10), which analyte material is then received at a sampling inlet (30) and passed towards a mass and/or ion mobility spectrometer (50) for analysis.
Claims18
A method of analysing a tissue sample, wherein the tissue sample comprises a tissue section mounted on a glass slide, the method comprising:
- automatically preparing and loading the tissue section onto a sample mounting stage of an analysis system, wherein automatically preparing and loading the tissue section onto a sample mounting stage of an analysis system uses at least a microtome;
- automatically identifying one or more regions of interest within the tissue sample based on a tissue stain that has been applied to the tissue sample, wherein the tissue stain is selected from the group comprising:
- (i) toluidine blue;
- (ii) methylene blue;
- (iii) cresyl violet;
- and (iv) nuclear fast red;
- generating analyte material from the one or more regions of interest identified based on the tissue stain using a direct surface sampling technique, wherein the direct surface sampling technique does not require an addition of a matrix to prepare the tissue sample, wherein the direct surface sampling technique comprises a desorption electrospray ionisation (“DESI”) or a DESI-derived process;
- receiving the generated analyte material at a sampling inlet;
- and
- passing the analyte material towards a mass and/or ion mobility spectrometer for analysis, wherein:
- the mass and/or ion mobility spectrometer is operated in negative ion mode to obtain negative ion spectra when the tissue stain exists as a positive ion;
- and
- the mass and/or ion mobility spectrometer is operated in positive ion mode to obtain positive ion spectra when the tissue stain exists as a negative ion;
- and
- a controller configured to automatically process an image of a tissue sample and
- wherein the controller when automatically processing an image of a tissue sample is configured to create a binary map and reject any objects in the binary map that are touching a border of an active area determined by the controller to show only an area of interest.
13 more elements
An analysis system comprising:
- a sample mounting stage for receiving a stained tissue sample to be analysed, wherein the tissue sample comprises a tissue section;
- an automated sample preparation and loading device comprising a microtome, the automated sample preparation and loading device for automatically preparing a tissue section to be analysed and loading the tissue section onto the sample mounting stage for analysis;
- a first device for generating analyte material from the tissue sample using any one of desorption electrospray ionisation (DESI) or a desorption electrospray ionisation (DESI)-derived process;
- a sampling inlet for receiving the generated analyte material;
- a mass and/or ion mobility spectrometer for analysing the generated analyte material,
- wherein the mass and/or ion mobility spectrometer is configured to (i) operate in negative ion mode to obtain negative ion spectra when the tissue stain exists as a positive ion, and (ii) operate in positive ion mode to obtain positive ion spectra when the tissue stain exists as a negative ion;
- transfer tubing for passing the analyte material towards the mass and/or ion mobility spectrometer for analysis;
- an image capture device such as a camera for obtaining an image of a tissue sample on the sample mounting stage to which a tissue stain has been applied, wherein the tissue stain is selected from the group comprising:
- (i) toluidine blue;
- (ii) methylene blue;
- (iii) cresyl violet;
- and (iv) nuclear fast red;
- and a controller configured to:
- automatically process an image of a tissue sample on the sample mounting stage to which a tissue stain has been applied to identify one or more regions of interest;
- and
- direct the first device to generate analyte material from the identified region(s) of interest of the stained tissue sample;
- wherein:
- the image capture device is configured to perform hyperspectral imaging targeted on one or more specific wavelengths of interest to obtain the image of the tissue sample on the sample mounting stage to which a tissue stain has been applied and the wavelength of interest is configured to target specific absorption wavelengths of the applied tissue stain and/or tissue sample components;
- and
- wherein the controller when automatically processing an image of a tissue sample is configured to create a binary map and reject any objects in the binary map that are touching a border of an active area determined by the controller to show only an area of interest.
17 more elements
An analysis system comprising:
- a sample mounting stage for receiving a stained tissue sample to be analysed, wherein the tissue sample comprises a tissue section;
- an automated sample preparation and loading device comprising a microtome, the automated sample preparation and loading device for automatically preparing a tissue section to be analysed and loading the tissue section onto the sample mounting stage for analysis;
- a first device for generating analyte material from the tissue sample using any one of desorption electrospray ionisation (DESI) or a desorption electrospray ionisation (DESI)-derived process;
- a sampling inlet for receiving the generated analyte material;
- a mass and/or ion mobility spectrometer for analysing the generated analyte material,
- wherein the mass and/or ion mobility spectrometer is configured to (i) operate in negative ion mode to obtain negative ion spectra when the tissue stain exists as a positive ion, and (ii) operate in positive ion mode to obtain positive ion spectra when the tissue stain exists as a negative ion;
- transfer tubing for passing the analyte material towards the mass and/or ion mobility spectrometer for analysis;
- an image capture device such as a camera for obtaining an image of a tissue sample on the sample mounting stage to which a tissue stain has been applied;
- and a controller configured to:
- automatically process an image of a tissue sample on the sample mounting stage to which a tissue stain has been applied to identify one or more regions of interest, wherein the tissue stain is selected from the group comprising:
- (i) toluidine blue;
- (ii) methylene blue;
- (iii) cresyl violet;
- and (iv) nuclear fast red;
- and
- direct the first device to generate analyte material from the identified region(s) of interest of the stained tissue sample:
- wherein the controller when automatically processing the image of the tissue sample on the sample mounting stage to which a tissue stain has been applied to identify the one or more regions of interest is configured to filter the image of the tissue sample on the sample mounting stage to which a tissue stain has been applied based on the applied tissue stain;
- and
- wherein the controller when automatically processing an image of a tissue sample is configured to create a binary map and reject any objects in the binary map that are touching a border of an active area determined by the controller to show only an area of interest.
16 more elements
Dependencies are inferred from the claim text.