Reduction of scan time in imaging mass spectrometry

• US 20070141719A1
• Filed: 12/19/2005
• Published: 06/21/2007
• Est. Priority Date: 12/19/2005
• Status: Active Grant

• Current Assignee: Thermo Finnigan LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Thermo Finnigan LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Bui, Huy
• Granted Patent: US 7,655,476 B2
• Time in Patent Office: Days
• US Class Current: 436/173
• CPC Class Codes: H01J 49/0004 Imaging particle spectrometry
• CPC Class Codes: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Techniques are disclosed for reducing scan times in mass spectral tissue imaging studies. According to a first technique, a tissue imaging boundary is defined that closely approximates the edges of a tissue sample. According to a second technique, a low-resolution scan is performed to identify one or more areas of interest within the tissue sample, and the identified areas of interest are subsequently scanned at higher resolution.

Claims

1. A method for irradiating tissue samples for mass spectral analysis, comprising steps of:

performing a first scan at relatively low resolution by irradiating a first set of target regions and acquiring mass spectral data at each target region of the first set;

analyzing the mass spectral data from the first scan using a processing unit to identify at least one area of interest within the tissue sample; and

performing a second scan at relatively high resolution by irradiating a second set of target regions located within the at least one identified area of interest and acquiring mass spectral data at each target region of the second set.

2. The method of claim 1, wherein the average spacing between target regions irradiated within the at least one area of interest is equal to or less than one-half of the average spacing between target regions irradiated outside of the at least one area of interest.

3. The method of claim 1, wherein the step of analyzing the mass spectral data includes identifying at least one area of interest having a relatively highly spatially differentiated abundance of ions having a selected mass-to-charge ratio.

4. The method of claim 1, wherein the target regions in the first set are distributed according to a randomized process.

5. The method of claim 1, further comprising a step of combining the mass spectral data from the first and second scans.

6. The method of claim 5, further comprising displaying a graphical depiction of the spatial distribution of an ion having a selected mass-to-charge ratio.

7. The method of claim 1, further comprising the steps of:

analyzing the mass spectral data from the first scan using a processing unit to identify at least one area of interest within the tissue sample; and

performing a third scan at a resolution higher than the second scan by irradiating a third set of target regions located within the at least one identified area of interest and acquiring mass spectral data at each target region of the third set.

8. The method of claim 4, wherein the target regions in the first set are randomly selected from a high-resolution target region list.

9. A mass spectrometer system, comprising:

a radiation source for irradiating selected target locations of a tissue sample to produce analyte ions;

a mass analyzer for generating mass spectral data representative of an abundance of at least one analyte ion or fragment thereof; and

a processing unit configured to;

cause the radiation source to sequentially irradiate a set of low-resolution target regions;

analyze mass spectral data associated with the low-resolution target regions to identify at least one area of interest within the tissue sample; and

cause the radiation source to sequentially irradiate a set of high-resolution target regions lying within the at least one area of interest.

10. The mass spectrometer system of claim 9, wherein the processing unit is configured to identify the at least one area of interest by locating areas of relatively high spatial differentiation.

11. The mass spectrometer system of claim 9, wherein the set of low-resolution target regions are randomly distributed.

12. The mass spectrometer system of claim 9, wherein the processing unit is configured to combine mass spectral data associated with the low-resolution and high-resolution target regions to generate a composite resolution tissue image, and to cause a graphical representation of the tissue image to be displayed.

13. A processing unit for a mass spectrometer configured to:

cause a radiation source to sequentially irradiate a set of low-resolution target regions;

analyze mass spectral data associated with the low-resolution target regions to identify at least one area of interest within the tissue sample; and

cause the radiation source to sequentially irradiate a set of high-resolution target regions lying within the at least one area of interest.

14. The processing unit of claim 13, wherein the processing unit is further configured to identify the at least one area of interest by locating areas of relatively high spatial differentiation.

15. The processing unit of claim 13, wherein the set of low-resolution target regions are randomly distributed.

16. The processing unit of claim 13, wherein the processing unit is further configured to combine mass spectral data associated with the low-resolution and high-resolution target regions to generate a composite resolution tissue image, and to cause a graphical representation of the tissue image to be displayed.