US 8,274,042 B2Granted

Imaging mass spectrometry for small molecules in two-dimensional samples

AssigneeBruker Daltonik GmbH

InventorArmin Holle

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Abstract

The invention relates to spatially resolved mass spectrometric measurement and visualization of the distribution of small molecules in a mass range from approximately 150 to 500 Daltons, for example drugs and their metabolites, in thin sections or other two-dimensional samples, preferably with ionization of the molecules by matrix-assisted laser desorption. The invention includes the steps measuring a daughter ion produced by forced decomposition of the molecular ion instead of the ionized analyte molecule itself, the daughter ion having a much better signal-to-noise ratio. The daughter ions are detected in a relatively simple reflector time-of-flight mass spectrometer instead of using an expensive time-of-flight tandem mass spectrometers for the measurement of the daughter ions. Advantageously, substantially faster and less expensive scanning of the thousands of mass spectra which serve as the basis for visualizing the spatial distribution of the analyte molecule is achieved, while the mass resolution and sensitivity are at least equally good.

Claims19

Dependent claims

A method for measuring spatial distribution of a single species of analyte molecules on or in a two-dimensional sample in a time-of-flight mass spectrometer with a reflector and a detector, the method comprising:

(a) ionizing at least some of the analyte molecules from one point on the sample to provide molecular ions, and accelerating the molecular ions;
(b) decomposing at least some of the molecular ions into daughter ions;
(c) selecting a species of the molecular ions of the single species of analyte molecules and corresponding daughter ions of the selected molecular ions with an ion selector, wherein the molecular weight of the selected molecular ions is below 1000 Daltons, and directing substantially all of the selected species of the molecular ions and the corresponding daughter ions from the ion selector to the reflector wherein the selected species of the molecular ions and the corresponding daughter ions are not substantially accelerated between the ion selector and the reflector;
(d) adjusting the reflector to a voltage setting that is optimal for one selected species of the corresponding daughter ions, and directing the selected species of daughter ions onto the detector, and measuring a daughter ion single spectrum of the selected species of daughter ions at the detector;
(e) repeating steps (a) to (d) at the same point on the sample, and combining the daughter ion single spectra of this location to form a sum spectrum;
(f) repeating steps (a) to (e) at different points on the sample;
and
(g) measuring the spatial distribution of the single species of analyte molecules by obtaining signal strengths of the one selected species of daughter ions at the individual locations on the sample from the sum spectra.

5 more elements

A method for the measurement the spatial distribution of analyte molecules on or in a two-dimensional sample in a time-of-flight mass spectrometer with a reflector and a detector comprising the following steps:

(a) ionizing at least some of the analyte molecules from a point on the sample to provide molecular ions, and accelerating the molecular ions;
(b) decomposing at least some of the molecular ions to into daughter ions;
(c) selecting a species of the molecular ions of the single species of analyte molecules and corresponding daughter ions of the selected molecular ions with an ion selector, wherein the molecular weight of the selected molecular ions is below 1000 daltons and substantially all of the selected species of the molecular ions and the corresponding daughter ions are directed from the ion selector to the reflector where the selected species of the molecular ions and the corresponding daughter ions are not substantially accelerated between the ion selector and the reflector,
(d) adjusting the reflector to a voltage setting for a selected species of the corresponding daughter ions, and directing the selected species of daughter ions onto the detector, and measuring a daughter ion single spectrum of the selected species of daughter ions at the detector;
(e) repeating steps (a) to (d) at the same point on the sample, and combining the daughter ion single spectra for this location to form a sum spectrum;
(f) repeating steps (a) to (e) for different points on the sample;
and
(g) measuring the spatial distribution of the selected analyte molecules by determining the signal strengths of the daughter ions in the sum spectrum at the individual locations on the sample.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/128,276Filed 28 May 2008
Priority: DE 10 2007 024 85729 May 2007
Published: US 2008/0296488 A14 Dec 2008
Granted: 25 Sep 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

H01J 49/004
Particle spectrometers or separator tubes: combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
H01J 49/0004
Particle spectrometers or separator tubes: imaging particle spectrometry
H01J 49/40
Dynamic spectrometers: time-of-flight spectrometers
H01J
Electric discharge tubes or discharge lamps