US 7,735,146 B2Granted

Protein microscope

AssigneeThe George Washington University

InventorsAkos Vertes, Mark E. Reeves, Fatah Kashanchi

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Abstract

A system and method for analyzing and imaging a sample containing molecules of interest combines modified MALDI mass spectrometer and SNOM devices and techniques, and includes: (A) an atmospheric-pressure or near-atmospheric-pressure ionization region; (B) a sample holder for holding the sample; (C) a laser for illuminating said sample; (D) a mass spectrometer having at least one evacuated vacuum chamber; (E) an atmospheric pressure interface connecting said ionization region and said mass spectrometer; (F) a scanning near-field optical microscopy instrument comprising a near-field probe for scanning the sample; a vacuum capillary nozzle for sucking in particles which are desorbed by said laser, the nozzle being connected to an inlet orifice of said atmospheric pressure interface; a scanner platform connected to the sample holder, the platform being movable to a distance within a near-field distance of the probe; and a controller for maintaining distance information about a current distance between said probe and said sample; (G) a recording device for recording topography and mass spectrum measurements made during scanning of the sample with the near-field probe; (H) a plotting device for plotting said topography and mass spectrum measurements as separate x-y mappings; and (I) an imaging device for providing images of the x-y mappings.

Claims20

Dependent claims

A system for analyzing and imaging a sample containing molecules of interest, the system having:

(A) an atmospheric-pressure or near-atmospheric-pressure ionization region;
(B) a sample holder for holding the sample, the sample holder being disposed within said ionization region, the sample comprising an analyte embedded in an ionization-assisting matrix chosen such that said matrix facilitates ionization of said analyte to form analyte ions upon light-induced release of said analyte from said sample;
(C) a laser for near field illumination of said sample, to induce said release of said analyte from said sample, and to induce ionization of said analyte to form said analyte ions;
(D) a mass spectrometer having at least one evacuated vacuum chamber;
(E) an atmospheric pressure interface connecting said ionization region and said mass spectrometer (a) for capturing said analyte ions and neutrals released from said sample, (b) for subjecting the neutrals to additional ionization or post ionization, and (c) for transporting said analyte ions to said spectrometer;
(F) a scanning near-field optical microscopy instrument comprising (a) a near-field apertureless probe in which said laser is focused onto a sharp metal or metalized tip for scanning the sample;
(b) a vacuum capillary nozzle with heating for sucking in particles which are desorbed by said laser, the nozzle being connected to an inlet orifice of said atmospheric pressure interface;
(c) a scanner platform connected to the sample holder, the platform being movable to a distance within a near-field distance of the probe;
and (d) a controller for maintaining distance information about a distance between said probe and said sample, to thereby hold said sample within said distance;
wherein an output of said probe has a spot size on said sample roughly equal to the output diameter of said probe;
(G) a recording device for recording topography and mass spectra made during scanning of the sample with the near-field probe;
(H) a plotting device for plotting said topography and mass spectrum measurements as separate x-y mappings;
and
(I) an imaging device for providing images of the x-y mappings.

11 more elements

A method for performing analysis and imaging of a sample comprising an analyte embedded in an ionization-assisting matrix, whereby said matrix facilitates ionization of said analyte to form analyte ions upon light-induced release of said analyte from said sample, the method comprising:

(1) providing a system for analyzing and imaging a sample, the system having:
(A) an atmospheric-pressure or near-atmospheric-pressure ionization region;
(B) a sample holder for holding the sample, the sample holder being disposed within said ionization region, the sample comprising an analyte embedded in an ionization-assisting matrix chosen such that said matrix facilitates ionization of said analyte to form analyte ions upon light-induced release of said analyte from said sample;
(C) a laser for illuminating said sample, to induce said release of said analyte from said sample, and to induce ionization of said analyte to form said analyte ions;
(D) a mass spectrometer having at least one evacuated vacuum chamber;
(E) an atmospheric pressure interface connecting said ionization region and said mass spectrometer for capturing said analyte ions released from said sample, subjecting the neutrals to additional ionization or post ionization, and for transporting said analyte ions to said spectrometer;
and
(F) a scanning near-field optical microscopy instrument comprising (a) an apertureless near-field probe in which said laser is focused onto a sharp metal or metalized tip for scanning the sample;
(b) a vacuum capillary nozzle with heating for sucking in particles which are desorbed by said laser, the capillary nozzle being connected to an inlet orifice of said atmospheric pressure interface;
(c) a scanner platform connected to the sample holder, the platform being movable to a distance within a near-field distance of the probe;
and (d) a controller for maintaining distance information about a current distance between said probe and said sample, to thereby hold said sample within said distance;
wherein an output of said probe has a spot size on said sample roughly equal to an output diameter of said probe;
(G) a recording device for recording topography and mass spectrum measurements made during scanning of the sample with the near-field probe;
and
(H) an imaging device for providing images of the x-y mappings;
(2) causing the laser to emit light of the proper wavelength and intensity;
(3) projecting the light onto the near-field probe to form a near field zone;
(4) positioning the sample to be analyzed within the near-field zone;
(5) irradiating the sample with the light to desorb ions and neutrals from the sample;
(6) sucking the desorbed ions and neutrals through the vacuum nozzle with heating and into the atmospheric pressure interface;
(7) causing the desorbed ions and neutrals to enter the mass spectrometer from the atmospheric pressure interface;
(8) causing the sample to be scanned relative to the near-field probe;
(9) at each pixel, measuring topographical vertical height of the sample and measuring a complete mass spectrum;
(10) causing the measurements made in step (9) to be recorded;
and
(11) generating images of the x-y mappings, wherein each color of each pixel represents an ion intensity value.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/795,687Filed 26 Jan 2006 · us provisional application
Priority: 27 Jan 2005
Published: US 2008/0149822 A126 Jun 2008
Granted: 8 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

G01Q 30/02
Auxiliary means serving to assist or improve the scanning probe techniques or apparatus, e.g. display or data processing devices: non-SPM…
B82Y 20/00
Nanooptics
B82Y 35/00
Methods or apparatus for measurement or analysis of nanostructures
G01Q 60/22
SNOM [Scanning Near-Field Optical Microscopy] or apparatus therefor, e.g. SNOM probes: probes, their manufacture, or their related…