US 8,286,260 B2Granted

Protein microscope

AssigneeThe George Washington University

InventorsAkos Vertes, Mark E. Reeves, Fatah Kashanchi

Life of this patent

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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 chamber; (E) an atmospheric pressure interface for connecting said ionization region and said mass spectrometer; (F) a scanning near-field optical microscopy instrument; (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.

Claims27

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 at least one analyte embedded in an ionization-assisting matrix such that said matrix facilitates ionization of said analyte forms 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;
and
(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 for sucking in particles which are ejected 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.

8 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) a near-field probe for scanning the sample;
(b) a vacuum capillary nozzle for sucking in particles which are ejected 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;
(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 eject ions and neutrals from the sample;
(6) subjecting the neutrals to additional ionization or post ionization;
(7) sucking the ejected ions and neutrals through the vacuum nozzle and into the atmospheric pressure interface;
(8) causing the produced ions and neutrals to enter the mass spectrometer from the atmospheric pressure interface;
(9) causing the sample to be scanned relative to the near-field probe;
and
(10) at each pixel, measuring topographical vertical height of the sample and measuring a complete mass spectrum.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/783,122Filed 19 May 2010 · continuation
Priority: 27 Jan 2005
Published: US 2010/0229263 A19 Sep 2010
Granted: 9 Oct 2012
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…

Family

Application60/646,994Us provisional application · filed 27 Jan 2005
PCT/US2006/002483Parent of this continuation · filed 26 Jan 2006
US 2010/0229263 A1Pre-grant publication · published 9 Sep 2010
Application11/795,687Parent of this continuation
US 7,735,146 B2Parent of this continuation
US 2008/0149822 A1Published application
US 8,286,260 B2This patent

From the US filing history. Foreign family members aren’t listed.