Specimen imaging systems and methods

Patent metadata

Field	Value
Publication number	US-12094701-B2
Application number	US-202017763294-A
Country	US
Kind code	B2
Filing date	Oct 2, 2020
Priority date	Oct 4, 2019
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

Disclosed herein are specimen imaging systems, comprising: a sample stage in a vacuum environment, the sample stage configured to support a specimen; an electron beam generator configured to focus an electron beam on a first predetermined location on the specimen; a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen; a mass spectrometer; and an extraction conduit configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer. The system can create a topological and chemical map of the specimen by analyzing at least a portion of the specimen with a mass spectrometer to determine a chemical composition of the specimen at the second predetermined location and analyzing at least a portion of the specimen with the electron beam to determine a surface topology.

First claim

What is claimed is:

1. A specimen imaging system comprising:
a sample stage in a vacuum environment configured to support a specimen;
an electron beam generator configured to generate an electron beam and focus the electron beam on a first predetermined location on the specimen;
a nanospray dispenser configured to dispense a nanospray having an energy per impacting molecule of 1 eV or less onto a second predetermined location on the specimen;
a mass spectrometer; and
an extraction conduit in fluid communication with the mass spectrometer and configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer.

2. The specimen imaging system of claim 1 , wherein the first predetermined location is a different location than the second predetermined location.

3. The specimen imaging system of claim 1 , wherein the electron beam generator is positioned above the sample stage.

4. The specimen imaging system of claim 1 , wherein the nanospray dispenser is oriented towards to the sample stage.

5. The specimen imaging system of claim 1 , wherein the nanospray dispenser and the electron beam generator are further configured to, simultaneously:
dispense the nanospray onto the second predetermined location of the specimen; and
focus the electron beam onto the first predetermined location of the specimen.

6. The specimen imaging system of claim 1 , wherein the nanospray dispenser is further configured to dispense the nanospray onto the second predetermined location of the specimen during a first time period;
wherein the electron beam generator is further configured to focus the electron beam onto the first predetermined location of the specimen during a second time period; and
wherein the first time period is different than the second time period.

7. The specimen imaging system of claim 1 , wherein the nanospray dispenser is further configured to dispense a nanospray onto the second predetermined location, such that the nanospray contacts the specimen as a charged, continuous liquid filament.

8. A specimen imaging system comprising:
a sample stage in a vacuum environment, the sample stage configured to support a specimen;
an electron beam generator configured to generate an electron beam and focus the electron beam on a first predetermined location on the specimen during a first time period;
a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen during a second time period;
a mass spectrometer; and
an extraction conduit in fluid communication with the mass spectrometer and configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer.

9. The specimen imaging system of claim 8 , wherein the nanospray dispenser is further configured to dispense a transport gas laterally across the sample stage, such that the transport gas carries at least a portion of the specimen that is forcibly desorbed from the specimen by the nanospray toward the extraction conduit.

10. The specimen imaging system of claim 9 , wherein the nanospray dispenser comprises a first outlet for ejecting the nanospray and a second outlet for ejecting the transport gas.

11. The specimen imaging system of claim 8 , wherein the specimen comprises one or more biological cells;
wherein either:
the first predetermined location is a same location as the second predetermined location; or
the first predetermined location is a different location than the second predetermined location;

wherein either:
the first time period is a same time period as the second time period such that the generating and the dispensing are simultaneous; or
the first time period is a different time period that the second time period;

wherein either:
the nanospray dispenser is further configured to dispense a nanospray onto the second predetermined location such that the nanospray contacts the specimen as a charged, continuous liquid filament; or
the nanospray dispenser is further configured to dispense a nanospray onto the second predetermined location such that the nanospray contacts the specimen as charged droplets;

wherein the electron beam generator is positioned above the sample stage; and
wherein the nanospray dispenser is oriented towards to the sample stage.

12. The specimen imaging system of claim 11 , wherein the nanospray dispenser is further configured to:
cause the nanospray to forcibly desorb a portion of the specimen; and
dispense the nanospray having an energy per impacting molecule of 1 eV or less.

13. The specimen imaging system of claim 12 , wherein the extraction conduit is further configured to receive the portion of the specimen forcibly desorbed and transfer at least a portion of the specimen forcibly desorbed to the mass spectrometer.

14. A method of imaging a specimen comprising:
profiling at least a portion of a surface of a specimen within a vacuum environment with an electron beam focused on a first predetermined location on the specimen to obtain a surface topology;
dispensing a nanospray onto a second predetermined location on the specimen; and
transferring charged particles from a desorbed portion of the specimen to a mass spectrometer.

15. The method of claim 14 , wherein the nanospray has an energy per impacting molecule of 1 eV or less; and
wherein either:
the first predetermined location is a same location as the second predetermined location; or
the first predetermined location is a different location than the second predetermined location.

16. The method of claim 15 , wherein the specimen is positioned on a sample stage within the vacuum environment;
wherein the electron beam is from an electron beam generator positioned above the sample stage;
wherein the nanospray is dispensed from a nanospray dispenser;
wherein the desorbed portion of the specimen is forcibly desorbed with the nanospray; and
wherein the charged particles are transferred from the vacuum environment into an extraction conduit in fluid communication with the mass spectrometer.

17. The method of claim 16 , wherein the nanospray dispenser is oriented towards to the sample stage.

18. The method of claim 16 further comprising dispensing a transport gas laterally across the sample stage, such that the transport gas carries at least a portion of the desorbed portion of the specimen toward the extraction conduit.

19. The method of claim 15 further comprising analyzing at least a portion of the desorbed portion of the specimen with the mass spectrometer to determine a chemical composition of the specimen at the second predetermined location.

20. The method of claim 14 , wherein the nanospray has an energy per impacting molecule from 0.001 eV to 1 eV.

Assignees

• Georgia Tech Res Inst

Inventors

• Fedorov Andrei G
• Kottke Peter Arthur

Classifications

• H01J49/147

  with electrons, e.g. electron impact ionisation, electron attachment (H01J49/145 takes precedence) · CPC title

• H01J37/26

  Electron or ion microscopes; Electron or ion diffraction tubes · CPC title

• H01J37/20

  Means for supporting or positioning the object or the material; Means for adjusting diaphragms or lenses associated with the support · CPC title

• H01J2237/2067

  Surface alteration · CPC title

• H01J2237/2803

  characterised by the imaging method · CPC title