System and method for preparation and delivery of biological samples for charged particle analysis

Patent metadata

Field	Value
Publication number	US-12165839-B2
Application number	US-202318354524-A
Country	US
Kind code	B2
Filing date	Jul 18, 2023
Priority date	Jun 28, 2019
Publication date	Dec 10, 2024
Grant date	Dec 10, 2024

Abstract

Systems and method for the preparation and delivery of biological samples for charged particle analysis are disclosed herein. An example system at least includes an ion filter coupled to select a sample ion from an ionized sample supply, the ion filter including a quadrupole filter to select the sample ion from the sample supply, an energy reduction cell coupled to receive the selected sample ion and reduce a kinetic energy of the sample ion, a validation unit coupled to receive the sample ion and determine whether the sample ion is a target sample ion, a substrate coupled to receive the sample, wherein the substrate is electron transparent, an ion transport module coupled to receive the sample ion from the ion filter and transport the sample ion to the substrate, and an imaging system arranged to image, with a low energy charged particle beam, the sample located on the substrate, wherein the substrate is arranged in an analysis location. The imaging system including a charge particle emitter coupled to direct coherent charged particles toward the sample; and a detector arranged to detect interference patterns formed from interaction of the coherent charged particles and the sample.

First claim

What is claimed is:

1. A sample preparation and delivery apparatus, the apparatus comprising:
a plurality of differential pumping stages arranged to receive a sample and deliver the sample to a substrate; and;
a decelerating lens coupled to or included with a final differential pumping stage of the plurality of differential pumping stages, the decelerating lens biased to reduce a velocity of the sample prior to the sample landing on the substrate, wherein the decelerating lens includes a plurality of lens elements.

2. The apparatus of claim 1 , wherein the plurality of lens elements of the decelerating lens includes two lens elements.

3. The apparatus of claim 1 , including a differential pumping aperture between adjacent differential pumping stages of the plurality of differential pumping stages.

4. The apparatus of claim 1 , including a gate valve disposed between two adjacent differential pumping stages of the plurality of pumping stages, wherein the gate valve is arranged to couple and decouple the two adjacent differential pumping stages.

5. The apparatus of claim 1 , wherein each differential pumping stage of the plurality of differential pumping stages is coupled to a respective vacuum pump.

6. The apparatus of claim 5 , wherein the vacuum level of each of the differential pumping stages increases in vacuum level from receipt of the sample to delivery of the sample to the substrate.

7. The apparatus of claim 1 , wherein each differential pumping stage of the plurality of differential pumping stages includes respective ion optics arranged for transporting the sample along the differential pumping stage.

8. The apparatus of claim 7 , wherein the ion optics included in each differential pumping stage includes at least one RF-driven quadrupole guide, wherein the RF-driven quadrupole guide is arranged to shape a charged particle beam including the sample and to further guide the sample along the respective differential pumping stage.

9. The apparatus of claim 1 , wherein each differential pumping stage of the plurality of differential pumping stages includes respective electrostatic lenses and apertures, wherein the apertures are disposed at interfaces between adjacent differential pumping stages.

10. A sample preparation and delivery apparatus, the apparatus comprising:
a plurality of differential pumping stages arranged to receive a sample and deliver the sample to a substrate; and;
a decelerating lens coupled to or included with a final differential pumping stage of the plurality of differential pumping stages, the decelerating lens biased to reduce a velocity of the sample prior to the sample landing on the substrate, wherein the decelerating lens includes a plurality of lens elements wherein a first lens element of the two lens elements is biased to a high negative potential and a second lens element of the two lens elements is at a ground potential, and wherein the second lens element is arranged closer to the substrate than the first lens element.

11. The apparatus of claim 10 , wherein the first lens element is biased to 350 V.

12. An apparatus comprising:
a sample preparation system coupled to filter an ionized sample from an ionized sample supply;
a sample delivery system coupled to receive the sample from the sample preparation system and deliver the ionized sample,
wherein the sample delivery system includes:
a plurality of differential pumping stages arranged to receive the ionized sample and guide the ionized sample along a path of the sample delivery system;
a decelerating lens coupled to or included with a final differential pumping stage of the plurality of differential pumping stages, the decelerating lens biased to reduce a velocity of the sample prior to the sample landing on the substrate, wherein the decelerating lens includes a plurality of lens elements; and

a substrate arranged to receive the ionized sample, wherein the substrate is disposed on a holder, the holder including one or more motors arranged to move the substrate around the holder so a location to deposit the ionized sample can be selected.

13. The apparatus of claim 12 , wherein the holder further includes one or more heaters arranged to raise the temperature of the substrate for in situ cleaning.

14. The apparatus of claim 12 , further including an optical energy source arranged to deliver optical energy to the substrate to heat the substrate for in situ cleaning.

15. The apparatus of claim 12 , wherein the holder includes on or more apertures formed through the substrate so that charged particle can pass through the holder.

16. The apparatus of claim 12 , further including a current monitor arranged behind the substrate, the current monitor coupled to measure where on the substrate the ionized sample deposits based on where current is generated on the substrate.

17. The apparatus of claim 12 , wherein the sample preparation system is a mass spectrometer.

18. The apparatus of claim 12 , wherein the substrate is formed from a two-dimensional material.

19. The apparatus of claim 12 , further including an analysis subsystem arranged to receive the substrate.

20. The apparatus of claim 19 , wherein the analysis subsystem is one of a charged particle microscope, an imaging system, and force-based microscope.

21. The apparatus of claim 20 , wherein the charged particle microscope is one of a scanning electron microscope (SEM), a transmission electron microscope (TEM), and a dual-beam microscope that includes an SEM and a focused ion beam.

22. The apparatus of claim 21 , wherein the TEM is a cryogenic enabled TEM.

23. The apparatus of claim 21 , wherein the imaging system is a holographic imaging system.

Assignees

• Fei Co

Inventors

• Straw Marcus
• Grinfeld Dmitry
• Makarov Alexander
• Bahm Alan
• Torok Aaron
• Liu Kun
• Christian Joseph
• Gilbert Josh
• Nichols Tom
• Kosmoski Jeff

Classifications

• H01J49/4215

  Quadrupole mass filters (H01J49/4225 takes precedence) · 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

• H01J2237/05

  Arrangements for energy or mass analysis · CPC title

• H01J2237/2614

  Holography or phase contrast, phase related imaging in general, e.g. phase plates · CPC title

• G01N35/10

  Devices for transferring samples {or any liquids} to, in, or from, the analysis apparatus, e.g. suction devices, injection devices {(G01N35/0099 takes precedence)} · CPC title