Method for temperature monitoring in cryo-electron microscopy

A technology of temperature sensor and electric current, applied in the direction of low temperature temperature measurement, low temperature thermostat, thermometer, etc.

Pending Publication Date: 2021-10-01
FEI CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In some cases, a significant amount of instrument time may be required to process the sample, only to discover later that the sample has not been properly maintained at the proper temperature

Method used

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  • Method for temperature monitoring in cryo-electron microscopy
  • Method for temperature monitoring in cryo-electron microscopy
  • Method for temperature monitoring in cryo-electron microscopy

Examples

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example 1

[0026] refer to figure 1 , a representative electron microscope system 100 includes an electron emitter 104 operable to emit electrons from a tip 106 . Condenser lens 110 is positioned to generate an electron beam from the emitted electrons and to direct the electron beam generally along axis 119 . Beam deflector 111 is positioned along axis 119 and can selectively deflect or scan the electron beam relative to sample S and generate deflected beam 130 . The sample S is positioned on a sample stage 140, which allows for translation and tilt adjustment of the sample S. The sample S is typically fixed to or formed on a sample holder 144, which may include a sensing region 142 formed from HTSC or other sensor material. Objective lens 132 is positioned to direct the electron beam from sample S to detector 146 . In some examples, one or more detectors, such as detector 148, are positioned to detect the electron beam or radiation responsive to the electron beam, such as secondary e...

example 2

[0035] exist figure 1 A representative sample holder used in the system 900 in Figures 9A-9B shown in . A perforated carbon film 904 is positioned to support a sample 903 (shown as one or more cells 902 ), and in turn is positioned on a metal grid 906 . Metal ring 908 is coupled to the perimeter of metal grid 906 . The temperature sensor material 910 is positioned at or on the metal ring 908, but may be positioned in other ways as discussed below.

example 3

[0037] refer to Figure 3A , a representative sample holder 380 includes a conductive grid 382 typically formed of a conductive perimeter ring 384, typically Cu, Rh, Au, or other metal. The regions between the gridlines may include a thin film, such as an amorphous carbon film with a plurality of holes or perforations. Such membranes are often referred to as "porous carbon membranes" and the samples to be studied can typically be fixed on the membrane by snap freezing. A temperature sensor 386 is positioned on the perimeter ring 384, and additional sensors may be provided on the perimeter ring 384, the conductive grid 382, ​​or the area between the grid lines. The following examples generally refer to the configuration of the temperature sensor, and details of sample mounting of such carbon films are omitted in some cases for ease of illustration.

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Abstract

The invention relates to a method for temperature monitoring in a cryo-electron microscopy. Temperatures of cryo-electron microscopy samples are assessed based on images portions associated with high temperature superconductor (HTSC) areas or other thermal sensor materials that are thermally coupled to or thermally proximate the samples. Such thermal areas can be provided on sample mounts such as metallic grids, carbon films, or on sample stages. In examples using HTSCs, HTSCs having critical temperatures between -175 DEG C and -135 DEG C are typically used.

Description

technical field [0001] The present disclosure relates to assessing sample temperature in cryo-electron microscopy. Background technique [0002] Cryo-electron tomography (cryo-ET) is based on a freezing technique that traps cellular water in an amorphous (glassy) layer within which all cellular components are embedded. This process is called vitrification. It is generally necessary to keep samples at temperatures below about -135°C to avoid devitrification or degradation, but in most cases temperatures below -150°C are preferred to provide a margin of error. In many cases, it is difficult to assess the temperature of such small samples, and to determine whether they have been properly maintained at cryogenic temperatures. This is especially challenging after mounting the sample on the electron microscope substrate stage. If the sample is not properly maintained at low temperature, the sample will no longer exhibit its original structure. In some cases, significant instru...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N23/203G01N23/225
CPCG01N23/203G01N23/225G01N2223/053G01N2223/071G01N2223/102H01J2237/2001H01J2237/24585H01J37/20B01L7/50G01K2203/00G01N1/2813G01N1/42H01J37/26H01J2237/2065
Inventor J·德拉霍斯基
Owner FEI CO
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