# US 11,307,020 B2 · Sample thickness measuring arrangement and method for measuring a thickness of a sample at cryogenic temperature by interferometry using a cryostat

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- Number: US 11,307,020 B2
- Document ID: US11307020B2
- Status: Granted
- Kind: B2
- Application number: 17/273,514
- Filed: 2019-09-13
- Published: 2021-11-04
- Granted: 2022-04-19
- Earliest claimed: 2018-09-18
- Assignees: European Molecular Biology Laboratory
- Applicants: European Molecular Biology Laboratory
- Inventors: Florent Cipriani; Gergely Papp
- Web page: https://patentgrep.com/patent/US11307020B2

## CPC

- G01B 11/06: for measuring thickness {; e.g. of sheet material (thickness measurement by thermal means G01B21/085)}
- G01N 1/42: Low-temperature sample treatment, e.g. cryofixation
- G01B: MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A sample thickness measuring arrangement and method for measuring a thickness of a sample are proposed. The sample thickness measuring arrangement comprises a sample thickness measuring unit for measuring the thickness of a sample based on interferometry. Furthermore, it comprises a cryostat comprising a coolant reservoir and a sample observation unit for observing characteristics of a sample. The sample observation unit comprises a tube enclosing an observation volume, a thermal tube insulation layer and a window arrangement. The tube is open at a distal end and at a proximal end. The distal end of the tube is arranged. within a storage volume of the coolant reservoir. The tube has two lateral openings in its tube walls at opposing sides with regards to the observation volume. The tube walls are covered at their external side with the thermal tube insulation layer having two openings adjacent to the openings in the tube walls. The window arrangement comprises two opposing panes, each pane being arranged at one of the openings in the thermal insulation layer. The panes are transparent to light of a laser beam. The proposed approach enable precise and stable sample thickness measurements at cryogenic temperatures.

## Claims

### Claim 1

Cryostat comprising:
a coolant reservoir for storing liquid coolant; and
a sample observation unit for observing characteristics of a sample;
wherein the coolant reservoir comprises a vessel enclosing a storage volume with walls of the vessel being thermally insulated with a thermal reservoir insulation layer such as to enable storing liquid coolant at temperatures below 150 K;
wherein the sample observation unit comprises:
a tube having tube walls enclosing a tube volume including an observation volume;
a thermal tube insulation layer; and
a window arrangement;
wherein the tube is open at a distal end and at a proximal end;
wherein the distal end of the tube is arranged within the storage volume of the coolant reservoir;
wherein the tube has two lateral openings in its tube walls at opposing sides with regards to the observation volume;
wherein the tube walls are covered at their external side with the thermal tube insulation layer;
wherein the thermal tube insulation layer has two openings adjacent to the openings in the tube walls, and
wherein the window arrangement comprises two opposing panes, each pane being arranged at one of the openings in the thermal insulation layer, the panes being transparent to light of a laser beam.

### Claim 2 (depends on 1)

Cryostat according to claim 1, wherein the tube is made with metal.

### Claim 3 (depends on 2)

Cryostat according to claim 2, wherein the panes are made with at least one of glass and transparent plastics.

### Claim 4 (depends on 2)

Cryostat according to claim 2, wherein the panes have a thickness of more than half of a thickness of the thermal tube insulation layer.

### Claim 5 (depends on 1)

Cryostat according to claim 1, wherein the tube is made with copper.

### Claim 6 (depends on 5)

Cryostat according to claim 5, wherein the panes are made with at least one of glass and transparent plastics.

### Claim 7 (depends on 5)

Cryostat according to claim 5, wherein the panes have a thickness of more than half of a thickness of the thermal tube insulation layer.

### Claim 8 (depends on 1)

Cryostat according to claim 1, wherein the panes are made with at least one of glass and transparent plastics.

### Claim 9 (depends on 8)

Cryostat according to claim 8, wherein the panes have a thickness of more than half of a thickness of the thermal tube insulation layer.

### Claim 10 (depends on 1)

Cryostat according to claim 1, wherein the panes have a thickness of more than half of a thickness of the thermal tube insulation layer.

### Claim 11 (depends on 1)

Cryostat according to claim 1, wherein the panes are hollow.

### Claim 12 (depends on 1)

Cryostat according to claim 1, further comprising a sample holder being arranged and configured for holding a sample within the observation volume of the sample observation unit at a location within the tube between the opposing panes.

### Claim 13 (depends on 12)

Cryostat according to claim 12, wherein the sample holder comprises tweezers for holding the sample in the observation volume.

### Claim 14 (depends on 12)

Cryostat according to claim 12, wherein the sample holder comprises a mechanically stabilizing core being made with a first material and an outer sheath enclosing at least a sample holding portion of the sample holder, the outer sheath being made with a second material having a lower thermal conductivity than the first material.

### Claim 15 (depends on 12)

Cryostat according to claim 12, wherein the sample holder is made with at least one of plastics, resin, glass loaded plastics and glass loaded resin.

### Claim 16 (depends on 1)

Sample thickness measuring arrangement comprising:
a cryostat according to claim 1;
a sample thickness measuring unit being arranged and configured for transmitting a laser beam through the window arrangement of the sample observation unit and for determining the thickness of a sample based on interferometry measurements with the transmitted laser beam.

### Claim 17 (depends on 16)

Sample thickness measuring arrangement according to claim 16, wherein the sample thickness measuring unit is configured for determining the thickness of the sample at various locations throughout the sample and for providing a 2-dimensional map representing the determined sample thicknesses.

### Claim 18 (depends on 1)

Method for measuring a thickness of a sample, the method comprising:
providing a cryostat according to claim 1;
establishing a low temperature coolant gas flow through the tube of the sample observation unit of the cryostat;
inserting the sample into the observation volume of the sample observation unit; and
measuring the thickness of the sample by transmitting a laser beam through the window arrangement of the sample observation unit and determining the sample thickness based on interferometry measurements with the transmitted laser beam.

### Claim 19 (depends on 18)

Method of claim 18, wherein the sample thickness is determined at various locations throughout the sample and a 2-dimensional map representing the determined sample thicknesses is provided.

### Claim 20 (depends on 1)

Cryostat according to claim 1, further comprising a homogenator configured and arranged for reducing at least one of inhomogeneities and turbulences within a flow of coolant gas throughout the tube in an area at and upstream of the observation volume.
