# US 10,481,055 B2 · System and method for refilling cryogen in microscope cryogen holders

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- Number: US 10,481,055 B2
- Document ID: US10481055B2
- Status: Granted
- Kind: B2
- Application number: 15/671,711
- Filed: 2017-08-08
- Published: 2018-03-01
- Granted: 2019-11-19
- Earliest claimed: 2016-08-26
- Assignees: Simple Origin, Inc.
- Applicants: Simple Origin, Inc.
- Inventors: Pushkarraj Deshmukh
- Web page: https://patentgrep.com/patent/US10481055B2

## CPC

- G01N 1/42: Low-temperature sample treatment, e.g. cryofixation
- F25D 3/10: using liquefied gases, e.g. liquid air {(for cooling semiconductor devices H10W40/305)}
- G01F 23/246: {thermal devices}
- G01F 23/296: Acoustic waves
- G01F 23/804: {containing circuits handling parameters other than liquid level}
- H01J 37/26: Electron or ion microscopes; Electron or ion diffraction tubes
- F25D 2400/30: Quick freezing
- H01J 2237/002: Cooling arrangements
- H01J 2237/022: Avoiding or removing foreign or contaminating particles, debris or deposits on sample or tube
- H01J 2237/028: Particle traps
- H01J 2237/2001: Maintaining constant desired temperature
- 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)
- F25D: REFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR (refrigerated showcases A47F3/04; thermally-insulated vessels for domestic use A47J41/00; refrigerated vehicles, see the appropriate subclasses of classes B60 - B64; containers with thermal insulation in general B65D81/38; heat-transfer, heat-exchange or heat-storage materials, e.g. refrigerants, or materials for the production of heat or cold by chemical reactions other than by combustion C09K5/00; thermally-insulated vessels for liquefied or solidified gases F17C; air-conditioning or air-humidification F24F; refrigeration machines, plants, or systems F25B; cooling of instruments or comparable apparatus without refrigeration G12B)
- G01F: MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

A cryogen refilling system includes a reservoir assembly for holding cryogen and a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder. The delivery channel includes at least one control valve. The system also includes a sensor-lid assembly and a controller. The sensor-lid assembly includes a sensor assembly configured to detect a level of cryogen in the microscope cryogen holder. The controller is configured to receive sensor data from the sensor assembly, analyze the sensor data to determine whether the microscope cryogen holder requires refilling, and in response to determining that the microscope cryogen holder requires refilling, cause a valve control mechanism to open the at least one control valve of the delivery channel.

## Claims

### Claim 1

A cryogen refilling system for a microscope cryogen holder, comprising:
a reservoir assembly for holding cryogen;
a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder, wherein the delivery channel comprises at least one control valve;
a sensor-lid assembly comprising:
a sensor assembly configured to detect sensor data corresponding to a level of cryogen in the microscope cryogen holder, and
a lid assembly configured to be mounted over an opening of the microscope cryogen holder, the lid assembly further comprising:
a first opening configured to receive the sensor assembly, and
a second opening configured to:
receive a delivery nozzle via a nozzle receiving component that has a reentrant tube design, wherein the delivery nozzle is in fluid communication with the delivery channel; and
a controller, wherein the controller comprises:
a processor in communication with the sensor assembly, and
a computer-readable medium containing programming instructions that are configured to, when executed by the processor, cause the processor to:
receive sensor data from the sensor assembly,
analyze the sensor data to determine whether the microscope cryogen holder requires refilling, and
in response to determining that the microscope cryogen holder requires refilling, cause a valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 2 (depends on 1)

The cryogen refilling system of claim 1, wherein the sensor assembly comprises:
a probe element comprising a first end and a second end, wherein:
the first end of the probe element is in contact with liquid cryogen in the microscope cryogen holder when the microscope cryogen holder does not require refilling, and
a temperature of the second end the probe element changes when the first end is in contact with liquid cryogen in the microscope cryogen holder compared to when the first end is not in contact with liquid cryogen; and
a sensor element configured to collect temperature data corresponding to a temperature of the second end and transmit the temperature data to the processor.

### Claim 3 (depends on 2)

The cryogen refilling system of claim 2, wherein the programming instructions that are configured to, when executed by the processor, cause the processor to analyze the temperature data to determine whether the microscope cryogen holder requires refilling, further comprise instructions to determine whether the temperature of the second end is above a threshold temperature.

### Claim 4 (depends on 3)

The cryogen refilling system of claim 3, wherein the threshold temperature is selected from the group comprising: about 20° C. to about −100° C., about 10° C. to about −90° C., about 0° C. to about −80° C., about −10° C. to about −70° C., about −20° C. to about −60° C., about −30° C. to about −50° C., about 20° C., about 10° C., about 0° C. about −10° C., about −20° C., about −30° C., about −40° C., about −50° C., about −60° C., about −70° C., about −80° C., about −90° C., about −100° C.

### Claim 5 (depends on 1)

The cryogen refilling system of claim 1, wherein the sensor assembly is configured to have a reentrant tube design.

### Claim 6 (depends on 1)

The cryogen refilling system of claim 1, further comprising a support frame, wherein:
the support frame comprises an arm segment and a vertical segment; and
the reservoir assembly is mounted on the arm segment via a sliding unit.

### Claim 7 (depends on 6)

The cryogen refilling system of claim 6, wherein the sliding unit is configured to move the reservoir assembly along an axis parallel to a length of the arm segment.

### Claim 8 (depends on 1)

The cryogen refilling system of claim 1, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, in response to determining that the microscope cryogen holder requires refilling, cause movement of at least one component of the cryogen refilling system such that the reservoir assembly is positioned to supply liquid cryogen to the microscope cryogen holder, before causing the valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 9 (depends on 1)

The cryogen refilling system of claim 1, wherein the reservoir assembly is configured to supply cryogen to the microscope cryogen holder using one or more of the following: gravity feeding, an external pump, or pressure feeding.

### Claim 10 (depends on 1)

The cryogen refilling system of claim 1, wherein the reservoir assembly is configured to hold about 5 litres to about 25 litres of liquid cryogen.

### Claim 11 (depends on 1)

The cryogen refilling system of claim 1, wherein the sensor assembly comprises a sensor element configured to collect sensor data corresponding to a change in cryogen level of the microscope cryogen holder and transmit the sensor data to the processor.

### Claim 12 (depends on 11)

The cryogen refilling system of claim 11, wherein the sensor element comprises an ultrasound sensor.

### Claim 13 (depends on 1)

The cryogen refilling system of claim 1, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, after causing the valve control mechanism to open the at least one control valve of the delivery channel:
analyze the sensor data to determine whether a cryogen level in the microscope cryogen holder has reached a threshold level; and
in response to determining that the cryogen level in the microscope cryogen holder has reached the threshold level, cause the valve control mechanism to close the at least one control valve of the delivery channel.

### Claim 14

A cryogen refilling system for a microscope cryogen holder, comprising:
a reservoir assembly for holding cryogen;
a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder, wherein the delivery channel comprises at least one control valve;
a sensor-lid assembly comprising a sensor assembly configured to detect sensor data corresponding to a level of cryogen in the microscope cryogen holder, wherein the sensor assembly is configured to have a reentrant tube design; and
a controller, wherein the controller comprises:
a processor in communication with the sensor assembly, and
a computer-readable medium containing programming instructions that are configured to, when executed by the processor, cause the processor to:
periodically, cause a valve control mechanism to open the at least one control valve of the delivery channel to deliver cryogen to the microscope cryogen holder,
receive sensor data from the sensor assembly,
analyze the sensor data to determine whether cryogen level in the microscope cryogen holder has reached a threshold level, and
in response to determining that the cryogen level in the microscope cryogen holder has reached the threshold level, cause the valve control mechanism to close the at least one control valve of the delivery channel.

### Claim 15

A cryogen refilling system for a microscope cryogen holder, comprising:
a reservoir assembly for holding cryogen;
a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder, wherein the delivery channel comprises at least one control valve;
a sensor-lid assembly comprising a sensor assembly configured to detect sensor data corresponding to a level of cryogen in the microscope cryogen holder, wherein the sensor assembly is configured to have a reentrant tube design; and
a controller, wherein the controller comprises:
a processor in communication with the sensor assembly, and
a computer-readable medium containing programming instructions that are configured to, when executed by the processor, cause the processor to:
receive sensor data from the sensor assembly,
analyze the sensor data to determine whether the microscope cryogen holder requires refilling, and
in response to determining that the microscope cryogen holder requires refilling, cause a valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 16 (depends on 15)

The cryogen refilling system of claim 15, wherein the sensor assembly comprises:
a probe element comprising a first end and a second end, wherein:
the first end of the probe element is in contact with liquid cryogen in the microscope cryogen holder when the microscope cryogen holder does not require refilling, and
a temperature of the second end the probe element changes when the first end is in contact with liquid cryogen in the microscope cryogen holder compared to when the first end is not in contact with liquid cryogen; and
a sensor element configured to collect temperature data corresponding to a temperature of the second end and transmit the temperature data to the processor.

### Claim 17 (depends on 16)

The cryogen refilling system of claim 16, wherein the programming instructions that are configured to, when executed by the processor, cause the processor to analyze the temperature data to determine whether the microscope cryogen holder requires refilling, further comprise instructions to determine whether the temperature of the second end is above a threshold temperature.

### Claim 18 (depends on 17)

The cryogen refilling system of claim 17, wherein the threshold temperature is selected from the group comprising: about 20° C. to about −100° C., about 10° C. to about −90° C., about 0° C. to about −80° C., about −10° C. to about −70° C., about −20° C. to about −60° C., about −30° C. to about −50° C., about 20° C., about 10° C., about 0° C. about −10° C., about −20° C., about −30° C., about −40° C., about −50° C., about −60° C., about −70° C., about −80° C., about −90° C., about −100° C.

### Claim 19 (depends on 15)

The cryogen refilling system of claim 15, wherein the sensor-lid assembly further comprises a lid assembly configured to be mounted over an opening of the microscope cryogen holder.

### Claim 20 (depends on 19)

The cryogen refilling system of claim 19, wherein the lid assembly comprises:
a first opening configured to receive the sensor assembly; and
a second opening configured to receive a delivery nozzle, wherein the delivery nozzle is in fluid communication with the delivery channel.

### Claim 21 (depends on 15)

The cryogen refilling system of claim 15, further comprising a support frame, wherein:
the support frame comprises an arm segment and a vertical segment; and
the reservoir assembly is mounted on the arm segment via a sliding unit.

### Claim 22 (depends on 21)

The cryogen refilling system of claim 21, wherein the sliding unit is configured to move the reservoir assembly along an axis parallel to a length of the arm segment.

### Claim 23 (depends on 15)

The cryogen refilling system of claim 15, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, in response to determining that the microscope cryogen holder requires refilling, cause movement of at least one component of the cryogen refilling system such that the reservoir assembly is positioned to supply liquid cryogen to the microscope cryogen holder, before causing the valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 24 (depends on 15)

The cryogen refilling system of claim 15, wherein the reservoir assembly is configured to supply cryogen to the microscope cryogen holder using one or more of the following: gravity feeding, an external pump, or pressure feeding.

### Claim 25 (depends on 15)

The cryogen refilling system of claim 15, wherein the reservoir assembly is configured to hold about 5 litres to about 25 litres of liquid cryogen.

### Claim 26 (depends on 15)

The cryogen refilling system of claim 15, wherein the sensor assembly comprises a sensor element configured to collect sensor data corresponding to a change in cryogen level of the microscope cryogen holder and transmit the sensor data to the processor.

### Claim 27 (depends on 26)

The cryogen refilling system of claim 26, wherein the sensor element comprises an ultrasound sensor.

### Claim 28 (depends on 15)

The cryogen refilling system of claim 15, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, after causing the valve control mechanism to open the at least one control valve of the delivery channel:
analyze the sensor data to determine whether a cryogen level in the microscope cryogen holder has reached a threshold level; and
in response to determining that the cryogen level in the microscope cryogen holder has reached the threshold level, cause the valve control mechanism to close the at least one control valve of the delivery channel.

### Claim 29

A cryogen refilling system for a microscope cryogen holder, comprising:
a reservoir assembly for holding cryogen;
a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder, wherein the delivery channel comprises at least one control valve;
a sensor-lid assembly comprising a sensor assembly configured to detect sensor data corresponding to a level of cryogen in the microscope cryogen holder;
a support frame, wherein:
the support frame comprises an arm segment and a vertical segment, and
the reservoir assembly is mounted on the arm segment via a sliding unit configured to move the reservoir assembly along an axis parallel to a length of the arm segment; and
a controller, wherein the controller comprises:
a processor in communication with the sensor assembly, and
a computer-readable medium containing programming instructions that are configured to, when executed by the processor, cause the processor to:
receive sensor data from the sensor assembly,
analyze the sensor data to determine whether the microscope cryogen holder requires refilling, and
in response to determining that the microscope cryogen holder requires refilling, cause a valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 30 (depends on 29)

The cryogen refilling system of claim 29, wherein the sensor assembly comprises:
a probe element comprising a first end and a second end, wherein:
the first end of the probe element is in contact with liquid cryogen in the microscope cryogen holder when the microscope cryogen holder does not require refilling, and
a temperature of the second end the probe element changes when the first end is in contact with liquid cryogen in the microscope cryogen holder compared to when the first end is not in contact with liquid cryogen; and
a sensor element configured to collect temperature data corresponding to a temperature of the second end and transmit the temperature data to the processor.

### Claim 31 (depends on 30)

The cryogen refilling system of claim 30, wherein the programming instructions that are configured to, when executed by the processor, cause the processor to analyze the temperature data to determine whether the microscope cryogen holder requires refilling, further comprise instructions to determine whether the temperature of the second end is above a threshold temperature.

### Claim 32 (depends on 31)

The cryogen refilling system of claim 31, wherein the threshold temperature is selected from the group comprising: about 20° C. to about −100° C., about 10° C. to about −90° C., about 0° C. to about −80° C., about −10° C. to about −70° C., about −20° C. to about −60° C., about −30° C. to about −50° C., about 20° C., about 10° C., about 0° C. about −10° C., about −20° C., about −30° C., about −40° C., about −50° C., about −60° C., about −70° C., about −80° C., about −90° C., about −100° C.

### Claim 33 (depends on 29)

The cryogen refilling system of claim 29, wherein the sensor-lid assembly further comprises a lid assembly configured to be mounted over an opening of the microscope cryogen holder.

### Claim 34 (depends on 33)

The cryogen refilling system of claim 33, wherein the lid assembly comprises:
a first opening configured to receive the sensor assembly; and
a second opening configured to receive a delivery nozzle, wherein the delivery nozzle is in fluid communication with the delivery channel.

### Claim 35 (depends on 29)

The cryogen refilling system of claim 29, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, in response to determining that the microscope cryogen holder requires refilling, cause movement of at least one component of the cryogen refilling system such that the reservoir assembly is positioned to supply liquid cryogen to the microscope cryogen holder, before causing the valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 36 (depends on 29)

The cryogen refilling system of claim 29, wherein the reservoir assembly is configured to supply cryogen to the microscope cryogen holder using one or more of the following: gravity feeding, an external pump, or pressure feeding.

### Claim 37 (depends on 29)

The cryogen refilling system of claim 29, wherein the reservoir assembly is configured to hold about 5 litres to about 25 litres of liquid cryogen.

### Claim 38 (depends on 29)

The cryogen refilling system of claim 29, wherein the sensor assembly comprises a sensor element configured to collect sensor data corresponding to a change in cryogen level of the microscope cryogen holder and transmit the sensor data to the processor.

### Claim 39 (depends on 38)

The cryogen refilling system of claim 38, wherein the sensor element comprises an ultrasound sensor.

### Claim 40 (depends on 29)

The cryogen refilling system of claim 29, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, after causing the valve control mechanism to open the at least one control valve of the delivery channel:
analyze the sensor data to determine whether a cryogen level in the microscope cryogen holder has reached a threshold level; and
in response to determining that the cryogen level in the microscope cryogen holder has reached the threshold level, cause the valve control mechanism to close the at least one control valve of the delivery channel.

### Claim 41

A cryogen refilling system for a microscope cryogen holder, comprising:
a reservoir assembly for holding cryogen;
a delivery channel in fluid communication with the reservoir assembly for delivering cryogen from the reservoir assembly to a microscope cryogen holder, wherein the delivery channel comprises at least one control valve;
a sensor-lid assembly comprising a sensor assembly configured to detect sensor data corresponding to a level of cryogen in the microscope cryogen holder; and
a controller, wherein the controller comprises:
a processor in communication with the sensor assembly, and
a computer-readable medium containing programming instructions that are configured to, when executed by the processor, cause the processor to:
receive sensor data from the sensor assembly,
analyze the sensor data to determine whether the microscope cryogen holder requires refilling, and
in response to determining that the microscope cryogen holder requires refilling:
cause movement of at least one component of the cryogen refilling system such that the reservoir assembly is positioned to supply liquid cryogen to the microscope cryogen holder, and
upon positioning of the reservoir assembly, cause a valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 42 (depends on 41)

The cryogen refilling system of claim 41, wherein the sensor assembly comprises:
a probe element comprising a first end and a second end, wherein:
the first end of the probe element is in contact with liquid cryogen in the microscope cryogen holder when the microscope cryogen holder does not require refilling, and
a temperature of the second end the probe element changes when the first end is in contact with liquid cryogen in the microscope cryogen holder compared to when the first end is not in contact with liquid cryogen; and
a sensor element configured to collect temperature data corresponding to a temperature of the second end and transmit the temperature data to the processor.

### Claim 43 (depends on 42)

The cryogen refilling system of claim 42, wherein the programming instructions that are configured to, when executed by the processor, cause the processor to analyze the temperature data to determine whether the microscope cryogen holder requires refilling, further comprise instructions to determine whether the temperature of the second end is above a threshold temperature.

### Claim 44 (depends on 43)

The cryogen refilling system of claim 43, wherein the threshold temperature is selected from the group comprising: about 20° C. to about −100° C., about 10° C. to about −90° C., about 0° C. to about −80° C., about −10° C. to about −70° C., about −20° C. to about −60° C., about −30° C. to about −50° C., about 20° C., about 10° C., about 0° C. about −10° C., about −20° C., about −30° C., about −40° C., about −50° C., about −60° C., about −70° C., about −80° C., about −90° C., about −100° C.

### Claim 45 (depends on 41)

The cryogen refilling system of claim 41, wherein the sensor-lid assembly further comprises a lid assembly configured to be mounted over an opening of the microscope cryogen holder.

### Claim 46 (depends on 45)

The cryogen refilling system of claim 45, wherein the lid assembly comprises:
a first opening configured to receive the sensor assembly; and
a second opening configured to receive a delivery nozzle, wherein the delivery nozzle is in fluid communication with the delivery channel.

### Claim 47 (depends on 41)

The cryogen refilling system of claim 41, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, in response to determining that the microscope cryogen holder requires refilling, cause movement of at least one component of the cryogen refilling system such that the reservoir assembly is positioned to supply liquid cryogen to the microscope cryogen holder, before causing the valve control mechanism to open the at least one control valve of the delivery channel.

### Claim 48 (depends on 41)

The cryogen refilling system of claim 41, wherein the reservoir assembly is configured to supply cryogen to the microscope cryogen holder using one or more of the following: gravity feeding, an external pump, or pressure feeding.

### Claim 49 (depends on 41)

The cryogen refilling system of claim 41, wherein the reservoir assembly is configured to hold about 5 litres to about 25 litres of liquid cryogen.

### Claim 50 (depends on 49)

The cryogen refilling system of claim 49, wherein the sensor assembly comprises a sensor element configured to collect sensor data corresponding to a change in cryogen level of the microscope cryogen holder and transmit the sensor data to the processor.

### Claim 51 (depends on 50)

The cryogen refilling system of claim 50, wherein the sensor element comprises an ultrasound sensor.

### Claim 52 (depends on 41)

The cryogen refilling system of claim 41, further comprising programming instructions that are configured to, when executed by the processor, cause the processor to, after causing the valve control mechanism to open the at least one control valve of the delivery channel:
analyze the sensor data to determine whether a cryogen level in the microscope cryogen holder has reached a threshold level; and
in response to determining that the cryogen level in the microscope cryogen holder has reached the threshold level, cause the valve control mechanism to close the at least one control valve of the delivery channel.