# US 9,752,814 B2 · Cooling apparatus used for cryonic preservation, and corresponding operating method

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- Number: US 9,752,814 B2
- Document ID: US9752814B2
- Status: Granted
- Kind: B2
- Application number: 14/047,570
- Filed: 2013-10-07
- Published: 2014-02-06
- Granted: 2017-09-05
- Earliest claimed: 2003-10-08
- Assignees: Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.
- Applicants: Fraunhofer-Gesellschaft zur Foerderung der angewandten Forschung, e.V.
- Inventors: Uwe Schon; Heiko Zimmermann; Guenter Fuhr
- Web page: https://patentgrep.com/patent/US9752814B2

## CPC

- F25D 3/10: using liquefied gases, e.g. liquid air {(for cooling semiconductor devices H10W40/305)}
- A01N 1/10: Preservation of living parts
- A01N 1/145: Stationary or portable vessels generating cryogenic temperatures, e.g. liquid nitrogen baths
- F25D 29/001: {for cryogenic fluid systems}
- G01N 1/42: Low-temperature sample treatment, e.g. cryofixation
- B01L 7/00: Heating or cooling apparatus (autoclaves B01J3/04); Heat insulating devices
- F25D 2700/12: Sensors measuring the inside temperature
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

The invention relates to a cooling apparatus, especially for cryogenically preserving biological samples, including a duct (5) for delivering a coolant (3) to a cooling chamber (1), a heater (6) that has an adjustable first heating performance (P2) for heating the coolant (3) delivered to the cooling chamber (1), a first temperature sensor (8-10) for measuring the temperature (T2-T4) in the cooling chamber (1), a second temperature sensor (7) for measuring the temperature (Ti) of the coolant (3) delivered to the cooling chamber (I), and a regulator (11) for regulating the temperature. The regulator (11) is embodied as a multiple regulator which detects several temperatures (T1-T4) as control variables and/or adjusts several heating performances (P1, P2) as manipulated variables. The invention further relates to a corresponding operating method.

## Claims

### Claim 1

Cooling equipment, comprising:
a) a cooling agent storage container housing a cooling agent;
b) a non-recirculating cooling chamber;
c) a cooling agent supply line connected to the cooling agent storage container for supplying the cooling agent to the non-recirculating cooling chamber;
d) an antechamber in fluid communication between the cooling agent supply line and the cooling chamber, said antechamber including a diffuser spatially diffusing the cooling agent directly from the cooling agent supply line into distinct channels for supply to the cooling chamber;
e) a heater with an adjustable first heating performance for heating the cooling agent supplied to the cooling chamber, wherein the heater is integrated in the cooling agent supply line;
f) an evaporator in the cooling agent storage container with an adjustable second heating performance for evaporating the cooling agent present in the cooling agent storage container;
g) a first temperature sensor for measuring the temperature in the cooling chamber;
h) a second temperature sensor for measuring an agent temperature of the cooling agent supplied to the cooling chamber; and
i) a controller for temperature control, the controller having an input side and an output side, the input side connected to the first temperature sensor and the second temperature sensor, the output side connected to the heater and the evaporator, wherein the controller:
(i) is adapted to detect several temperatures from said first temperature sensor and said second temperature sensor as control variables;
(ii) is a multiple controller; and
(iii) adjusts said first heating performance and said second heating performance as manipulated variables based on said temperatures detected by said first temperature sensor and said second temperature sensor;
wherein said multiple controller includes:
a first control circuit that detects temperature from the first temperature sensor in the cooling chamber as a first control variable and adjusts said adjustable second heating performance of the evaporator as a first manipulated variable based on the first control variable; and
a second control circuit that detects temperature from the second temperature sensor measuring temperature of the cooling agent before entering the cooling chamber as a second control variable and adjusts said adjustable first heating performance of the heater as a second manipulated variable based on the second control variable;
wherein the heater is between the evaporator and the first temperature sensor, and the first temperature sensor controls the evaporator; and
wherein the second temperature sensor is between the evaporator and the first temperature sensor, and the second temperature sensor controls the heater.

### Claim 2 (depends on 1)

The cooling equipment according to claim 1, wherein several temperature sensors connected to the controller are provided for measuring the chamber temperature in the cooling chamber.

### Claim 3 (depends on 2)

The cooling equipment according to claim 2, wherein the temperature sensors are arranged in a spatially distributed manner for measuring a spatial distribution of temperature.

### Claim 4 (depends on 2)

The cooling equipment according to claim 2, wherein at least one of the temperature sensors is a thermocouple and at least one of the temperature sensors is a temperature-dependent electrical resistor.

### Claim 5 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling agent is nitrogen.

### Claim 6 (depends on 1)

The cooling equipment according to claim 1, wherein the first temperature sensor and the second temperature sensor are connected to storage equipment that stores temperature courses.

### Claim 7 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling agent supply line is adapted to empty via the diffuser into the cooling chamber.

### Claim 8 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling agent supply line is adapted to empty laterally into the cooling chamber.

### Claim 9 (depends on 8)

The cooling equipment according to claim 8, wherein the cooling agent supply line is adapted to empty into the cooling chamber only on one side of the cooling chamber.

### Claim 10 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling agent supply line is adapted to empty into the cooling chamber at the top of the cooling chamber.

### Claim 11 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling chamber is closed.

### Claim 12 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling chamber is open on its bottom.

### Claim 13 (depends on 1)

The cooling equipment according to claim 1, wherein the cooling chamber is portable.

### Claim 14 (depends on 1)

The cooling equipment according to claim 1, wherein the first temperature sensor is arranged inside the cooling chamber and at an interval from a wall of the cooling chamber.

### Claim 15 (depends on 14)

The cooling equipment according to claim 14, wherein the first temperature sensor is fastened to the cooling chamber by holding equipment extending into the cooling chamber.

### Claim 16 (depends on 14)

The cooling equipment according to claim 14, wherein the first temperature sensor is attached to a sample or to a sample holder.

### Claim 17 (depends on 1)

The cooling equipment according to claim 1, wherein the first temperature sensor is connected to a transponder that transmits a measured temperature in a wireless manner to the controller.

### Claim 18 (depends on 17)

The cooling equipment according to claim 17, wherein the transponder is selected from the group consisting of a radio transponder, an ultrasonic transponder, an optical transponder and an infrared transponder.

### Claim 19

An operating method for cooling equipment, said method comprising:
a) introducing a cooling agent from a cooling agent supply line into a non-recirculating cooling chamber for cooling cooled material, the introducing step including spatially diffusing the cooling agent directly from the cooling agent supply line into distinct channels for supply of the cooling agent to the non-recirculating cooling chamber via a diffuser of an antechamber in fluid communication between the cooling agent supply line and the non-recirculating cooling chamber;
b) heating with a heater the cooling agent prior to the introducing step with an adjustable first heating performance;
c) measuring an agent temperature of the heated cooling agent prior to being supplied to the cooling chamber;
d) measuring of a chamber temperature in the non-recirculating cooling chamber; and
e) controlling the agent temperature and the chamber temperature in that both temperatures are detected as control variables, including controlling the adjustment of a second heating performance of said cooling agent prior to heating in step b) as another manipulated variable in addition to controlling of the first heating performance based on said measured agent temperature and said measured chamber temperature;
wherein step e) includes the steps of:
detecting temperature in the cooling chamber as a first control variable and adjusting heating performance of an evaporator in a cooling agent storage container that supplies the cooling agent to the cooling chamber as a first manipulated variable based on the first control variable; and
detecting temperature of the cooling agent after leaving the cooling agent storage container and before entering the cooling chamber as a second control variable and adjusting the heating in step b) as a second manipulated variable based on the second control variable, wherein the heating is after the cooling agent storage container;
wherein the heater is between the evaporator and a first temperature sensor that detects temperature in the cooling chamber, and the first temperature sensor controls the evaporator; and
wherein a second temperature sensor that detects temperature of the cooling agent after leaving the cooling agent storage container and before entering the cooling chamber is between the evaporator and the first temperature sensor, and the second temperature sensor controls the heater.

### Claim 20 (depends on 19)

The operating method according to claim 19, further comprising the following steps:
f) evaporating the liquid cooling agent in a cooling agent storage container with an adjustable second heating performance to provide an evaporated cooling agent;
g) heating the evaporated cooling agent prior to the introducing step with the adjustable first heating performance; and
h) multiple controlling of the first heating performance and of the second heating performance.

### Claim 21 (depends on 19)

The operating method according to claim 19, further comprising the following steps:
f) measuring of several spatially distributed temperatures inside the cooling chamber; and
g) multiple controlling of the first heating performance and of the second heating performance as a function of the different temperatures inside the cooling chamber.

### Claim 22 (depends on 19)

The operating method according to claim 19, further comprising the following steps:
f) measuring with a thermocouple the chamber temperature and the agent temperature prior to the introducing step;
g) measuring with a temperature-dependent resistor the chamber temperature and the agent temperature prior to the introducing step; and
h) multiple controlling of the first heating performance and of the second heating performance as a function of temperatures measured by the thermocouple and of temperatures measured by the temperature-dependent resistor.

### Claim 23 (depends on 19)

The operating method according to claim 19, further comprising the following steps:
f) setting a target value in the cooling chamber,
g) controlling the agent temperature of the cooling agent entering into the cooling chamber in accordance with the target value set for the cooling chamber by adjusting the first heating performance.

### Claim 24 (depends on 23)

The operating method according to claim 23, wherein the agent temperature of the cooling agent entering into the cooling chamber is controlled to the target value for the chamber temperature in the cooling chamber.

### Claim 25 (depends on 1)

A method of cryopreserving a biological sample comprising cooling the biological sample in the cooling equipment according to claim 1.

### Claim 26 (depends on 1)

The cooling equipment according to claim 1, wherein the second temperature sensor measures temperature at a location before the cooling chamber and after the evaporator.