Cell cooling device having cooling rate control function and cooling rate control method thereof
The cell cooling device addresses the challenge of uncontrolled cooling rates by using a temperature control system to manage the cooling process, ensuring precise temperature control and minimizing cell damage, thus enabling safe and effective cell cooling.
Patent Information
- Application Number
- PCT/KR2024/007790
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-07-19
- Filing Date
- 2024-06-07
- Publication Date
- 2025-01-23
AI Technical Summary
Conventional cell cooling devices lack precise control over the cooling rate, leading to potential damage from excessive cooling, which can result in side effects such as cell destruction, edema, blister formation, infection, pigment degeneration, and scar formation due to the rapid and uncontrolled cooling effects of coolants like liquid nitrogen and CO2.
A cell cooling device equipped with a coolant supply unit, a nozzle, a temperature control member that adjusts coolant temperature using electrical energy, and a control unit that monitors the cell surface temperature to maintain a predetermined cooling rate, ensuring the coolant reaches the target temperature efficiently and safely.
This solution allows for precise control of the cooling rate, minimizing unwanted cell damage and enabling effective cell death processes by adjusting the cooling rate in real-time based on temperature feedback, thereby preventing excessive cooling and ensuring cells are cooled to the desired temperature accurately.
Smart Images

Figure KR2024007790_23012025_PF_FP_ABST
Abstract
Description
Cell cooling device having cooling rate control function and cooling rate control method thereof
[0001] The present invention relates to a device for cooling cells and a method for controlling the same, and more particularly, to a cell cooling device having a cooling rate control function for cooling various cells (in vivo, in vitro) for therapeutic or experimental purposes, and a method for controlling the cooling rate thereof.
[0002] Currently, cooling devices are being used to safely block the nerves and metabolism of cells or perform various treatments through cooling for therapeutic or experimental purposes targeting various cells (in vivo, in vitro), and research related to this is actively being conducted.
[0003] As a cooling device conventionally used in the medical field, there is a skin cooling device disclosed in Korean Patent Publication No. 10-2010-0054097.
[0004] Published conventional technologies developed for medical local cooling utilize cryogenic coolants such as liquid nitrogen and dry ice for local cooling. However, the specific temperature of these coolants is significantly lower than the cell death temperature, making it difficult to reliably achieve cooling conditions that produce effects such as cryoanesthesia and immune activation, thus limiting their use in various clinical settings. This lack of technology fundamentally stems from the high specific heat capacity of cells, making it difficult to precisely control the temperature of coolants capable of delivering the high cooling output required for effective cell cooling at any temperature outside of their specific temperature range.
[0005] And conventional medical cooling devices use refrigerants such as liquid nitrogen and CO2, and the cooling effect is strong and fast due to the latent heat of the phase change of these refrigerants.
[0006] However, common medical coolants, including liquid nitrogen and CO2, have temperatures significantly lower than the temperature at which cells are physically destroyed. Failure to properly control the coolant temperature can cause the temperature in the treatment area to drop below the safe range, potentially causing excessive destruction of surrounding normal cells. Side effects resulting from this excessive destruction of normal cells include hematoma, edema, blistering, infection, pigmentation changes, paresthesia, and scarring.
[0007] To solve these problems, Korean Patent No. 10-2168702 discloses a medical cooling device that can stably implement cooling conditions required for various clinical effects, such as effective destruction of lesion cells, minimization of destruction of surrounding normal cells, cooling anesthesia, and immune activation by cooling, by spraying a coolant on the lesion cells.
[0008] The medical cooling device of the above-mentioned registered patent includes a cyclone generator having a first diagonal flow path formed therein to spray a coolant in a diagonal direction, and a cryogen cyclone generator that induces the coolant sprayed from the cyclone generator into a rotational motion, thereby enabling the coolant to reach a preset thermodynamic state with a rapid dynamic response by continuously maintaining the pressure of the coolant at a position adjacent to the cyclone generator, and providing an advantage in that the temperature of the coolant sprayed on the treatment site can be adjusted to a desired temperature by controlling the thermodynamic phase of the coolant just before it is sprayed on the treatment site.
[0009] However, conventional medical cooling devices, including the medical cooling device of the above-mentioned registered patent, do not control the cooling speed in the process of cooling cells by spraying a coolant, but are simply controlled to cool the cells at a target cooling speed. If the cooling proceeds too quickly or too slowly, there is a high possibility that the state of the cells will not be made into the intended state.
[0010] The present invention is intended to solve the above-mentioned problem, and an object of the present invention is to provide a cell cooling device and method having a cooling rate control function capable of accurately controlling the cooling rate in the process of cooling cells by spraying a coolant on the cells.
[0011] In order to achieve the above object, a cell cooling device having a cooling rate control function according to the present invention may include: a coolant supply unit for supplying a coolant; a nozzle for spraying a coolant supplied from the coolant supply unit toward a cell; a coolant temperature control unit having a temperature control unit for controlling the temperature of the coolant by heating or cooling the coolant supplied from the coolant supply unit to the nozzle while generating or absorbing heat by externally applied electric energy; a temperature sensor for detecting the surface temperature of the cell in a non-contact manner; and a control unit for controlling the operation of the temperature control unit for a set unit time such that the cooling rate of the cell follows a pre-input cooling rate and is cooled to a target temperature based on temperature information detected by the temperature sensor.
[0012] The above control unit controls the current temperature (T) within a set cooling rate. sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference As the temperature of the measured cell decreases, the electrical energy applied to the temperature control member can be controlled to decrease.
[0013] The above control unit changes the amount of heat energy of the temperature control member through PID control of the temperature control member. can control.
[0014] The above control unit can control the electric energy applied to the temperature control member so that the unit time becomes shorter as the set cooling speed becomes faster.
[0015] The above control unit can control the operation of the temperature control unit so that the cell is cooled to a target temperature at a predetermined cooling rate after the cell is pre-cooled to a predetermined starting temperature set in advance by the control unit.
[0016] A method for controlling the cooling speed of a cell cooling device according to the present invention may include the following steps.
[0017] (S1) A step of inputting a cooling rate, or unit time and cooling rate, for cell cooling control to the control unit;
[0018] (S2) A step in which the control unit operates the coolant temperature control unit and the coolant supply unit to inject coolant into the cell through the nozzle;
[0019] (S3) A step of detecting the surface temperature of a cell using a temperature sensor; and,
[0020] (S4) A step in which the control unit controls the operation of the temperature control member of the coolant temperature control unit by unit time so that the cell cooling rate follows a pre-input cooling rate based on the temperature information detected by the temperature sensor and is cooled to the target temperature.
[0021] In the above step (S4), the control unit determines the current temperature (T) within a set cooling rate. sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference As the temperature of the measured cell decreases, the electrical energy applied to the temperature control member can be controlled to decrease.
[0022] In the above step (S1), when only the cooling rate is input to the control unit, the control unit can set the unit time according to the cooling rate. At this time, in the above step (S4), the control unit can control the unit time to become shorter as the input cooling rate becomes faster.
[0023] Before performing the above step (S2), the control unit can precool the cell by spraying a coolant to the cell so that the temperature of the cell becomes a predetermined starting temperature.
[0024] According to the present invention, since the cooling rate is controlled to reach the target temperature in accordance with the unit time in each target temperature section for each unit time, cells can be precisely cooled to the desired target temperature and rate, and unwanted cell damage can be prevented or an effective cell death process can be induced.
[0025] Figure 1 is a schematic diagram showing the configuration of a cell cooling device according to one embodiment of the present invention.
[0026] Figure 2 is a graph explaining a cooling speed control method performed by a cell cooling device according to the present invention and a cooling speed control method performed by a conventional cell cooling device.
[0027] Figure 3 is a graph showing an example of cooling speed control using a conventional cell cooling device.
[0028] Figure 4 is a graph showing an example of cooling speed control by the cell cooling device of the present invention.
[0029]
[0030] <Explanation of symbols>
[0031] C: Cell 10: Coolant supply
[0032] 20: Solenoid valve 30: Coolant temperature control unit
[0033] 31: Reservoir 32: Temperature control member
[0034] 40: Nozzle 50: Temperature sensor
[0035] 60: Control unit
[0036] Hereinafter, a cell cooling device having a cooling rate control function and a cooling rate control method thereof according to embodiments of the present invention will be described in detail with reference to the attached drawings. The present invention may be modified in various ways and may take various forms, and specific embodiments will be illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to a specific disclosed form, but should be understood to include all modifications, equivalents, and substitutes included in the spirit and technical scope of the present invention. In describing each drawing, similar reference numerals are used to refer to similar components. In the attached drawings, the dimensions of structures are illustrated in an enlarged form compared to actual size to ensure clarity of the present invention, or in a reduced form compared to actual size to understand the schematic configuration.
[0037] Furthermore, while terms such as "first" and "second" may be used to describe various components, these components should not be limited by these terms. These terms are used solely to distinguish one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as the "second component," and similarly, the second component may also be referred to as the "first component." Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and shall not be interpreted in an idealized or overly formal sense unless explicitly defined herein.
[0038] FIG. 1 illustrates a configuration of a cell cooling device according to one embodiment of the present invention, and the cell cooling device may include a coolant supply unit (10) for supplying a coolant, a nozzle (40) for spraying the coolant supplied from the coolant supply unit (10) toward cells, a coolant temperature control unit (30) for controlling the temperature of the coolant supplied from the coolant supply unit (10) to the nozzle (40), a temperature sensor (50) for detecting the surface temperature of a target object, i.e., a cell (C), in a non-contact manner, and a control unit (60) for controlling the operation of the coolant temperature control unit (30) for each set unit time (Δt) so that the cooling rate of the cell (C) follows a pre-input cooling rate based on the temperature information detected by the temperature sensor (50) and is cooled to a target temperature.
[0039] The above coolant supply unit (10) may be configured to supply coolant stored in a storage container at a constant pressure using a pump or compressor. Liquid nitrogen, CO2, etc. may be used as the coolant.
[0040] A solenoid valve (20) for controlling the supply of coolant may be arranged in the passage between the coolant supply unit (10) and the coolant temperature control unit (30). The solenoid valve (20) is electrically connected to the control unit (60) and is turned on / off by an electric signal applied from the control unit (60) to open and close the passage, thereby controlling the supply of coolant from the coolant supply unit (10) to the coolant temperature control unit (30).
[0041] The coolant temperature control unit (30) is configured to control the temperature of the coolant supplied from the coolant supply unit (10) to the nozzle (40) and to control the cooling speed of the cell (C) by supplying the coolant to the nozzle (40). The coolant temperature control unit (30) may include a reservoir (31) through which the coolant passes, and a temperature control unit (32) that is installed in contact with one side of the reservoir (31) and electrically connected to the control unit (60) to cool or heat the coolant through heat exchange with the coolant passing through the reservoir (31) while generating or absorbing heat by electric energy applied from the control unit (60).
[0042] The temperature control member (32) can apply a thermoelectric module that rapidly cools or heats a fluid precisely using the Peltier effect. The Peltier effect refers to a phenomenon in which, when n-type and p-type thermoelectric materials are paired and current is passed through them, one side generates heat and the other side absorbs (cools) heat. This Peltier effect can be referred to as a heat pump that allows for electrical feedback control in another sense.
[0043] When a thermoelectric element is applied as a temperature control member (32) and the thermoelectric element is to be used in a manner that cools the coolant, the heat absorption part of the temperature control member (32) may be installed in contact with the reservoir (31), and the heat dissipation part of the temperature control member (32) may be installed spaced apart from the reservoir (31). In this case, when the control part (60) applies current to the temperature control member (32), the surface of the temperature control member (32) that comes into contact with the reservoir (31) absorbs heat due to the Peltier effect, so that the coolant in the reservoir (31) is cooled, and heat is generated in the heat dissipation part (not shown). Although not shown in the drawing, the heat dissipation unit can be configured by applying a heat conductive metal plate, a heat conductive heat sink, etc., which is in direct contact with the surface opposite to the surface that contacts the reservoir (31) of the temperature control member (32) or is connected via a separate heat pipe or heat conductive rod.
[0044] When a thermoelectric element is applied as a temperature control member (32) and the thermoelectric element is to be used in a manner that cools the coolant, if the direction of the current applied to the temperature control member (32) is reversed, the heat absorption part can be converted into a heat dissipation part and vice versa, thereby applying heat to the coolant to achieve a temperature raising effect. When a thermoelectric element is applied as the temperature control member (32) in this way, the direction of the current applied to the temperature control member (32) from the control unit (60) can be controlled to absorb the heat of the coolant and cool it, or apply heat to the coolant and heat it, depending on the type or temperature of the coolant, thereby facilitating temperature control of the coolant.
[0045] In addition to the thermoelectric element, any cooling element or heating element such as a heater that can provide heat energy transferred to the coolant by electric energy applied from the control unit (60) by adjusting it as desired can be used as the temperature control element (32).
[0046] The nozzle (40) sprays the coolant, the temperature of which is controlled while passing through the coolant temperature control unit (30), at a predetermined pressure onto the cooling target, i.e., the cooling target cell (C). The nozzle (40) may be configured to spray the coolant while maintaining a predetermined distance from the cooling target cell (C).
[0047] The temperature sensor (50) non-contactly measures the temperature of the target cell (C) to be cooled and transmits the measured temperature information to the control unit (60) in real time. The temperature sensor (50) can be configured by applying a non-contact infrared (IR) temperature sensor.
[0048] The control unit (60) is electrically connected to the coolant supply unit (10), the solenoid valve (20), the temperature control member (32) of the coolant temperature control unit (30), and the temperature sensor (50) to control their operation. In addition, the control unit (60) can input or store various information for cell cooling control. For example, the control unit (60) can input or store information such as the cell cooling target temperature, cooling rate, unit time (Δt) for cooling rate control, and starting temperature of cooling control through a keypad or touch screen, a mobile communication terminal, or wireless or wired communication with an external server.
[0049] In addition, the control unit (60) can control the cooling speed differently depending on the type of cell to be cooled, etc. The control unit (60) controls the operation of the temperature control member (32) of the coolant temperature control unit (30) for a set unit time (Δt) so that the cooling speed of the cell to be cooled follows the cooling speed input in advance to the control unit (60) based on the temperature information detected by the temperature sensor (50) and is cooled to the target temperature.
[0050] For example, the control unit (60) controls the change in thermal energy (by PID control of the temperature control member (32) of the coolant temperature control unit (30) ) can be used to control the temperature of the coolant, thereby controlling the cooling rate of the target cell (C). When the temperature of the coolant is low, a phenomenon occurs in which the temperature change becomes greater for the same injection pressure (Joule-Tomson effect), so the control unit (60) controls the current temperature (T) as in the following mathematical expression 1 within a set cooling rate. sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference The smaller the measured cell temperature, the lower the control.
[0051]
[0052] That is, within the same cooling rate, the current temperature (T sur ) is lowered The operation of the temperature control member (32) is controlled by changing the PID control variable in such a way that the value of is reduced. For example, the change in the amount of heat energy generated in the temperature control member (32) from 16 to 4°C ( ) The amount of change in heat energy generated from the temperature control member (32) is 4 to -4 ℃ ( ) can be controlled to precisely control the cooling speed.
[0053] In addition, the control unit (60) can control the target cooling rate by modifying the unit time (Δt) and unit temperature difference of the section for each cooling rate. At this time, the control unit (60) can perform more precise cooling rate control by controlling the unit time (Δt) to become shorter as the cooling rate increases. For example, if the cooling rate is to be controlled to 1°C / s, the unit time (Δt) is set to 2 seconds and controlled by 2°C for 2 seconds. However, if the cooling rate is to be controlled to 7°C / s, the unit time (Δt) is set to 1 second and controlled by 7°C instead of 2 seconds and controlled by 14°C.
[0054] Before the control unit (60) performs cooling rate control on the target cell (C), it is preferable to precool the cell (C) by spraying a coolant to the cell (C) to a predetermined starting temperature and then control the operation of the coolant temperature control unit (30) so that the cell (C) is cooled to the target temperature at a predetermined cooling rate. For example, when controlling cell cooling at each cooling rate as shown in the graph in Fig. 4, a precooling step of spraying a coolant to cool the cell so that the starting temperature of the cooling rate control becomes 17°C can be performed, thereby starting the cooling rate control from the same temperature.
[0055] In this way, by performing cooling speed control by adjusting the starting temperature of cooling speed control through precooling, there is an advantage in that more precise cooling speed control is possible.
[0056] This method of controlling the cooling rate of a cell cooling device provides the advantage of enabling more precise cooling rate control compared to the cooling rate control method applied to existing cell cooling devices.
[0057] To explain more specifically, the cooling speed control method of the existing cell cooling device controls by setting the same control variable and target temperature (target temperature 1 to 4) for a unit time (Δt), as illustrated in Fig. 2. For example, if the unit time (Δt) is set to 2 seconds and the target temperature section is set to 1℃, when performing control in each section, the target temperature is reached in 0.5 seconds and the same temperature is maintained, and the target temperature is reached in 1 second and the same temperature is maintained (case 1).
[0058] As illustrated in Fig. 3, these conventional control methods control the average speed of the entire section, resulting in a significant difference from the desired section target speed. Furthermore, they have limitations in reducing unit time due to control issues such as overshooting. In particular, it was confirmed that accuracy deteriorates as the cooling rate increases and the current temperature decreases.
[0059] However, the cooling speed control method of the present invention is a method of controlling to reach the target temperature in each target temperature section (e.g., target temperatures 1 to 4 in FIG. 2) (case 2 in FIG. 2), and as described above, the current temperature (T) is controlled for each unit time (Δt). sur ) is lower, the current temperature (T sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference By controlling this to be small, the target temperature is reached in each target temperature range within a unit time (Δt).
[0060] A method for controlling the cooling speed of a cell cooling device according to the present invention may include the following steps.
[0061] First, before executing cooling of the target cell, a target cooling rate for cooling control of the target cell (C) is input into the control unit (60). At this time, the unit time can be automatically set according to the target cooling rate. Alternatively, the unit time and target cooling rate can be input separately into the control unit (60).
[0062] And, when a cooling execution command is input to the control unit (60), the control unit (60) applies a control signal to the solenoid valve (20) to open the flow path and operates the coolant supply unit (10) and the coolant temperature control unit (30) to perform a precooling step of adjusting the cells to the set starting temperature, thereby injecting the coolant into the cells (C).
[0063] At this time, if the temperature of the cell (C) measured by the temperature sensor (50) is detected to have reached the starting temperature of the cooling rate control, the control unit (60) performs cooling rate control to the target temperature per a predetermined unit time (Δt). At this time, the cooling rate control performed by the control unit (60) is performed at the current temperature (T) as described above. sur ) is lower, the current temperature (T sur ) and target temperature (Ttarget ) The amount of change in thermal energy applied to the coolant compared to the difference By controlling this to be small, the target temperature is reached within the unit time in each target temperature range.
[0064] When the surface temperature of the cell measured by the temperature sensor (50) reaches the final target temperature, the control unit (60) maintains the target temperature through the coolant temperature control unit (30) or causes the solenoid valve (20) to close the flow path and stops the operation of the coolant supply unit (10) and the coolant temperature control unit (30).
[0065] The cell cooling device of the present invention can be used as a device for observing or experimenting with the death and activation process of new cells in an actual medical field, but can also be used as a device for treating or performing procedures for skin diseases by spraying a cooling agent on the skin.
[0066] Although the detailed description of the present invention described above has been described with reference to preferred embodiments of the present invention, it will be understood by those skilled in the art or having ordinary knowledge in the art that various modifications and changes can be made to the present invention without departing from the spirit and technical scope of the present invention as set forth in the claims to be described later.
[0067] The present invention can be applied to a cell cooling device that cools various cells (in vivo, in vitro) for treatment or experimental purposes in the medical device field and bio field.
Claims
1. Coolant supply section that supplies coolant; A nozzle that sprays coolant supplied from the coolant supply unit toward the cells; A coolant temperature control unit having a temperature control member that controls the temperature of the coolant by heating or cooling the coolant supplied from the coolant supply unit to the nozzle while generating or absorbing heat by electric energy applied from the outside; A temperature sensor that detects the surface temperature of a cell in a non-contact manner; and A control unit that controls the operation of the temperature control member for each set unit time so that the cell cooling rate follows a pre-input cooling rate based on the temperature information detected by the temperature sensor and is cooled to a target temperature; A cell cooling device including:
2. In paragraph 1, The above control unit controls the current temperature (T) within a set cooling rate. sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference A cell cooling device that controls the electrical energy applied to the temperature control member so that it decreases as the temperature of the measured cell decreases.
3. In paragraph 2, The above control unit changes the amount of heat energy of the temperature control member through PID control of the temperature control member. Cell cooling device that controls the .
4. In paragraph 1, The above control unit is a cell cooling device that controls the electric energy applied to the temperature control member so that the unit time becomes shorter as the set cooling speed becomes faster.
5. In paragraph 1, The above control unit is a cell cooling device that controls the operation of the temperature control unit so that the cell is cooled to a target temperature at a predetermined cooling rate after the cell is pre-cooled to a predetermined starting temperature set in advance by the control unit.
6. A method for controlling the cooling speed of a cell cooling device according to any one of clauses 1 to 5, (S1) A step of inputting a cooling rate, or unit time and cooling rate, for cell cooling control to the control unit; (S2) A step in which the control unit operates the coolant temperature control unit and the coolant supply unit to inject coolant into the cell through the nozzle; (S3) A step of detecting the surface temperature of a cell using a temperature sensor; and, (S4) A step in which the control unit controls the operation of the temperature control member of the coolant temperature control unit by unit time so that the cell cooling rate follows a pre-input cooling rate based on the temperature information detected by the temperature sensor and is cooled to the target temperature; A method for controlling the cooling rate of a cell cooling device including a .
7. In paragraph 6, In the above step (S4), the control unit determines the current temperature (T) within a set cooling rate. sur ) and target temperature (T target ) The amount of change in thermal energy applied to the coolant compared to the difference A method for controlling the cooling speed of a cell cooling device that controls the electric energy applied to a temperature control member so that the lower the temperature of the measured cell, the smaller the amount of energy.
8. In paragraph 7, A cooling speed control method of a cell cooling device, wherein in the above step (S4), the control unit controls the unit time to become shorter as the set cooling speed becomes faster.
9. In paragraph 6, A method for controlling the cooling speed of a cell cooling device, wherein the control unit pre-cools the cell by injecting a coolant into the cell before performing the above step (S2) so that the temperature of the cell reaches a predetermined starting temperature.
Citation Information
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