WO2024016377A1

WO2024016377A1 - Thermal-field generation apparatus capable of realizing automatic temperature control, and manufacturing method therefor

Info

Publication number: WO2024016377A1
Application number: PCT/CN2022/109479
Authority: WO
Inventors: 邵玥; 郑伊凡
Original assignee: 清华大学
Priority date: 2022-07-18
Filing date: 2022-08-01
Publication date: 2024-01-25
Also published as: CN115134955B; CN115134955A

Abstract

Provided in the present application are a thermal-field generation apparatus capable of realizing automatic temperature control, and a manufacturing method therefor. The thermal-field generation apparatus capable of realizing automatic temperature control comprises a plurality of automatic temperature control elements (2), which form an array, wherein each automatic temperature control element (2) comprises an automatic-temperature-control element loading structure (21) and an automatic-temperature-control heat source (22); and the automatic-temperature-control heat source (22) is disposed on the automatic-temperature-control element loading structure (21), and the automatic-temperature-control heat source (22) contains magnetic nanoparticles and hydrogel, which magnetic nanoparticles are dispersed in the hydrogel, and can generate heat in an alternating magnetic field.

Description

Self-controlled temperature thermal field generating device and manufacturing method thereof

References to related applications

This application requires the priority of the prior invention patent application submitted in China with the filing date of July 18, 2022, the application number is 202210843870. The entire contents of the earlier application are incorporated herein by reference.

Technical field

This application belongs to the field of medicine and bioengineering, and particularly relates to a self-controlled temperature thermal field generating device and a manufacturing method thereof.

Background technique

Temperature has a broad and important impact on living organisms, especially humans. Clinically, heat is used as a treatment method, for example, using heat to specifically kill tumor tissue. It can also quickly kill cells in the diseased area in an extremely frozen state, allowing the diseased area to recover normally. However, current surgical techniques are limited to cell killing caused by extreme high/low temperatures. There are still many unclear biological effects and mechanisms of non-cell killing temperature ranges, which are also temperature ranges that are more likely to occur under physiological and pathological conditions. , which also limits the design and application of thermotherapy.

The current heat generation methods include heating by Joule heating of current through resistive elements and "Peltier elements". Temperature control can be carried out by arranging multiple temperature sensors for continuous real-time monitoring and using the proportional integral method to measure the heating power in real time. Negative feedback adjustment.

In addition to electric heating, photothermal is also a means of generating heat. However, photothermal requires complex optical components to be integrated, and the penetration depth is limited, making it difficult to implement a high-throughput system with intelligent self-temperature control. It is difficult to implement a high-throughput thermal screening system with intelligent self-temperature control using existing heating and temperature control technologies.

Contents of the invention

This application aims to propose a self-controlled temperature thermal field generating device to solve the problem of high-throughput temperature-controlled heating.

This application also proposes a method for manufacturing a self-controlled temperature thermal field generating device.

The embodiment of the present application proposes a self-controlled temperature thermal field generating device, which includes a plurality of self-temperature control elements, and the plurality of self-temperature control elements form an array,

Wherein, the self-temperature control element includes a self-temperature control element loading structure and a self-control temperature heat source. The self-temperature control heat source is arranged in the self-temperature control element loading structure. The self-temperature control heat source includes magnetic nanoparticles and water. Gel, the magnetic nanoparticles are dispersed in the hydrogel, and the magnetic nanoparticles are capable of generating heat in an alternating magnetic field.

In at least one possible embodiment, the plurality of self-temperature-controlling elements include the self-temperature-controlling elements having different mass concentrations and/or different types of magnetic nanoparticles.

In at least one possible embodiment, the self-temperature control element further includes a thermal insulation layer,

The self-temperature control element loading structure includes a heat source shell and a heat insulation layer shell. The self-temperature control heat source is arranged inside the heat source shell. The heat source shell is arranged on the inside of the heat insulation layer shell. Inside, the heat insulation layer is disposed between the heat source housing and the heat insulation layer housing.

In at least one possible implementation, the self-temperature element loading structure includes a heat transfer layer, and the heat transfer layer covers the self-temperature heat source.

In at least one possible implementation, the self-controlling temperature thermal field generating device further includes a thermal field bottom plate, and the thermal field bottom plate is provided with a plurality of installation slots for accommodating the self-controlling temperature elements. The temperature control element can be detachably installed in the installation groove.

In at least one possible implementation, the plurality of self-temperature control elements can be detachably installed in different installation slots of the thermal field base plate, so that the plurality of self-temperature control elements can be freely combined.

In at least one possible embodiment, the self-controlled temperature thermal field generating device is used to intervene in the temperature of the cell culture well plate.

The embodiment of the present application also proposes a manufacturing method of a self-controlled temperature thermal field generating device, which includes the following steps:

Prepare a self-temperature control component loading structure and use the base material to form a shell shape;

Prepare a self-controlling temperature heat source, mix magnetic nanoparticles and hydrogel and install them into the self-controlling temperature element loading structure, and then cause the magnetic nanoparticles and the hydrogel to ignite through free radical initiation, photoinitiation or chemical initiation. The mixture changes from a fluid state to a colloidal state, and the self-temperature control heat source colloid is formed on the self-temperature control element loading structure to form a self-temperature control element; and

The self-temperature control elements are connected to form an array.

In at least one possible implementation, the following steps are also included:

Preparing a thermal field base plate, using a base material to form a thermal field base plate capable of installing the self-temperature control element; and

The self-temperature control elements are installed on the thermal field bottom plate to form an array.

In at least one possible implementation, the following steps are also included:

Prepare a heat-insulating layer, and set the heat-insulating layer outside the self-controlled temperature heat source.

In at least one possible implementation, the following steps are also included:

A fluid mixture of magnetic nanoparticles and hydrogel is placed inside a vacuum chamber to expel air bubbles.

In at least one possible implementation, the following steps are also included:

The heat generation capacity and heat dissipation rate of the self-controlled temperature heat source are measured to obtain the corresponding relationship between the mass concentration of the magnetic hydrogel and the temperature field.

In at least one possible implementation, the following steps are also included:

Install the self-controlled temperature thermal field generator and the heating target, and then measure the calibrated temperature rise data on the heating target.

By adopting the above technical solution, a self-controlled temperature heat source including magnetic nanoparticles and hydrogel can generate heat in an alternating magnetic field, so that multiple self-temperature controlled elements can form an array to achieve high-throughput temperature-controlled heating.

Description of drawings

Figure 1 shows a schematic structural diagram of a self-controlled temperature thermal field generating device according to an embodiment of the present application.

Figure 2 shows a schematic structural diagram of the thermal field bottom plate of the self-controlled temperature thermal field generating device according to an embodiment of the present application.

Figure 3 shows a schematic structural diagram of the self-temperature control element of the self-control temperature thermal field generating device according to an embodiment of the present application.

FIG. 4 shows a schematic structural diagram of a self-temperature control element (the heat transfer layer is not shown) of a self-control temperature thermal field generating device according to an embodiment of the present application.

FIG. 5 shows a schematic diagram of the self-temperature control element loading structure of the self-control temperature thermal field generating device according to an embodiment of the present application.

Figure 6 shows a schematic diagram of a self-controlled temperature thermal field generating device and a cell culture well plate according to an embodiment of the present application.

Figure 7 shows a thermogravimetric analysis diagram of the magnetic nanoparticles of the self-controlled temperature thermal field generating device according to an embodiment of the present application and the derivation curve diagram.

FIG. 8 shows a schematic structural diagram of the calorific value measuring device of the self-controlled temperature thermal field generating device according to an embodiment of the present application.

Figure 9 shows the specific loss rate of the self-temperature control element of the self-control temperature thermal field generation device at different temperatures according to an embodiment of the present application.

Figure 10 shows a schematic structural diagram of a self-controlled temperature thermal field generating device according to an embodiment of the present application.

Figure 11 shows a schematic diagram of the calibrated steady-state temperature of the self-controlled temperature thermal field generating device according to an embodiment of the present application.

Explanation of reference signs

100 self-controlled temperature thermal field generator 200 cell culture well plates

1 Thermal field base plate 11 Installation slot

2 Self-control temperature component 21 Self-control temperature component loading structure 211 Heat source shell 212 Heat insulation layer shell 22 Self-control temperature heat source 23 Heat insulation layer 24 Heat transfer layer.

Detailed ways

In order to more clearly explain the above objects, features and advantages of the present application, specific implementation modes of the present application are described in detail in this section with reference to the accompanying drawings. In addition to the various embodiments described in this section, the present application can also be implemented in other different ways. Without violating the spirit of the present application, those skilled in the art can make corresponding improvements, modifications and replacements. Therefore, the present application It is not limited to the specific embodiments disclosed in this section. The scope of protection of this application shall be determined by the claims.

As shown in Figures 1 to 6, the embodiment of the present application proposes a self-controlled temperature thermal field generating device 100. The self-controlled temperature thermal field generating device of the embodiment of the present application is a device that achieves heating through a space non-contact magnetic induction heating method. device.

Space non-contact magnetic induction heating is a heating method that uses an alternating magnetic field with strong penetration and is not limited by space and media to accurately heat a specific area where the magnetic response medium is located. Magnetic nanoparticles are a type of nanoparticles with controllable shape, good stability and good dispersion. Under medium and high-frequency alternating magnetic fields, ferromagnetic phase magnetic nanoparticles can pass through hysteresis loss and Nair relaxation according to different particle sizes. Heaviness and Brownian relaxation generate heat, and the heat generation rate can be adjusted by adjusting the type and concentration of magnetic nanoparticles.

The self-controlled temperature thermal field generating device 100 includes a heat field base plate 1 and a plurality of self-temperature control elements 2. The plurality of self-temperature control elements 2 can be detachably connected to the heat field base plate 1.

Multiple self-temperature control elements 2 can have different calorific values. According to actual needs, the self-temperature control elements 2 with different calorific values can be freely arranged and installed on the thermal field base plate 1 to form an array. For example, the calorific value of each row of self-temperature control elements 2 can be the same (there may be a certain error), and the calorific value of each column of self-temperature control elements 2 can change in a gradient.

It can be understood that in at least one possible implementation, multiple self-temperature control elements 2 can also be connected to themselves to form an array by, for example, bonding, snapping, etc., without relying on the thermal field bottom plate to provide support.

As shown in Figure 2, the thermal field base plate 1 may be, for example, rectangular. The bottom of the thermal field base plate 1 may be provided with a plurality of installation slots 11 for accommodating the self-temperature control elements 2. For example, the installation slots 11 may be provided with 12 rows and 8 rows. columns, a total of 96 mounting slots 11.

As shown in Figures 3 and 5, the self-temperature control element 2 includes a self-temperature control element loading structure 21, a self-temperature control heat source 22, a heat insulation layer 23 and a heat transfer layer 24.

The self-temperature control element loading structure 21 includes a heat source housing 211 and a heat insulation layer housing 212. The heat source housing 211 is arranged inside the heat insulation layer housing 212. The heat source housing 211 can be cylindrical with one end open, and is heat-insulated. The layer housing 212 may be in the shape of a rectangular tube with one end open. The self-temperature control heat source 22 may be disposed inside the heat source housing 211 , and the heat insulation layer 23 may be disposed between the heat source housing 211 and the heat insulation layer housing 212 . The thermal insulation layer 23 may include foamed polyurethane, which has good thermal insulation properties.

The self-controlled temperature heat source 22 includes magnetic nanoparticles and hydrogel (or dispersion system), and the dispersion system can serve as a stable dispersion carrier for the magnetic nanoparticles.

The magnetic nanoparticles can be spinel ferrite doped with zinc, aluminum and manganese elements, and their Curie temperature can be 59.33°C.

The Curie temperature (magnetic transition point) is an inherent characteristic of magnetic nanoparticles. When the temperature of the magnetic nanoparticles is higher than its own Curie temperature, the ferromagnetic phase magnetic nanoparticles will instantly transform into the paramagnetic phase magnetic phase nanoparticles. Particles, at this time the magnetic nanoparticles no longer have a magnetocaloric response to the alternating magnetic field. The Curie temperature of magnetic nanoparticles can utilize the physical phase change properties of the heat-generating medium itself for self-control temperature. The self-control temperature heat source 22 with magnetic nanoparticles is conducive to the integration of a simple, high-throughput self-control temperature heat field generating device. .

The hydrogel can be polyacrylamide gel (PAAG). Polyacrylamide has the same fluidity as water when no cross-linking agent is added. After adding cross-linking agents such as 10% ammonium persulfate and tetramethylethylenediamine (TEMED), it will form a stable colloid like jelly. , so that magnetic nanoparticles are dispersed in the colloid of hydrogel.

It can be understood that the magnetic nanoparticles and hydrogels selected in the above specific embodiments are only examples, and in other possible embodiments, other types of magnetic nanoparticles and hydrogels can be used.

As shown in FIG. 6 , the self-controlled temperature thermal field generating device 100 can be placed under the heating target. For example, the heating target can be a 96-well cell culture plate. The cell culture well plate 200 is heated by placing the self-controlled temperature thermal field generating device 100 and the cell culture well plate 200 in an alternating magnetic field. This application does not limit the number of holes of the cell culture well plate 200, which can be 96 holes, 48 holes, etc. The self-controlled temperature thermal field generating device 100 of the present application can match the number of holes of the cell culture well plate 200, and is especially suitable for high-throughput applications. The high-throughput of well plate heating means that different wells of the cell culture well plate can be heated independently at one time.

The advantages of self-controlled temperature thermal field generating devices include:

(1) The self-controlled temperature thermal field generating device 100 can achieve high-throughput temperature-controlled heating by forming an array of multiple self-controlled temperature elements.

(2) Multiple self-temperature control elements can be combined as needed, and the heating mode can be easily changed. It has a greater degree of freedom and universality, thereby completing multiple customized high-throughput thermobiochemical response screening tasks. Moreover, the self-controlled temperature thermal field generating device 100 can be expanded arbitrarily and can be easily integrated with various analysis and screening platforms.

(3) Relying on the inherent Curie temperature characteristics, the self-controlled temperature thermal field generating device 100 can accurately control the thermal field temperature without temperature detection and feedback adjustment.

The embodiment of the present application also proposes a manufacturing method of a self-controlled temperature thermal field generating device, which includes the following steps.

S1. Preparation of thermal field bottom plate and self-temperature control element loading structure

As shown in Figures 2 and 5, the thermal field base plate 1 and the self-temperature control element loading structure 21 can be made through additive manufacturing. For example, a high-temperature resistant resin substrate can be selected to prepare the thermal field base plate 1 through light-curing 3D printing. and a self-temperature control element loading structure 21.

In other possible implementations, the thermal field bottom plate 1 and the self-temperature control element loading structure 21 can be prepared by subtractive manufacturing methods such as machining and laser cutting.

Optionally, use chemical polishing to remove the print marks formed on the surface of the component after 3D printing, making the surface of the component smoother and easier for subsequent assembly.

S2. Prepare self-controlled temperature heat source

The self-controlled temperature heat source 22 includes magnetic nanoparticles and hydrogel, and the magnetic nanoparticles and hydrogel are prepared respectively.

S2.1. Preparation of magnetic nanoparticles

Spinel ferrite with a hexahedral structure is synthesized by, for example, a hydrothermal method or a high-temperature thermal decomposition method. The spinel ferrite is doped with zinc, aluminum and manganese elements. The magnetic parameters and intrinsic Curie temperature of the prepared magnetic nanoparticles were measured through vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA) tests.

Figure 7 shows the thermogravimetric analysis diagram and Curie temperature of magnetic nanoparticles. The abscissa corresponding to the peak point of the curve obtained by derivation of the normalized mass of the thermogravimetric analysis diagram with respect to temperature is the Curie temperature. For example, the Curie temperature of the magnetic nanoparticles of this embodiment is 59.33°C.

S2.2. Preparation of hydrogel

Configure hydrogels with fluid-solid phase change properties, such as polyacrylamide gel (PAAG) or heat-sensitive hydrogels (such as gelatin).

Measure the proportion of 30% acrylamide, 5×TBE buffer (Tris-borate electrophoresis buffer diluted 5 times in volume) and ultrapure water into a 100ml beaker, and stir with a glass rod to mix. The gel is in a pre-gelled state (completely water-like flow state).

S2.3. Preparation of magnetic hydrogel

The prepared magnetic nanoparticles are weighed with a precision balance and then added to the pre-gelled hydrogel to form a fluid magnetic hydrogel (a mixture of magnetic nanoparticles and hydrogel) with adjustable shape and heat generation capacity. . The shape of the fluid magnetic hydrogel can change with the shape of the container, and the heat generation capacity can be adjusted by the type and amount of magnetic nanoparticles.

The fluid magnetic hydrogel is then placed in a vacuum box for a period of time to expel bubbles to avoid affecting thermal conductivity. Then, the flow-dynamic magnetic hydrogel is quantitatively injected into the heat source housing 211 of the self-temperature control element loading structure 21 through a pipette, and the flow-dynamic magnetic hydrogel is rapidly formed through free radical initiation, photo-initiation or chemical initiation. The glue is stable, allowing the self-controlled temperature heat source 22 to be stably shaped into the heat source housing 211.

Specifically, a micropipette can be used to add 10% ammonium persulfate and tetramethylethylenediamine (TEMED) in a preformed gelling ratio into the heat source housing 211 , and repeatedly pump evenly to make the self-temperature heat source 22 It can be stably set into the heat source housing 211 for a long time.

S3. Obtain the corresponding relationship between the mass concentration and temperature field of the magnetic hydrogel.

S3.1. Measure the heat production capacity of the self-controlled temperature heat source

As shown in Figure 8, the self-controlled temperature heat source 22 (magnetic hydrogel) is placed in the plastic tube 3, and the outside of the plastic tube 3 is wrapped with a heat insulation pad 4. The heat insulation pad 4 can be an airgel composite nano heat insulation pad 4. A flexible heating film 5 is wrapped around the outside of the thermal insulation pad 4. The flexible heating film 5 can be connected to a heating controller 51 to regulate the heating temperature. The flexible heating film 5 can include polyimide. The outside of the flexible heating film 5 is wrapped with an electromagnetic wave-absorbing copper mesh 6. The electromagnetic wave-absorbing copper mesh 6 can protect the flexible heating film 5 in the magnetic field. The optical fiber temperature sensor 7 is inserted into the self-controlled temperature heat source 22 .

Place the above device into an alternating magnetic field and adjust the input alternating current size and frequency. For example, the alternating current size is 800A and the frequency is 100KHz. The flexible heating film 5 can increase the ambient temperature and prevent the heat generated by the self-controlled temperature heat source 22 from being dissipated into the environment and affecting the accuracy of temperature measurement. The optical fiber temperature sensor 7 inserted into the self-controlled temperature heat source 22 can monitor the temperature curve in real time. The heat generation capacity of the magnetic hydrogel under an alternating magnetic field can be calculated through the temperature curve using the following formula.

Among them, Q represents the heat flux released per unit volume of MHG, MHG represents each magnetic hydrogel domain, C(MHG) represents the mass concentration of the magnetic hydrogel, and SLP represents the experimentally determined configuration of the magnetic nanoparticles. The specific loss rate (heat dissipation rate) of the heat source of the magnetic hydrogel MHG, c _MHG represents the specific heat capacity of the magnetic hydrogel, m _MHG represents the mass of the magnetic hydrogel, m _MNPs represents the mass of the magnetic nanoparticles, dT/dt Represents the first derivative of temperature with respect to time, T _MHG = T _environment indicates that the temperature of MHG is equal to the ambient temperature.

S3.2. Measure the specific loss rate (heat dissipation rate) of magnetic hydrogel

Simulation of heat transfer in magnetic hydrogels via fluid-structure coupling-conjugate heat transfer finite element

1. First, based on the joint geometric model of the self-controlled temperature thermal field generating device 100, the cell culture well plate 200, the culture medium, and the two-way coupled natural convection air domain (set as a cuboid domain of appropriate size), and then use the tetrahedral unit and Hexahedral elements perform structured meshing of the joint body.

2. Enter the thermophysical parameters of all materials (including density of solid materials, constant pressure heat capacity, density of fluid materials, constant pressure heat capacity, thermal conductivity, specific heat rate, etc.), and then assign the complete geometry and mesh model Multiphysics coupling governing equations, for the heat source domain:

Among them, MHG represents each magnetic hydrogel domain, ρ _MHG represents the density of magnetic hydrogel,

represents the partial derivative of temperature with respect to time, K represents the heat transfer coefficient, ▽ represents the vector differential operator, C(MHG) represents the mass concentration of the magnetic hydrogel, and SLP represents the experimentally determined configuration of the magnetic nanoparticles into the magnetic hydrogel MHG. The specific loss rate (heat dissipation rate) of the heat source, c _MHG represents the specific heat capacity of the magnetic hydrogel, m _MHG represents the mass of the magnetic hydrogel, and m _MNPs represents the mass of the magnetic nanoparticles.

For the air domain of natural convection coupled with heat transfer, the heat transfer and flow governing equations (assuming that the air flow domain is laminar flow of weakly compressible fluid):

Simplified Navier-Stokes equation for the above model:

Continuity equation:

Among them, ρ _air represents the density of the air flow field, c _air represents the specific heat capacity of the air, T (r (x, y, z), t) represents the instantaneous temperature of a certain point in the Cartesian coordinate system, ▽ represents the vector differential calculation symbol, u represents the flow field velocity of the air, p represents the pressure of the air flow field, μ represents the dynamic viscosity of the air flow field, g represents the acceleration of gravity, and ρ represents the density field of the air fluid field.

D means the reciprocal operator.

Other solid and fluid domain heat transfer governing equations in the above model:

Set appropriate initial conditions and boundary conditions for the model. For example, the initial state is room temperature (20°C), the flow field velocity of the air is 0m/s, the air boundary layer is set to a virtual infinity domain, and the heat sink condition is -20°. The experimentally measured specific loss rate (heat dissipation rate) of magnetic nanoparticles configured into magnetic hydrogel is shown in Figure 9. Then, the Newton-Raphson iterative numerical algorithm for nonlinear partial differential equations is used to solve the problem, and the thermal field spatio-temporal data of all grid points in the entire model and the steady-state thermal field cloud map are obtained, which is helpful to Judge and calibrate the experimental temperature field in advance.

The corresponding relationship between the mass concentration of the magnetic hydrogel and the temperature field can be obtained through the heat generation capacity and specific loss rate of the magnetic hydrogel under an alternating magnetic field, which is helpful for calibrating the steady state of the temperature field.

S4. Connect the self-temperature control element and the thermal field base plate to form an array.

As shown in FIG. 4 , the self-controlled temperature heat source 22 is placed in the heat source housing 211 , and foamed polyurethane with good thermal insulation properties is added as the insulation layer 23 between the heat source housing 211 and the heat insulation layer housing 212 .

Use laser cutting to cut the heat transfer layer 24, such as a silicone heat transfer sheet, into a sheet shape that is slightly larger than the outer diameter of the upper surface of the self-control temperature heat source 22, and then bond the heat transfer layer 23 to the self-control temperature heat source 22. surface to reduce the thermal resistance of the self-controlled temperature thermal field generating device 100 in transmitting heat to the heating target. According to actual needs, multiple self-temperature control elements 2 and the thermal field base plate 1 are connected to form an array.

S5. Calibrate the experimental temperature of the self-controlled temperature thermal field generating device

The self-temperature control elements 2 can be arranged and installed in a thermal field pattern as shown in Figure 10.

Furthermore, the mass concentration of the magnetic hydrogel in the outermost self-temperature controlling element 2 of the self-controlling temperature thermal field generating device 100 can be slightly higher than that of the adjacent inner layer of the self-temperature controlling element 2, for example, it can be 5 mg higher. /ml, thereby compensating for heat transfer losses at boundary locations. Ensure constant temperature performance in the row direction (horizontal direction in Figure 9) and temperature gradient/flux in the column direction (longitudinal direction in Figure 9). Considering the adaptation of the self-controlled temperature thermal field generating device 100 and the cell culture well plate 200, the mass concentration of the magnetic hydrogel can be increased only at the edges in the column direction, for example, the concentration in columns 2 to 7 of row A is 80 mg/ml. The concentration in

columns

1 and 8 is 85mg/ml. From row A to row L, the concentration in each row can gradually decrease.

The self-controlling temperature thermal field generating device 100 and the cell culture well plate 200 are assembled together. The self-controlling temperature thermal field generating device 100 may be located below the cell culture well plate 200 . The cell culture well plate 200 is formed into a heating pattern in which the heating temperature in each row is the same and the heating temperature in each column changes gradiently.

Put the self-controlled temperature thermal field generating device 100 and the cell culture well plate 200 installed together into an alternating magnetic field, and adjust the input alternating current size and frequency. For example, the alternating current size is 800A and the frequency is 100KHz. The temperature rise curve of the target well of the cell culture well plate 200 is monitored and recorded throughout the process. For example, a high-precision infrared thermal imager with adjusted emissivity is used to monitor and record the temperature rise curves of all target wells in the cell culture well plate 200 throughout the entire process. In this way, the spatio-temporal temperature data of the self-controlled temperature thermal field generating device 100 in the thermal field mode can be calibrated at once.

As shown in Figure 11, in this embodiment, after the temperature rise reaches a steady state, the 8 holes in the row direction are at constant temperature, the 12 holes in the column direction form a temperature gradient from the highest 56°C to the lowest 20°C, and the 8 holes in the row direction form a temperature gradient. The temperature unevenness of each hole can be less than 2 degrees.

It can be understood that the array formed in this embodiment is only an example. The arrangement of the self-temperature-controlling elements 2 may not change in a gradient. The arrangement of the self-temperature-controlling elements 2 may be freely changed according to the needs of the experiment. The self-control temperature thermal field generating device 100 of a new thermal field mode can be reassembled by adjusting the assembly position of each self-temperature control element 2,

By changing the arrangement of the self-temperature control elements 2, a variety of high-flux thermal field modes and thermal field patterns with constant temperature and gradient combinations can be combined. Repeat step S5 to calibrate again to obtain a new thermal field of the self-control temperature thermal field generating device 100. model.

Although the present application has been described in detail using the above embodiments, it is obvious to those skilled in the art that the present application is not limited to the embodiments described in this specification. This application can be modified and implemented as a modified embodiment without departing from the gist and scope of the application defined by the claims. Therefore, the description in this specification is for the purpose of illustration and does not have any restrictive meaning on the present application.

Claims

A self-controlling temperature thermal field generating device, characterized in that it includes a plurality of self-controlling temperature elements (2), and the plurality of self-controlling temperature elements (2) form an array,

Wherein, the self-temperature control element (2) includes a self-temperature control element loading structure (21) and a self-temperature heat source (22), and the self-temperature control heat source (22) is arranged in the self-temperature control element loading structure (21). 21), the self-controlled temperature heat source (22) includes magnetic nanoparticles and hydrogel, the magnetic nanoparticles are dispersed in the hydrogel, and the magnetic nanoparticles can generate heat in an alternating magnetic field.
The self-controlled temperature thermal field generating device according to claim 1, characterized in that the plurality of self-temperature control elements (2) include the self-temperature control elements with different mass concentrations and/or different types of magnetic nanoparticles. (2).
The self-controlled temperature thermal field generating device according to claim 1, characterized in that the self-controlled temperature element (2) further includes a heat insulation layer (23),

The self-temperature control element loading structure (21) includes a heat source housing (211) and a heat insulation layer housing (212), and the self-temperature control heat source (22) is arranged inside the heat source housing (211), The heat source housing (211) is provided inside the heat insulation layer housing (212), and the heat insulation layer (23) is provided between the heat source housing (211) and the heat insulation layer housing (212). 212).
The self-control temperature thermal field generating device according to claim 1, characterized in that the self-control temperature element loading structure (21) includes a heat transfer layer (24), and the heat transfer layer (24) covers the self-control temperature field. Warm heat source (22).
The self-controlled temperature thermal field generating device according to claim 1, characterized in that the self-controlled temperature thermal field generating device further includes a thermal field bottom plate (1), and the thermal field bottom plate (1) is provided with a plurality of In the installation groove (11) of the self-temperature control element (2), the plurality of self-temperature control elements (2) can be detachably installed in the installation groove (11).
The self-controlled temperature thermal field generating device according to claim 5, characterized in that the plurality of self-controlled temperature components (2) can be detachably installed in different installation slots (11) of the thermal field bottom plate (1). ), so that the plurality of self-temperature control elements (2) can be freely combined.
The self-controlled temperature thermal field generating device according to claim 1, characterized in that the self-controlled temperature thermal field generating device (100) is used to intervene in the temperature of the cell culture well plate (200).
A method of manufacturing a self-controlled temperature thermal field generating device, which is characterized by including the following steps:

Prepare a self-temperature control element loading structure (21), using a base material to form a shell shape;

Prepare a self-controlling heat source (22), mix magnetic nanoparticles and hydrogel and load them into the self-controlling element loading structure (21), and then cause the magnetic nanoparticles to ignite through free radical initiation, photoinitiation or chemical initiation. The mixture with the hydrogel changes from a fluid state to a colloidal state, and the self-control temperature heat source (22) is colloid-molded on the self-control temperature element loading structure (21) to form a self-control temperature element (2); and

The self-temperature control elements (2) are connected to form an array.
The method for manufacturing a self-controlled temperature thermal field generating device according to claim 8, further comprising the following steps:

Preparing a thermal field base plate (1), using a base material to form a thermal field base plate (1) capable of installing the self-temperature control element (2); and

The self-temperature control element (2) is installed on the thermal field bottom plate (1) to form an array.
The method for manufacturing a self-controlled temperature thermal field generating device according to claim 8, further comprising the following steps:

Prepare a heat insulation layer (23), and set the heat insulation layer (23) outside the self-controlled temperature heat source (22).
The method for manufacturing a self-controlled temperature thermal field generating device according to claim 8, further comprising the following steps:

A fluid mixture of magnetic nanoparticles and hydrogel is placed inside a vacuum chamber to expel air bubbles.
The method for manufacturing a self-controlled temperature thermal field generating device according to claim 8, further comprising the following steps:

The heat generation capacity and heat dissipation rate of the self-controlled temperature heat source (22) are measured to obtain the corresponding relationship between the mass concentration of the magnetic hydrogel and the temperature field.
The method for manufacturing a self-controlled temperature thermal field generating device according to claim 8, further comprising the following steps:

Install the self-controlled temperature thermal field generator and the heating target, and then measure the calibrated temperature rise data on the heating target.