CN113926352A

CN113926352A - Microbubble preparation instrument and microbubble preparation method

Info

Publication number: CN113926352A
Application number: CN202111273076.8A
Authority: CN
Inventors: 康裕建; 冯琦璞; 任柏冰; 康昊南; 曾鸿晋; 秦铭; 王俊歌
Original assignee: West China Hospital of Sichuan University
Current assignee: West China Hospital of Sichuan University
Priority date: 2021-10-29
Filing date: 2021-10-29
Publication date: 2022-01-14

Abstract

The present disclosure provides a microbubble preparation instrument and a microbubble preparation method. The microbubble preparation appearance includes microbubble generating device and temperature control system, and temperature control system includes: the first fluid circulation loop comprises a first circulation pipeline, a heat exchange container and a first driving device, wherein the heat exchange container and the first driving device are connected to the first circulation pipeline; and a temperature regulating device configured to regulate a temperature of the first fluid heat exchange medium within the first circulation line.

Description

Microbubble preparation instrument and microbubble preparation method

Technical Field

The disclosure relates to the technical field of microbubble preparation, and in particular relates to a microbubble preparation instrument and a microbubble preparation method.

Background

Microbubbles are closed micron-sized gas-containing microbubbles that are commonly used in medical ultrasound imaging as diagnostic agents-ultrasound contrast agents-to enhance medical ultrasound imaging signals. Besides being used as an ultrasonic contrast agent, the microvesicles are widely applied to targeted delivery of drugs, gene targeted delivery, thrombolysis and the like, mainly because the microvesicles can generate cavitation in combination with ultrasonic, and can also realize local controlled release of drugs to play roles in local treatment and expected physiological effects.

The microbubbles are usually made of perfluorocarbon, sulfur hexafluoride, or the like as an inner core gas and albumin, phospholipid, or the like as a shell membrane material. When preparing the microbubbles, firstly, filling core gas into a shell-membrane solution made of a shell-membrane material in a microbubble preparation container, and then generating the microbubbles by using an ultrasonic cavitation method, a mechanical shearing method and the like.

With the application of microbubbles in the fields of targeted delivery of drugs, thrombolysis, gene targeted delivery and the like, the production line for mass production of microbubbles on a large scale cannot meet the market demand, and the demand for miniaturization of microbubble preparation equipment is increasing day by day. The miniaturized microbubble preparation instrument takes small-scale production as a starting point, and the preparation process is more flexible and controllable. When the medicine-carrying microvesicle is prepared, the microvesicle preparation instrument can flexibly prepare the formula, the dosage and the concentration of the microvesicle carried medicine, and is favorable for meeting the requirements of personalized customization in laboratories and hospitals.

The microbubble generator is usually ultrasonic cavitated. The ultrasonic cavitation method is to generate micro cavities in the shell membrane solution by utilizing the cavitation effect of ultrasonic waves, so that the core gas is dispersed in the shell membrane solution and micro bubbles are generated. The core component of the microbubble preparation instrument adopting the ultrasonic cavitation method is an ultrasonic probe, and compared with other microbubble generation units, such as a large-size stirring paddle adopted by a mechanical stirring method, the ultrasonic probe has the characteristic of small size, the diameter is usually 1cm-5cm, the ultrasonic probe is suitable for being used as the microbubble generation unit of a small microbubble preparation instrument, and a mechanism which has requirements on microbubbles and the capability of preparing the microbubbles by individuals are endowed.

The ultrasonic cavitation method for preparing the microbubbles mainly comprises the following steps: placing a shell membrane solution, such as an albumin solution, into a microbubble preparation container, filling an inner core gas, such as perfluoropropane, into the albumin solution, and vibrating with an ultrasonic probe for a certain time to prepare an albumin microbubble suspension.

Disclosure of Invention

An object of the present disclosure is to provide a microbubble generator and a microbubble preparation method that aim to maintain a preparation substance in a desired temperature range during microbubble preparation.

The first aspect of the present disclosure provides a microbubble preparation instrument, including a microbubble generation device and a temperature control system, the microbubble generation device includes a microbubble preparation container, the temperature control system includes:

a first fluid circulation loop comprising a first circulation line, a heat exchange container connected to the first circulation line, and a first driving device configured to drive a first fluid heat exchange medium to circulate in the first fluid circulation loop, the heat exchange container having a fluid housing space configured to house the micro-bubble preparation container and circulate the first fluid heat exchange medium to heat exchange the first fluid heat exchange medium with the micro-bubble preparation container; and

a temperature adjustment device configured to adjust a temperature of the first fluid heat exchange medium within the first circulation line.

In some embodiments, the heat exchange vessel comprises:

the inner shell is provided with a first accommodating space and a fluid inlet communicated with the first accommodating space, and the first circulating pipeline is connected with the fluid inlet; and

the first circulation pipeline is connected with the fluid outlet, and the first accommodating space is communicated with the second accommodating space;

wherein the fluid-containing space includes the first containing space and the second containing space, the first containing space being configured to place the micro-bubble preparation container.

In some embodiments, the fluid inlet and the fluid outlet are both located at the bottom of the heat exchange container, and the top of the first accommodating space is communicated with the second accommodating space.

In some embodiments, the inner and outer shells of the heat exchange container are open at the top.

In some embodiments, the first fluid circulation loop comprises a first medium vessel disposed on the first circulation line configured to hold the first fluid heat exchange medium.

In some embodiments, the first driving means comprises:

a first pump disposed on the first circulation line between the first medium vessel and the heat exchange vessel and configured to convey the first fluid heat exchange medium in the first circulation line into the heat exchange vessel; and

a second pump disposed on the first circulation line between the heat exchange vessel and the first medium vessel and configured to convey the first fluid heat exchange medium in the first circulation line into the first medium vessel.

In some embodiments, the temperature control system comprises:

a temperature measurement device configured to collect temperature information of the temperature control system; and

the controller is in signal connection with the temperature measuring device and the temperature adjusting device and is configured to control the temperature adjusting device to work according to control information so as to adjust the temperature of the first fluid heat exchange medium, and the control information comprises the temperature information collected by the temperature measuring device.

In some embodiments, the temperature control system further comprises an input device in signal connection with the controller, the controller configured to receive input information of the input device, wherein the control information comprises the input information.

In some embodiments, the temperature adjustment device comprises:

the semiconductor refrigeration piece is provided with a first heat exchange surface and a second heat exchange surface, the first fluid circulation loop comprises a first heat exchange part connected to the first circulation pipeline, and the first heat exchange part comprises a first heat exchange wall surface exchanging heat with the first heat exchange surface; and

a heat exchange device configured to exchange heat with the second heat exchange surface.

In some embodiments, the temperature control system has:

a cooling mode in which the first heat exchange surface of the semiconductor chilling plate chills and the second heat exchange surface generates heat; and

a preheat mode in which the first heat exchange surface of the semiconductor chilling plate generates heat and the second heat exchange surface chills.

In some embodiments, the heat exchanging device comprises a second fluid circulation loop, the second fluid circulation loop comprises a second circulation line, a second heat exchanging part connected to the second circulation line, and a second driving device, the second driving device is configured to drive a second fluid heat exchanging medium to circulate in the second fluid circulation loop, and the second heat exchanging part comprises a second heat exchanging wall surface exchanging heat with the second heat exchanging surface.

In some embodiments of the present invention, the,

the second fluid circulation loop also comprises a third heat exchange part which is arranged on the second circulation pipeline and is provided with a third heat exchange wall surface for exchanging heat with the environment;

the heat exchange device further comprises a fan configured to enhance heat exchange of the third heat exchange wall with the environment to exchange heat of the second fluid heat exchange medium with the environment.

In some embodiments, heat exchange fins are arranged outside the third heat exchange wall surface.

In some embodiments, the second fluid circulation loop comprises a second medium vessel disposed on the second circulation line configured to hold the second fluid heat exchange medium.

In some embodiments, the temperature control system comprises:

the controller is in signal connection with the temperature measuring device and the temperature adjusting device and is configured to control the temperature adjusting device to work according to control information so as to adjust the temperature of the first fluid heat exchange medium, and the control information comprises the temperature information collected by the temperature measuring device;

the controller is in signal connection with the temperature measuring device and the semiconductor chilling plate, and the control of the temperature adjusting device comprises control of working parameters of the semiconductor chilling plate.

In some embodiments, the temperature measurement device comprises:

a first temperature sensor configured to collect a temperature of the first fluid heat exchange medium, the temperature information comprising the temperature of the first fluid heat exchange medium; and/or

A second temperature sensor configured to acquire a temperature of the second fluid heat exchange medium, the temperature information including the temperature of the second fluid heat exchange medium.

In some embodiments of the present invention, the,

the heat exchange device further comprises a fan configured to enhance heat exchange of the third heat exchange wall surface with the environment to exchange heat of the second fluid heat exchange medium with the environment;

the controller is in signal connection with the fan, and the control of the work of the temperature adjusting device comprises the control of the action of the fan.

In some embodiments, the temperature control system further comprises an insulation material disposed in a location of the temperature control system that does not require heat exchange with the environment.

In some embodiments, the microbubble generator comprises an ultrasound probe for generating microbubbles.

A second aspect of the present disclosure provides a method for preparing microbubbles by using the apparatus for preparing microbubbles according to the first aspect of the present disclosure, comprising:

step 10, starting a temperature control system;

step 30, adjusting the temperature of the first fluid heat exchange medium in the first fluid circulation loop by taking the temperature set value as a target temperature; and

step 50, the microbubble generating device prepares microbubbles.

In some embodiments, there is further included step 20 of setting an initial said temperature set point.

In some embodiments, further comprising:

step 70, detecting the quality of the prepared microbubble finished product and obtaining a detection result;

step 90, keeping or adjusting the temperature set value according to the detection result; and

the steps 30 and 50 are re-executed.

In some embodiments, the step 90 comprises:

if macroscopic floc or sediment exists in the finished microbubble product, reducing the temperature set value;

if the microbubble finished product is in a clear liquid state, increasing the temperature set value;

and if the finished microbubble product is milky, keeping the temperature set value unchanged.

Based on this disclosure provides a microbubble preparation appearance for the microbubble preparation container of microbubble generating device can be in the fluid accommodation space of heat exchange container with the heat transfer medium heat transfer of the first fluid that flows, thereby does benefit to the heat transfer of preparation material and first fluid heat transfer medium in the microbubble production process, maintains the preparation material and is in required temperature range.

The microbubble preparation method provided by the disclosure has the advantages of the microbubble preparation instrument provided by the disclosure. Moreover, the preparation material in the microbubble preparation container can be effectively maintained in a required temperature range, so that the microbubble with better quality can be obtained, and the number of unqualified microbubbles can be reduced.

Other features of the present disclosure and advantages thereof will become apparent from the following detailed description of exemplary embodiments thereof, which proceeds with reference to the accompanying drawings.

Drawings

The accompanying drawings, which are included to provide a further understanding of the disclosure and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the disclosure and together with the description serve to explain the disclosure and not to limit the disclosure. In the drawings:

fig. 1 is a schematic structural diagram of a temperature control system of a microbubble generator according to an embodiment of the present disclosure.

Fig. 2 is a schematic diagram of another angle of the temperature control system shown in fig. 1.

Fig. 3 is a schematic diagram of a further angle of the temperature control system shown in fig. 1.

Fig. 4 is a flowchart of a method for preparing microbubbles according to an embodiment of the disclosure.

Fig. 5 is a schematic structural diagram of a microbubble generator according to an embodiment of the present disclosure.

In fig. 1 to 3, each reference numeral represents:

1. a fan;

2. a heat exchange vessel; 201. an inner housing; 202. an outer housing; c1, a first accommodating space; c2, a second accommodating space;

3. a first pump;

4. a second pump;

5. a first media container;

6. a first temperature sensor;

7. a second medium container;

8. a second temperature sensor;

9. a third pump;

10. a semiconductor refrigeration sheet;

11. a controller;

12. a third heat exchanging portion;

13. a first heat exchanging portion;

14. a second heat exchanging portion;

15. a first circulation line;

16. a second circulation line;

17. a circuit cable;

100. a first fluid circulation loop;

200. a second fluid circulation loop;

300. a microbubble generation device;

301. a microbubble preparation container;

302. an ultrasonic probe.

Detailed Description

The technical solutions in the embodiments of the present disclosure will be clearly and completely described below with reference to the drawings in the embodiments of the present disclosure, and it is obvious that the described embodiments are only a part of the embodiments of the present disclosure, and not all of the embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the disclosure, its application, or uses. All other embodiments, which can be derived by a person skilled in the art from the embodiments disclosed herein without making any creative effort, shall fall within the protection scope of the present disclosure.

The relative arrangement of the components and steps, the numerical expressions, and numerical values set forth in these embodiments do not limit the scope of the present disclosure unless specifically stated otherwise. Meanwhile, it should be understood that the sizes of the respective portions shown in the drawings are not drawn in an actual proportional relationship for the convenience of description. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values. It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, further discussion thereof is not required in subsequent figures.

In the description of the present disclosure, it should be understood that the terms "first", "second", etc. are used to define the components, and are used only for convenience of distinguishing the corresponding components, and if not otherwise stated, the terms have no special meaning, and thus, should not be construed as limiting the scope of the present disclosure.

In the description of the present disclosure, it is to be understood that the orientation or positional relationship indicated by the orientation terms is generally based on the orientation or positional relationship shown in the drawings, and is for convenience only to facilitate the description of the present disclosure and to simplify the description, and in the case of not having been stated to the contrary, these orientation terms do not indicate and imply that the device or element being referred to must have a particular orientation or be constructed and operated in a particular orientation, and therefore should not be taken as limiting the scope of the present disclosure; the terms "inner and outer" refer to the inner and outer relative to the profile of the respective component itself.

In the process of researching the microbubble preparation instrument, the inventor finds that when the miniature microbubble preparation instrument utilizing the ultrasonic cavitation method is used for preparing microbubbles, the quality of microbubble finished products is unstable, and precipitation or denaturation is easy to occur. It has been found that the above problems are caused by temperature instability of the preparation substance (including the shell membrane solution, the microbubble suspension and/or the core gas) within the microbubble preparation vessel during microbubble preparation. The inventors further investigated and found that the reason for the temperature instability of the prepared material is as follows:

the thermal effect of ultrasonic cavitation causes the microbubble suspension to increase in temperature. Because the miniature microbubble preparation instrument generally adopts an ultrasonic cavitation method to prepare microbubbles, when the miniature microbubble preparation instrument works, ultrasonic waves not only can generate a cavitation effect, but also can generate a thermogenesis effect concomitantly, and under the action of the thermogenesis effect, the temperature of the ultrasonic probe can be inevitably increased, and the preparation temperature of microbubble suspension is influenced.

During microbubble preparation, the microbubble suspension temperature must be strictly maintained within a suitable temperature range. In the case of preparing microbubbles by ultrasonic cavitation, the temperature of the suspension of microbubbles also needs to be maintained within a desired temperature range, in other words, the suspension of microbubbles has a minimum allowable temperature and a maximum allowable temperature, and if the temperature of the suspension of microbubbles is lower than the minimum allowable temperature, the shell of microbubbles cannot be molded, and if the temperature of the suspension of microbubbles exceeds the maximum allowable temperature, the suspension of microbubbles is easy to precipitate or denature.

For example: common albumin microbubbles, i.e., microbubbles in which the shell-membrane solution is albumin, have a minimum allowable temperature of 45 ℃ and a maximum allowable temperature of 60 ℃ during their preparation; if other drug-loaded microbubbles, such as "copper albumin microbubbles" loaded with metal elements, are prepared, the allowable temperature range becomes narrower.

The miniaturization of the microbubble preparation instrument enables the temperature of the prepared substance to easily generate abrupt change. The ultrasonic probe usually needs to operate at high power to generate sufficient cavitation effect, so that microbubble preparation is completed smoothly, the temperature of the ultrasonic probe and prepared substances can be greatly increased, in a small microbubble preparation instrument, the space of a microbubble preparation container is narrow, only a small amount of prepared substances can be stored, and the temperature of the prepared substances is changed rapidly due to the heating of the ultrasonic probe, so that the quality fluctuation of microbubble finished products is caused finally.

In order to overcome the defect that the quality of a microbubble finished product is unstable due to the fact that the temperature of a preparation substance is easy to change sharply in the microbubble generating process, the embodiment of the disclosure provides microbubble preparation equipment and a microbubble preparation method.

As shown in fig. 5, the microbubble generator includes a microbubble generating apparatus 300 and a temperature control system. The microbubble generation apparatus 300 includes, for example, a microbubble preparation container 301 and an ultrasonic probe 302 to prepare microbubbles by an ultrasonic cavitation method.

Fig. 1 to 3 are schematic structural diagrams illustrating a temperature control system of a microbubble generator according to an embodiment of the present disclosure. As shown in fig. 1 to 3, the microbubble generator according to the embodiment of the present disclosure includes a first fluid circulation circuit 100 and a temperature adjustment device.

The first fluid circulation loop 100 circulates a first fluid heat exchange medium, and includes a first circulation line 15, a heat exchange container 2 connected to the first circulation line 15, and a first driving device. The first driving means is configured to drive a first fluid heat exchange medium to circulate within the first fluid circulation loop 100. The heat exchange container 2 has a fluid housing space configured to house the micro-bubble preparation container 301 and to circulate a first fluid heat exchange medium to exchange heat with the micro-bubble preparation container 301. The temperature regulating device is configured to regulate the temperature of the first fluid heat exchange medium in the first circulation line 15.

According to the micro-bubble preparation instrument disclosed by the embodiment of the disclosure, due to the arrangement of the heat exchange container 2, the micro-bubble preparation container 301 of the micro-bubble generation device 300 can exchange heat with the flowing first fluid heat exchange medium in the fluid accommodating space of the heat exchange container 2, so that the heat exchange between the preparation substance and the first fluid heat exchange medium in the micro-bubble production process is facilitated, and the preparation substance is maintained within a required temperature range.

Due to the arrangement of the first fluid circulation loop 100, the first fluid heat exchange medium in the heat exchange container 2 is kept flowing through the first circulation pipeline 15 and the first driving device arranged on the first circulation pipeline 15, and the temperature adjusting device is arranged to adjust the temperature of the first fluid heat exchange medium in the first circulation pipeline 15, so that the temperature of the preparation material can be adjusted within a required temperature range by actively adjusting the temperature of the first fluid heat exchange medium.

Meanwhile, because the heat exchange container 2 is in the first fluid circulation loop 100, the first fluid heat exchange medium is kept in a flowing state in the heat exchange container 2, on one hand, the heat exchange between the micro-bubble preparation container 301 and the first fluid heat exchange medium is sufficient, on the other hand, the temperature of the first fluid heat exchange medium exchanging heat with the micro-bubble preparation container 301 is relatively stable, and the heat dissipation environment of the micro-bubble preparation container 301 cannot be deteriorated due to the fact that the first fluid heat exchange medium stays in the fluid accommodating space for a long time, therefore, the temperature of the shell membrane solution is kept in a required temperature range, and the quality stability of a micro-bubble finished product is further facilitated.

The first fluid heat exchange medium may be, for example, a fluid with heat transfer capability, such as water or a refrigerant.

As shown in fig. 2 and 3, the heat exchange container 2 includes an inner shell 201 and an outer shell 202. The inner case 201 has a first accommodating space C1 and a fluid inlet communicating with the first accommodating space C1, to which the first circulation line 15 is connected. The inner casing 201 is disposed inside the outer casing 202, and a second accommodating space C2 is formed between the inner casing 201 and the outer casing 202. The outer case 202 has a fluid outlet communicating with the second accommodating space C2, and the first circulation line 15 is connected to the fluid outlet. The first accommodating space C1 is communicated with the second accommodating space C2. Wherein the fluid accommodating space includes a first accommodating space C1 and a second accommodating space C2, and the first accommodating space C1 is configured to accommodate the micro-bubble preparation container 301.

The arrangement of the double-layer shell above the heat exchange container 2 is beneficial to extending the heat path for exchanging heat between the first heat exchange fluid in the first accommodating space C1 and the external environment through the first heat exchange fluid in the second accommodating space C2, and is beneficial to maintaining the temperature stability of the first heat exchange fluid in the first accommodating space C1, so that the preparation material in the microbubble preparation container 301 is beneficial to maintaining in the required temperature range.

As shown in fig. 1-3, in some embodiments, the first fluid circulation loop 100 includes a first medium container 5, the first medium container 5 being disposed on the first circulation line 15 and configured to contain a first fluid heat exchange medium. The provision of the first medium container 5 increases the total capacity of the first fluid heat exchange medium in the first fluid circulation loop 100, which is advantageous for improving the stability of the temperature of the first fluid heat exchange medium.

As shown in fig. 1-3, in some embodiments, the temperature control system includes a temperature measurement device and a controller 11. The temperature measurement device is configured to collect temperature information of the temperature control system. The controller 11 is in signal connection with the temperature measuring device and the temperature adjusting device, and is configured to control the temperature adjusting device to operate according to the control information to adjust the temperature of the first fluid heat exchange medium. The control information includes temperature information collected by the temperature measuring device.

The temperature measuring device and the controller 11 are arranged, so that the automatic control of the temperature control system is facilitated, and the temperature of the preparation material in the microbubble preparation container 301 is more accurately controlled.

As shown in fig. 1 to 3, in some embodiments, the temperature regulation device includes a semiconductor chilling plate 10 and a heat exchange device. The semiconductor chilling plates 10 have a first heat exchange surface and a second heat exchange surface, the first fluid circulation loop 100 includes a first heat exchanging part 13 connected to the first circulation pipe 15, and the first heat exchanging part 13 includes a first heat exchanging wall surface exchanging heat with the first heat exchange surface. The heat exchange means is configured to exchange heat with the second heat exchange surface.

The first heat exchange surface and the first heat exchange wall surface can be directly attached, and heat exchange can be realized through heat-conducting substances such as silicone grease, silica gel and the like. The refrigerating capacity of the semiconductor refrigerating sheet 10 is beneficial to being accurately and rapidly controlled through the working parameters thereof, thereby being beneficial to more accurately controlling the temperature of the preparation material in the micro-bubble preparation container 301.

As shown in fig. 1 to 3, in some embodiments, the heat exchanging device includes a second fluid circulation loop 200, the second fluid circulation loop 200 includes a second circulation line 16, a second heat exchanging part 14 connected to the second circulation line 16, and a second driving device configured to drive a second fluid heat exchanging medium to circulate in the second fluid circulation loop 200, and the second heat exchanging part 14 includes a second heat exchanging wall surface exchanging heat with the second heat exchanging surface.

The second heat exchange surface and the second heat exchange wall surface can be directly attached, and heat exchange can be realized through heat-conducting substances such as silicone grease, silica gel and the like.

The second fluid circulation loop 200 may exchange heat with the second heat exchange surface of the semiconductor chilling plate 10 to facilitate continuous and stable operation of the semiconductor chilling plate 10.

The second fluid heat exchange medium may be, for example, a fluid with heat transfer capability, such as water or a refrigerant. The second fluid heat exchange medium and the first fluid heat exchange medium may be the same kind of fluid or different kinds of fluids.

As shown in fig. 1 to 3, in some embodiments, the second fluid circulation loop 200 further includes a third heat exchanging part 12, the third heat exchanging part 12 is disposed on the second circulation line 16 and has a third heat exchanging wall surface for exchanging heat with the environment; the heat exchange device further comprises a fan 1, and the fan 1 is configured to enhance the heat exchange of the third heat exchange wall surface with the environment.

The third heat exchanging portion 12 is, for example, a third heat exchanging cavity, and includes an inlet and an outlet, and an inner cavity of the third heat exchanging cavity is used for circulating a second fluid heat exchanging medium.

As shown in fig. 1-3, in some embodiments, the second fluid circulation loop 200 includes a second medium container 7, the second medium container 7 being disposed on the second circulation line 16 and configured to contain a second fluid heat exchange medium. The second medium container 7 facilitates an increase in the stability of the temperature of the second fluid heat exchange medium by increasing the total capacity of the second fluid heat exchange medium in the second fluid circulation loop 200.

As shown in fig. 1-3, in some embodiments, the temperature control system includes a temperature measurement device and a controller 11. The temperature measurement device is configured to collect temperature information of the temperature control system. The controller 11 is in signal connection with the temperature measuring device and the temperature adjusting device, and is configured to control the temperature adjusting device to operate to adjust the temperature of the first fluid heat exchange medium according to control information, where the control information includes temperature information collected by the temperature measuring device. The controller 11 is in signal connection with the temperature measuring device and the semiconductor chilling plate 10, and the control of the temperature adjusting device comprises control of working parameters of the semiconductor chilling plate 10. The operating parameters of the semiconductor chilling plate 10 may include, for example, operating voltage, current, and/or duty cycle.

The temperature measuring device and the controller 11 are arranged, and the controller 11 controls the working parameters of the semiconductor refrigeration sheet 10 according to the temperature information of the temperature control system, so that the temperature control system can more accurately and automatically control the temperature of the preparation material in the microbubble preparation container 301.

As shown in fig. 1-3, in some embodiments, the temperature measurement device includes at least one of a first temperature sensor 6 and a second temperature sensor 8. A first temperature sensor 6 configured to acquire a temperature of the first fluid heat exchange medium, the temperature information comprising the temperature of the first fluid heat exchange medium. The second temperature sensor 8 is configured to acquire the temperature of the second fluid heat exchange medium, the temperature information comprising the temperature of the second fluid heat exchange medium.

In some embodiments, the temperature control system may further include an input device in signal connection with the controller 11, the controller 11 being configured to receive input information from the input device. Wherein the control information comprises input information.

The input device can intervene in the operation of the temperature control system through input information input from the outside, for example, the target temperature (temperature set value) of the first fluid heat exchange medium can be adjusted according to the quality of the finished product of the micro-bubbles, so that the quality of the micro-bubble generator can be improved.

The specific form of the input device is not limited as long as the input of the input information to the control device can be realized, and the input device may include a button, a mouse, a man-machine interaction screen, a voice input device, and the like.

As shown in fig. 1 to 3, in some embodiments, in the case that the second fluid circulation loop 200 includes the third heat exchanging portion 12 and the heat exchanging device includes the fan 1, the controller 11 may be further connected with the fan 1 by signals, and the controlling the operation of the temperature adjusting device includes controlling the operation of the fan 1. At this time, the controller 11 is configured to control the fan 1 to operate to adjust the temperature of the second fluid heat exchange medium according to the temperature information.

The controller 11 controls the fan 1 to act, so that the heat exchange degree between the third heat exchange part 12 and the environment can be adjusted, the temperature of the second fluid heat exchange medium can be controlled, the semiconductor refrigeration piece 10 can work stably, and the temperature of the first fluid heat exchange medium and the temperature of the preparation substance in the microbubble preparation container 301 can be controlled accurately.

The microbubble generator and the microbubble preparation method according to the embodiment of the present disclosure will be further described with reference to fig. 1 to 4.

The microbubble generator 300 can be used to prepare ultrasound contrast microbubbles or drug-loaded microbubbles. The ultrasonic contrast microvesicle is also called as ultrasonic contrast agent, and is injected into the body through vein, and ultrasonic imaging is carried out in vitro, when the ultrasonic wave passes through the microvesicle, the scattering signal generated by the microvesicle is greatly enhanced, and then the contrast between tissues and blood can be obviously enhanced, and the resolution of the ultrasonic imaging is improved. The drug-loaded microvesicles are targeted therapeutic drugs constructed by combining microvesicles with drugs, such as microvesicles and copper ion compositions, and can be used for targeted therapy of diseases such as atherosclerosis.

The microbubble generating apparatus 300 of the microbubble generator according to the embodiment of the present disclosure mainly includes an air supply system and a microbubble generating system.

The gas supply system is used for introducing core gas into the shell membrane solution in the microbubble preparation container 301, and mainly comprises a gas source, a valve assembly and a pipeline assembly.

The microbubble generation system is used for performing sound vibration treatment on the shell membrane solution and the inner core gas so as to form microbubble suspension. The microbubble generation system of the microbubble generation apparatus 300 of the present disclosure includes an ultrasonic probe 302 and a microbubble preparation container 301. The microbubble generation device 300 employed in the embodiment of the present disclosure is easy to realize a miniaturized design.

The microbubble preparation container 301 contains a shell membrane solution before sound vibration and gas filling, a shell membrane solution and core gas before sound vibration and during gas filling and after gas filling, a shell membrane solution, core gas and microbubble suspension in sound vibration, and mainly contains microbubble suspension after sound vibration is completed. The substance contained in the microbubble preparation container 301 in each process of microbubble preparation is referred to as a preparation substance.

As an embodiment, the ultrasound probe 302 may be, for example, a BRANSON Sonifier series S450D sonicator, the probe having a diameter of 18 mm. The microbubble preparation container 301 may be, for example, a test tube having a diameter of 22mm, or other containers may be used as the microbubble preparation container, such as a vial.

The temperature control system controls the temperature of the preparation substance in the microbubble preparation container 301 by controlling the temperature of the first fluid heat exchange medium and exchanging heat between the first fluid heat exchange medium and the microbubble preparation container 301. Because the microbubble preparation instrument of the embodiment of the present disclosure employs the temperature control system to control the temperature of the microbubble preparation container 301 of the microbubble generation device 300, when preparing microbubbles, for example, microbubbles combined with pharmaceutical ingredients, it is possible to effectively avoid the situation of preparation failure caused by temperature fluctuation of microbubble suspensions.

In the embodiment shown in fig. 1 to 3, the temperature control system mainly comprises a first fluid circulation circuit 100, a temperature adjustment device, a temperature measurement device, a controller 11 and an input device. The temperature adjusting device comprises a semiconductor refrigerating sheet 10 and a heat exchange device. The heat exchange means comprises a second fluid circulation loop 200 and a fan 1.

A first fluid heat exchange medium circulates in the first fluid circulation loop 100. The first fluid circulation circuit 100 includes a first circulation line 15, and a first pump 3, a heat exchange container 2, a second pump 4, a first medium container 5, and a first heat exchanging portion 13 connected to the first circulation line 15 in this order in a flow direction of a first fluid heat exchange medium. Wherein the first pump 3 and the second pump 4 are used as a first driving device to drive the first fluid heat exchange medium to circulate in the first fluid circulation loop 100. The first pump 3 provides motive force for the flow of the first fluid heat exchange medium at the stage of supply from the semiconductor chilling plates 10 to the heat exchange vessel 2. The second pump 4 provides the first fluid heat exchange medium with a flow power for returning the first fluid heat exchange medium from the heat exchange container 2 to the first medium container 5, and the second pump 4 is arranged to provide the first fluid heat exchange medium with a sufficient flow power for returning the first fluid heat exchange medium from the outer casing C2 to the first medium container 5 after overflowing from the inner casing C1 to the outer casing C2.

As shown in fig. 1 to 3, the outlet of the first medium tank 5 and the inlet of the first heat exchanging part 13, the outlet of the first heat exchanging part 13 and the inlet of the first pump 3, the outlet of the first pump 3 and the fluid inlet of the heat exchanging tank 2, the fluid outlet of the heat exchanging tank 2 and the inlet of the second pump 4, and the outlet of the second pump 4 and the inlet of the first medium tank 5 are connected by the first circulation line 15.

The temperature measuring device is used for detecting temperature information of the temperature control system. The temperature measuring means comprises a first temperature sensor 6 and a second temperature sensor 8. The first temperature sensor 6 is adapted for collecting the temperature of the first fluid heat exchange medium, e.g. mounted on the first medium container 5, such as on a side wall thereof, for collecting the temperature of the first fluid heat exchange medium inside the first medium container 5. The second temperature sensor 8 is adapted for sensing the temperature of the second fluid heat exchange medium, e.g. mounted on the second medium container 7, such as on a side wall thereof, for sensing the temperature of the second fluid heat exchange medium inside the second medium container 7.

The first temperature sensor 6, the second temperature sensor 8, the semiconductor chilling plate 10 and the fan 1 are in signal connection with the controller 11. As shown in fig. 1 to 3, the first temperature sensor 6, the second temperature sensor 8, the semiconductor chilling plate 10 and the fan 1 are electrically connected to the controller 11 through a circuit cable 17. The temperature of the first fluid heat exchange medium collected by the first temperature sensor 6 and the temperature of the second fluid heat exchange medium collected by the second temperature sensor 8 are transmitted to the controller 11 as temperature information collected by the temperature measuring device, the controller 11 uses the temperature information as at least one part of control information and generates a control instruction according to the control information, and the semiconductor refrigerating sheet 10 and the fan 1 are controlled to work so as to adjust the temperature of the first fluid heat exchange medium.

The temperature control system further comprises an input device in signal connection with the controller 11, the controller 11 being configured to receive input information of the input device, the control information comprising the input information. The input information may include, for example, a temperature preset value for the first fluid heat exchange medium, a temperature preset value for the second fluid heat exchange medium, ambient temperature information, and the like.

The temperature control system may further comprise a display connected to the controller 11, the display having a temperature display function. For example, the display can display the current temperature values measured by the first temperature sensor 6 and the second temperature sensor 8, so as to help the operator confirm whether the temperature control system achieves the expected temperature control effect.

The semiconductor chilling plates 10 are main temperature adjusting components in the temperature control system in this embodiment, and the semiconductor chilling plates 10 receive the control instruction of the controller 11, and control the temperature of the first working surface by adjusting the working parameters of the semiconductor chilling plates 10, so as to control the temperature of the first fluid heat exchange medium, so that the first fluid heat exchange medium in the first fluid circulation loop 100 is maintained at the set working temperature or working temperature range. The operating parameters of the semiconductor chilling plate 10 may include at least one of an operating voltage, current and duty cycle. The first fluid heat exchange medium exchanges heat with the microbubble preparation container 301, so that the temperature rise of the ultrasonic probe 302 can be counteracted through the refrigeration of the semiconductor refrigeration sheet 10, and the temperature of the microbubble suspension in the microbubble preparation container 301 is kept relatively stable.

The first heat exchange surface of the semiconductor chilling plates 10 exchanges heat with the first heat exchange wall surface of the first heat exchanging part 13 of the first fluid circulation loop 100, so that the semiconductor chilling plates 10 can exchange heat with the first fluid heat exchanging medium in the first heat exchanging part 13 to change the temperature of the first fluid heat exchanging medium in the first fluid circulation loop 100. The first fluid heat exchange medium in the first fluid circulation loop 100 exchanges heat with the micro-bubble preparation container 301 in the fluid accommodating space of the heat exchange container 2, so that the heat exchange between the semiconductor refrigeration fins 10 and the micro-bubble preparation container 301 can be realized through the first fluid medium circulating in the first fluid circulation loop 100. For example, when the temperature of the microbubble suspension is increased by the heat generated by the ultrasonic probe 302 in the microbubble preparation container 301, the temperature increase of the shell membrane solution and the microbubble suspension caused by the heat generated during the ultrasonic wave emitted from the ultrasonic probe 302 can be balanced by the first fluid heat exchange medium circulating in the first fluid circulation loop 100, which is beneficial to keeping the microbubble preparation container 301 and the substances prepared inside the microbubble preparation container at a constant temperature or within a required temperature range.

According to the semiconductor refrigeration principle, the semiconductor refrigeration plate 10 has two heat exchange surfaces, and in the powered working state, the first heat exchange surface generates heat, and the second heat exchange surface refrigerates, and vice versa. Wherein the first heat exchange surface of the semiconductor chilling plate 10 exchanges heat with the first heat exchanging part 13 of the first fluid circulation loop 100. The first heat exchange surface of the semiconductor chilling plate 10 can exchange heat with the first fluid circulation loop 100 through the first heat exchanging portion 13, so as to regulate and control the temperature of the first fluid heat exchange medium.

The first heat exchanging portion 13 is, for example, a first heat exchanging cavity and includes an inlet and an outlet, and an inner cavity of the first heat exchanging cavity is used for flowing a first fluid heat exchanging medium. The first heat exchanging part 13 is connected to the first circulation line 15 through an inlet and an outlet thereof.

Typically, a temperature control system is used to cool the first fluid heat exchange medium to balance the heat generated by the ultrasonic probe 302. The second heat exchange surface exchanges heat with the second heat exchanging part 14 of the second fluid circulation loop 200, transfers the heat generated by the semiconductor chilling plate 10 to the second fluid heat exchanging medium of the second fluid circulation loop 200, and then dissipates the heat generated by the semiconductor chilling plate 10 to the external environment through the third heat exchanging part 12 and the fan 1.

The first fluid circulation loop 100 in the temperature control system provides a first fluid heat exchange medium which flows circularly, the first fluid heat exchange medium exchanges heat with the microbubble preparation container 301 which contains preparation substances (including shell membrane solution, microbubble suspension and/or core gas) in the fluid accommodating space of the heat exchange container 2, the temperature of the preparation substances is prevented from being increased rapidly under the influence of heat generated by the ultrasonic probe 302, and the effect of regulating and maintaining the temperature of the preparation substances in the microbubble preparation container 301 is achieved.

The first medium vessel 5 is a vessel of the first fluid circulation loop 100 that stores and recovers the first fluid heat exchange medium. The first medium container 5 can increase the capacity of the first fluid heat exchange medium in the first fluid circulation loop 100, and slow down the rate of temperature change of the first fluid heat exchange medium in the working state of the microbubble generation device 300, thereby being beneficial to maintaining the stability of the working temperature of the first fluid heat exchange medium and being beneficial to more accurate and stable temperature control of the prepared substance.

The heat exchange container 2 is a container for heat exchange between the first fluid heat exchange medium and the microbubble preparation container 301 containing the microbubble suspension, and in this embodiment, heat exchange is indirectly performed between the first fluid heat exchange medium and the microbubble suspension through a container wall of the microbubble preparation container 301, so that the temperature of the microbubble suspension is consistent with the temperature of the heat exchange medium.

As shown in fig. 2, in order to make the first fluid heat exchange medium in the heat exchange container 2 and the micro bubble preparation container 301 containing the preparation material always flow relatively, improve the heat exchange efficiency and ensure the heat exchange effect, the heat exchange container 2 includes an inner shell 201 and an outer shell 202. The inner case 201 has a first accommodating space C1 and a fluid inlet communicating with the first accommodating space C1, to which the first circulation line 15 is connected. The inner casing 201 is disposed inside the outer casing 202, and a second accommodating space C2 is formed between the inner casing 201 and the outer casing 202. The outer case 202 has a fluid outlet communicating with the second accommodating space C2, and the first circulation line 15 is connected to the fluid outlet. The first accommodating space C1 is communicated with the second accommodating space C2. Wherein the fluid accommodating space includes a first accommodating space C1 and a second accommodating space C2, and the first accommodating space C1 is configured to accommodate the micro-bubble preparation container 301.

In the embodiment shown in fig. 1 to 3, the fluid inlet and the fluid outlet are both located at the bottom of the heat exchange container 2, and the top of the first accommodating space C1 is communicated with the second accommodating space C2. This arrangement is favorable to the first fluid heat transfer medium to flow in the heat exchange container 2 in the order of ascending first and then descending, makes the flowing first fluid heat transfer medium flow on the whole and immerses the part below the liquid level of the first accommodation space C1 through the microbubble preparation container 301, is favorable to the first fluid heat transfer medium to fully exchange heat with the preparation material, thereby is favorable to the temperature control of the preparation material.

As shown in fig. 2 and 3, in some embodiments, the top of the inner and

outer housings

201, 202 of the heat exchange container 2 are open. This arrangement makes the heat exchange container 2 form an open structure, and makes the first fluid heat exchange medium flow strictly according to the flow path from the fluid inlet to the first accommodating space C1, then to the second accommodating space C2, and then to the fluid outlet, which is favorable for preventing the first fluid heat exchange medium from locally flowing back, and is further favorable for temperature control of the preparation substance in the microbubble preparation container 301.

In the embodiment shown in fig. 2, the structure of the heat exchange vessel 2 is a double-sleeve fountain-type structure. The heat exchange container 2 includes a cylindrical inner case 201 and a cylindrical outer case 202. The hollow portion of the inner case 201 forms a first accommodation space C1. The bottom of the inner shell 201 is provided with a fluid inlet into which a first fluid heat exchange medium flows. The annular space between the outer housing 202 and the inner housing 201 forms a second accommodation space C2. The bottom of the outer case 202 is provided with a fluid outlet communicating with the second accommodating space C2. The top of the inner case 201 is lower than the outer case 202, so that the first accommodating space C1 is communicated with the second accommodating space C2 at the top.

The flow path of the first heat exchange medium in the heat exchange vessel 2 is as follows: the first fluid heat exchange medium flows into the first accommodating space C1 in the inner casing 201 from the fluid inlet at the bottom of the inner casing 201, overflows to the second accommodating space C2 from the top of the inner casing 201, and then flows out of the heat exchange container 2 from the fluid outlet at the bottom of the outer casing 202.

The dual-sleeve fountain type structure enables the first fluid heat exchange medium to have good fluidity in the heat exchange container 2, thereby improving the heat exchange efficiency of the first fluid heat exchange medium and the microbubble preparation container 301 and ensuring the heat exchange effect.

In addition, the top end of the outer shell 202 is higher than that of the inner shell 201, which is beneficial to reducing the possibility that the first fluid heat exchange medium may splash out of the heat exchange container 2 when overflowing from the first accommodating space C1 to the second accommodating space C2.

The first accommodating space C1 in the inner shell 201 of the heat exchange container 2 is used for accommodating the microbubble preparation container 301 containing the preparation material, and at the sound vibration stage of microbubble preparation, the part of the microbubble preparation container 301 which is positioned below the liquid level of the microbubble suspension can be immersed in the first fluid heat exchange medium in the inner shell 201 of the heat exchange container 2, so that the microbubble preparation container 301 corresponding to the microbubble suspension and the flowing first fluid heat exchange medium exchange heat in the inner shell 201 of the heat exchange container 2, and the microbubble suspension can be stably maintained at the required preparation temperature in the sound vibration process.

As shown in fig. 1 to 3, the first driving means includes a first pump 3 and a second pump 4. The first pump 3 is disposed on the first circulation line 15 between the first medium container 5 and the heat exchange container 2, and is configured to convey the first fluid heat exchange medium in the first circulation line 15 into the heat exchange container 2. The second pump 4 is disposed on the first circulation line 15 between the heat exchange container 2 and the first medium container 5, and is configured to convey the first fluid heat exchange medium in the first circulation line 15 into the first medium container 5.

The first pump 3 and the second pump 4 work in series in the first fluid circulation loop 100, both providing the motive force for the first fluid heat exchange medium to circulate in the first fluid circulation loop. Wherein the first pump 3 is as main circulating pump, and second pump 4 is as the output circulation pump, and the power of second pump 4 is greater than first pump 3.

Since the heat exchange container 2 has a double-shell structure including an inner shell 201 and an outer shell 202, such as a double-sleeve fountain structure, which is an open structure, after the first fluid heat exchange medium overflows from the inner shell 201 to the outer shell 202 of the heat exchange container 2, the power of the first fluid heat exchange medium flowing back from the outer shell 202 to the first medium container 5 may be insufficient. The second pump 4 is arranged to provide flow power for the first fluid heat exchange medium to flow back from the heat exchange vessel 2 to the first medium vessel 5.

As shown in fig. 1 to 3, the first pump 3 is located between the first heat exchanging portion 13 and the heat exchanging container 2. An inlet of the first pump 3 is connected to an outlet of the first heat exchanging part 13, and an outlet of the first pump 3 is connected to a fluid inlet of the bottom of the inner case 201 of the heat exchange container 2. A second pump 4 is arranged between the heat exchange container 2 and the first medium container 5. The inlet of the second pump 4 is connected to the fluid outlet at the bottom of the outer casing 202 of the heat exchange vessel 2 and the outlet of the second pump 4 is connected to the inlet of the first medium container 5. The second pump 4 provides flowing power for the first fluid heat exchange medium to flow to the first medium container 5 after completing the heat exchange of the micro-bubble preparation container 301 in the inner shell 201 of the heat exchange container 2 and overflowing to the outer shell 202.

The first driving device in the form of double pumps of the first pump 3 and the second pump 4 is arranged, so that smooth driving of the first fluid heat exchange medium is facilitated when the heat exchange container 2 adopts an open structure with an open top.

The first pump 3 provides motive force for the flow of the first fluid heat exchange medium at the stage of supply from the first medium vessel 5 to the heat exchange vessel 2. After the first pump 3 is started, the first fluid heat exchange medium flows from the outlet of the first medium container 5 to the inlet of the first heat exchange portion 13, then enters the first pump 3 through the outlet of the first heat exchange portion 13, then flows into the heat exchange container 2 from the outlet of the first pump 3, then flows into the second pump 4 from the fluid outlet of the heat exchange container 2, and finally flows back to the first medium container 5 from the outlet of the second pump 4, thereby completing the circulating flow of the first fluid heat exchange medium in the first fluid circulation loop 100.

The number of the semiconductor chilling plates 10 may be set according to the heat dissipation requirement of the micro-bubble preparation container 301 of the micro-bubble generation apparatus 300. For example, in the embodiment shown in fig. 1 to 3, two semiconductor chilling plates 10 are provided.

The number of the first heat exchanging parts 13 may be set according to the number and arrangement of the semiconductor chilling plates 10. In the embodiment shown in fig. 1 to 3, a first heat exchanging portion 13 is provided, and the first heat exchanging surfaces of the two semiconductor chilling plates 10 exchange heat with the chamber walls of the two first heat exchanging portions 13 respectively.

A second fluid heat exchange medium is circulated within the second fluid circulation loop 200. The second fluid circulation loop 200 is mainly used to dissipate heat generated by the second heat exchanging surface of the semiconductor chilling plate 10 to the external environment. The second fluid circulation circuit 200 includes a second circulation line 16, and a third pump 9, a third heat exchanging part 12, a second medium container 7, and a second heat exchanging part 14 connected to the second circulation line 16 in this order in the flow direction of the second fluid heat exchanging medium. Wherein the third pump 9 is used as a second driving device to drive the second fluid heat exchange medium to circulate in the first fluid circulation loop 200.

As shown in fig. 1 to 3, the outlet of the second medium tank 7 is connected to the inlet of the second heat exchanging unit 14 through the second circulation line 16, the outlet of the second heat exchanging unit 14 is connected to the inlet of the third pump 9, the outlet of the third pump 9 is connected to the inlet of the third heat exchanging unit 12, and the outlet of the third heat exchanging unit 12 is connected to the inlet of the second medium tank 7.

The second heat exchanging portion 14 is configured to exchange heat between the second fluid heat exchanging medium in the second fluid circulation loop 200 and the second heat exchanging surface of the semiconductor chilling plate 10, so as to ensure that the semiconductor chilling plate 10 can be kept in a temperature range of normal operation, avoid overheating or overcooling, perform continuous and stable refrigeration, and enable the first fluid circulation loop 100 to provide the first fluid heat exchanging medium with a set operating temperature.

The second heat exchanging portion 14 is, for example, a second heat exchanging cavity, and includes an inlet and an outlet, and an inner cavity of the second heat exchanging cavity is used for circulating a second fluid heat exchanging medium. The second heat exchanging part 14 is connected to the second circulation line 16 through an inlet and an outlet thereof.

The number of the second heat exchanging parts 14 may be set according to the number and arrangement of the semiconductor chilling plates 10. In the embodiment shown in fig. 1 to 3, two second heat exchanging portions 14 are provided, and the two semiconductor chilling plates 10 and the first heat exchanging portion 13 are located between the two second heat exchanging portions 14. The cavity walls of the two second heat exchanging parts 14 exchange heat with the second heat exchanging surfaces of the two semiconductor chilling plates 10 respectively.

Silicone grease may be disposed between the two heat exchange surfaces of the semiconductor chilling plates 10 and the first and second

heat exchange portions

13 and 14 as a heat conductive substance to achieve a more excellent heat exchange effect.

The third heat exchanging portion 12 and the fan 1 are used for heat exchange between the second fluid heat exchanging medium that completes heat exchange with the second heat exchanging surface of the semiconductor chilling plate 10 and the environment, and ensuring the working state and temperature operation requirement of the second heat exchanging surface of the semiconductor chilling plate 10 and the second fluid heat exchanging medium that performs heat exchange with the second heat exchanging surface, so as to keep continuous operation of the semiconductor chilling plate 10.

Heat exchange fins may be disposed on an outer side of a third heat exchange wall surface of the third heat exchange portion 12 to improve heat exchange capability between the third heat exchange portion 12 and the ambient air.

The fan 1 is used to realize heat exchange between the third heat exchanging portion 12 and the environment. The fan 1 increases the heat exchange efficiency between the third heat exchanging part 12 and the environment by increasing the air flow rate on the surface of the third heat exchanging part 12, such as the surface of the heat exchanging fins, so as to enhance the heat exchange of the second fluid heat exchanging medium flowing through the inside of the third heat exchanging part 12 and keep the working temperature of the second fluid heat exchanging medium stable.

The number of the fans 1 may be set according to the heat dissipation requirement of the second fluid heat exchange medium, and may be, for example, 1, two, or more than three. As shown in fig. 1 to 3, in the present embodiment, two fans 1 are respectively disposed on two sides of the third heat exchanging portion 12 to enhance the heat dissipation effect of the third heat exchanging portion 12.

The fan 1 and the third heat exchanging part 12 may be combined to form an integral structure, and the fan 1 is installed outside the third heat exchanging surface of the third heat exchanging part 12.

When the first heat exchange surface of semiconductor refrigeration piece 10 refrigerates, the second heat exchange surface can be corresponding generate heat, in order to make semiconductor refrigeration piece 10 steady operation, need in time spill out the heat on second heat exchange surface, second fluid heat transfer medium carries out even heat exchange through second heat transfer portion 14 and the second heat exchange surface of semiconductor refrigeration piece 10, heat exchange efficiency between the second heat exchange surface of heat transfer medium and semiconductor refrigeration piece 10 has been promoted through increasing second heat transfer portion 14, make the heat exchange that semiconductor refrigeration piece 10 and second fluid heat transfer medium last in order to keep stable operating temperature.

The second medium container 7 is used for storing and recycling a second fluid heat exchange medium and increasing the capacity of the second fluid heat exchange medium in circulation, so that the temperature change range of the second fluid heat exchange medium is reduced in the working state of the temperature control system, the working temperature of the second fluid heat exchange medium is stabilized, the overall energy storage capacity of the second fluid heat exchange medium is improved, and the semiconductor refrigeration sheet 10 can continuously run at a relatively stable working temperature.

The third pump 9 is used as a second driving device for providing power for circulating the second fluid heat exchange medium from the second medium container 7 to the second heat exchange part 14, then to the third pump 9, then to the third heat exchange part 12, and finally back to the second medium container 7. Under the driving of the third pump 9, the second fluid heat exchange medium in the second fluid circulation circuit 200 flows from the outlet of the second medium container 7 into the inlet of the second heat exchange portion 14, then flows from the outlet of the second heat exchange portion 14 into the inlet of the third pump 9, then flows from the outlet of the third pump 9 into the inlet of the third heat exchange portion 12, and then flows from the outlet of the third heat exchange portion 12 into the inlet of the second medium container 7, thereby completing the circulation flow of the second fluid heat exchange medium in the second fluid circulation circuit 200.

The signal input end of the controller 11 is respectively connected with the first temperature sensor 6 and the second temperature sensor 8 through a circuit cable 17, and the output end of the controller 11 is respectively connected with the semiconductor refrigerating sheet 10 and the fan 1 through a circuit cable.

When the temperature control system is started, a first fluid heat exchange medium and a second fluid heat exchange medium are respectively filled into the first medium container 5 and the second medium container 7, and the first medium container 5 and the second medium container 7 are closed after the filling is finished. And then starting the controller 11 to start self-test, starting the first temperature sensor 6 and the second temperature sensor 8 and monitoring the temperature, and starting the first pump 3, the second pump 4 and the third pump 9 after obtaining the corresponding temperatures. The first fluid heat exchange medium and the second fluid heat exchange medium are circulated in the first fluid circulation loop 100 and the second fluid circulation loop 200, respectively, for a period of time to discharge air in the first fluid circulation loop 100 and the second fluid circulation loop 200 until the circulation is stabilized. And then the fan 1 is started through the controller 11, and the semiconductor refrigerating sheet 10 is started after the first fluid circulation loop 100 and the second fluid circulation loop 200 are circulated and stabilized, so that the whole temperature control system enters a formal operation state. Then, the temperature set value of the first fluid circulation loop 100 can be set as the target temperature of the first fluid heat exchange medium according to the actual operation condition, and the warning temperature of the second fluid circulation loop 200 can also be set as the temperature limit value of the second fluid heat exchange medium, so as to ensure the stable operation of the temperature control system.

The Controller 11 may be implemented as a general purpose Processor, a Programmable Logic Controller (PLC), a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Field Programmable Gate Array (FPGA) or other Programmable Logic device, discrete Gate or transistor Logic, discrete hardware components, or any suitable combination thereof for performing the functions described in this disclosure.

The input device is in signal connection with the controller 11, and the controller 11 can control the temperature adjusting device to work together according to the input information of the input device and the temperature information detected by the temperature detecting device.

In some embodiments, the temperature control system further comprises an insulating material disposed in a portion of the temperature control system that does not require heat exchange with the environment. In the embodiment shown in fig. 1 to 3, the first fluid circulation loop 100 is wrapped with a thermal insulation material except for the open top portion of the heat exchange container 2. All the other elements and circulation pipelines except the third heat exchanging part 12 and the fan 1 in the second fluid circulation loop 200 are wrapped with heat insulating materials.

In the embodiment shown in fig. 1 to 3, both the first fluid heat exchange medium and the second fluid heat exchange medium are water, also referred to as recycled water in the following description.

Although the structure and the operation principle of the related components are described by using the first heat exchange surface of the semiconductor chilling plate 10 for refrigeration and the second heat exchange surface for heat generation when describing the temperature control system, in the temperature control system of the embodiment of the present disclosure, based on the characteristic that the polarities of the voltages at the two sides of the semiconductor chilling plate 10 can be exchanged, the refrigeration and heat generation functions of the first heat exchange surface and the second heat exchange surface of the semiconductor chilling plate 10 can be switched to each other by causing the current to flow in the opposite direction, so that the first heat exchange surface of the semiconductor chilling plate 10 for heat generation and the second heat exchange surface for refrigeration can be set according to the current working environment, such as in a cold working environment, so as to increase the temperature of the preparation substance in the microbubble preparation container 301 and make the temperature reach the required range.

That is, the temperature control system of the embodiments of the present disclosure may operate in two operating modes:

1. a cooling mode in which the first heat exchange surface of the semiconductor chilling plate 10 chills and the second heat exchange surface generates heat; and

2. a preheating mode in which the first heat exchange surface of the semiconductor chilling plate 10 generates heat and the second heat exchange surface chills.

In the cooling mode, the temperature control system can function to cool the preparation substance in the microbubble preparation container 301 during the preparation process of the microbubbles. As described above, since the temperature of the preparation material increases with the increase of the working temperature of the ultrasonic probe 302 during the preparation process, the temperature control system provides the first fluid heat exchange medium after being cooled down, so that the first fluid heat exchange medium exchanges heat with the microbubble preparation container 301, and thus exchanges heat with the preparation material therein, at this time, since the relative temperature of the first fluid heat exchange medium is low, the first fluid heat exchange medium can cool down the preparation material, and thus the heat generated by the ultrasonic probe 302 can be balanced during the microbubble preparation process, and the temperature of the preparation material can be maintained within the required temperature range.

In the preheat mode, the temperature control system preheats the preparation material prior to microbubble preparation. The first fluid heat exchange medium which is heated and preheated is provided by the temperature control system, so that the first fluid heat exchange medium exchanges heat with the microbubble preparation container 301, and the heat exchange is carried out with the preparation substance. At the moment, because the relative temperature of the first fluid heat exchange medium is higher, the first fluid heat exchange medium can heat and preheat the preparation substance which does not reach the required temperature range, so that the temperature of the preparation substance is increased to some extent, and finally the temperature of the preparation substance is kept within the required temperature range. The preheat mode ensures that the microbubble generation device 300 can be used normally when the ambient temperature at which it operates is below the required temperature range.

A method for preparing microbubbles by the microbubble generator according to the embodiment of the present disclosure will be described below with reference to fig. 4.

As shown in fig. 4, the microbubble preparation method comprises:

step 10, starting a temperature control system;

step 30, adjusting the temperature of the first fluid heat exchange medium in the first fluid circulation loop 100 by taking the temperature set value as a target temperature; and

in step 50, the microbubble generator 300 prepares microbubbles.

The temperature set value may be a point value or a temperature range.

In some embodiments, the microbubble preparation method further comprises: an initial temperature set point is set, step 20.

In some embodiments, the microbubble preparation method further comprises:

step 90, keeping or adjusting a temperature set value according to the detection result; and

step 30 and step 50 are re-executed.

Wherein step 90 comprises:

if the microbubble finished product has macroscopic floccules or precipitates, reducing the temperature set value;

if the microbubble finished product is in a clear liquid state, the temperature set value is increased;

if the finished microbubble is milky, the temperature set point is maintained.

The microbubble preparation method provided by the disclosure has the advantages of the microbubble preparation instrument provided by the disclosure. Since the preparation material in the microbubble preparation container 301 can be effectively maintained within a required temperature range, it is advantageous to obtain microbubbles of superior quality and to reduce the number of defective microbubbles.

The temperature of the first fluid heat exchange medium in the first fluid circulation loop 100 is regulated and controlled by the first temperature sensor 6, the controller 11, the semiconductor chilling plates 10 and the fan 1. First, the controller 11 gives a command to activate the first pump 3 and the second pump 4 in the first fluid circulation loop 100 to circulate the first fluid heat exchange medium in the first circulation line 15 of the first fluid circulation loop 100. The first temperature sensor 6 arranged in the first fluid circulation loop 100 detects the current temperature value of the first fluid heat exchange medium in the first fluid circulation loop 100 in real time, and the first temperature sensor 6 transmits the detected current temperature value to the controller 11. The controller 11 controls the working states of the semiconductor chilling plates 10 and the fan 1 according to the current temperature value and the temperature set value measured by the first temperature sensor 6, so as to realize the heating, chilling or temperature maintaining work of the first fluid heat exchange medium, and thus the temperature of the first fluid heat exchange medium in the first fluid circulation loop 100 reaches or is kept at the temperature set value.

In addition, the controller 11 also regulates and controls the working state of the fan 1 according to the current temperature value and the temperature set value measured by the first temperature sensor 6, so as to radiate the redundant heat generated by the second heat exchange surface of the semiconductor chilling plate 10 to the environment.

When the microbubble generating apparatus 300 generates microbubbles, a preparation substance in the microbubble preparation container 3012, such as a mixture of an albumin solution and perfluoropropane gas, is ultrasonically oscillated by the ultrasonic probe 302 after being started to generate albumin microbubbles. As an example, the ultrasound probe 302 may be: it is believed that the ultrasonic disruptor of S450D, the ultrasonic probe 302, has a diameter of 3/4 ". The microbubble preparation vessel 301 is, for example, a Beckman Polyallemer centrifuge tube, the volume of which is 38 mL. The operating parameters of the ultrasonic probe 302 are: the acoustic vibration was performed in two steps in total, first with a 60% amplitude for 150 seconds, with each cycle period: the sound vibration is interrupted for 30 seconds in 10 seconds for 15 cycles, and then is acted on for 30 seconds by 80 percent of amplitude, and each cycle period is as follows: the sound vibration was interrupted for 10 seconds and for 30 seconds for 3 cycles.

After the preparation of the microbubbles, the finished microbubbles are contained in the microbubble preparation container 301, but it is difficult to determine whether the quality of the finished microbubbles is qualified because it is not known whether the temperature in the microbubble preparation container 301 exceeds an allowable value during the preparation process, and therefore, the quality of the finished microbubbles needs to be detected. The detection and judgment of whether the quality of the microbubble finished product is qualified can be finished by naked eyes or by an instrument.

For example, an operator can judge whether the quality of the microbubble finished product is qualified or not through the following visual observation mode, and adjust or maintain the temperature preset value according to the detection result:

if macroscopic floc or precipitate exists in the microbubble preparation container 301, the quality of the microbubble finished product is judged to be unqualified, and the floc or precipitate indicates that the temperature of the microbubble suspension is higher in the microbubble preparation process, and the temperature set value of the first fluid circulation loop 100 needs to be reduced.

If the microbubble preparation container 301 is in a clear liquid state, the quality of the microbubble finished product is judged to be unqualified, and the state of the clear liquid indicates that the temperature of the microbubble suspension is low in the microbubble preparation process, and the temperature set value of the first fluid circulation loop 100 needs to be increased.

If the microbubble preparation container 301 is milky, the quality of the microbubble finished product is judged to be qualified, and the milky state indicates that the albumin solution and the perfluoropropane preparation substance generate cavitation and emulsification through ultrasonic oscillation at a proper temperature, so that the albumin solution and the perfluoropropane preparation substance are finally white milky suspension.

The temperature measuring device in the embodiment of the present disclosure is used for monitoring the temperature information of the temperature control system in real time, and the controller 11 uses the temperature information as a part of the control information to adjust the operating state of the temperature control system. Because the flow of the first fluid heat exchange medium in the first medium container 5 is smooth, the capacity is large, the temperature change is smooth, and the monitored temperature accuracy is high, the first temperature sensor 6 is installed on the first medium container 5 to monitor the temperature of the first fluid heat exchange medium in the first fluid circulation loop 100. The detection part of the first temperature sensor 6 can be arranged in the first medium container 5, and the temperature of the first fluid heat exchange medium in the first medium container 5 can be directly monitored, so that the working temperature of the first fluid heat exchange medium can be more accurately reflected. A second temperature sensor 8 is mounted on the second medium container 7 for monitoring the temperature of the second fluid heat exchange medium, reflecting the current temperature of the second fluid heat exchange medium at the second medium container 7. After the second temperature sensor 8 monitors the current temperature of the second fluid heat exchange medium and feeds back the temperature to the operator, the operator can accordingly determine whether effective heat exchange is performed between the temperature control system and the microbubble preparation container 301.

The input device is used to input a temperature set point of the first fluid circulation loop 100 to the controller 11. The controller 11 controls the operation states of the semiconductor chilling plates 10 and the fan 1 based on the temperature information detected by the first and

second temperature sensors

6 and 8 and the temperature set value of the first fluid circulation circuit 100 that has been input.

In some embodiments, not shown, the temperature adjustment device may take other forms. For example, the second fluid circulation loop 200 and the fan 1 may be integrally replaced by an air-cooled heat dissipation system of a fin group and fan combination to exchange heat with the second heat exchange surface of the semiconductor chilling plate 10.

The number and positions of the temperature sensors of the temperature measuring device can be changed according to actual use requirements.

The type of the first fluid heat exchange medium can also be changed according to the actual use requirement, and besides the circulating water in the above embodiment, oil or other cooling liquid can also be used as the heat exchange medium.

As can be seen from the above description, the microbubble generator according to the embodiment of the present disclosure further has at least one of the following technical effects:

the microbubble preparation instrument of the embodiment of the disclosure utilizes the microbubble preparation container to adjust the temperature of the preparation material, and the temperature control process is as follows: when the temperature of the prepared substance is controlled, the microbubble preparation container of the microbubble generation device can exchange heat with the flowing first fluid heat exchange medium in the fluid containing space of the heat exchange container, so that the microbubble preparation container and the prepared substance inside the microbubble preparation container are subjected to heat exchange through the first fluid heat exchange medium in the microbubble production process, and the prepared substance is maintained in a required temperature range. Therefore, in the whole temperature control process, only the temperature parameter of the microbubble preparation container needs to be adjusted, the feeding process does not need to be changed, other key process parameters influencing the physical characteristics of the microbubbles cannot be changed, the temperature of the prepared substance is effectively regulated and controlled under the condition that other microbubble preparation process parameters are kept unchanged, the single-variable regulation of the microbubble preparation process parameters is facilitated (for example, the power of an ultrasonic probe can be independently adjusted under the condition that the parameters such as microbubble stock solution and the like are not changed), and the stability and the consistency of the preparation process and the product quality are facilitated.

The microbubble preparation instrument provided by the embodiment of the disclosure adopts the microbubble preparation container to conduct heat on the prepared material, and the material of the microbubble preparation container has the characteristic of high heat conductivity, so that the heat dissipation efficiency is high, and the microbubble preparation instrument is particularly suitable for the extreme preparation environment with strict requirement on the temperature fluctuation range of the prepared material, for example, the preparation environment with the temperature easily and rapidly rising in a small space, such as a small microbubble preparation instrument, and is beneficial to effectively solving the problem that the microbubble quality is influenced by the rapid rising of the temperature of the prepared material in the process of preparing microbubbles by an ultrasonic cavitation method.

The microbubble preparation instrument provided by the embodiment of the disclosure actively intervenes in the temperature of the microbubble preparation container and the prepared substance in the microbubble preparation container by utilizing the heat exchange of the first fluid heat exchange medium. Because the temperature of the first fluid heat exchange medium is not limited by the microbubble preparation process, the first fluid heat exchange medium can adopt liquid with enough low temperature as required to form enough high temperature difference to carry out high-efficiency active cooling heat dissipation. For example, the temperature adjusting devices such as the semiconductor refrigeration sheet provided by the embodiment of the disclosure can enable the first fluid heat exchange medium to reach a very low temperature so as to expand the temperature difference, and achieve the refrigeration efficiency enough to meet the heat dissipation requirement of the microbubble preparation instrument. Meanwhile, the first driving device provided by the disclosure drives the first fluid heat exchange medium to circularly flow in the first circulation loop, and the first fluid heat exchange medium with low temperature is continuously supplied to the heat exchange container and is in a flowing state, so that the temperature control system is further ensured to provide stable heat dissipation efficiency, and the heat dissipation efficiency is high. Compared with a temperature regulation mode in the prior art in which the albumin solution with the preset temperature is continuously and circularly filled so as to enable the solution in the microbubble preparation container to be integrally maintained at the preset temperature, the microbubble preparation instrument provided by the embodiment of the disclosure can meet higher temperature regulation requirements. This is because: the microbubble preparation process of the related art has certain requirements on the lowest temperature and the highest temperature of the injected albumin solution, the temperature regulation range adopting the temperature regulation mode is limited, and for the preparation environment with higher heat dissipation requirement, enough temperature difference is difficult to generate, the cooling efficiency is insufficient, and the required heat dissipation effect cannot be achieved.

The microbubble preparation instrument provided by the embodiment of the disclosure adopts the microbubble preparation container to regulate and control the temperature of the prepared substance, and the microbubble preparation container is a conventional part of microbubble preparation equipment, so that the temperature control system can be deployed only by adding the heat exchange container and the matching parts at the original microbubble preparation container without changing the feeding process and the structural parts, and the microbubble preparation instrument is simple in structure and easy to implement and deploy.

The temperature control system in the microbubble preparation instrument provided by the embodiment of the disclosure can be used as an independent temperature control system to independently control the temperature of the prepared substance, can also be compatible with other temperature control modes to carry out combined temperature control as a supplementary means for improving the temperature control efficiency, and has good compatibility and wide application range.

The microbubble preparation instrument provided by the embodiment of the disclosure adopts the microbubble preparation container to implement temperature control on the preparation material, provides a temperature control system which can be compatible and suitable for a small-batch single-tube preparation mode, and solves the technical problem that the related art can not carry out effective temperature control on a microbubble preparation device in an automatic instrument mode.

Finally, it should be noted that: the above examples are intended only to illustrate the technical solutions of the present disclosure and not to limit them; although the present disclosure has been described in detail with reference to preferred embodiments, those of ordinary skill in the art will understand that: modifications to the embodiments of the disclosure or equivalent replacements of parts of the technical features may be made, which are all covered by the technical solution claimed by the disclosure.

Claims

1. A micro-bubble preparation apparatus comprising a micro-bubble generating device (300) and a temperature control system, the micro-bubble generating device (300) comprising a micro-bubble preparation container (301), characterized in that the temperature control system comprises:

a first fluid circulation loop (100) comprising a first circulation line (15), a heat exchange vessel (2) connected to the first circulation line (15), and a first driving device configured to drive a first fluid heat exchange medium to circulate within the first fluid circulation loop (100), the heat exchange vessel (2) having a fluid housing space configured to house the micro-bubble preparation vessel (301) and to circulate the first fluid heat exchange medium to heat exchange the first fluid heat exchange medium with the micro-bubble preparation vessel (301); and

a temperature regulating device configured to regulate the temperature of the first fluid heat exchange medium within the first circulation line (15).

2. The apparatus according to claim 1, wherein the heat exchange container (2) comprises:

an inner case (201) having a first accommodating space (C1) and a fluid inlet communicating with the first accommodating space (C1), the first circulation line (15) being connected with the fluid inlet; and

an outer housing (202), the inner housing (201) being disposed inside the outer housing (202) and forming a second accommodating space (C2) with the outer housing (202), the outer housing (202) having a fluid outlet communicating with the second accommodating space (C2), the first circulation line (15) being connected with the fluid outlet, the first accommodating space (C1) being communicated with the second accommodating space (C2);

wherein the fluid containing space comprises the first containing space (C1) and the second containing space (C2), the first containing space (C1) being configured to place the micro bubble preparation container (301).

3. The apparatus according to claim 2, wherein the fluid inlet and the fluid outlet are both located at the bottom of the heat exchange container (2), and the top of the first housing space (C1) is in communication with the second housing space (C2).

4. The apparatus according to claim 2, wherein the inner (201) and outer (202) shells of the heat exchange vessel (2) are open at the top.

5. The apparatus according to claim 1, wherein the first fluid circulation circuit (100) comprises a first medium container (5), the first medium container (5) being arranged on the first circulation line (15) and being configured to contain the first fluid heat exchange medium.

6. The apparatus according to claim 5, wherein the first driving means comprises:

-a first pump (3) arranged on the first circulation line (15) between the first medium container (5) and the heat exchange container (2) configured to convey the first fluid heat exchange medium in the first circulation line (15) into the heat exchange container (2); and

-a second pump (4) arranged on the first circulation line (15) between the heat exchange vessel (2) and the first medium container (5) and configured to convey the first fluid heat exchange medium in the first circulation line (15) into the first medium container (5).

7. The apparatus according to claim 1, wherein the temperature control system comprises:

a controller (11), in signal connection with the temperature measuring device and the temperature adjusting device, configured to control the temperature adjusting device to operate to adjust the temperature of the first fluid heat exchange medium according to control information, where the control information includes the temperature information collected by the temperature measuring device.

8. The apparatus according to claim 7, wherein the temperature control system further comprises an input device in signal connection with the controller (11), the controller (11) being configured to receive input information from the input device, wherein the control information comprises the input information.

9. The apparatus according to any one of claims 1 to 8, wherein the temperature adjusting means comprises:

the semiconductor refrigeration piece (10) is provided with a first heat exchange surface and a second heat exchange surface, the first fluid circulation loop (100) comprises a first heat exchange part (13) connected to the first circulation pipeline (15), and the first heat exchange part (13) comprises a first heat exchange wall surface exchanging heat with the first heat exchange surface; and

10. The apparatus according to claim 9, wherein the temperature control system comprises:

a cooling mode in which the first heat exchange surface of the semiconductor chilling plate (10) chills and the second heat exchange surface generates heat; and

a preheating mode in which the first heat exchange surface of the semiconductor chilling plate (10) generates heat and the second heat exchange surface chills.

11. The apparatus according to claim 9, wherein the heat exchange means comprises a second fluid circulation circuit (200), the second fluid circulation circuit (200) comprises a second circulation line (16), a second heat exchanging portion (14) connected to the second circulation line (16), and a second driving means configured to drive a second fluid heat exchanging medium to circulate in the second fluid circulation circuit (200), and the second heat exchanging portion (14) comprises a second heat exchanging wall surface for exchanging heat with the second heat exchanging surface.

12. The apparatus for preparing microvesicles according to claim 11,

the second fluid circulation loop (200) further comprises a third heat exchanging part (12), and the third heat exchanging part (12) is arranged on the second circulation pipeline (16) and is provided with a third heat exchanging wall surface for exchanging heat with the environment;

the heat exchange device further comprises a fan (1), the fan (1) being configured to enhance the heat exchange of the third heat exchange wall with the environment to exchange heat of the second fluid heat exchange medium with the environment.

13. A micro bubble preparation instrument according to claim 12, wherein heat exchange fins are provided on the outside of the third heat exchange wall surface.

14. The apparatus according to claim 11, wherein the second fluid circulation circuit (200) comprises a second medium container (7), the second medium container (7) being arranged on the second circulation line (16) and being configured to contain the second fluid heat exchange medium.

15. The apparatus according to claim 11, wherein the temperature control system comprises:

a controller (11), in signal connection with the temperature measuring device and the temperature adjusting device, configured to control the temperature adjusting device to operate to adjust the temperature of the first fluid heat exchange medium according to control information, where the control information includes the temperature information collected by the temperature measuring device;

the controller (11) is in signal connection with the temperature measuring device and the semiconductor refrigerating sheet (10), and the control of the temperature adjusting device comprises the control of working parameters of the semiconductor refrigerating sheet (10).

16. The apparatus according to claim 15, wherein the temperature measuring means comprises:

a first temperature sensor (6) configured to acquire a temperature of the first fluid heat exchange medium, the temperature information comprising the temperature of the first fluid heat exchange medium; and/or

A second temperature sensor (8) configured to acquire a temperature of the second fluid heat exchange medium, the temperature information comprising the temperature of the second fluid heat exchange medium.

17. The apparatus for preparing microvesicles according to claim 15,

the heat exchange device further comprises a fan (1), the fan (1) being configured to enhance the heat exchange of the third heat exchange wall with the environment to exchange heat of the second fluid heat exchange medium with the environment;

the controller (11) is in signal connection with the fan (1), and the control of the work of the temperature adjusting device comprises the control of the action of the fan (1).

18. The apparatus according to any one of claims 1 to 8, wherein the temperature control system further comprises a thermal insulation material disposed at a location of the temperature control system where heat exchange with the environment is not required.

19. The apparatus according to any one of claims 1 to 8, wherein the microbubble generator (300) comprises an ultrasonic probe (302) for generating microbubbles.

20. A method for preparing microbubbles using the apparatus for preparing microbubbles according to any one of claims 1 to 19, comprising:

step 10, starting a temperature control system;

step 30, adjusting the temperature of the first fluid heat exchange medium in the first fluid circulation loop (100) by taking the temperature set value as a target temperature; and

in step 50, the microbubble generator (300) prepares microbubbles.

21. The method for preparing microbubbles according to claim 20, further comprising a step 20 of setting an initial set value of the temperature.

22. The method for producing microvesicles according to claim 20 or 21, further comprising:

the steps 30 and 50 are re-executed.

23. The method for preparing microvesicles according to claim 20 or 21, wherein said step 90 comprises: