Real-time monitoring cell culture system and culture method thereof

文档序号:1691105 发布日期:2019-12-10 浏览:30次 中文

阅读说明:本技术 实时监控的细胞培养系统及其培养方法 (Real-time monitoring cell culture system and culture method thereof ) 是由 李阳 高毅 钟克波 彭青 于 2019-07-25 设计创作,主要内容包括:为了在维持培养细胞微环境的稳定性的情况下观察细胞培养装置内部环境,本申请提供一种实时监控的细胞培养系统,所述实时监控的细胞培养系统包括:影像采集装置,用于采集所述培养系统内细胞的影像;细胞培养装置,包括用于培养细胞的细胞培养腔并与影像采集装置相对运动;旋转传动装置,用于提供所述影像采集装置和细胞培养装置之间相对周向运动的动力。本申请的技术方案可以令使用者无需开启细胞培养腔就可以观察到细胞培养的状态,有利于维持培养细胞的微环境平衡,同时降低使用者频繁开启或闭合的工作量,还有利于降低细胞培养过程中细菌侵入的风险,提升细胞培养的存活率。(in order to observe the internal environment of a cell culture device while maintaining the stability of the microenvironment of cultured cells, the present application provides a real-time monitored cell culture system comprising: the image acquisition device is used for acquiring images of cells in the culture system; the cell culture device comprises a cell culture cavity for culturing cells and moves relative to the image acquisition device; and the rotary transmission device is used for providing power for the relative circumferential motion between the image acquisition device and the cell culture device. The technical scheme of this application can make the user need not to open the state that the cell culture chamber just can observe the cell culture, is favorable to maintaining the microenvironment balance who cultivates the cell, reduces the frequent opening of user or closed work load simultaneously, still is favorable to reducing the risk that the bacterium invaded among the cell culture process, promotes the survival rate of cell culture.)

1. A real-time monitored cell culture system, comprising:

The image acquisition device is used for acquiring images of cells in the culture system;

The cell culture device comprises a cell culture cavity for culturing cells and moves relative to the image acquisition device;

And the rotary transmission device is used for providing power for the relative circumferential motion between the image acquisition device and the cell culture device.

2. The real-time cell culture system according to claim 1, wherein the rotation transmission device comprises a rotation rod disposed inside the cell culture device, and the image capturing device is disposed on the rotation rod, and the rotation rod rotates around a longitudinal axis to drive the image capturing device to capture images of different regions of the cell culture device.

3. The real-time cell culture system of claim 2, wherein the rotating rod is connected to the image capturing device through a connecting member, the connecting member comprises a first connecting sub-member connected to the rotating rod and a second connecting sub-member connected to the image capturing device, and the first connecting sub-member and the second connecting sub-member are connected through at least one of screwing, clamping, bonding, concave-convex connection or magnetic connection.

4. The real-time monitoring cell culture system of claim 3, wherein the rotating rod and the image acquisition device are powered and/or transmitted through a wireless transmission assembly built in the connecting piece, the wireless transmission assembly comprises a first sub-coil built in the rotating rod and a second sub-coil built in the image acquisition device, and the first sub-coil and the second sub-coil are capacitively coupled.

5. The real-time monitoring cell culture system according to claim 4, wherein the image acquisition device at least comprises a camera and a data transmission module connected with the camera and transmitting image data, and the data transmission module performs data interaction with the outside by using wireless data transmission between the first sub-coil and the second sub-coil.

6. The real-time cell culture system of claim 3, wherein the rotating rod and the image capturing device are installed with magnetic alignment components, the magnetic alignment components comprise at least a first magnetic component and a second magnetic component, the first magnetic component and the second magnetic component are arranged in pairs close to the surface of the rotating rod and the surface of the image capturing device, and when the first magnetic component and the second magnetic component attract each other, the rotating rod and the image capturing device are aligned and fixed.

7. The real-time monitored cell culture system according to claim 1, wherein the rotary actuator further comprises a stirring component for stirring the cells to a suspension state, and the stirring component is at least one component selected from a group consisting of a magnetic rotor, a fan blade and a spray head.

8. The real-time monitoring cell culture system according to claim 7, wherein the stirring component is a spray head, the real-time monitoring cell culture system further comprises a culture fluid circulation device, the culture fluid circulation device at least comprises a liquid pump, a waste fluid delivery pipe connected with the liquid pump, and a culture fluid delivery pipe connected with the spray head, culture fluid is pumped to the culture fluid delivery pipe through the liquid pump and is sprayed out through the spray head, and cells in the cell culture device are stirred.

9. the real-time cell culture system according to claim 8, wherein the image capturing device is further provided with a liquid level sensor for detecting a liquid level, and when the liquid level sensor detects that the liquid level of the culture solution in the cell culture device is lower than a set value, the liquid pump is controlled to pump the culture solution and eject the culture solution through the nozzle.

10. A cell culture method, characterized in that the cell culture is performed using the real-time monitored cell culture system according to any one of claims 1 to 9.

Technical Field

The application mainly relates to the fields of biology and cell culture, in particular to a real-time monitoring cell culture system and a culture method thereof.

Background

Cell culture is an important scientific research and production means, and the requirement of cell culture on equipment is high, so close observation is needed. The existing cell culture mainly cultures under a constant temperature and humidity state, and often depends on equipment such as a constant temperature and humidity box, and the growth state of cells is often required to be observed in the cell culture process for recording or serving as a basis for adjusting culture conditions and other states.

In a conventional cell culture apparatus, particularly a pressurizing apparatus, the atmosphere in which cultured cells are taken out to affect the cultured cells to some extent is, for example, the temperature and humidity, the carbon dioxide content, and the like. Meanwhile, the stability of the culture environment can be influenced by frequent opening, the pollution risk of the culture medium can be increased, and the operation time of operators is prolonged.

Therefore, how to observe the condition of the cultured cells and the culture environment while keeping the culture environment unaffected has become a technical problem to be solved.

Disclosure of Invention

In order to solve the above technical problem of how to observe the condition of the cultured cells and the culture environment while keeping the culture environment unaffected, the present application provides a technical solution as follows.

The present application provides a real-time monitoring cell culture system, comprising:

The image acquisition device is used for acquiring images of cells in the culture system;

The cell culture device comprises a cell culture cavity for culturing cells and moves relative to the image acquisition device;

A rotation transmission device: the power for providing relative circumferential motion between the image acquisition device and the cell culture device.

In the cell culture system with real-time monitoring of an embodiment, the rotation transmission device includes a rotation rod disposed inside the cell culture device, the image acquisition device is disposed on the rotation rod, and the rotation rod rotates around a longitudinal axis to drive the image acquisition device to acquire images of different areas of the cell culture device.

in the real-time cell culture system of real-time monitoring of an embodiment, be connected through the connecting piece between rotatory member and the image acquisition device, the connecting piece including connect in rotatory member's first connecting sub-spare with connect in image acquisition device's second connecting sub-spare, first connecting sub-spare and second connecting sub-spare are connected through at least one mode of closure soon, joint, bonding or magnetic force connection.

In the cell culture system with real-time monitoring of an embodiment, the rotating rod and the image acquisition device are powered and/or transmitted through a wireless transmission assembly built in the connecting piece, the wireless transmission assembly comprises a first sub-coil built in the rotating rod and a second sub-coil built in the image acquisition device, and the first sub-coil and the second sub-coil are coupled in a capacitive mode.

In the cell culture system with real-time monitoring of an embodiment, the image acquisition device at least comprises a camera and a data transmission module which is connected with the camera and transmits image data, and the data transmission module performs data interaction with the outside by utilizing wireless data transmission between the first sub-coil and the second sub-coil.

in the real-time cell culture system of an embodiment, the rotating rod and the image acquisition device are provided with magnetic alignment components, the magnetic alignment components at least comprise a first magnetic part and a second magnetic part, the first magnetic part and the second magnetic part are arranged on the surface of the rotating rod in pairs and close to the surface of the image acquisition device, and when the first magnetic part and the second magnetic part attract each other, the rotating rod and the image acquisition device are aligned and are in a fixed state.

In one embodiment, the cell culture system is monitored in real time, and the rotation transmission device further comprises a stirring component for stirring the cells to a suspension state, wherein the stirring component is selected from at least one component of a magnetic rotor, a fan blade and a spray head.

In an embodiment of the cell culture system with real-time monitoring, the stirring component is a spray head, the cell culture system with real-time monitoring further comprises a culture fluid circulating device, the culture fluid circulating device at least comprises a liquid suction pump, a waste fluid conveying pipe connected with the liquid suction pump and a culture fluid conveying pipe connected with the spray head, and the culture fluid is sucked to the culture fluid conveying pipe through the liquid suction pump and sprayed out through the spray head to stir cells in the cell culture device.

In an embodiment of the cell culture system with real-time monitoring, the image acquisition device is further provided with a liquid level sensor, and when the liquid level sensor detects that the liquid level of the culture solution in the cell culture device is lower than a set value, the liquid pump is controlled to pump the culture solution and spray the culture solution through the spray head.

In an embodiment of the present application, there is also provided a cell culture method using the real-time monitoring cell culture system, wherein the cell culture is performed by using the real-time monitoring cell culture system of any one of the embodiments.

In order to observe the internal environment of the cell culture vessel and maintain the stability of the microenvironment of the cultured cells, the embodiment of the application provides a technical scheme of a real-time monitoring cell culture system, and the real-time monitoring cell culture system comprises: the image acquisition device is used for acquiring images of cells in the culture system; the cell culture device comprises a cell culture cavity for culturing cells and moves relative to the image acquisition device; and the rotary transmission device is used for providing power for the relative circumferential motion between the image acquisition device and the cell culture device. Aforementioned technical scheme can make the user need not to open the cell culture chamber just can observe cell culture's state, is favorable to maintaining the microenvironment balance who cultivates the cell, reduces the frequent work load of opening or closed of user simultaneously, still is favorable to reducing the risk that bacterium, virus or mycoplasma invaded among the cell culture process, promotes cell culture's quality.

Drawings

The foregoing and/or additional aspects and advantages of the present application will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:

FIG. 1 is a schematic diagram of a real-time monitoring cell culture system according to the present embodiment;

FIG. 2 is a schematic perspective view of a real-time monitoring cell culture system according to the present embodiment;

Fig. 3 is a perspective structural diagram of the image capturing device of the present embodiment;

FIG. 4 is a schematic structural diagram of the image capturing device according to the embodiment in the direction A-A;

FIG. 5 is a partial cross-sectional view of the image capturing device of the present embodiment taken along the line B-B;

fig. 6 is a perspective view schematically illustrating a structure of a rotary actuator according to the present embodiment;

Fig. 7 is a partial sectional view in the C-C direction of the rotary drive device of the present embodiment.

Detailed Description

Reference will now be made in detail to embodiments of the present application, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present application and are not to be construed as limiting the present application. In order to facilitate the demonstration of the practical application of the real-time monitoring cell culture system, the following embodiments will introduce specific operation steps of the method, so that the application and effect of the real-time monitoring cell culture system can be more fully and conveniently demonstrated, and it should be noted that the scope of the present application is not limited thereto.

Referring to fig. 1, fig. 1 shows a real-time monitoring cell culture system 1, in which a pressurizing device, an air-conditioning device, an opening and closing device, a rotary motor, etc. are hidden in fig. 1 for the convenience of display and the simplification of the display structure. FIG. 1 shows a cell culture system 1 in which an image acquisition device 11 and a cell culture device 12 are already connected.

The cell culture system 1 for real-time monitoring includes:

The image acquisition device 11 is used for acquiring images of cells in the cell culture system 1;

the cell culture device 12 comprises a cell culture cavity 121 for culturing cells and moves relative to the image acquisition device 11;

And the rotation transmission device 13 is used for providing power for the relative circumferential motion between the image acquisition device 11 and the cell culture device 12.

the relative circumferential movement between the image acquisition device 11 and the cell culture device 12 may be that the image acquisition device 11 rotates and the cell culture device 12 is relatively fixed, or that the image acquisition device 11 is relatively fixed and the cell culture device 12 rotates.

The image acquisition device 11 can acquire the image of the change of the culture environment in the cell culture chamber 121 of the cell culture device 12 and also can acquire the image of the change of the cells in the growth state. The cell culture chamber 121 in the cell culture device 12 can adopt a cell culture mode of suspension cell culture.

in this embodiment, the image capturing device 11 and the rotation transmission device 13 are in a shape of a slender cylinder, the image capturing device 11 and the rotation transmission device 13 may be made of engineering plastics, and waterproof treatments such as gluing, adding a rubber ring, and thermosetting are performed on an assembly gap between the image capturing device 11 and the rotation transmission device 13.

With reference to fig. 1, in the present embodiment, the rotation transmission device 13 includes a rotation rod 131 disposed inside the cell culture device 12, the image capturing device 11 is disposed on the rotation rod 131, and the rotation rod 131 rotates around a longitudinal axis to drive the image capturing device 11 to capture images of different regions of the cell culture device 12.

The rotation of the rotary drive 13 may be carried out periodically or at predetermined times and frequency, and thus for a predetermined number of times and duration, according to a predetermined program. For example, for a certain cell, the growth state of the cell does not change much, the rotation transmission device 13 can rotate for 4 weeks within 48 hours, and the image acquisition device 11 performs image acquisition while the rotation transmission device 13 rotates according to a set program. In addition, the image capturing device 11 can actively capture the cell growth status of a specific region according to the control of the program. The image collection time and the number of times of collection can be adjusted according to the type of the cultured cells.

When the rotation transmission device 13 rotates, the image capturing device 11 can capture the growth state of cells up to 360 ° circumferentially. When the rotation transmission device 13 is stationary, the image acquisition device 11 can acquire the cell growth state within the range of the visual angle of the camera equipment.

in the present embodiment, the rotation transmission device 13 may rotate in one direction or back and forth. In order to protect the internal lines and the infusion lines, the rotation transmission device 13 may be set to rotate in one direction by a maximum angle or a maximum number of turns. When the rotation angle of the rotation transmission device 13 exceeds the maximum angle or the number of rotation turns exceeds the maximum number of turns, the rotation transmission device 13 is controlled to stop or rotate reversely.

referring to fig. 2 in conjunction with fig. 1, the rotating rod 131 is connected to the image capturing device 11 through a connecting member 14, the connecting member 14 includes a first connecting sub-member 141 connected to the rotating rod 131 in the rotating transmission device 13 and a second connecting sub-member 142 connected to the image capturing device 11, and the first connecting sub-member 141 and the second connecting sub-member 142 may be connected by at least one of screwing, clamping, bonding, concave-convex connection or magnetic connection.

Considering the application scenario of the technical solution, the cell culture has a high requirement for preventing the risk of bacterial contamination, so the embodiment further provides a technical solution for reducing the connection gap between the connecting pieces 14 and the complexity of the connection structure. Referring to fig. 2, 3, 5 to 7, fig. 3 shows the components of the image capturing device 11 being pulled out separately for viewing the structure of the second connecting sub-element 142 of the connecting member 14; fig. 6 shows the rotary drive 13 separately drawn out to facilitate viewing of the configuration of the first coupling sub 141 in the coupling member 14; fig. 5 is a schematic structural view of the image capturing device 11 viewed from the direction B-B and partially cut away to show the structure of the second connecting sub-element 142 in the connecting member 14; fig. 7 is a schematic structural view of the rotary transmission 13 viewed from the direction C-C and partially cut away so as to show the structure of the first connecting sub 141 in the connecting member 14.

The first connecting member 141 and the second connecting member 142 are connected by a male-female coupling structure, i.e., male-female coupling. Specifically, the first connecting member 141 is composed of a square platform protruding at the center and an annular groove surrounding the square platform, and the second connecting member 142 is composed of a square platform-shaped groove recessed at the center and an annular protrusion surrounding the square platform-shaped groove. The square platform of the first connecting member 141 and the square platform-shaped groove of the second connecting member 142 can be matched, and the annular groove of the first connecting member 141 and the annular protrusion of the second connecting member 142 can be matched.

It should be noted that the specific shape of the concave-convex connection is not limited, and other concave-convex connection structures may be adopted in this embodiment. Other concave-convex connection structures may be, for example, a frustum-shaped, a rectangular parallelepiped-shaped, a hexagonal-shaped connection structure, or the like. Besides the concave-convex connection, a connection mode of strong magnetic connection can be adopted, so that the surface of the connecting element 14 can be set to be a smooth plane, and the influence of gaps or the shape of the connecting element 14 on the residue or adhesion of metabolic substances and cell debris is further reduced.

The embodiment also provides a technical scheme for wireless signal transmission and wireless energy supply.

Referring to fig. 3 and fig. 5 to fig. 7 in conjunction with fig. 2, the rotation rod 131 and the image capturing device 11 are powered and signal-transmitted through a wireless transmission assembly 143 disposed in the connecting member 14, the wireless transmission assembly 143 includes a first sub-coil 143-a disposed in the rotation rod 131 and a second sub-coil 143-B disposed in the image capturing device 11, and the first sub-coil 143-a and the second sub-coil 143-B are capacitively coupled.

Referring to fig. 5, the second sub-coil 143-B embedded in the second connecting member 142 is annular and circumferentially surrounds the annular protrusion of the second connecting member 142, and the second sub-coil 143-B is close to the surface of the second connecting member 142 for signal transmission or energy transfer.

referring to fig. 7, the first sub-coil 143-a disposed in the first connection element 141 is annular and circumferentially surrounds the annular groove of the first connection element 141, and the first sub-coil 143-a is close to the surface of the first connection element 142 so as to be capacitively coupled to the second sub-coil 143-B, so that the energy of the first sub-coil 143-a is transmitted to the second sub-coil 143-B and is supplied to other electrical components. The second sub-coil 143-B may also transmit the collected information to the second sub-coil 143-B and then transmit the information to various places through coupling with the first sub-coil 143-A, that is, near field communication.

Adopt wireless transmission subassembly 143 to carry out the technical scheme of communication or energy supply in this embodiment, can satisfy between image acquisition device 11 and the rotary transmission device 13 can dismantle with waterproof prerequisite under, can also transmit data such as control signal, influence information between image acquisition device 11 and rotary transmission device 13, can also supply energy to the electrical components in the image acquisition device 11 through the coil on the rotary transmission device 13 simultaneously, solved power supply and data transmission's problem. By arranging the wireless transmission assembly 143, the image acquisition device 11 and the rotation transmission device 13 can simultaneously realize whole body water resistance without affecting power supply and data transmission.

Referring to fig. 2 or fig. 3, the image capturing device 11 at least includes a camera 111 and a data transmission module 112 connected to the camera 111 and transmitting image data, and the data transmission module 112 performs data interaction with the outside by using wireless data transmission between the first sub-coil 143-a and the second sub-coil 143-B. The first sub-coil 143-A is connected to a peripheral device 19 outside the cell culture chamber 121, and the peripheral device 19 may be a power module for supplying power, a processor module for processing image data transmitted from the first sub-coil 143-B, and a data module for transmitting data to the outside in a wireless or wired manner. In addition, the peripheral device 19 and the data transmission module 112 can synchronously transmit information including image data and culture data (temperature, pressure, etc.) to the outside, and the transmission speed is increased, so that the information can be acquired in real time. Under the condition of low requirement on transmission speed, the data module in the peripheral device 19 and the data transmission module 112 may also work alternately to save energy.

In this embodiment, the camera 111 may be a wide-angle camera or a color camera, and in some cases, the camera 111 may be a camera that can be attached with a microlens structure, and the microlens structure may be installed outside the camera 111. In addition, in some embodiments, the camera 111 may further include a slide rail that can drive the camera 111 to slide linearly on the image capturing device 11 or the image capturing device 11 and the rotation transmission device 13 in an assembled state, so as to increase a shooting range of the camera 111.

In addition, in other embodiments, in order to protect the camera 111, the camera 111 may be embedded in the tubular image capturing device 11, so as to avoid collision of the camera 111.

in order to assist in assembling the image capturing device 11 and the rotation transmission device 13, so that the image capturing device 11 and the rotation transmission device 13 can be accurately aligned, the present embodiment provides a technical solution. Referring to fig. 3 and fig. 5 to fig. 7 in conjunction with fig. 2, the magnetic alignment component 15 is installed on the rotating rod 131 and the image capturing device 11, the magnetic alignment component 15 at least includes a first magnetic member 151 disposed close to the surface of the rotating rod 131 and a second magnetic member 152 disposed close to the surface of the image capturing device 11 in pair, and when the first magnetic member 151 and the second magnetic member 152 attract each other, the rotating rod 131 and the image capturing device 11 are aligned and in a fixed state. The mutual attraction between the first magnetic member 151 and the second magnetic member 152 can also assist in aligning the wireless transmission assembly 143, which is beneficial to improving the efficiency of wireless signal transmission and wireless energy supply, and avoiding heat generation due to energy loss.

In the above process, the first magnetic member 151 and the second magnetic member 152 are attracted to each other in opposite directions, which helps the assembler to confirm that the image capturing device 11 and the rotation transmitting device 13 are already in the aligned assembled state. In this embodiment, two sets of magnetic alignment components 15 are disposed on the rotating rod 131 and the image capturing device 11 for better alignment. In this embodiment, the symmetrical first magnetic members 151 are arranged with opposite polarities, and the symmetrical second magnetic members 152 are arranged with opposite polarities, so that when the image capturing device 11 and the rotation transmission device 13 are not aligned, the image capturing device 11 and the rotation transmission device 13 will generate a certain repulsive force, and an assembler can sense the assembly state and does not need to directly observe the inside of the cell culture chamber 121, thereby facilitating the assembly of the cell culture chamber 121 in a state where the observation is inconvenient.

Of course, in other embodiments of the present application, the magnetic alignment component 15 may be arranged appropriately according to the shape of the connecting component 14 to instruct the assembler to mount the image capturing device 11 and the rotation transmission device 13 in alignment. Besides, the present embodiment can prompt the assembler to align and mount the image capturing device 11 and the rotation transmission device 13 by vibration, visual indication (flashing or fixing alignment marks), buzzer, and the like.

The present embodiment further provides a technical solution more advantageously used for cell suspension culture, and the rotation transmission device 13 further comprises a stirring component for stirring the cells to a suspension state, wherein the stirring component is at least one component selected from a magnetic rotor, a fan blade and a spray head. Referring to fig. 1, 2 and 6, the nozzle 132 is used as a stirring component in the present embodiment. The spray head 132 may spray a culture solution, and the sprayed culture solution may agitate cells cultured in suspension in the cell culture chamber 121. When the rotary actuator 13 rotates, the nozzle may rotate following the rotary actuator 13 so as to agitate the circumferentially 360 ° floating cells. When the culture medium is ejected, care must be taken to set the speed of the culture medium to be transported so as to avoid damage to the cells due to an excessively high ejection speed.

Of course, the stirring assembly may also be a magnetic rotor, a fan blade, or the like, and the magnetic rotor is matched with the magnetic rotator outside the cell culture chamber 121 to stir the cells in the cell culture chamber to a suspended state. For example, the present embodiment may further include a protruding wing blade on the rotary rod 131 of the rotary actuator 13, and the culture solution may be agitated when the rotary rod 131 of the rotary actuator 13 rotates to facilitate cell resuspension. Besides, the wing-shaped fan blade may also be disposed on the image capturing device 11.

In order to further reduce the number of times the cell culture apparatus 12 is turned on, this embodiment also provides a solution. Referring to fig. 1 and fig. 2, in this embodiment, taking the stirring assembly as an example of the spray head 132, the cell culture system 1 for real-time monitoring further includes a culture fluid circulation device 16, the culture fluid circulation device at least includes a liquid pump 161, a waste fluid delivery pipe 162 connected to the liquid pump 161, and a culture fluid delivery pipe 163 connected to the spray head 132, and the culture fluid is pumped to the culture fluid delivery pipe 163 through the liquid pump 161 and sprayed out through the spray head 132 to stir the cells cultured in suspension in the cell culture device 12.

in this embodiment, the culture solution is stored in the culture solution storage chamber 164, the culture solution storage chamber 164 is further provided with a culture solution input pipe 164-A for inputting a reagent or discharging the culture solution, a culture solution pressure-regulating pipe 164-B for equalizing air pressure or regulating pressure, and the culture solution input pipe 164-A is further provided with an extraction pump 161. The waste liquid in the cell culture chamber 121 is pumped out of the cell culture chamber 121 by the liquid pump 161, and is input into the waste liquid delivery pipe 162 through the waste liquid inlet 167, and enters the waste liquid storage chamber 165. The waste liquid storage chamber 165 is further provided with a waste liquid discharge tube 165-A and a waste liquid pressure regulating tube 165-B for equalizing air pressure or regulating pressure. A cell strainer 167-1 is further clamped at the waste liquid inlet 167, and the cell strainer 167-1 can prevent cells or cell debris from entering the waste liquid delivery pipe 162 and causing blockage.

In this embodiment, a semi-permeable membrane 166 is disposed between the waste fluid storage compartment 164 and the waste fluid storage compartment 165, and the semi-permeable membrane 166 can appropriately filter the metabolites in the waste fluid and retain the metabolites in the waste fluid storage compartment 165, and can convert a portion of the waste fluid into the culture fluid, which enters the waste fluid storage compartment 164.

Above-mentioned culture solution circulating device 16 can the certain degree cycle update use culture solution, perhaps renews the culture solution in culture solution circulating device 16, further reduces opening of cell culture device 12 in cell culture system 1 of real time monitoring, can avoid the microenvironment change of cultivateing the cell and effectively reduce the risk of bacterium, virus or mycoplasma pollution.

In the embodiment of the present application, in order to maintain the culture solution in the cell culture apparatus 12 at a certain volume, a technical solution is provided in this embodiment, which avoids the increase of the number of cells and the shortage of the number of the culture solution, and further avoids the concentration of the metabolic substances to be too high, and finally avoids the decrease of the cell survival rate. Referring to fig. 1 to 4, in the present embodiment, the image capturing device 11 is further provided with a liquid level sensor 17 for detecting a liquid level of the culture fluid in the cell culture device 12, and when the liquid level sensor 17 detects that the liquid level of the culture fluid is lower than a predetermined value, the liquid pump 161 is controlled to pump the culture fluid and eject the culture fluid through the nozzle 132.

Wherein, the liquid level sensor 17 can be arranged at the top end of the image acquisition device 11. Of course, in some embodiments, the liquid level sensor 17 may also be disposed on the image capturing device 11 or the rotation transmission device 13, and the level of the culture liquid level may be known by detecting whether there is liquid. The processor in the cell culture system 1 may control the drawing pump 161 to draw the culture liquid and eject it through the ejection head 132 when the culture liquid level is below a certain value, and the processor in the cell culture system 1 may control the drawing pump 161 to draw the culture liquid through the waste inlet 167 when the culture liquid level is above a certain value.

In order to further maintain the constant or predetermined microenvironment of the cell culture device 12, this embodiment also provides a constant temperature solution. Referring to fig. 1, the cell culture system 1 in fig. 1 further includes a temperature adjustment and preservation assembly 18, the temperature adjustment and preservation assembly 18 includes a temperature adjustment layer 182 and a heat preservation layer 181, and the heat preservation layer 181 wraps the outside of the temperature adjustment layer 182. The temperature adjusting layer 182 can select liquid heat transfer or heating wire heating, the liquid heat transfer can be stably heated, the temperature can be adjusted to be increased or decreased, the heating wire heating mode is single, the operation is difficult, and the temperature rise is easily caused to be too high. In this embodiment, liquid heat transfer is adopted, and the temperature regulation and insulation assembly 18 further comprises a booster pump for pumping heat transfer liquid, and a cold liquid storage tank and a hot liquid storage tank according to the temperature regulation requirement. During temperature adjustment, the rotary transmission device 13 will rotate synchronously to increase the speed of temperature adjustment, so that the whole temperature can be kept consistent. In addition, when the temperature is adjusted, the image acquisition device 11 can be synchronously started to monitor the cell state in real time, and the increase of the cell death rate caused by local overheating or local supercooling is avoided. In addition, temperature sensors can be dispersedly arranged in the cell culture cavity 121 during temperature adjustment, so that the temperature change in the cell culture cavity 21 can be further monitored, and real-time early warning can be realized.

In order to facilitate the assembling of the image capturing device 11 and the rotation transmission device 13 by the assembler, a technical solution is provided in the present embodiment. Referring to fig. 1 and 4, the image capturing device 11 of the present embodiment is provided with a handle 113 at the top end thereof for facilitating twisting. Because avoid being infected with cell or cell metabolite, lead to being difficult to wash, and then lead to the promotion of bacterial infection risk, can do on image acquisition device 11 and the rotary transmission device 13 more smoothly or cover and have anti-sticking coating, consequently the assembler grasps image acquisition device 11 and rotary transmission device 13 all more difficultly, has consequently set up handle 113 and can be convenient for the assembler to assemble. In this embodiment, the handle 113 is a straight handle, but in other embodiments, the handle may also be a cross-shaped or S-shaped handle. In some cases, the handle 113 may also be configured as a wing-type handle, in which case the handle 113 may also serve as a stirring assembly when the rotating rod 131 is rotated, thereby performing the dual functions of stirring and handle. The handle 113 may be suitably coated with a material for easy gripping so as to improve gripping ability.

Of course, the handle 113 may be disposed at other positions of the image capturing device 11 and the rotation transmitting device 13 for easy grasping. In addition to the handle 113 shown in the drawings and the above-mentioned forms, a groove, an anti-slip projection, and the like may be provided to improve the convenience of assembly.

In this embodiment, the image capturing device 11 and the rotation transmission device 13 may also be through fittings, which facilitates replacement of parts and improves versatility. The image acquisition device 11 and the rotation transmission device 13 may be further provided with other sensors for collecting other data in the cell culture chamber 121, such as temperature, pressure, pH value, etc.

In this embodiment, the observer can also be connected to the cell culture system 1 monitored in real time through a terminal such as a mobile phone, a tablet, a computer, etc., so as to control the state of the cell culture system 1 monitored in real time, such as the replacement and replenishment of the culture solution, the opening and closing of the camera 111, and the transmission angle and direction of the rotating rod 131; the observer can also directly observe the image inside the cell culture cavity 121 through the display of the terminal; the observer can add the image to the test log and record and save different observation modes (including parameters such as observation frequency, observation angle, observation depth, single observation time length and the like) according to different types of cell cultures so as to facilitate subsequent direct calling. In addition, the wireless transmission adopted by the data transmission module 112 or the peripheral device 19 may be bluetooth, wireless lan, contactless near field communication, or the like. In order to cooperate with the user through the non-contact short-distance communication, in this embodiment, a communication coil may be further disposed outside the temperature-adjusting and heat-preserving component 18, and the communication coil may communicate with the coil of the terminal and transmit the data.

in the present embodiment, the cell culture method used for culturing cells can be applied to the cell culture system 1 for real-time monitoring according to any of the above-described embodiments.

In order to observe the internal environment of the cell culture vessel and maintain the stability of the microenvironment of the cultured cells, the embodiment of the present application provides a technical solution of the cell culture system 1 monitored in real time, and the cell culture system 1 monitored in real time includes: an image acquisition device 11 for acquiring images of cells in the culture system 1; the cell culture device 12 comprises a cell culture cavity 121 for culturing cells and moves relative to the image acquisition device 11; and the rotation transmission device 13 is used for providing power for the relative circumferential motion between the image acquisition device 11 and the cell culture device 12. Aforementioned technical scheme can make the user need not to open cell culture chamber 121 and just can observe cell culture's state, is favorable to maintaining the microenvironment balance who cultivates the cell, reduces the frequent opening of user or closed work load simultaneously, still is favorable to reducing the risk that the bacterium invaded among the cell culture process, promotes cell culture's survival rate.

the foregoing is only a partial embodiment of the present application, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the inventive concept of the present application, and these modifications and decorations should also be regarded as the protection scope of the present application.

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