Cell culture monitoring device

Abstract

The application provides a cell culture monitoring device, which comprises a cell culture box and a monitoring module. The cell culture box is used for mounting a microfluidic chip and further comprises a first observation window used for exposing an observation area of the microfluidic chip. The monitoring module comprises an imaging assembly used for collecting an image of the microfluidic chip from the first observation window. The cell culture monitoring device can realize real-time and online monitoring of a cell growth process.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organ-on-chip, and in particular to a cell culture monitoring device. BACKGROUND

[0002] In recent years, microfabrication and microfluidic technology have developed rapidly. Through microfluidic chip technology, the microenvironment of cell culture can be well simulated. Therefore, using microfluidic chips to establish a cell culture system has gradually become a trend in the field.

[0003] In the early stage, cell culture in a microfluidic chip often relies on manual operation, which requires staff to change the liquid at regular intervals and observe the culture state every day. This manual culture method is time-consuming and labor-intensive, and consumes a lot of staff effort.

[0004] To solve the above problems, some related technologies propose an automated cell culture device. This kind of device installs a microfluidic chip on a special culture tool, and continuously provides culture liquid for the microfluidic chip through the pipeline connected to the culture tool, thereby reducing the labor demand for cell culture.

[0005] However, in the related art, the microfluidic chip still needs to be taken out periodically and placed under a microscope for observation. At this time, the connection between the microfluidic chip and the pipeline often needs to be disconnected, which leads to complicated observation operation of the microfluidic chip, and the disconnection of the pipeline also interferes with the growth process of the cells, affecting the accuracy of observation and the culture effect of the cells.

[0006] In addition, some related technologies use bolts and other fasteners to achieve the installation and fixation of the culture tool (such as a cell culture box) through the pressing method of a pressing plate, which makes the assembly and disassembly and maintenance of the culture tool more inconvenient. SUMMARY

[0007] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application proposes a cell culture monitoring device, which can realize real-time and online monitoring of the cell growth process.

[0008] According to the cell culture monitoring device provided by the present application, the cell culture monitoring device comprises a cell culture box and a monitoring module, the cell culture box is used to install a microfluidic chip, the cell culture box comprises a first observation window, the first observation window is used to expose an observation area of the microfluidic chip, and the monitoring module comprises an imaging assembly, the imaging assembly is used to collect an image of the microfluidic chip from the first observation window.

[0009] According to the cell culture monitoring device provided in the application, at least the following technical effects are achieved: the microfluidic chip is placed in the cell culture box for cell culture, during the culture, the monitoring module can monitor the growth condition of the cells through the first observation window, without taking the microfluidic chip out of the cell culture box or moving the cell culture box out of the cell culture monitoring device, that is, the fluid supply module can always maintain the connection and control of the cell culture box, thereby avoiding interfering with the growth process of the cells, and the cell culture monitoring device can realize real-time and online monitoring of the cell growth process.

[0010] According to some embodiments of the application, the cell culture monitoring device comprises a stage and a tray, the cell culture box is placed on the tray, and the tray is detachably installed on the stage.

[0011] According to some embodiments of the application, the stage comprises a track groove, and the tray is inserted into the track groove.

[0012] According to some embodiments of the application, the stage comprises a first buckling structure, the tray comprises a second buckling structure matched with the first buckling structure, and the first buckling structure and the second buckling structure can be buckled with each other to position and lock the tray.

[0013] According to some embodiments of the application, the first buckling structure comprises a lock catch, the second buckling structure comprises a lock tongue, and the lock catch and the lock tongue constitute a quick detachable click lock.

[0014] According to some embodiments of the application, the tray comprises a second containing groove matched with the shape of the bottom of the cell culture box, and the cell culture box is embedded in the second containing groove.

[0015] According to some embodiments of the application, an inner side wall of the second containing groove is formed with a protruding second positioning part for contacting and positioning the cell culture box.

[0016] According to some embodiments of the application, the imaging assembly is located below the stage, the first observation window is located at the bottom of the cell culture box, the tray comprises a second observation window, and the stage comprises a third observation window, and the first observation window, the second observation window and the third observation window are at least partially aligned to allow the imaging assembly to capture images of the cells through the first observation window, the second observation window and the third observation window.

[0017] According to some embodiments of the application, the monitoring module comprises a first driver capable of driving the imaging assembly to move on a set track to switch pairing between the imaging assembly and different cell culture boxes.

[0018] According to some embodiments of the present application, the monitoring module comprises a slide rail extending in a first direction, the imaging assembly is mounted on the slide rail, and the first driver is capable of driving the imaging assembly to move along the slide rail.

[0019] According to some embodiments of the present application, the monitoring module further comprises a second driver for driving the imaging assembly to move in a second direction, the first direction and the second direction are both perpendicular to the optical axis of the imaging assembly and have an included angle with each other.

[0020] According to some embodiments of the present application, the imaging assembly comprises an objective lens, a light source and an image sensor, the objective lens and the light source are directed towards the first observation window, light from the microfluidic chip enters the objective lens and is irradiated on the image sensor via an imaging light path.

[0021] According to some embodiments of the present application, the imaging assembly comprises an autofocus device for adjusting the focal length of the imaging assembly.

[0022] According to some embodiments of the present application, the cell culture monitoring device further comprises a fluid supply module for providing fluid medium for the microfluidic chip.

[0023] According to some embodiments of the present application, the fluid medium is a pressure medium, and the fluid supply module comprises an air pump for providing the pressure medium.

[0024] According to some embodiments of the present application, the cell culture box comprises a container cavity, the air pump is in communication with the container cavity through a supply pipeline, and the container cavity is in communication with the microfluidic chip.

[0025] According to some embodiments of the present application, the fluid supply module comprises a backup gas cylinder, the backup gas cylinder is in communication with the microfluidic chip through the supply pipeline, and the fluid supply module can switch to use the air pump or the backup gas cylinder to provide the pressure medium.

[0026] According to some embodiments of the present application, the fluid supply module comprises a pressure regulator, the pressure regulator is located in the supply pipeline, and the pressure regulator is used to adjust the pressure of the pressure medium.

[0027] According to some embodiments of the present application, the fluid supply module comprises a filter, the filter is located in the supply pipeline, and the filter is used to filter the pressure medium.

[0028] According to some embodiments of the present application, the container cavity comprises at least a liquid injection cavity, the liquid injection cavity is used to store culture solution, and the liquid injection cavity is in communication with the liquid inlet flow channel of the microfluidic chip.

[0029] According to some embodiments of the present application, the cavity includes a recovery cavity, the recovery cavity being in communication with an outlet flow channel of the microfluidic chip.

[0030] According to some embodiments of the present application, the microfluidic chip is a lung organ chip, the microfluidic chip includes a culture chamber, the microfluidic chip further includes a culture membrane, the culture membrane separates the culture chamber into a first culture chamber and a second culture chamber, wherein one group of the injection cavities and the recovery cavities are in communication with the first culture chamber, and another group of the injection cavities and the recovery cavities are in communication with the second culture chamber.

[0031] According to some embodiments of the present application, the microfluidic chip includes an actuation chamber, the microfluidic chip further includes an actuation membrane, the actuation membrane separates the second culture chamber and the actuation chamber, the actuation chamber defines a deformable region of the actuation membrane.

[0032] According to some embodiments of the present application, the cavity includes a pressure cavity, the pressure cavity is used to communicate with the actuation chamber, the fluid supply module is capable of introducing and discharging pressure medium into the pressure cavity, so as to adjust the pressure of the actuation chamber, and then actuate the culture membrane through the actuation membrane.

[0033] According to some embodiments of the present application, at least two of the actuation chambers are arranged equidistantly along a circumferential direction of an axis of the second culture chamber.

[0034] According to some embodiments of the present application, the cell culture monitoring device includes a stage, the cell culture cartridge is placed on the stage, the cell culture monitoring device further includes a pressing module, the pressing module includes a second pressing member, the second pressing member is arranged opposite to the stage, and the second pressing member presses the cell culture cartridge against the stage.

[0035] According to some embodiments of the present application, the second pressing member is provided with a medium hole, the supply pipeline is in communication with the medium hole, the second pressing member is capable of being pressed against the cell culture cartridge, so that the medium hole is in communication with the cavity, and the second pressing member tightly seals a joint between the medium hole and the cell culture cartridge.

[0036] According to some embodiments of the present application, the pressing module includes a third pressing member, the third pressing member is located on a side of the second pressing member away from the cell culture cartridge, and the third pressing member is capable of pushing the second pressing member to press against the cell culture cartridge.

[0037] According to some embodiments of the present application, the third pressing member includes a main shaft and a protruding portion protruding from a side surface of the main shaft, the protruding portion is used to contact the second pressing member, and the main shaft is capable of rotating to push the second pressing member through the protruding portion.

[0038] According to some embodiments of the present application, the protruding part comprises a third fixing base and a rolling body, the third fixing base is installed on the main shaft, and the rolling body is installed on the third fixing base and in contact with the first pressing member.

[0039] According to some embodiments of the present application, the pressing module comprises a third driver, the third driver is connected with the main shaft, and the third driver is used to drive the main shaft to rotate.

[0040] According to some embodiments of the present application, the pressing module comprises an elastic member, the elastic member is connected with the second pressing member, and the elastic member can drive the second pressing member to move away from the cell culture box. BRIEF DESCRIPTION OF DRAWINGS

[0041] The above and / or additional aspects and advantages of the present application will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings in which:

[0042] Figure 1 is a structural schematic diagram of a cell culture monitoring device according to an embodiment of the present application;

[0043] Figure 2 is a structural schematic diagram of a cell culture monitoring device according to an embodiment of the present application;

[0044] Figure 3 is a partial structural schematic diagram of a cell culture monitoring device according to an embodiment of the present application;

[0045] Figure 4 is an exploded structural schematic diagram of a cell culture box according to an embodiment of the present application;

[0046] Figure 5 is an exploded structural schematic diagram of a cell culture box according to an embodiment of the present application;

[0047] Figure 6 is a structural schematic diagram of a cell culture box placed in a tray according to an embodiment of the present application;

[0048] Figure 7 is a structural schematic diagram of a monitoring module according to an embodiment of the present application;

[0049] Figure 8 is an actuation principle diagram for culturing a lung qi official chip according to an embodiment of the present application;

[0050] Figure 9 is a structural schematic diagram of a pressing module according to an embodiment of the present application;

[0051] Figure 10 is a structural schematic diagram of a first pressing member according to an embodiment of the present application;

[0052] Figure 11is Figure 2 A local enlarged view of the middle A region.

[0053] Reference signs:

[0054] Cell culture box 1000, box body 1100, liquid injection cavity 1110, recovery cavity 1120, pressure cavity 1130, first overflow hole 1140, shaft hole 1150, second buckle part 1160, first pressing part 1200, first observation window 1210, bottom plate 1220, first positioning part 1230, shaft part 1240, first buckle part 1250, box cover 1300, second overflow hole 1310, first sealing part 1400,

[0055] Fluid supply module 2000, air pump 2210, pressure regulator 2220, spare gas cylinder 2240,

[0056] Monitoring module 3000, imaging assembly 3100, objective lens 3110, light source 3120, image sensor 3130, autofocus 3140, first driver 3210, slide rail 3220, first fixed seat 3230, second fixed seat 3240, second driver 3250,

[0057] Carrying table 4100, track groove 4110, lock catch 4120, third observation window 4130, tray 4200, lock tongue 4210, second positioning part 4220, second observation window 4230, second containing groove 4240,

[0058] Pressing module 5000, second pressing part 5100, medium hole 5110, second sealing part 5120, photoelectric sensor 5130, pressure sensor 5140, third pressing part 5200, main shaft 5210, third fixed seat 5220, rolling body 5230, third driver 5300, guide shaft 5410, guide sleeve 5420, first mounting seat 5510, second mounting seat 5520,

[0059] Microfluidic chip 9000, first culture chamber 9100, second culture chamber 9200, culture membrane 9300, actuating chamber 9400, actuating membrane 9500. DETAILED DESCRIPTION

[0060] Embodiments of the present application are described in detail below with reference to examples thereof illustrated in the accompanying drawings, in which like reference numerals are used throughout the different drawings to designate like elements or elements with similar functions. The embodiments described below are examples only, and are not to be construed as limiting the present application.

[0061] In the description of the present application, it should be understood that the orientation description, such as the orientation or position relationship indicated by up, down, front, back, left, right and the like, is based on the orientation or position relationship shown in the drawings, and is only for the purpose of facilitating the description of the present application and simplifying the description, and does not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation of the present application.

[0062] In the description of the present application, the meaning of several is one or more, the meaning of multiple is more than two, greater than, less than, more than and the like are understood as not including the number, above, below, within and the like are understood as including the number. If it is described as first, second, it is only for the purpose of distinguishing technical features, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or the sequence of indicated technical features.

[0063] In the description of the present application, unless otherwise explicitly limited, the words such as setting, installing, connecting and the like should be broadly understood, and the person skilled in the art can reasonably determine the specific meaning of the above words in the present application in combination with the specific content of the technical scheme.

[0064] The microfluidic chip can effectively simulate the microenvironment of cell growth. On the one hand, thanks to the microfluidic system, the specific surface area ratio will increase significantly, and the faster the oxygen diffuses, the more efficient the cell gas supply will be. On the other hand, due to the small size of the microfluidic chip, the amount of drugs and culture necessities consumed by the cell culture system is also less than that of the traditional cell culture method.

[0065] Due to the size limitation of the microfluidic chip, the microfluidic chip generally needs to be installed on a special culture tool during automated culture. In the related art, the microfluidic chip needs to be removed from the culture tool and transferred to the microscope before the cells in the microfluidic chip can be observed. This leads to the observation operation of the microfluidic chip being cumbersome, and removing the microfluidic chip also interferes with the growth process of the cells, affecting the accuracy of observation and the culture effect of the cells.

[0066] With reference to Figure 1 and Figure 2 The first aspect of the embodiment of the cell culture monitoring device provided by the present application comprises a cell culture box 1000 and a monitoring module 3000, and the cell culture box 1000 is used to install a microfluidic chip 9000.

[0067] Further referring to Figure 3 , Figure 4 and Figure 5The cell culture box 1000 comprises a first observation window 1210 for exposing an observation area of the microfluidic chip 9000, and the monitoring module 3000 comprises an imaging assembly 3100 for capturing images of the microfluidic chip 9000 from the first observation window 1210.

[0068] According to the cell culture monitoring device provided in the present application, the microfluidic chip 9000 is placed in the cell culture box for cell culture, so as to create a suitable environment for the cells in the microfluidic chip to grow. During the culture, the monitoring module 3000 can monitor the growth of the cells through the first observation window 1210, without the need to take out the microfluidic chip 9000 from the cell culture box 1000 or to move the cell culture box 1000 together with the microfluidic chip 9000 out of the cell culture monitoring device, that is, the fluid supply module 2000 can always maintain the connection and control of the cell culture box 1000, so as to avoid interfering with the growth process of the cells, and the cell culture monitoring device can realize real-time and online monitoring of the cell growth process.

[0069] "Exposure" means that the first observation window 1210 allows light to pass through, so that the monitoring module 3000 can receive reflected light from the microfluidic chip 9000. In the present application, the first observation window 1210 can be made of transparent material or designed as an open hole.

[0070] The cell culture monitoring device usually further comprises a stage 4100, on which the microfluidic chip 9000 is placed for culture and monitoring. It can be understood that the size of a single microfluidic chip 9000 is small, and in order to make full use of the cell culture monitoring device and improve the experimental efficiency of the microfluidic chip 9000, the cell culture monitoring device can be designed to culture multiple microfluidic chips 9000 at the same time, specifically, one cell culture box 1000 can accommodate multiple microfluidic chips 9000 and / or the cell culture monitoring device comprises multiple cell culture boxes 1000.

[0071] For example, the cell culture monitoring device can comprise multiple cell culture boxes 1000, each of which accommodates one microfluidic chip 9000, for example, referring to Figure 3 In an embodiment of the first aspect, in order to facilitate batch handling and transfer of the cell culture box 1000, the cell culture monitoring device comprises a tray 4200, on which multiple cell culture boxes 1000 are placed, and the tray 4200 is detachably mounted on the stage 4100.

[0072] Specifically, the carrier 4100 can further include a track slot 4110, and the tray 4200 is inserted into the track slot 4110. The track slot 4110 plays a guiding and preliminary positioning role for the tray 4200, and improves the installation accuracy of the tray 4200. So as to be observed by the imaging assembly 3100.

[0073] However, only using the track slot 4110 cannot completely position the cell culture box 1000, and misalignment may occur. Therefore, positioning is also needed between the carrier 4100 and the tray 4200, and between the tray 4200 and the cell culture box 1000.

[0074] The positioning between the carrier 4100 and the tray 4200 and / or between the tray 4200 and the cell culture box 1000 can be achieved by buckles that can be buckled to each other.

[0075] For example, the carrier 4100 can include a first buckling structure, and the tray 4200 can include a second buckling structure matched with the first buckling structure, and the first buckling structure and the second buckling structure can be buckled to each other to position and lock the tray 4200. For example, referring to Figure 3 and Figure 6 In an embodiment of the first aspect, the first buckling structure includes a lock catch 4120, and the second buckling structure includes a lock tongue 4210, and the lock catch 4120 and the lock tongue 4210 constitute a snap bead lock that can be quickly assembled and disassembled. Thus, the tray 4200 can be conveniently assembled and disassembled on the carrier 4100.

[0076] The positioning between the carrier 4100 and the tray 4200 and / or between the tray 4200 and the cell culture box 1000 can also be achieved by a card slot and a card column that can be fitted.

[0077] For example, continuing to refer to Figure 6 The tray 4200 includes a second accommodating slot 4240 matched with the shape of the bottom of the cell culture box 1000, and the cell culture box 1000 is embedded into the second accommodating slot 4240 to achieve the positioning and installation of the cell culture box 1000 on the tray 4200. The inner side wall of the second accommodating slot 4240 is further formed with a protruding second positioning portion 4220, and the second positioning portion 4220 is used to contact and position the cell culture box 1000, and the second positioning portion 4220 can play a role in improving the positioning accuracy.

[0078] Alternatively, a protruding positioning pin can be installed on the tray 4200, and the cell culture box 1000 is provided with a positioning hole matched with the positioning pin to achieve the positioning and installation.

[0079] Of course, in other embodiments, the positioning between the stage 4100 and the tray 4200 and between the tray 4200 and the cell culture box 1000 can also be achieved by other types of designs, and feasible positioning manners can refer to related prior art, which will not be described here.

[0080] It should be noted that since the first and second buckling structures can already achieve accurate positioning of the tray 4200 on the stage 4100, the stage 4100 can only include the first buckling structure without the track slot 4110.

[0081] In the cell culture monitoring device, the position of the imaging assembly 3100 and the observation direction depend on the placement position of the microfluidic chip 9000 on the cell culture box 1000 and the orientation of the first observation window 1210.

[0082] For example, referring to Figure 3 In an embodiment of the first aspect, the first observation window 1210 is located at the bottom of the cell culture box 1000, and the microfluidic chip 9000 is located above the first observation window 1210. Correspondingly, the imaging assembly 3100 is arranged below the first observation window 1210.

[0083] And since the cell culture box 1000 is placed on the tray 4200, and the tray 4200 is placed on the stage 4100, the imaging assembly 3100 should be located below the stage 4100. The tray 4200 includes a second observation window 4230, and the stage 4100 includes a third observation window 4130. The first observation window 1210, the second observation window 4230, and the third observation window 4130 are at least partially aligned to allow the imaging assembly to capture images of the cells through the first observation window 1210, the second observation window 4230, and the third observation window 4130.

[0084] Similarly, the third observation window 4130 and the second observation window 4230 can also be made of transparent material or designed as a hole.

[0085] It can be understood that in other embodiments, the third observation window 4130 and the second observation window 4230 can also not be designed. For example, the microfluidic chip 9000 can be placed on the side of the cell culture box 1000, so that the observation area of the microfluidic chip 9000 faces the side. At this time, the imaging assembly 3100 is aligned with the microfluidic chip 9000 from one side of the cell culture box 1000, and the tray 4200 and the stage 4100 do not block the observation area, so that the third observation window 4130 and the second observation window 4230 are not designed.

[0086] Since multiple microfluidic chips 9000 are generally present in the cell culture monitoring device at the same time, the imaging assembly 3100 can be designed to be able to switch pairing with different cell culture boxes 1000. Specifically, either the imaging assembly 3100 is stationary and the switching pairing is achieved by the movement of the cell culture box 1000, or the cell culture box 1000 is stationary and the switching pairing is achieved by the movement of the imaging assembly 3100, but considering that a relatively stable external environment is needed during the cell culture process, it is preferred that the switching pairing is achieved by the movement of the imaging assembly 3100.

[0087] Exemplarily, the monitoring module 3000 comprises a first driver 3210 capable of driving the imaging assembly 3100 to move on a set trajectory, so that the set trajectory of the imaging assembly 3100 corresponds to the placement mode of the microfluidic chip 9000.

[0088] For example, with reference to Figure 3 In an embodiment of the first aspect, the cell culture monitoring device accommodates two rows of microfluidic chips 9000, and two imaging assemblies 3100 are respectively responsible for the monitoring of the two rows of microfluidic chips 9000, so that the set trajectory of the imaging assembly 3100 is a straight line trajectory. For the straight line trajectory, with reference to Figure 7 , the monitoring module 3000 can comprise a slide rail 3220 extending in a first direction (i.e. a direction parallel to the arrangement direction of the microfluidic chips 9000), the imaging assembly 3100 is installed on the slide rail 3220, and the first driver 3210 (here a rotating motor) is capable of driving the imaging assembly 3100 to move along the slide rail 3220.

[0089] In other embodiments, the imaging assembly 3100 can also adopt different set trajectories, depending on the specific placement mode of the cell culture box 1000. For example, the cell culture boxes 1000 can be arranged at intervals on a set circumference, and the monitoring module 3000 can comprise a turntable, the imaging assembly 3100 is installed on the turntable and switches pairing with different cell culture boxes 1000 as the turntable rotates. Other possible set trajectories and corresponding driving modes can be referred to related prior art, which will not be described here.

[0090] On the one hand, using one imaging assembly 3100 to pair multiple microfluidic chips 9000 can reduce the number of imaging assemblies 3100, effectively reducing the cost of the cell culture monitoring device; on the other hand, considering that the size of the imaging assembly 3100 is generally much larger than that of the microfluidic chip 9000, reducing the number of imaging assemblies 3100 can also make the structural design of the cell culture monitoring device more compact, facilitating the miniaturization of the cell culture monitoring device.

[0091] Due to positioning errors of the microfluidic chip 9000, installation errors of the imaging assembly 3100, and the like, the microfluidic chip 9000 can not be in the center of the field of view of the image sensor 3130, affecting the imaging effect. For this purpose, the monitoring module 3000 can further include a second driver 3250 for driving the imaging assembly 3100 to move in a second direction, the first direction and the second direction are both perpendicular to the optical axis of the imaging assembly 3100 (in this embodiment, the objective lens 3110 in the imaging assembly 3100) and have an included angle between each other, and the first driver 3210 and the second driver 3250 combine to make the imaging assembly 3100 have a planar motion degree of freedom, so that the imaging assembly 3100 can be more accurately aligned with the microfluidic chip 9000.

[0092] For example, with reference to Figure 7 In an embodiment of the first aspect, the monitoring module 3000 further includes a first fixed seat 3230 and a second fixed seat 3240, the first fixed seat 3230 is installed on the slide rail 3220, the second fixed seat 3240 and the second driver 3250 are installed on the first fixed seat 3230, the driving direction of the second driver 3250 is perpendicular to the extension direction of the slide rail 3220, the second driver 3250 (here, a linear motor or an electric cylinder) can drive the second fixed seat 3240 to move close to or away from the first fixed seat 3230, and the imaging assembly 3100 is installed on the second fixed seat 3240.

[0093] In order to realize the observation of the microfluidic chip 9000, the imaging assembly 3100 at least needs to include an objective lens 3110, a light source 3120 and an image sensor 3130, the objective lens 3110 and the light source 3120 are directed towards the first observation window 1210, the light source 3120 illuminates the microfluidic chip 9000, the reflected light from the microfluidic chip 9000 enters the objective lens 3110, and is irradiated on the image sensor 3130 through an imaging light path. The image sensor 3130 receives the incident light, thereby generating a corresponding image signal, and then sends the image signal to an upper terminal (such as a mobile phone, a computer, and the like) and displays it in a graphical manner.

[0094] For example, with reference to Figure 7 In order to improve the lighting effect, the light source 3120 can select a coaxial light source, which makes the light irradiated to the microfluidic chip 9000 parallel to the optical path of the imaging assembly 3100, thereby avoiding the interference of diffuse reflection and specular reflection on imaging. In addition, the imaging assembly 3100 can also include an autofocus device 3140 for adjusting the focal length of the imaging assembly 3100.

[0095] The objective lens 3110 can be detachably mounted, so that different objective lenses 3110 can be replaced according to the magnification requirement; the coaxial light source and the automatic focusing device 3140 can be standard components, and the specific specifications can refer to the related prior art, which will not be described here.

[0096] It can be understood that during the cultivation of cells, the cells need to be continuously supplied with culture solution. Therefore, the cell culture monitoring device further comprises a fluid supply module 2000 for providing fluid medium for the microfluidic chip 9000.

[0097] The fluid supply module 2000 can be designed to directly supply the culture solution to the microfluidic chip 9000, in which case the fluid medium provided by the fluid supply module 2000 is the culture solution, or the fluid supply module 2000 can also be designed to indirectly supply the culture solution to the microfluidic chip 9000. In the embodiment of indirectly supplying the culture solution, the fluid medium provided by the fluid supply module 2000 can be a pressure medium, and the cell culture box 1000 comprises a container cavity in communication with the microfluidic chip 9000, and some of the container cavities store the culture solution required by the microfluidic chip 9000. The fluid supply module 2000 increases the pressure in the container cavity storing the culture solution through the pressure medium, so that the culture solution is input into the microfluidic chip 9000.

[0098] Correspondingly, with reference to Figure 1 and Figure 2 , the fluid supply module 2000 usually further comprises a gas pump 2210 for providing the pressure medium, and the gas pump 2210 is in communication with the container cavity through a supply pipeline. Of course, the fluid supply module 2000 can also not be provided with the gas pump 2210, but be connected to a gas source outside the cell culture monitoring device.

[0099] In the cell culture box 1000, the container cavity can be used to achieve different purposes. First, in order to provide the culture solution, the container cavity at least comprises a liquid injection cavity 1110 for storing the culture solution, and the liquid injection cavity 1110 is in communication with the liquid inlet flow channel of the microfluidic chip 9000. The fluid supply module 2000 increases the pressure in the liquid injection cavity 1110 through the pressure medium, so that the culture solution is input into the microfluidic chip 9000.

[0100] Generally, the container cavity further comprises a recovery cavity 1120 for communicating with the liquid outlet flow channel of the microfluidic chip 9000, so as to collect the waste liquid flowing out of the microfluidic chip 9000. Of course, it is also not excluded that in some embodiments, the recovery cavity is designed to be independent of the cell culture box 1000.

[0101] The number of the liquid injection cavity 1110 and the recovery cavity 1120 and the connection mode between them and the microfluidic chip 9000 depend on the specifications and purposes of the microfluidic chip 9000.

[0102] Exemplarily, in the embodiment of the first aspect, the microfluidic chip 9000 is a lung organ chip. Figure 4 and Figure 5 Further, the structure of the cell culture box 1000 in the embodiment of the first aspect is shown, Figure 8 The culture principle of the microfluidic chip 9000 as a lung organ chip is shown. In combination with the description of Figure 4 , Figure 5 and Figure 8 , the microfluidic chip 9000 is formed with a culture chamber, and the microfluidic chip 9000 further comprises a culture membrane 9300, which separates the culture chamber into a first culture chamber 9100 and a second culture chamber 9200.

[0103] Correspondingly, one set of injection cavities 1110 and recovery cavities 1120 of the cell culture box 1000 are used to communicate with the first culture chamber 9100, and the other set of injection cavities 1110 and recovery cavities 1120 are used to communicate with the second culture chamber 9200, so that the cell culture box 1000 can adjust the first culture chamber 9100 and the second culture chamber 9200 respectively, and meet the different needs of the cells (epithelial cells and endothelial cells in the lung organ chip) on both sides.

[0104] Further, in combination with the description of Figure 8 , the microfluidic chip 9000 is further formed with an actuation chamber 9400 when it is a lung organ chip, and the microfluidic chip 9000 further comprises an actuation membrane 9500, which separates the second culture chamber 9200 and the actuation chamber 9400. The actuation chamber 9400 defines a deformable region of the actuation membrane 9500. The microfluidic chip 9000 can cause the pressure change of the second culture chamber 9200 through the deformation of the actuation membrane 9500, and further cause the deformation of the culture membrane 9300, so that the culture membrane 9300 simulates the expansion and contraction of the alveoli during breathing.

[0105] Correspondingly, the container cavity further comprises a pressure cavity 1130, which is used to communicate with the actuation chamber 9400. The fluid supply module 2000 can introduce and discharge pressure medium into the pressure cavity 1130, so as to adjust the pressure of the actuation chamber 9400, and further actuate the culture membrane 9300 through the actuation membrane 9500.

[0106] It can be understood that the alveoli always circulate between expansion and contraction. In order to more truly simulate the dynamic environment of cell and tissue growth, the pressure of the actuation chamber 9400 also needs to change reciprocally according to the set conditions. The reciprocating pressure change will affect the flow field in the second culture chamber 9200. If there is only one actuation chamber 9400 which is not coaxial with the culture membrane 9300, the culture membrane 9300 is easy to appear uneven force in different regions under the influence of the flow field when it expands.

[0107] To this end, the microfluidic chip 9000 can be further designed such that the at least two actuating chambers 9400 are arranged equidistantly along the circumferential direction of the axis of the second culture chamber 9200. When simulating the reciprocating expansion and contraction of the alveolar wall, the forces generated by the plurality of actuating chambers 9400 can balance each other, so that the traction force on the culture membrane 9300 is more uniform, and the uneven stress on the culture membrane 9300 during expansion is alleviated or even eliminated, and the lung organ chip can more realistically simulate the physiological changes of the alveoli during the breathing process.

[0108] It can be understood that the cell culture box 1000 also needs to form the first overflow hole 1140 and the second overflow hole 1310, and the cavities are respectively communicated with the first overflow hole 1140 and the second overflow hole 1310. The cavities are communicated with the microfluidic chip 9000 through the first overflow hole 1140, and the cavities are communicated with the supply pipeline of the fluid supply module 2000 through the second overflow hole 1310.

[0109] In Figure 4 and Figure 5 , the second overflow hole 1310 and the first overflow hole 1140 are respectively located on the opposite two surfaces of the cell culture box 1000, that is, the top surface and the bottom surface. In other embodiments, the second overflow hole 1310 and the first overflow hole 1140 can also be respectively located on adjacent two surfaces or the same surface, and the present application does not limit this as long as the positions of the second overflow hole 1310 and the first overflow hole 1140 do not cause interference between structures.

[0110] The cell culture box 1000 can adopt different designs to construct the placement position of the microfluidic chip 9000 and the required cavities. Exemplarily, with reference to Figure 4 and Figure 5 , in an embodiment of the first aspect, the cell culture box 1000 comprises a box body 1100 and a first pressing member 1200, the cavities and the first overflow hole 1140 are located in the box body 1100, and the first observation window 1210 is located in the first pressing member 1200. The first pressing member 1200 can be close to or away from the box body 1100 to press or release the microfluidic chip 9000 located between the box body 1100 and the first pressing member 1200.

[0111] The first pressing member 1200 can be detachably and / or movably mounted to realize the function of pressing or releasing the microfluidic chip 9000. For example, in Figure 4 and Figure 5 , the first pressing member 1200 comprises a shaft portion 1240, the box body 1100 comprises a shaft hole 1150, the shaft portion 1240 is inserted into the shaft hole 1150, and the first pressing member 1200 is mounted on the box body 1100 through the shaft portion 1240. The first pressing member 1200 can be flipped around the shaft portion 1240 as the pivot.

[0112] In addition, the shaft hole 1150 can also be arranged to be open on the side away from the first pressing member 1200, so that the shaft part 1240 is detachably connected with the shaft hole 1150, which facilitates the dismounting of the microfluidic chip 9000 together with the first pressing member 1200 from the box body 1100, and facilitates the carrying of the microfluidic chip 9000.

[0113] The first pressing member 1200 can also serve as a carrier of the microfluidic chip 9000, in other words, the first pressing member 1200 is located below the box body 1100, the first pressing member 1200 contacts and supports the lower surface of the microfluidic chip 9000, and the box body 1100 presses the upper surface of the microfluidic chip 9000. As shown in the figure, at this time the first pressing member 1200 can be designed to include a bottom plate 1220 and a wall plate, the wall plate protruding from the bottom plate 1220, the wall plate enclosing a first accommodating groove matching the shape of the microfluidic chip 9000, and the microfluidic chip 9000 being embedded in the first accommodating groove, so as to better carry the microfluidic chip 9000. Figure 4

[0114] In order to accurately position the position of the microfluidic chip 9000, the inner side of the wall plate can also include a protruding first positioning part 1230, the first positioning part 1230 being used to contact and position the microfluidic chip 9000, the first positioning part 1230 reducing the contact area between the wall plate and the microfluidic chip 9000, changing from surface contact to approximate point contact, thereby improving the positioning accuracy of the microfluidic chip 9000 and reducing the risk of leakage between the cell culture box 1000 and the microfluidic chip 9000.

[0115] Of course, in addition to using the flipping manner to realize the rotatable installation, in other embodiments, the first pressing member 1200 can also use the sliding groove manner to realize the movable installation, or use the pin hole cooperation manner to realize the detachable installation, the above and other feasible installation manners can refer to the related prior art, which will not be described here.

[0116] In addition to the box body 1100 and the first pressing member 1200, the cell culture box 1000 also includes a box cover 1300, the box cover 1300 being capable of closing or opening the container cavity, and the second flow hole 1310 can be located on the box cover 1300. When the container cavity is opened, it is convenient to add or take out the culture solution or other substances in the container cavity, and when the container cavity is closed, it is convenient for the fluid supply module 2000 to control the pressure in the container cavity.

[0117] ​To avoid pressure leakage, a first sealing member 1400 can be further arranged between the box cover 1300 and the box body 1100, and the box cover 1300 presses the first sealing member 1400 against the box body 1100, so that the first sealing member 1400 avoids leakage between the cavities and between the cavities and the external environment. The first sealing member 1400 can be a sealing gasket as shown in Figure 4 、 Figure 5 or can be a sealing ring or other designs that can achieve a sealing effect.

[0118] Next, return to the fluid supply module 2000, in addition to the gas source (for example, the air pump 2210) for providing the pressure medium, the fluid supply module 2000 also needs to include a pressure regulator 2220, which is arranged in the supply pipeline (not shown in the figure), and the pressure regulator 2220 is used to adjust the pressure of the pressure medium. Exemplarily, refer to Figure 1 and Figure 2 In an embodiment of the first aspect, one cell culture box 1000 has five cavities, two liquid injection cavities 1110, two recovery cavities 1120, and one pressure cavity 1130, and the cell culture monitoring device is correspondingly provided with a pressure regulator 2220 in a group of five, and each pressure regulator 2220 corresponds to the regulation of the pressure of one cavity, so as to achieve accurate regulation.

[0119] The pressure regulator 2220 can be selected from existing standard products. For example, in an embodiment of the first aspect, the pressure regulator 2220 needs to meet the positive pressure and negative pressure requirements of the pressure cavity 1130, and therefore a proportional valve can be selected. The selection of the pressure regulator 2220 can refer to related prior art, which will not be described here.

[0120] Cells are sensitive to the culture environment, and impurities (for example, bacteria) in the pressure medium are easy to enter the microfluidic chip 9000 with the culture solution, affecting the normal growth of the cells, and even causing cell death. Therefore, the fluid supply module 2000 can include a filter (not shown in the figure), which is arranged in the supply pipeline. The filter can be selected from existing products with filter membranes or other filtering sizes that can meet the requirements, which will not be described here.

[0121] The air pump 2210 will generate a certain vibration when running, and if the vibration isolation effect is not good, the vibration can be transmitted to the monitoring module 3000, causing the imaging of the microfluidic chip 9000 to be blurred and jittered. Refer to Figure 1 and Figure 2In an embodiment of the first aspect, the fluid supply module 2000 specifically comprises a backup gas cylinder 2240, which is in communication with the microfluidic chip 9000 through the supply pipeline, and the fluid supply module 2000 is capable of switching to use the backup gas cylinder 2240 to provide pressure medium instead of the gas pump 2210. When the monitoring module 3000 is imaging, the gas pump 2210 is turned off, and the backup gas cylinder 2240 is switched to supply gas to the supply pipeline, thereby eliminating the negative interference of the vibration of the gas pump 2210 on imaging.

[0122] That is, in the use of the cell culture monitoring device, the fluid supply module 2000 is provided with a first state and a second state, in the first state, the fluid supply module 2000 opens the gas pump 2210 to supply gas; in the second state, the fluid supply module 2000 closes the gas pump 2210 and switches to the backup gas cylinder 2240 to supply gas. When the monitoring module 3000 is monitoring cells, the fluid supply module 2000 is switched to the second state, and after the monitoring is completed, the fluid supply module 2000 is switched to the first state.

[0123] In addition, the backup gas cylinder 2240 can also play a role in redundancy backup, that is, as an emergency gas source when the gas pump 2210 fails, thereby improving the operation reliability of the cell culture monitoring device.

[0124] In addition to the fluid supply module 2000 and the monitoring module 3000, the cell culture monitoring device can further comprise a pressing module 5000, which comprises a second pressing member 5100, which is arranged opposite to the stage 4100, and the second pressing member 5100 presses the cell culture box 1000 to the stage 4100. On the one hand, the second pressing member 5100 presses and fixes the cell culture box 1000, which can avoid the position of the cell culture box 1000 from being deviated, and on the other hand, with reference to Figure 3 and Figure 4 Since the box cover 1300 is designed on the top of the cell culture box 1000, the second pressing member 5100 can also press the box cover 1300, which helps to press and seal between the box cover 1300 and the box body 1100.

[0125] In order to more fully exert the pressing effect of the second pressing member 5100, with reference to Figure 9 , the second pressing member 5100 can be further provided with a medium hole 5110, and the supply pipeline of the fluid supply module 2000 is in communication with the medium hole 5110, and the second pressing member 5100 can be pressed to the cell culture box 1000 to make the medium hole 5110 communicate with the cavity. The design of the supply pipeline through the medium hole 5110 to communicate with the cavity can facilitate the loading and unloading of the cell culture box 1000.

[0126] Specifically, when the cell culture box 1000 needs to be removed, the second pressing member 5100 is controlled to release the cell culture box 1000, and meanwhile, the connection between the supply pipeline and the cavity is also released. When a new cell culture box 1000 is placed in place, the second pressing member 5100 is controlled to press the cell culture box 1000, and meanwhile, the supply pipeline is also connected to the cavity through the medium hole 5110, so that the use and operation of the cell culture monitoring device are more convenient.

[0127] Meanwhile, the second pressing member 5100 can also press the joint part of the medium hole 5110 and the cavity.

[0128] In order to improve the sealing effect, the second pressing member 5100 can also include a second sealing member 5120, which is located between the second pressing member 5100 and the cell culture box 1000, and is used to seal the joint part of the medium hole 5110 and the cavity.

[0129] Exemplarily, with reference to Figure 10 In the embodiment of the first aspect, the second pressing member 5100 is provided with a mounting groove for mounting the second sealing member 5120. The second sealing member 5120 is a sealing ring, and the mounting grooves are arranged one by one corresponding to the medium holes 5110. Each mounting groove surrounds the outer periphery of the corresponding medium hole 5110. The second sealing member 5120 is embedded in the mounting groove. When the second pressing member 5100 is pressed towards the cell culture box 1000, the sealing between the medium hole 5110 and the cell culture box 1000 (specifically, the second flow hole 1310) is realized through the extrusion deformation of the second sealing member 5120.

[0130] In order to control the size of the pressing force of the second pressing member 5100, the second pressing member 5100 can also include a pressure sensor 5140. The fluid supply module 2000 is feedback adjusted based on the value of the pressing force detected by the pressure sensor 5140, so as to avoid that the sealing effect is not good due to the too small pressing force, or the cell culture box 1000 is damaged due to the too large pressing force.

[0131] In addition, the second pressing member 5100 can also include a photoelectric sensor 5130, which is directed towards the direction where the cell culture box 1000 is located. One photoelectric sensor 5130 corresponds to one cell culture box 1000. The photoelectric sensor 5130 can detect whether the cell culture box 1000 is on the tray 4200, so as to control the on-off of the medium hole 5110.

[0132] The pressing module 5000 can push the second pressing member 5100 towards the cell culture cartridge 1000 by a third pressing member 5200, which is located on the side of the second pressing member 5100 away from the cell culture cartridge 1000, contacts the second pressing member 5100 and applies a force to the second pressing member 5100 towards the cell culture cartridge 1000.

[0133] The third pressing member 5200 can apply the force to the second pressing member 5100 by rotating or moving, etc. For example, referring to Figure 9 , the third pressing member 5200 includes a main shaft 5210 and a protruding part protruding from the side of the main shaft 5210, the protruding part is used to contact the second pressing member 5100, and the main shaft 5210 can rotate to push the second pressing member 5100. The main shaft 5210 can be rotated in the opposite direction to release the pressure on the second pressing member 5100. Compared with applying pressure to the second pressing member 5100 by a fastener, using the third pressing member 5200 with the main shaft 5210 helps to achieve fast assembly and disassembly of the cell culture cartridge 1000.

[0134] In order to reduce the contact friction between the protruding part and the second pressing member 5100, the protruding part can further include a third fixing seat 5220 and a rolling body 5230, the third fixing seat 5220 is installed on the main shaft 5210, and the rolling body 5230 is installed on the third fixing seat 5220 and contacts the second pressing member 5100. The rolling body 5230 can be a roller (such as a bearing) or a ball, etc. The rolling body 5230 forms a rolling friction between the protruding part and the second pressing member 5100, so that the movement of the third pressing member 5200 is smoother.

[0135] The third pressing member 5200 can be connected to a third driver 5300 to achieve automatic pressing. The third driver 5300 can be a rotating motor, and the main shaft 5210 is directly installed on the output end of the third driver 5300. The third driver 5300 can also be a linear motor, which converts linear motion into rotation of the third pressing member 5200 through a transmission mechanism.

[0136] In the embodiment of the first aspect, the third pressing member 5200 only contacts the second pressing member 5100, and the two are not connected together, so that the third pressing member 5200 can only drive the second pressing member 5100 to approach the cell culture cartridge 1000. In order to enable the second pressing member 5100 to automatically move away from the cell culture cartridge 1000, the pressing module 5000 further includes a resilient member connected to the second pressing member 5100, and the resilient member can drive the second pressing member 5100 to move away from the cell culture cartridge 1000.

[0137] When the third driver 5300 actuates the third pressing member 5200, the force of the third pressing member 5200 makes the second pressing member 5100 press the cell culture box 1000 against the elastic force of the elastic member, and when the third driver 5300 reverses, the force of the third pressing member 5200 disappears, and the elastic force of the elastic member makes the second pressing member 5100 move away from the cell culture box 1000.

[0138] The elastic member can adopt a compression spring, a tension spring, a torsion spring, an air spring or other structure capable of exerting a force on the second pressing member 5100 in the direction away from the cell culture box 1000. For example, refer to Figure 9 and Figure 11 The pressing module 5000 further comprises a guide shaft 5410 and a guide sleeve 5420, the guide shaft 5410 is installed on the table 4100, the guide sleeve 5420 is installed on the second pressing member 5100, the guide shaft 5410 is arranged in the guide sleeve 5420, the elastic member adopts a compression spring (not shown in the figure), the compression spring is sleeved on the guide shaft 5410, and the two ends of the compression spring abut against the table 4100 and the second pressing member 5100 respectively. The second pressing member 5100 is pushed away from the cell culture box 1000 by the elastic force of the compression spring. The guide sleeve 5420 can adopt a linear bearing to further reduce the frictional resistance when the second pressing member 5100 moves.

[0139] In other embodiments, the third pressing member 5200 can also be connected with the second pressing member 5100, so as to drive the second pressing member 5100 to move close to or away from the cell culture box 1000. For example, the third pressing member 5200 adopts a screw nut mechanism, the third driver 5300 is connected with a screw rod, a nut is installed on the screw rod, and the second pressing member 5100 is installed on the nut. The screw rod is driven to rotate forward and reverse to drive the second pressing member 5100 to move close to or away from the cell culture box 1000.

[0140] In order to realize the installation of the pressing module 5000, for example, in the embodiment of the first aspect, the pressing module 5000 can further comprise a first mounting seat 5510, two first mounting seats 5510 are arranged at intervals, and the main shaft 5210 is arranged between the two first mounting seats 5510. Refer to Figure 9 The first mounting seat 5510 can be designed in the form of a portal frame, that is, composed of two legs and a main beam, so that the structure is reliable and occupies small space. The third driver 5300 can also be installed on the first mounting seat 5510, or as Figure 9 shown, the pressing module 5000 can further comprise a second mounting seat 5520, the third driver 5300 (here a rotating motor) is installed on the second mounting seat 5520, and the third driver 5300 is connected with the main shaft 5210 through a shaft coupling.

[0141] Exemplarily, the cell culture monitoring device can be used in the following manner. First, the required cells are introduced into the microfluidic chip 9000, and the microfluidic chip 9000 is installed in the cell culture box 1000. Then, the cell culture box 1000 is placed on the tray 4200, and the tray 4200 is placed on the stage 4100, and the cell culture box 1000 is fixed by the pressing module 5000. After that, the microfluidic chip 9000 is supplied with fluid medium by the fluid supply module 2000, and the cells are cultured. When it is required to observe the culture state of the cells, the fluid supply module 2000 is switched to supply gas from the standby gas cylinder 2240, and then the imaging assembly 3100 moves to the position corresponding to the microfluidic chip 9000 to be observed, and the cells are observed.

[0142] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "exemplary embodiment", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the exemplary description of the above terms does not necessarily mean the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0143] In some alternative embodiments, the functions / operations mentioned in the block diagram can not occur in the order mentioned in the operation diagram. For example, depending on the functions / operations involved, two blocks shown in succession can actually be executed substantially simultaneously or the blocks can sometimes be executed in reverse order. In addition, the embodiments presented and described in the flowcharts of the present application are provided by way of example, with the purpose of providing a more comprehensive understanding of the technology. The disclosed method is not limited to the operations and logical flows presented herein. Alternative embodiments are contemplated in which the order of various operations is changed and in which sub-operations described as part of larger operations are independently executed.

[0144] Although the embodiments of the present application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and the scope of the present application, which is defined by the claims and their equivalents.

Claims

1. A cell culture monitoring device, characterized in that, The cell culture monitoring device comprises a stage and a tray, the cell culture box is placed on the tray, and the tray is detachably installed on the stage. The stage comprises a track groove, and the tray is inserted into the track groove. The stage comprises a first buckling structure, the tray comprises a second buckling structure matched with the first buckling structure, and the first buckling structure and the second buckling structure can be buckled with each other to position and lock the tray. The stage comprises a first buckling structure, the tray comprises a second buckling structure matched with the first buckling structure, and the first buckling structure and the second buckling structure can be buckled with each other to position and lock the tray.

2. The cell culture monitoring device of claim 1, wherein, ​ 3. The cell culture monitoring device of claim 2, wherein, ​ 4. The cell culture monitoring device of claim 3, wherein, ​ 5. The cell culture monitoring device of claim 4, wherein, The first buckling structure comprises a lock catch, and the second buckling structure comprises a lock tongue, which constitute a snap lock.

6. The cell culture monitoring device of claim 5, wherein, The tray comprises a second accommodating groove matching the shape of the bottom of the cell culture box, and the cell culture box is embedded in the second accommodating groove.

7. The cell culture monitoring device of claim 6, wherein, An inner side wall of the second accommodating groove is formed with a protruding second positioning part for contacting and positioning the cell culture box.

8. The cell culture monitoring device of claim 2, wherein, The imaging assembly is located below the stage, the first observation window is located at the bottom of the cell culture box, the tray comprises a second observation window, and the stage comprises a third observation window, which are at least partially aligned to allow the imaging assembly to capture images of the cells through the first, second and third observation windows.

9. The cell culture monitoring device of claim 1 or 8, wherein, The monitoring module comprises a first driver capable of driving the imaging assembly to move along a set trajectory to switch pairing between the imaging assembly and different cell culture boxes.

10. The cell culture monitoring device of claim 9, wherein, The monitoring module comprises a slide rail extending in a first direction, and the imaging assembly is mounted on the slide rail, and the first driver is capable of driving the imaging assembly to move along the slide rail.

11. The cell culture monitoring device of claim 10, wherein, The monitoring module further comprises a second driver for driving the imaging assembly to move in a second direction, and the first and second directions are both perpendicular to the optical axis of the imaging assembly and have an included angle therebetween.

12. The cell culture monitoring device of claim 1, wherein, The imaging assembly comprises an objective lens, a light source and an image sensor, the objective lens and the light source are directed towards the first observation window, light from the microfluidic chip enters the objective lens and is irradiated on the image sensor through an imaging light path.

13. The cell culture monitoring device of claim 12, wherein, The imaging assembly comprises an autofocus device for adjusting the focal length of the imaging assembly.

14. The cell culture monitoring apparatus of claim 1, wherein, The cell culture monitoring device further comprises a fluid supply module for providing fluid medium for the microfluidic chip.

15. The cell culture monitoring device of claim 14, wherein, The fluid medium is a pressure medium, and the fluid supply module comprises a gas pump for providing the pressure medium.

16. The cell culture monitoring device of claim 15, wherein, The cell culture box comprises a cavity, the gas pump is communicated with the cavity through a supply pipeline, and the cavity is communicated with the microfluidic chip.

17. The cell culture monitoring device of claim 16, wherein, The fluid supply module comprises a backup gas cylinder communicated with the microfluidic chip through the supply pipeline, and the fluid supply module can switch to use the gas pump or the backup gas cylinder to provide the pressure medium.

18. The cell culture monitoring device of claim 16, wherein, The fluid supply module comprises a pressure regulator in the supply pipeline, and the pressure regulator is used to adjust the pressure of the pressure medium.

19. The cell culture monitoring device of claim 16, wherein, The fluid supply module comprises a filter in the supply pipeline, and the filter is used to filter the pressure medium.

20. The cell culture monitoring device of claim 16, wherein, The cavity comprises at least a liquid injection cavity for storing culture solution, and the liquid injection cavity is communicated with the liquid inlet flow channel of the microfluidic chip.

21. The cell culture monitoring device of claim 20, wherein, The cavity comprises a recovery cavity communicated with the liquid outlet flow channel of the microfluidic chip.

22. The cell culture monitoring device of claim 21, wherein, The microfluidic chip comprises an actuating chamber, and further comprises an actuating membrane, which separates the second culture chamber and the actuating chamber, and the actuating chamber defines a deformable region of the actuating membrane.

23. The cell culture monitoring device of claim 22, wherein, The cavity comprises a pressure cavity for communicating with the actuating chamber, and the fluid supply module can introduce and discharge pressure medium into the pressure cavity to adjust the pressure of the actuating chamber, so as to actuate the culture membrane through the actuating membrane.

24. The cell culture monitoring device of claim 22, wherein, The at least two actuating chambers are arranged at equal intervals along the circumferential direction of the axis of the second culture chamber.

Images