An adherent cell culture device

Abstract

The application provides a novel adherent cell culture device, which comprises a PCB circuit board, an image acquisition device arranged on the upper surface of the PCB circuit board, the image acquisition device being connected with a controller, a cell culture container for providing a container for adherent cells, the cell culture container being arranged above the image acquisition device and the bottom of the sidewall of the cell culture container being abutted against the upper surface of the image acquisition device, the bottom of the cell culture container being provided with an opening for exposing the image acquisition device, the image acquisition device acquiring images of the adherent cells through the opening and outputting the acquired images to the controller, and the controller processing the images to obtain growth data of the adherent cells and transmitting the growth data to an externally connected display terminal. The adherent cells in the cell culture container can be monitored in real time, the monitoring precision of the adherent cells is improved, the real-time monitoring space is saved, and the monitoring cost is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological cell culture, in particular to a novel adherent cell culture device. BACKGROUND

[0002] Cell culture is an essential process in biological engineering technology, which can make a cell become a simple single cell or a few differentiated multicellular through a large number of culture. A large number of cells or their metabolites can be obtained through cell culture. Since most biological products are obtained from cells, cell culture technology is the most core and basic technology in biotechnology. Cell culture work has been widely used in various fields such as biology, medicine, new drug research and development, and it plays a crucial role in the whole life science research.

[0003] However, the current novel adherent cell culture device is only used as a cell culture container. When the growth condition of the cells needs to be observed, the existing culture container needs to be taken out of the incubator, then placed under a microscope for observation, and then placed back in the incubator for continuous culture after the observation is completed.

[0004] That is, the above-mentioned prior art is not only troublesome to operate, but also the cells are easily contaminated by bacteria, fungi and the like, so the above-mentioned prior art has deficiencies in real-time image monitoring. SUMMARY

[0005] In view of the above problems existing in the prior art, a novel adherent cell culture device for real-time monitoring of adherent cells in a cell culture container is provided.

[0006] The specific technical solutions are as follows:

[0007] A novel adherent cell culture device, comprising:

[0008] A PCB circuit board;

[0009] An image acquisition device is arranged on the upper surface of the PCB circuit board, and the image acquisition device is connected with a controller;

[0010] A cell culture container is provided for adherent cells, and the cell culture container is arranged above the image acquisition device, and the bottom of the side wall of the cell culture container is in contact with the upper surface of the image acquisition device, and the bottom of the cell culture container is provided with an opening for exposing the image acquisition device;

[0011] The image acquisition device acquires images of the adherent cells through the opening and outputs the acquired images to the controller;

[0012] The controller processes the images to obtain growth data of the adherent cells, and transmits the growth data to an external display terminal.

[0013] Preferably, the novel adherent cell culture device, wherein the image acquisition device comprises an image acquisition chip, the image acquisition chip is packaged in a packaging shell, the electrodes of the packaged image acquisition chip are arranged on the back and / or side of the packaging shell, the packaging shell with the packaged image acquisition chip is welded on the upper surface of the PCB circuit board, the image acquisition chip is exposed in the middle of the upper surface of the packaging shell, and the image acquisition chip is surrounded by the bottom of the side wall of the cell culture container.

[0014] Preferably, the novel adherent cell culture device, wherein the image acquisition chip is provided with UV glue at the joint with the packaging shell.

[0015] Preferably, the novel adherent cell culture device, wherein the image acquisition chip protrudes from the packaging shell.

[0016] Preferably, the novel adherent cell culture device, wherein the image acquisition chip comprises a detector array composed of a plurality of detector units.

[0017] Preferably, the novel adherent cell culture device, wherein the detector array adopts any one of a CMOS image sensor array, a half-floating gate transistor array, a composite dielectric gate photosensitive detector array, a double-device photosensitive detection unit array based on a composite dielectric gate, and a split gate type MOSFET imaging detector array.

[0018] Preferably, the novel adherent cell culture device, wherein the size of the detector unit is ≤1μm, and the number of detector units in the detector array is ≥100 million.

[0019] Preferably, the novel adherent cell culture device, wherein the cell culture container comprises a cell culture tank and a top cover matched with the cell culture tank, the upper surface of the cell culture tank is provided with a top opening, the cell culture tank is covered by the top cover, and the cell culture tank and the top cover are detachably arranged.

[0020] Preferably, the novel adherent cell culture device, wherein the top cover is provided with a cover eave, an inner thread is arranged on the inner side wall of the cover eave, an outer thread matched with the inner thread is arranged on the outer side wall of the cell culture tank, and the top cover and the cell culture tank are detachably arranged through the inner thread and the outer thread.

[0021] Preferably, the novel adherent cell culture device, wherein the top cover is provided with a cover eave, a protrusion is arranged on the inner side wall of the cover eave, and a gap is maintained between the top cover and the side wall of the cell culture tank through the protrusion.

[0022] Preferably, the novel adherent cell culture device, wherein the shape of the cavity of the cell culture container comprises any one of a cylinder, a cuboid and a rounded cuboid.

[0023] Preferably, the novel adherent cell culture device, wherein the shape of the cell culture container comprises any one of a cylinder, a cuboid and a rounded cuboid.

[0024] Preferably, the novel adherent cell culture device, wherein the shape of the opening comprises any one of an ellipse, a circle, a rectangle or a rounded parallelogram.

[0025] Preferably, the novel adherent cell culture device, wherein the shape of the cell culture container comprises at least one of a petri dish shape and a flask shape.

[0026] Preferably, the novel adherent cell culture device, wherein the number of the cell culture containers is at least one, each cell culture container corresponds to an image acquisition device, and each cell culture container is placed above the corresponding image acquisition device.

[0027] Preferably, the novel adherent cell culture device, wherein the plurality of cell culture containers are arranged side by side, the image acquisition device corresponding to each cell culture container is arranged side by side on the upper surface of the PCB circuit board, and each image acquisition device is connected to the controller.

[0028] Preferably, the novel adherent cell culture device, wherein when the plurality of cell culture containers are included, all the cell culture containers include a top cover, and the top cover covers all the cell culture containers.

[0029] Preferably, the novel adherent cell culture device, wherein when the cell culture container is placed above the image acquisition device, the center of the opening is close to the center of the image acquisition device.

[0030] Preferably, the novel adherent cell culture device, wherein the cell culture container is a transparent container made of glass or organic polymer.

[0031] Preferably, the novel adherent cell culture device, wherein the controller outputs the growth data to a local or remote display terminal through wired or wireless means.

[0032] A novel adherent cell culture device comprises at least one culture container for culturing adherent cells and an imaging chip for image acquisition, the top surface of the culture container is open, and the bottom surface is provided with an imaging hole, the imaging chip is located in the center of the imaging hole, the imaging chip is packaged in a tube shell, the back or side of the tube shell is provided with an electrode after the imaging chip is packaged, for input and output between the imaging chip and an external control system, and the upper surface of the tube shell is attached to the lower surface of the culture container.

[0033] The attachment refers to the combination of the upper surface of the tube shell and the lower surface of the culture container without gap, for example, adhesive bonding.

[0034] Preferably, the tube shell with the imaging chip packaged by the PLCC mode is welded to the PCB circuit board, and the welding position is wrapped with ultraviolet glue for isolating the welding pad from the surrounding environment. Then, the PCB circuit board is connected to the external control system in a mode selected from a flat cable, a gold finger connector and the like.

[0035] Preferably, the culture container includes at least one culture groove, and each culture groove is provided with a developing hole with the same central axis as the bottom surface of the culture container. A corresponding imaging chip is arranged in the center of each developing hole.

[0036] Preferably, the culture container is provided with a top cover on the open top surface. The inner side wall of the top cover is uniformly distributed with a plurality of protrusions. The top cover is detachably connected to the side wall of the culture container through the protrusions.

[0037] Preferably, the detector array of the imaging chip is one of a CMOS image sensor array, a semi-floating gate transistor array, a composite dielectric gate photosensitive detector array, a double-device photosensitive detector unit array based on a composite dielectric gate, or a split-gate MOSFET imaging detector array.

[0038] The semi-floating gate transistor can be the semi-floating gate transistor structure described in the literature (Wang P, Lin X, Liu L, et al. A semi-floating gate transistor for low-voltage ultrafast memory and sensing operation. [J]. Science (New York, N.Y.), 2013, 341(6146): 640-643.) or the semi-floating gate transistor structure described in Chinese patent CN201410201614.6, which includes a semiconductor substrate (P type), an N+ type source formed by ion implantation in the semiconductor substrate, a large N type drain formed by two-step ion implantation, a bottom dielectric, a semi-floating gate, a top dielectric, a control gate, and a slot formed in the middle of the bottom dielectric by etching, so that the semi-floating gate directly contacts the drain. Compared with the traditional floating gate transistor, the semi-floating gate transistor uses the quantum tunneling effect of the TFET in the silicon body and replaces the traditional silicon oxide data erasing window with a PN junction diode.

[0039] The composite medium gate photosensitive detector may be, for example, the photosensitive composite medium gate MOSFET detector described in Chinese patent CN200910024504.6. The photosensitive detector comprises: a semiconductor substrate (P type); a bottom layer insulating medium, a photoelectron storage layer, a top layer insulating medium and a control gate arranged in sequence on the top of the semiconductor substrate; and N type source and drain formed by ion implantation and doping in the semiconductor substrate (close to both sides of the stacked medium). By applying a gate voltage greater than the threshold voltage to the control gate, the voltage difference between the source and the drain is 0, and a large voltage difference is set between the P type substrate and the source to generate a relatively wide depletion region on the substrate. The cold electrons generated in the substrate are accelerated by the electric field in the depletion region to obtain energy, and when the energy is greater than the potential barrier between the substrate and the bottom layer medium, the electrons directly cross the potential barrier into the bottom layer medium and move at a high speed in the direction of the gate under the action of the electric field in the bottom layer medium, thereby generating gate injection current.

[0040] The double-device photosensitive detection unit based on the composite medium gate may be, for example, the double-device photosensitive detection unit based on the composite medium gate described in Chinese patent CN201610592997.3. The photosensitive detection unit comprises a composite medium gate MOS-C part with a photosensitive function and a composite medium gate MOSFET part with an information reading function, and the two parts are formed on the top of the same P type semiconductor substrate; the composite medium gate MOS-C part comprises a charge coupling layer, a first top layer medium layer and a first control gate arranged in sequence on the top of the P type semiconductor substrate, wherein an N type injection layer is arranged in the P type semiconductor substrate and below the charge coupling layer; the composite medium gate MOSFET part comprises a bottom layer medium layer, the charge coupling layer, a second top layer medium layer and a second control gate arranged in sequence on the top of the P type semiconductor substrate, wherein an N type source region and an N type drain region are arranged in the P type semiconductor substrate and close to one side of the bottom layer medium layer, and a threshold adjustment injection region is arranged in the P type semiconductor substrate and below the bottom layer medium layer; in the P type semiconductor substrate, the N type injection layer is separated from the N type source region and the N type drain region by a shallow trench isolation region and a P+ type injection region. When working: the control gate is applied with 0 bias, and the substrate is applied with a negative bias pulse to form a depletion layer in the substrate. When photons are absorbed by the semiconductor when light is incident into the depletion layer, photoelectrons are generated, which are driven by the gate voltage to move to the substrate and gate oxide interface, where they are accumulated, so that the threshold voltage of the reading transistor changes, thereby representing the number of photoelectrons, and converting the optical signal into a quantifiable electrical signal.

[0041] The split-gate MOSFET imaging detector can be the split-gate MOSFET imaging detector described in Chinese patent CN201210349285.0. The structure of the imaging detector comprises: two layers of insulating medium materials and a control gate are respectively arranged on the top of a substrate P-type semiconductor material, and a photoelectron storage layer is arranged between the two layers of insulating medium materials. The control gate surface or the substrate layer has at least one window which is transparent or semi-transparent to light in the wavelength range detected by the detector. Two sides of the floating gate MOSFET on the substrate P-type semiconductor material are provided with selection gates, and an insulating medium layer is arranged between the selection gates and the substrate, and the insulating medium layer has the same material and thickness as the bottom insulating medium layer. An N-type semiconductor region is arranged on the peripheral P-type substrate of the substrate controlled by the two selection gates, thereby forming a source and a drain of the split-gate MOSFET. The two selection gates are arranged on the two sides of the floating gate MOSFET, and the selection gates are separated from the control gate and the photoelectron storage layer by an insulating medium material, and the substrate controlled by the control gate is separated from the source and the drain of the imaging detector. The second layer of insulating medium layer in contact with the control gate is a material for preventing the stored charges in the photoelectron storage layer from flowing to the control gate, and the first layer of insulating medium layer in contact with the substrate P-type semiconductor material, i.e. the bottom layer of medium, effectively isolates the substrate channel controlled by the control gate from the photoelectron storage layer, and when the gate voltage is high enough or the incident photon energy is high, the electrons in the channel are swept into the photoelectron storage layer. When a positive bias pulse is applied to the control gate and a negative bias pulse is applied to the P-type semiconductor substrate, a negative bias pulse is applied to the two selection gates, a depletion layer is formed in the P-type semiconductor substrate controlled by the control gate, and when the light is incident into the depletion layer, the photoelectrons are generated by the semiconductor absorption, and the photoelectrons are moved to the interface between the channel and the bottom insulating layer under the drive of the gate voltage. Since a negative bias is applied to the two selection gates, a high electron barrier is formed in the P-type semiconductor substrate controlled by the selection gate, which effectively separates the substrate controlled by the control gate from the N-type source and drain, thereby preventing the collected photoelectrons in the substrate depletion layer from flowing to the source and drain, and the electrons in the source and drain are also hindered by the high barrier from entering the substrate depletion layer. When the positive bias applied to the control gate is large enough, the collected photoelectrons in the substrate depletion layer will enter the photoelectron storage layer through F-N tunneling; if the incident photon energy is high enough, greater than the band gap width of the semiconductor and the bottom insulating medium layer, the photoelectrons can enter the photoelectron storage layer through direct tunneling. During the collection of photoelectrons, the source and the drain can be appropriately applied with a positive bias of appropriate size, or directly floated.

[0042] Preferably, the size of a single detector unit of the imaging chip is ≤1 μm, and the scale of the detector array is ≥100 million, so as to ensure a large field of view and high resolution during microscopic imaging of a liquid-based cell sample.

[0043] Preferably, the shape of the imaging hole and the culture groove is selected from one of an oval, a circle, a rectangle or a rounded parallelogram.

[0044] Preferably, the culture container and the top cover are both completely transparent and are made of glass or organic polymer.

[0045] The external control system comprises a control module, a light source module, a data acquisition and processing module, a data transmission module, an image analysis and display module, and a data storage module. The control module is connected to the light source module and the data acquisition and processing module. The data acquisition and processing module is also connected to the data transmission module. The data transmission module comprises at least one of a WIFI module, a Bluetooth module or a GSM module, and is connected to the image analysis and display module and the data storage module. The image analysis and display module is connected to the data storage module.

[0046] The control module can be an FPGA, which is used to control the imaging chip and the opening and closing of the light source module (lighting lamp) during imaging. After the data acquisition and processing module receives the microscopic images collected by the imaging chip, it removes and suppresses the noise in the projected microscopic images through relevant image processing algorithms, and processes the image data with poor imaging effects, such as weak signal, blurred edges, and low signal-to-noise ratio, through image enhancement, pseudo-color coloring and image segmentation.

[0047] The data transmission module comprises a WIFI module, a Bluetooth module or a GSM module, which is used to transmit the processed projected microscopic images collected by the chip during the cell culture process to the image analysis and display module and the data storage module.

[0048] The image analysis and display module is used to receive the processed image data for further interactive analysis and display of the final imaging results. It can be a mobile phone, a tablet computer, a notebook computer, etc. The interactive analysis includes deleting, reducing, enlarging, rotating, selecting a specific area and labeling a target of the image.

[0049] The data storage module is used to establish an image database to store the image data after the data acquisition and processing module or the image data after the image analysis and display module. The data storage module contains a database, which can be stored locally or on a cloud server. The data storage module saves the data processed by the data acquisition and processing module or the data after the image analysis and display module into the local database or uploads it to the cloud server through the network, and can search, add or delete, modify and back up the image data in the database.

[0050] The above technical solution has the following advantages or beneficial effects:

[0051] First, by directly setting the cell culture container above the image acquisition device, the image acquisition device can acquire images of the adherent cells through the opening, so that the adherent cells can be imaged without the objective, thereby effectively overcoming the limitation of small focal depth in microscopic imaging, and the imaging quality is clearer;

[0052] Second, the culture device can not only be a cell culture container, but also output the collected images to the controller through the image acquisition device, process the images to obtain the growth of the adherent cells, and output the growth data of the adherent cells to the external display terminal to directly record the growth data of the adherent cells, so that the growth data of the adherent cells can be obtained in real time, and the user can understand the growth of the adherent cells in real time;

[0053] Third, as long as the cell culture container is set above the image acquisition device, the adherent cells in the cell culture container can be monitored in real time, which not only improves the monitoring accuracy of the adherent cells, but also saves the real-time monitoring space, thereby reducing the monitoring cost. BRIEF DESCRIPTION OF DRAWINGS

[0054] Reference is made to the accompanying drawings to more fully describe embodiments of the present application. However, the accompanying drawings are only used for illustration and explanation, and do not constitute a limitation on the scope of the present application.

[0055] Figure 1 Structure diagram of the novel adherent cell culture device embodiment one of the present application Figure 1 ;

[0056] Figure 2 Structure diagram of the novel adherent cell culture device embodiment one of the present application Figure 2 ;

[0057] Figure 3 Structure diagram of the novel adherent cell culture device embodiment one of the present application Figure 3 ;

[0058] Figure 4 Structure diagram of the top cover of the novel adherent cell culture device embodiment one of the present application

[0059] Figure 5 Principle block diagram of the image acquisition chip of the novel adherent cell culture device embodiment one of the present application

[0060] Figure 6 Structure diagram of the novel adherent cell culture device embodiment one of the present application Figure 4 ;

[0061] Figure 7The principle block diagram of the novel adherent cell culture device of the present application;

[0062] Figure 8 The structure diagram of the second embodiment of the novel adherent cell culture device of the present application Figure 1 ;

[0063] Figure 9 The structure diagram of the second embodiment of the novel adherent cell culture device of the present application Figure 2 ;

[0064] Figure 10 The structure diagram of the second embodiment of the novel adherent cell culture device of the present application Figure 3 ;

[0065] Figure 11 The principle block diagram of the image acquisition chip of the second embodiment of the novel adherent cell culture device of the present application;

[0066] Figure 12 The schematic diagram of the detector array of the image acquisition chip of the novel adherent cell culture device of the present application;

[0067] Figure 13 The structure diagram of the CMOS image sensor of the novel adherent cell culture device of the present application;

[0068] Figure 14 The structure diagram of the semi-floating gate transistor of the novel adherent cell culture device of the present application;

[0069] Figure 15 The structure diagram of the composite dielectric gate light-sensitive detector of the novel adherent cell culture device of the present application;

[0070] Figure 16 The structure diagram of the double-device light-sensitive detection unit based on the composite dielectric gate of the novel adherent cell culture device of the present application Figure 1 ;

[0071] Figure 17 The structure diagram of the double-device light-sensitive detection unit based on the composite dielectric gate of the novel adherent cell culture device of the present application Figure 2 ;

[0072] Figure 18 The structure diagram of the double-device light-sensitive detection unit based on the composite dielectric gate of the novel adherent cell culture device of the present application Figure 3 ;

[0073] Figure 19 The structure diagram of the double-device light-sensitive detection unit based on the composite dielectric gate of the novel adherent cell culture device of the present application Figure 4 ;

[0074] Figure 20The structure diagram of a split gate MOSFET imaging detector of a novel adherent cell culture device. DETAILED DESCRIPTION

[0075] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the present application.

[0076] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict.

[0077] The present application will be further described below with reference to the drawings and specific embodiments, but is not limited to the present application.

[0078] Embodiment one;

[0079] The present application includes a novel adherent cell culture device, as shown in Figures 1-3 The present application includes a novel adherent cell culture device, as shown in

[0080] PCB circuit board 5;

[0081] Image acquisition device 20 is arranged on the upper surface of the PCB circuit board 5, and the image acquisition device 20 is connected with a controller 9;

[0082] Cell culture container 1 provides a container for adherent cells, and the cell culture container 1 is arranged above the image acquisition device 20, and the bottom of the side wall of the cell culture container 1 is attached to the upper surface of the image acquisition device 20, and the bottom of the cell culture container 1 is provided with an opening 3 for exposing the image acquisition device;

[0083] The image acquisition device 20 acquires images of the adherent cells through the opening 3, and outputs the acquired images to the controller 9;

[0084] The controller 9 processes the images to obtain growth data of the adherent cells, and transmits the growth data to an external display terminal.

[0085] In the above embodiment, the cell culture container 1 is directly arranged above the image acquisition device 20, and the bottom of the side wall of the cell culture container 1 is attached to the upper surface of the image acquisition device 20, so that the image acquisition device 20 acquires images of the adherent cells through the opening 3 at the bottom. Therefore, the present embodiment does not need an objective lens, and can effectively overcome the limitation of small focal depth in microscopic imaging, and the imaging quality is clearer.

[0086] And in the above embodiment, the culture device in the present embodiment can not only be used as a cell culture container, but also can output the collected image to the controller 9 through the image acquisition device 20, and the controller 9 processes the image to obtain the growth data of the adherent cells and outputs the growth data of the adherent cells to the external display terminal, so as to directly record the growth data of the adherent cells, thereby realizing the real-time acquisition of the growth data of the adherent cells, and further enabling the user to realize the real-time growth of the adherent cells.

[0087] And in the above embodiment, as long as the cell culture container 1 is arranged above the image acquisition device 20, the adherent cells in the cell culture container 1 can be monitored in real time, which not only improves the monitoring accuracy of the adherent cells, but also saves the real-time monitoring space, thereby reducing the monitoring cost.

[0088] In the above embodiment, the cell culture container 1 can be arranged in close contact with the image acquisition device 20, so as to avoid displacement of the cell culture container 1 during operation.

[0089] For example, the lower surface of the bottom of the side wall of the cell culture container 1 is adhered to the upper surface of the image acquisition device 20 by an adhesive;

[0090] For example, the cell culture container 1 is fixed above the image acquisition device 20 by an adhesive along the side wall of the cell culture container 1.

[0091] Further, in the above embodiment, the image acquisition device 20 comprises an image acquisition chip 2, the image acquisition chip 2 is packaged in a packaging tube shell 4, the electrodes of the packaged image acquisition chip 2 are arranged on the back surface and / or side surface of the packaging tube shell 4, the packaging tube shell 4 packaging the image acquisition chip 2 is welded on the upper surface of the PCB circuit board 5, and the image acquisition chip 2 is exposed in the middle of the upper surface of the packaging tube shell 4, so that the image acquisition chip 2 is surrounded by the bottom of the side wall of the cell culture container 1, that is, the side wall of the cell culture container 1 is wrapped into a structure which is closed laterally and open at the upper and lower ends, and the opening of the lower end of the structure surrounds the image acquisition chip 2.

[0092] In the above embodiment, the image acquisition chip 2 is packaged in the packaging tube shell 4 to isolate the image acquisition chip 2 from the surrounding environment, thereby prolonging the service life of the image acquisition chip 2.

[0093] In the above embodiment, the electrodes of the packaged image acquisition chip 2 are arranged on the back surface and / or side surface of the packaging tube shell 4, so as to avoid arranging the electrodes of the packaged image acquisition chip 2 on the front surface of the packaging tube shell 4, thereby avoiding the interference of the electrodes of the packaged image acquisition chip 2 with the image acquisition of the image acquisition chip 2 on the adherent cells.

[0094] In the above embodiment, when the packaging tube 4 is welded on the upper surface of the PCB circuit board 5, the welding parts, such as the pins, electrodes and the like, can be sealed by the sealing material. By sealing the welding parts of the packaging tube 4 and the PCB circuit board 5 by the sealing material, the welding parts of the packaging tube 4 and the PCB circuit board 5 can be prevented from being oxidized or short-circuited in a humid environment.

[0095] Preferably, the sealing material can be selected as UV glue.

[0096] In the above embodiment, the electrodes of the packaged image acquisition chip 2 can realize the input and output between the image acquisition chip 2 and the controller 9.

[0097] In the above embodiment, as shown in Figure 5 The image acquisition chip 2 can include a cell adhesion judgment unit 21 for judging whether the cells in the cell culture container 1 are adhered to the upper surface of the image acquisition chip 2.

[0098] The image acquisition chip 2 can include an image acquisition unit 22 connected with the cell adhesion judgment unit 21 and directly recording the projection microscopic image of the adhered cells after the cells are adhered to the upper surface of the image acquisition chip 2.

[0099] In the above embodiment, the cell culture container 1 can be arranged in close contact with the packaging tube 4, so as to avoid displacement of the cell culture container 1 during operation.

[0100] For example, the lower surface of the bottom of the side wall of the cell culture container 1 is bonded without gap to the upper surface of the packaging tube 4 by an adhesive;

[0101] For example, the cell culture container 1 is fixed above the packaging tube 4 by an adhesive along the side wall of the cell culture container 1.

[0102] As a preferred embodiment, a groove 18 for placing the packaging tube 4 packaging the image acquisition chip 2 can be arranged on the PCB circuit board 5, so that the upper surface of the packaging tube 4 is flush with the upper surface of the PCB circuit board 5.

[0103] Further, as a preferred embodiment, the junction of the image acquisition chip 2 and the packaging tube 4 is provided with UV glue (UV glue).

[0104] In the above preferred embodiment, by arranging the UV glue around the junction of the packaging tube 4 and the image acquisition chip 2, the corners of the image acquisition chip 2 and the packaging tube 4 can be isolated, so as to improve the service life of the image acquisition chip 2.

[0105] Further, as a preferred embodiment, the image acquisition chip 2 protrudes from the package tube 4.

[0106] Further, in the above embodiment, as shown in Figure 12 , the image acquisition chip 2 comprises a detector array 10 composed of a plurality of detector units 11.

[0107] In the above embodiment, the detector array 10 comprises a plurality of identical single detector units 11.

[0108] Further, in the above embodiment, the detector array 10 can adopt any one of a CMOS image sensor array, a half-float gate transistor array, a composite dielectric gate photosensitive detector array, a composite dielectric gate-based dual-device photosensitive detection unit array, and a split gate type MOSFET imaging detector array, and in the embodiment, the detector array 10 adopts a CMOS image sensor array.

[0109] The structure of the single detector unit 11 can be a CMOS image sensor as shown in Figure 13 , a half-float gate transistor as shown in Figure 14 , a composite dielectric gate photosensitive detector as shown in Figure 15 , a composite dielectric gate-based dual-device photosensitive detection unit as shown in Figure 16 , Figure 17 , Figure 18 , Figure 19 , or a split gate type MOSFET imaging detector as shown in Figure 20 .

[0110] Further, in the above embodiment, the size of the detector unit 11 is ≤1 μm, and the number of the detector units 11 in the detector array 10 is ≥100 million.

[0111] As a preferred embodiment, the size of the detector unit 11 can be 0.5 μm, and the number of the detector units 11 in the detector array 10 can be 250 million, so as to ensure that the image acquisition device 20 can acquire images of adherent cells with large field of view and high resolution.

[0112] Further, in the above embodiment, as shown in Figures 1-3 , the cell culture container 1 comprises a cell culture tank 8 and a top cover 6 matched with the cell culture tank 8, the upper surface of the cell culture tank 8 is provided with a top opening, the cell culture tank 8 covers the top opening by the top cover 6, and the cell culture tank 8 and the top cover 6 are detachably arranged.

[0113] Further, in the above embodiment, as shown in Figure 4 , the cell culture tank 8 comprises a cell culture tank body 9 and a cell culture tank cover 7, the cell culture tank cover 7 is detachably arranged on the cell culture tank body 9, and the cell culture tank cover 7 is provided with a plurality of cell culture cavities 5.As shown, the top cover 6 is provided with a cover rim, and a protrusion 7 is provided on the inner side wall of the cover rim. The top cover 6 maintains a gap with the side wall of the cell culture tank 8 through the protrusion 7.

[0114] In the above embodiment, a plurality of protrusions 7 are evenly distributed on the inner sidewall of the cover, and the top cover 6 maintains a gap with the sidewall of the cell culture tank 8 through the plurality of protrusions 7. This gap provides the water vapor and air required for cell culture, so that the user can not only intervene in the culture process of adherent cells without opening the top cover 6, but also reuse the cell culture container 1.

[0115] Furthermore, in the above embodiments, the shape of the cavity of the cell culture container 1 may include different shapes;

[0116] For example, the shape of the cavity of cell culture container 1 can be a cylinder, a cuboid, or a rounded cuboid.

[0117] Furthermore, in the above embodiments, the shape of the cell culture container 1 may include different shapes;

[0118] For example, the cell culture container 1 can be shaped like a cylinder, a cuboid, or a rounded cuboid.

[0119] Furthermore, in the above embodiments, the shape of the cavity of the cell culture container 1 and the shape of the cell culture container 1 can be the same or different.

[0120] For example, when the cavity of cell culture container 1 is cylindrical, the shape of cell culture container 1 can also be cylindrical;

[0121] For example, such as Figure 3 As shown, when the cavity of cell culture container 1 is cylindrical, the shape of cell culture container 1 can be cuboid or rounded cuboid.

[0122] Furthermore, in the above embodiments, the shape of the opening 3 may include different shapes;

[0123] For example, the shape of opening 3 can be ellipse, circle, rectangle, or rounded parallelogram.

[0124] Furthermore, as a preferred embodiment, the shape of the bottom of the cavity of the cell culture container 1 and the shape of the opening 3 can be the same;

[0125] For example, when the cavity of cell culture container 1 is not a perfect cylinder, the bottom of the cavity of cell culture container 1 can be elliptical, and the opening 3 is also elliptical in shape.

[0126] For example, when the shape of the cavity of the cell culture container 1 is a right circular cylinder, the shape of the bottom of the cavity of the cell culture container 1 can be circular, and the shape of the opening 3 is also circular at this time.

[0127] For example, when the shape of the cavity of the cell culture container 1 is a rectangular parallelepiped, the shape of the bottom of the cavity of the cell culture container 1 can be rectangular, and the shape of the opening 3 is also rectangular at this time.

[0128] Further, in the above embodiment, the height of the cell culture container 1 can be different;

[0129] For example, the shape of the cell culture container 1 can be a culture dish shape with a lower height;

[0130] For example, as shown in FIG. 1, the shape of the cell culture container 1 can be a culture bottle shape with a higher height. Figure 6

[0131] Further, in the above embodiment, the number of cell culture containers 1 is at least one, each cell culture container 1 corresponds to an image acquisition device 20, and each cell culture container 1 is placed above the corresponding image acquisition device 20.

[0132] Further, in the above embodiment, a plurality of cell culture containers 1 are arranged side by side, and the image acquisition device 20 corresponding to each cell culture container 1 is arranged side by side on the upper surface of the PCB circuit board 5, and each image acquisition device 20 is connected with the controller 9.

[0133] For example, a plurality of cell culture containers 1 can be arranged in a row, and each image acquisition device 20 is also arranged in a row on the upper surface of the PCB circuit board 5, and each cell culture container 1 is arranged corresponding to an image acquisition device 20, and each image acquisition device 20 can be connected with a controller 9.

[0134] For example, a plurality of cell culture containers 1 can be arranged in multiple rows, and each image acquisition device 20 is also arranged in multiple rows on the upper surface of the PCB circuit board 5, and the cell culture container 1 is arranged corresponding to the image acquisition device 20, and each image acquisition device 20 can be connected with a controller 9.

[0135] In the above preferred embodiment, by arranging a plurality of cell culture containers 1 and image acquisition devices 20 corresponding to each cell culture container 1 on a PCB circuit board 5, it is convenient to carry in and out of the cell culture box, and the culture space is saved, and then the cells in a plurality of cell culture containers 1 can be cultured at the same time, and the culture time is saved.

[0136] ​Further, in the above embodiment, when a plurality of cell culture containers 1 are included, all the cell culture containers 1 are capped by one top cover 6.

[0137] In the above embodiment, the shape of the top cover 6 can be set according to the shape of the combination of all the cell culture containers 1.

[0138] For example, when each cell culture container 1 is in the shape of a cuboid, i.e., the upper end of each cell culture container 1 is in the shape of a rectangle, and each cell culture container 1 is closely arranged, the shape of the top cover 6 can be in the shape of a rectangle, and one top cover 6 can cap all the rectangular cell culture containers 1.

[0139] For example, when each cell culture container 1 is in the shape of a cylinder, i.e., the upper end of each cell culture container 1 is in the shape of a circle, and each cell culture container 1 is closely arranged, the shape of the top cover 6 can be in the shape of a plurality of circles connected to each other, and one top cover 6 can cap all the circular cell culture containers 1.

[0140] In this embodiment, the same is true for the top cover 6 to cap each cell culture container 1, and the necessary water vapor and air flow means are provided, such as a through hole provided at the position of the top cover 6 corresponding to each cell culture container 1, or a protrusion provided in the inner side wall and top surface of the top cover 6 corresponding to each cell culture container 1, so that there is a gap between the top cover 6 and the side wall of each cell culture container 1.

[0141] Further, in the above embodiment, when the cell culture container 1 is placed above the image acquisition device 20, the center of the opening 3 of the cell culture container 1 is close to the center of the image acquisition device 20.

[0142] In the above embodiment, by arranging the center of the opening 3 of the cell culture container 1 close to the center of the image acquisition device 20, the image acquisition device 20 can acquire images of the adherent cells in the largest range.

[0143] Further, in the above embodiment, the cell culture container 1 is a transparent container made of glass or organic polymer.

[0144] In the above preferred embodiments, the transparent material used for the cell culture container 1 can be PC (polycarbonate), PMMA (poly-methylmethacrylate), PS (polystyrene), PET (polyethylene terephthalate), PVC (polyvinyl chloride), PFA (perfluoroalkoxy), FEP (fluorinated ethylene propylene), COC (Cyclic Olefin Copolymer), TPE (Thermoset Polyester), PUMA (Polyurethane Methacrylate), etc.

[0145] In the above preferred embodiments, the cell culture container 1 can be integrally injection molded from an organic polymer.

[0146] Further, in the above embodiments, the controller 9 outputs the growth data to the display terminal locally or remotely via wired or wireless means.

[0147] In the above embodiments, as shown in FIG. 1, the controller 9 can include: Figure 7

[0148] a light source module 13 for providing light source for the image acquisition device 20;

[0149] a control module 12 connected with the light source module 13 for controlling the operation of the image acquisition device 20 and the opening and closing of the light source module 13,

[0150] a data acquisition and processing module 14 connected with the control module 12 for receiving the images of the adherent cells acquired when the image acquisition device 20 is working, and performing image processing on the images of the adherent cells to obtain processed images, wherein the processed images are used to represent the growth data of the adherent cells;

[0151] an image analysis and display module 16 connected with the data acquisition and processing module 14 and the external display terminal via the data transmission module 15 for receiving the processed images after processing to perform interactive analysis, and transmitting the analyzed processed images to the external display terminal;

[0152] a data storage module 17 connected with the image analysis and display module 16 via the data transmission module 15 for storing the processed images analyzed by the image analysis and display module 16.​

[0153] In the above embodiment, the light source module 13 can be a lighting lamp, such as an LED lamp, to provide light source for the image acquisition device 20.

[0154] As a preferred embodiment, the control module 12 can be an FPGA.

[0155] As a preferred embodiment, the display terminal can be a local display terminal.

[0156] As a preferred embodiment, the display terminal can be a remote display terminal.

[0157] For example, the display terminal can be a mobile phone, a tablet computer, a notebook computer, and the like.

[0158] In the above embodiment, the interactive analysis includes deleting, zooming out, zooming in, rotating, selecting a specific area, and labeling a target on the processed image.

[0159] In the above embodiment, the data acquisition and processing module 14 can remove and suppress noise in the image of the adherent cell by using relevant image processing algorithms, and process image data with poor imaging effect to obtain a processed image, which is used to represent the growth data of the adherent cell.

[0160] As a preferred embodiment, the data acquisition and processing module 14 can perform image enhancement, pseudo-color coloring, and image segmentation on image data with weak signal, blurred edges, and low signal-to-noise ratio, and the like, by using relevant image processing algorithms.

[0161] In the above embodiment, the data storage module 17 is used to establish an image database, which can store images collected by the data acquisition module, images processed by the data processing module, and processed images analyzed by the image analysis and display module 16.

[0162] As a preferred embodiment, the image database can be established locally, and the data storage module 17 saves the images collected by the data acquisition module, the images processed by the data processing module, and the processed images analyzed by the image analysis and display module 16 into the local image database, and can search, add or delete, modify, and back up the image data in the local image database.

[0163] As a preferred embodiment, the image database can also be established on a cloud server; the data storage module 17 uploads the images collected by the data acquisition module, the images processed by the data processing module, and the processed images analyzed by the image analysis and display module 16 to the cloud server through a network, and can search, add or delete, modify, and back up the image data in the image database in the cloud server.

[0164] In the above embodiment, the data transmission module 15 includes wired transmission and wireless transmission;

[0165] The wireless transmission includes at least one of a WIFI module, a Bluetooth module, or a GSM module.

[0166] The process of monitoring the adherent cell culture using the device of the present embodiment is briefly described as follows:

[0167] (1) The cell culture container 1 and the top cover 6 are sterilized, and the sterilization method can be ultraviolet irradiation for 10 min or immersion in a 75% alcohol solution for 15 min;

[0168] (2) 2 ml of culture medium (DMEM+10% FBS) is added to the cell culture tank 8 of the cell culture container 1, and 10 μL of HCT116 cell suspension with good growth conditions is added to the culture medium, and the top cover 6 is covered;

[0169] (3) The cell culture tank 8 is connected to the controller 9, the culture device switch is turned on, and the entire culture device is placed in the incubator;

[0170] (4) The external tablet computer can be connected and communicated with the entire culture device through the WIFI module, and the image data collection time interval of the device is set through the tablet computer, and the global observation image data collected is viewed to understand the growth condition of the cells at the current time.

[0171] Embodiment two;

[0172] The present application includes a novel adherent cell culture device, as shown in Figures 7-10 , comprising:

[0173] A PCB circuit board 5;

[0174] An image acquisition device 20 is arranged on the upper surface of the PCB circuit board 5, and the image acquisition device 20 is connected to a controller 9;

[0175] A cell culture container 1 is provided for adherent cells, and the cell culture container 1 is placed above the image acquisition device 20, and the bottom of the cell culture container 1 is provided with an opening 3 exposing the image acquisition device 20;

[0176] The image acquisition device 20 acquires images of adherent cells through the opening 3 and outputs the acquired images to the controller 9;

[0177] The controller 9 transmits the obtained growth data of the adherent cells to an external display terminal.

[0178] In the above embodiment, the cell culture container 1 is directly placed above the image acquisition device 20, so that the image acquisition device 20 can acquire images of the adherent cells through the opening 3. Therefore, this embodiment does not require an objective lens, which can effectively overcome the limitation of small depth of focus in microscopic imaging and result in clearer image quality.

[0179] Furthermore, in the above embodiments, the culture device in this embodiment can not only serve as a container for cell culture, but also output the acquired images to the controller 9 through the image acquisition device 20. The controller 9 processes the images to obtain the growth data of the adherent cells and outputs the growth data of the adherent cells to an external display terminal to directly record the growth data of the adherent cells, thereby enabling the real-time acquisition of the growth data of the adherent cells, so that the user can understand the growth status of the adherent cells in real time.

[0180] Furthermore, in the above embodiments, as long as the cell culture container 1 is placed above the image acquisition device 20, real-time monitoring of the adherent cells in the cell culture container 1 can be achieved, which not only improves the monitoring accuracy of the adherent cells, but also saves real-time monitoring space and thus reduces monitoring costs.

[0181] As a preferred embodiment, the cell culture container 1 can be placed directly above the image acquisition device 20, making the placement operation simple.

[0182] In a preferred embodiment, the cell culture container 1 can be detachably mounted above the image acquisition device 20 to prevent the cell culture container 1 from shifting.

[0183] For example, such as Figure 10 As shown, a groove 18 adapted to the cell culture container 1 is provided, and an image acquisition device 20 is provided at the center of the groove 18. When the cell culture container 1 is placed in the groove 18, the cell culture container 1 is located directly above the image acquisition device 20.

[0184] The groove 18 can be detachably connected to the cell culture container 1 via threads;

[0185] The cell culture container 1 can fit perfectly into the groove 18.

[0186] Furthermore, in the above embodiments, the image acquisition device 20 includes an image acquisition chip 2, which is encapsulated in a package 4. The electrodes of the encapsulated image acquisition chip 2 are disposed on the back and / or side of the package 4. The package 4 containing the image acquisition chip 2 is soldered to the upper surface of the PCB circuit board 5. The image acquisition chip 2 is exposed in the middle of the upper surface of the package 4. The image acquisition chip 2 is surrounded by the bottom of the side wall of the cell culture container 1.

[0187] In the above embodiment, by encapsulating the image acquisition chip 2 in the encapsulation tube shell 4, the image acquisition chip 2 is isolated from the surrounding environment, thereby prolonging the service life of the image acquisition chip 2.

[0188] In the above embodiment, by arranging the electrodes of the encapsulated image acquisition chip 2 on the back and / or side of the encapsulation tube shell 4, the electrodes of the encapsulated image acquisition chip 2 are avoided to be arranged on the front of the encapsulation tube shell 4, thereby avoiding the electrodes of the encapsulated image acquisition chip 2 to interfere with the image acquisition of the image acquisition chip 2 to the adherent cells.

[0189] In the above embodiment, when the encapsulation tube shell 4 is welded on the upper surface of the PCB circuit board 5, the welding parts such as pins, electrodes and the like of the encapsulation tube shell 4 can be sealed by the sealing material. By sealing the welding parts of the encapsulation tube shell 4 and the PCB circuit board 5 by the sealing material, the welding parts of the encapsulation tube shell 4 and the PCB circuit board 5 can be prevented from being oxidized or short-circuited in a humid environment.

[0190] Preferably, the sealing material can be selected as UV glue.

[0191] In the above embodiment, the electrodes of the encapsulated image acquisition chip 2 can realize the input and output between the image acquisition chip 2 and the controller 9.

[0192] In the above embodiment, as shown in Figure 11 The image acquisition chip 2 can include a cell recognition unit 23, and the adherent cells in the cell culture container 1 are recognized by the cell recognition unit 23;

[0193] The image acquisition chip 2 can include a cell motion detection unit 24 connected with the cell recognition unit 23, for recording the motion trajectory of the adherent cells.

[0194] In the above embodiment, the cell culture container 1 can be arranged in close contact with the encapsulation tube shell 4, thereby avoiding the cell culture container 1 to be displaced during operation.

[0195] For example, the lower surface of the bottom of the side wall of the cell culture container 1 is bonded without gap to the upper surface of the encapsulation tube shell 4 by an adhesive;

[0196] For example, the cell culture container 1 is fixed above the encapsulation tube shell 4 by an adhesive along the side wall of the cell culture container 1.

[0197] As a preferred embodiment, a groove 18 for placing the encapsulation tube shell 4 encapsulating the image acquisition chip 2 can be arranged on the PCB circuit board 5, so that the upper surface of the encapsulation tube shell 4 is flush with the upper surface of the PCB circuit board 5.

[0198] Further, as a preferred embodiment, the junction between the image acquisition chip 2 and the package tube 4 is provided with UV glue.

[0199] In the above preferred embodiment, by providing the UV glue around the junction between the package tube 4 and the image acquisition chip 2, the corner isolation between the image acquisition chip 2 and the package tube 4 can be achieved, thereby improving the service life of the image acquisition chip 2.

[0200] Further, as a preferred embodiment, the image acquisition chip 2 protrudes from the package tube 4.

[0201] Further, in the above embodiment, as shown in Figure 12 the image acquisition chip 2 includes a detector array 10 composed of a plurality of detector units 11.

[0202] In the above embodiment, the detector array 10 includes a plurality of identical single detector units 11.

[0203] Further, in the above embodiment, the detector array 10 can adopt any one of a CMOS image sensor array, a half-floating gate transistor array, a composite dielectric gate photosensitive detector array 10, a composite dielectric gate-based dual-device photosensitive detector unit array, and a split-gate MOSFET imaging detector array 10, and in the present embodiment, the detector array 10 adopts a CMOS image sensor array.

[0204] Further, in the above embodiment, the size of the detector unit 11 is ≤1μm, and the number of detector units 11 in the detector array 10 is ≥100 million.

[0205] As a preferred embodiment, the size of the detector unit 11 can be 0.5μm, and the number of detector units 11 in the detector array 10 can be 250 million, so as to ensure that the image acquisition device 20 can acquire images of adherent cells with large field of view and high resolution.

[0206] Further, in the above embodiment, the cell culture container 1 includes a cell culture tank 8 and a top cover 6 matched with the cell culture tank 8, the upper surface of the cell culture tank 8 is provided with a top opening, the cell culture tank 8 covers the top opening by the top cover 6, and the cell culture tank 8 and the top cover 6 are detachably arranged.

[0207] Further, in the above embodiment, the top cover 6 is provided with a cover eave, an inner thread is arranged on the inner side wall of the cover eave, an outer thread that is matched with the inner thread is arranged on the outer side wall of the cell culture tank 8, and the top cover 6 is detachably arranged with the cell culture tank 8 through the inner thread and the outer thread. On this basis, a through hole can be arranged on the top cover 6 to provide the water vapor and air required for cell culture. The through hole provides the water vapor and air required for cell culture, so that the user can not only intervene in the culture process of the adherent cells without opening the top cover 6 in the culture process of the adherent cells; but also can recycle the cell culture container 1 again.

[0208] Further, in the above embodiment, the shape of the cavity of the cell culture container 1 can include different shapes;

[0209] For example, the shape of the cavity of the cell culture container 1 can be a cylinder, a cuboid, a rounded cuboid.

[0210] Further, in the above embodiment, the shape of the cell culture container 1 can include different shapes;

[0211] For example, the shape of the cell culture container 1 can be a cylinder, a cuboid, a rounded cuboid.

[0212] Further, in the above embodiment, the shape of the cavity of the cell culture container 1 and the shape of the cell culture container 1 can be the same or different;

[0213] For example, when the shape of the cavity of the cell culture container 1 is a cylinder, the shape of the cell culture container 1 can also be a cylinder;

[0214] For example, when the shape of the cavity of the cell culture container 1 is a cylinder, the shape of the cell culture container 1 can be a cuboid or a rounded cuboid.

[0215] Further, in the above embodiment, the shape of the opening 3 can include different shapes;

[0216] For example, the shape of the opening 3 can be oval, circular, rectangular, or rounded parallelogram.

[0217] Further, as a preferred embodiment, the shape of the bottom of the cavity of the cell culture container 1 and the shape of the opening 3 can be consistent;

[0218] For example, when the shape of the cavity of the cell culture container 1 is a non-cylinder, the shape of the bottom of the cavity of the cell culture container 1 can be oval, and the shape of the opening 3 at this time is also oval;

[0219] For example, when the shape of the cavity of the cell culture container 1 is a right circular cylinder, the shape of the bottom of the cavity of the cell culture container 1 can be circular, and the shape of the opening 3 is also circular at this time.

[0220] For example, when the shape of the cavity of the cell culture container 1 is a cuboid, the shape of the bottom of the cavity of the cell culture container 1 can be rectangular, and the shape of the opening 3 is also rectangular at this time.

[0221] Further, in the above embodiment, the height of the cell culture container 1 can be different;

[0222] For example, the shape of the cell culture container 1 can be a culture dish shape with a lower height;

[0223] For example, the shape of the cell culture container 1 can be a culture bottle shape with a higher height.

[0224] Further, in the above embodiment, the number of cell culture containers 1 is one, the cell culture container 1 corresponds to the image acquisition device 20, and the cell culture container 1 is placed above the image acquisition device 20.

[0225] Further, in the above embodiment, when the cell culture container 1 is placed above the image acquisition device 20, the center position of the opening 3 of the cell culture container 1 is close to the center position of the image acquisition device 20.

[0226] In the above embodiment, by setting the center position of the opening 3 of the cell culture container 1 close to the center position of the image acquisition device 20, the image acquisition device 20 can acquire images of the adherent cells in the largest range.

[0227] Further, in the above embodiment, the cell culture container 1 is a transparent container made of glass or an organic polymer.

[0228] In the above preferred embodiment, the transparent material used by the cell culture container 1 can be PC, PMMA, PS, PET, PVC, PFA, FEP, COC, TPE, PUMA, etc.

[0229] In the above preferred embodiment, the cell culture container 1 can be integrally injection molded by an organic polymer.

[0230] Further, in the above embodiment, the controller 9 outputs the growth data to the display terminal locally or remotely by wired or wireless means.

[0231] In the above embodiment, the controller 9 can include:

[0232] The light source module 13 is used to provide a light source for the image acquisition device 20;

[0233] The control module 12 is connected with the light source module 13, and is configured to control the image acquisition device 20 to work and control the light source module 13 to be turned on and turned off.

[0234] The data acquisition and processing module 14 is connected with the control module 12, and is configured to receive the image of the adherent cells collected when the image acquisition device 20 works, and perform image processing on the image of the adherent cells to obtain a processed image, wherein the processed image is used to represent growth data of the adherent cells.

[0235] The image analysis and display module 16 is connected with the data acquisition and processing module 14 and the external display terminal through the data transmission module 15, and is configured to receive the processed image after processing to perform interactive analysis, and transmit the processed image after analysis to the external display terminal.

[0236] The data storage module 17 is connected with the image analysis and display module 16 through the data transmission module 15, and is configured to store the processed image after analysis of the image analysis and display module 16.

[0237] In the above embodiment, the light source module 13 can be a lighting lamp, such as an LED lamp, which provides a light source for the image acquisition device 20.

[0238] As a preferred embodiment, the control module 12 can be an FPGA.

[0239] As a preferred embodiment, the display terminal can be a local display terminal.

[0240] As a preferred embodiment, the display terminal can be a remote display terminal.

[0241] For example, the display terminal can be a mobile phone, a tablet computer, a notebook computer, or the like.

[0242] In the above embodiment, the interactive analysis includes deleting, reducing, enlarging, rotating, selecting a specific area, and labeling a target on the processed image.

[0243] In the above embodiment, the data acquisition and processing module 14 can remove and suppress noise in the image of the adherent cells by using a related image processing algorithm, and process image data with poor imaging effect to obtain a processed image, wherein the processed image is used to represent growth data of the adherent cells.

[0244] As a preferred embodiment, the data acquisition and processing module 14 can perform image enhancement, pseudo-color coloring, and image segmentation on image data with weak signals, blurred edges, and low signal-to-noise ratio by using a related image processing algorithm.

[0245] In the above embodiment, the data storage module 17 is used to establish an image database, which can store the images collected by the data collection module, the images processed by the data processing module, and the processed images analyzed by the image analysis and display module 16.

[0246] As a preferred embodiment, the image database can be established locally, and the data storage module 17 saves the images collected by the data collection module, the images processed by the data processing module, and the processed images analyzed by the image analysis and display module 16 into the local image database, and can search, add or delete, modify and back up the image data in the local image database.

[0247] As a preferred embodiment, the image database can also be established on a cloud server; the data storage module 17 uploads the images collected by the data collection module, the images processed by the data processing module, and the processed images analyzed by the image analysis and display module 16 to the cloud server through the network, and can search, add or delete, modify and back up the image data in the image database in the cloud server.

[0248] In the above embodiment, the data transmission module 15 includes wired transmission and wireless transmission.

[0249] The wireless transmission includes at least one of a WIFI module, a Bluetooth module, or a GSM module.

[0250] The following is a brief description of the process of monitoring the culture of adherent cells using the device of the present embodiment:

[0251] (1) Sterilize the cell culture container 1 and the top cover 6 proposed in the present application, and the sterilization method can be ultraviolet irradiation for 10 minutes or immersion in a 75% alcohol solution for 15 minutes;

[0252] (2) Add 2ml of culture medium (DMEM+10%FBS) to the cell culture tank 8 of the cell culture container 1, take 10μL of HCT116 cell suspension with good growth conditions and add it to the culture medium, and cover the top cover 6;

[0253] (3) Connect the cell culture tank 8 to the controller 9, turn on the culture device switch, and place the entire culture device in the incubator;

[0254] (4) The external tablet computer can be connected and communicated with the entire culture device through the WIFI module, and the image data collection time interval of the device can be set through the tablet computer, and the global observation image data collected can be viewed to understand the growth status of the cells at the current time.

[0255] Example Three;

[0256] A novel adherent cell culture device, such as Figure 8 As shown, the device includes a circular culture container 1 for culturing adherent cells and an imaging chip 2 for image acquisition. The top surface of the culture container 1 is open, and the bottom surface has an imaging aperture 3. The culture container 1 includes a culture tank 8. The imaging aperture 3 and the culture tank 8 have the same central axis. Both the imaging aperture 3 and the culture tank 8 are circular. The imaging chip 2 is encapsulated in a shell 4. The back of the shell 4 is provided with electrodes for the encapsulated imaging chip 2, which are used for input and output between the imaging chip 2 and an external control system. The upper surface of the shell 4 is bonded to the lower surface of the culture container 1 with adhesive without gaps.

[0257] The casing 4 containing the imaging chip 2 is soldered onto the PCB circuit board 5 using a PLCC method. The solder joint is surrounded by UV adhesive to isolate the solder pad from the surrounding environment. Then, the PCB circuit board 5 is connected to an external control system. The connection method between the PCB circuit board 5 and the external control system can be ribbon cable, gold finger connector, etc. In this embodiment, the gold finger connector method is used.

[0258] The culture container 1 has a top cover 6 on its open top surface, such as... Figure 4 As shown, a number of protrusions 7 are evenly distributed on the inner sidewall of the top cover 6, and the top cover 6 is detachably fitted to the culture container 1 through the protrusions 7.

[0259] Both the culture container 1 and the top cover 6 are completely transparent and are integrally injection molded from polystyrene (PS).

[0260] The structure of the imaging chip 2 detector array 10 is as follows: Figure 12 As shown, the detector array 10 is composed of a large number of identical individual detector units 11, and the structure of the individual detector unit 11 can be as follows: Figure 13 The CMOS image sensor shown can also be as follows: Figure 14 The semi-floating gate transistor shown can also be as follows: Figure 15 The composite dielectric grating photodetector shown can also be as follows: Figure 16 , Figure 17 , Figure 18 , Figure 19 The dual-device photosensitive detection unit based on a composite dielectric grating shown can also be as follows: Figure 20 The split-gate MOSFET imaging detector shown. The detector array 10 used in the imaging chip 2 of this embodiment is as follows... Figure 15The composite dielectric grating photosensitive detector shown has a single detector unit 11 of the imaging chip 2 with a size of 0.5 μm and a detector array size of 150 million, which is used to ensure a large field of view and high resolution when imaging liquid-based cell samples.

[0261] like Figure 7 As shown, the external control system 9 includes a control module 12, a light source module 13, a data acquisition and processing module 14, a data transmission module 15, an image analysis and display module 16, and a data storage module 17. The control module 12 is connected to the light source module 13 and the data acquisition and processing module 14 respectively. The data acquisition and processing module 14 is also connected to the data transmission module 15. The data transmission module 15 includes at least one of a WIFI module, a Bluetooth module, or a GSM module, and is connected to both the image analysis and display module 16 and the data storage module 17. The image analysis and display module 16 is connected to the data storage module 17.

[0262] The control module 12 can be an FPGA, used to control the operation of the imaging chip and to control the on / off state of the light source module (illumination lamp) during imaging. After receiving the microscopic image acquired by the imaging chip 2, the data acquisition and processing module 14 removes and suppresses noise in the projected microscopic image through relevant image processing algorithms, and performs image enhancement, pseudo-color coloring and image segmentation on image data with poor imaging effect, such as image data with weak signal, blurred edges and low signal-to-noise ratio.

[0263] The data transmission module 15 includes a WIFI module, a Bluetooth module or a GSM module, and is used to transmit the processed projection microscopic images of the cell culture process acquired by the chip to the image analysis and display module 16 and the data storage module 17.

[0264] The image analysis and display module 16 is used to receive the processed image data for further interactive analysis and to display the final imaging result. It can be a mobile phone, tablet computer, laptop computer, etc. The interactive analysis includes deleting, shrinking, enlarging, rotating, selecting specific areas, and labeling targets in the image.

[0265] The data storage module 17 is used to establish an image database to store image data after processing by the data acquisition and processing module 14 or the image data after processing by the image analysis and display module 16. The data storage module 17 includes a database, which can be stored locally or on a cloud server. The data storage module 17 saves the data processed by the data acquisition and processing module 14 or the data after processing by the image analysis and display module 16 into the local database or uploads it to the cloud server via the network. It can also search, query, add, delete, modify, and back up the image data in the database.

[0266] The process of monitoring the culture of adherent cells using the device of the present embodiment is briefly described as follows:

[0267] (1) The culture container 1 and the top cover 6 are sterilized, and the sterilization method can be ultraviolet light irradiation for 10 min or immersion in a 75% alcohol solution for 15 min.

[0268] (2) 2 ml of culture medium (DMEM + 10% FBS) is added to the culture tank 8 of the culture container 1, 10 μL of HCT116 cell suspension with good growth conditions is added to the culture medium, and the top cover 6 is covered.

[0269] (3) The culture container 1 is connected to the external control system, the culture device switch is turned on, and the entire culture device is placed in the incubator.

[0270] (4) The external tablet computer can be connected and communicated with the entire culture device through the WIFI module, and the time interval for collecting image data by the device can be set through the tablet computer. The global observation image data collected is viewed to understand the growth status of the cells at the current time.

[0271] Example Four;

[0272] A novel adherent cell culture device, as shown in Figure 3 , comprises a rectangular culture container 1 for culturing adherent cells and an imaging chip 2 for image acquisition. The top surface of the culture container 1 is open, and the culture container 1 includes a plurality of culture tanks 8. Each culture tank 8 is provided with a visualization hole 3 corresponding to the central axis of the bottom surface of the culture container 1. Each visualization hole 3 is provided with an imaging chip 2 in the center. The shapes of the visualization hole 3 and the culture tank 8 are both circular. The imaging chip 2 is packaged in a tube shell 4. The back surface of the tube shell 4 is provided with electrodes after packaging of the imaging chip 2, which are used for input and output between the imaging chip 2 and the external control system. The upper surface of the tube shell 4 is adhesively bonded to the lower surface of the culture container 1 without gap.

[0273] The tube shell 4 with the imaging chip 2 packaged by the PLCC method is welded to the PCB circuit board 5, and the welding area is wrapped with ultraviolet glue to isolate the solder pad from the surrounding environment. Then, the PCB circuit board 5 is connected to the external control system. The connection between the PCB circuit board 5 and the external control system can be achieved by wire, gold finger connector, etc. In this embodiment, the gold finger connector is used.

[0274] The culture container 1 has a top cover 6 on its open top surface. The inner sidewall of the top cover 6 has several protrusions 7 evenly distributed. The top cover 6 is detachably fitted to the culture container 1 through the protrusions 7.

[0275] Both the culture container 1 and the top cover 6 are completely transparent and are integrally injection molded from polystyrene (PS).

[0276] The structure of the imaging chip 2 detector array 10 is as follows: Figure 12 As shown, the detector array 10 is composed of a large number of identical individual detector units 11, and the structure of the individual detector unit 11 can be as follows: Figure 13 The CMOS image sensor shown can also be as follows: Figure 14 The semi-floating gate transistor shown can also be as follows: Figure 15 The composite dielectric grating photodetector shown can also be as follows: Figure 16 , Figure 17 , Figure 18 , Figure 19 The dual-device photosensitive detection unit based on a composite dielectric grating shown can also be as follows: Figure 20 The split-gate MOSFET imaging detector shown. The detector array 10 used in the imaging chip 2 of this embodiment is as follows... Figure 16 The composite dielectric grating photosensitive detector shown has a single detector unit 11 of the imaging chip 2 with a size of 0.5 μm and a detector array size of 250 million, which is used to ensure a large field of view and high resolution when imaging liquid-based cell samples.

[0277] like Figure 7 As shown, the external control system 9 includes a control module 12, a light source module 13, a data acquisition and processing module 14, a data transmission module 15, an image analysis and display module 16, and a data storage module 17. The control module 12 is connected to the light source module 13 and the data acquisition and processing module 14 respectively. The data acquisition and processing module 14 is also connected to the data transmission module 15. The data transmission module 15 includes at least one of a WIFI module, a Bluetooth module, or a GSM module, and is connected to both the image analysis and display module 16 and the data storage module 17. The image analysis and display module 16 is connected to the data storage module 17.

[0278] The control module 12 can be selected from an FPGA, which is used for controlling the imaging chip to work and controlling the opening and closing of the light source module (illumination lamp) during imaging. After the data acquisition and processing module 14 receives the microscopic images collected by the imaging chip 2, the noise in the projection microscopic images is removed and suppressed through relevant image processing algorithms, and the image data with poor imaging effect, such as weak signal, blurred edge, and low signal-to-noise ratio, is processed through image enhancement, pseudo-color coloring, and image segmentation.

[0279] The data transmission module 15 includes a WIFI module, a Bluetooth module, or a GSM module, which is used for transmitting the processed projection microscopic images collected by the chip during the cell culture process to the image analysis and display module 16 and the data storage module 17.

[0280] The image analysis and display module 16 is used for receiving the processed image data for interactive analysis and displaying the final imaging results. The image analysis and display module 16 can be a mobile phone, a tablet computer, a notebook computer, or the like. The interactive analysis includes deleting, reducing, enlarging, rotating, selecting a specific area, and labeling a target.

[0281] The data storage module 17 is used for establishing an image database to store the image data after the data acquisition and processing module 14 or the image data after the image analysis and display module 16. The data storage module 17 includes a database, which can be stored locally or in a cloud server. The data storage module 17 saves the data processed by the data acquisition and processing module 14 or the data after the image analysis and display module 16 into a local database or uploads the data to a cloud server through a network, and can search, add or delete, modify, and back up the image data in the database.

[0282] The process of monitoring the culture of adherent cells by using the device of the present embodiment is described as follows:

[0283] (1) The culture container 1 and the top cover 6 are sterilized. The sterilization method can be ultraviolet irradiation for 10 min or immersion in a 75% alcohol solution for 15 min.

[0284] (2) 2 ml of culture medium (DMEM+10% FBS) is added to the culture groove 8 of the culture container 1, 10 μL of HCT116 cell suspension with good growth is taken and added to the culture medium, and the top cover 6 is covered.

[0285] (3) The culture container 1 is connected to the external control system, the culture device switch is turned on, and the entire culture device is placed in a culture box.

[0286] (4)External tablet can be connected and communicated with the whole culture device through WIFI module, and the time interval of image data acquisition of the device is set through the tablet, and the global observation image data collected is viewed to understand the growth status of the cells at the current time.

[0287] Example five;

[0288] A novel adherent cell culture device, as shown in the figure, comprises six circular culture containers 1 for culturing adherent cells and imaging chips 2 for image acquisition, the top surface of the culture container 1 is open, and each culture container 1 comprises a culture groove 8, each culture groove 8 is provided with an imaging hole 3 with the same central axis as the culture container 1, and each imaging hole 3 is provided with an imaging chip 2 in the center, the shapes of the imaging hole 3 and the culture groove 8 are circular, the imaging chip 2 is packaged in a tube shell 4, the side of the tube shell 4 is provided with an electrode after the imaging chip 2 is packaged, which is used for input and output between the imaging chip 2 and the external control system, the upper surface of the tube shell 4 is bonded to the lower surface of the culture container 1 without gap by adhesive,

[0289] The tube shell 4 with the imaging chip 2 packaged by the PLCC method is welded to the PCB circuit board 5, and the welding place is wrapped with ultraviolet glue to isolate the pad from the surrounding environment, then the PCB circuit board 5 is connected to the external control system, and the connection mode between the PCB circuit board 5 and the external control system can be selected from the wire, the gold finger connector and other modes, and the wire mode is adopted in this embodiment.

[0290] The top surface of the culture container 1 is provided with a top cover 6, the inner side wall of the top cover 6 is uniformly distributed with a plurality of protrusions 7, and the top cover 6 is detachably matched with the culture container 1 through the protrusions 7.

[0291] The culture container 1 and the top cover 6 are completely transparent and are integrally formed by organic glass.

[0292] The structure of the detector array 10 of the imaging chip 2 is as shown in the figure, the detector array 10 is composed of a large number of same single detector units 11, the structure of the single detector unit 11 can be a CMOS image sensor as shown in the figure, a half-floating gate transistor as shown in the figure, a composite dielectric gate photosensitive detector as shown in the figure, a double-device photosensitive detection unit based on composite dielectric gate as shown in the figure, or a composite dielectric gate as shown in the figure. Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 ​​​​​​​​​Figure 20 The split-gate MOSFET imaging detector is shown. The imaging chip 2 of the present embodiment adopts a detector array 10 as shown Figure 14 The composite medium gate photosensitive detector is shown. The size of a single detector unit 11 of the imaging chip 2 is equal to 1 μm, and the scale of the detector array is equal to 100 million, so as to ensure a large field of view and high resolution in microscopic imaging of a liquid-based cell sample.

[0293] As shown in Figure 7 The external control system 9 includes a control module 12, a light source module 13, a data acquisition and processing module 14, a data transmission module 15, an image analysis and display module 16, and a data storage module 17. The control module 12 is connected to the light source module 13 and the data acquisition and processing module 14. The data acquisition and processing module 14 is also connected to the data transmission module 15. The data transmission module 15 includes at least one of a WIFI module, a Bluetooth module, or a GSM module, and is connected to the image analysis and display module 16 and the data storage module 17. The image analysis and display module 16 is connected to the data storage module 17.

[0294] The control module 12 can be an FPGA, which is used to control the operation of the imaging chip and the opening and closing of the light source module (illumination lamp) during imaging. After the data acquisition and processing module 14 receives the microscopic images collected by the imaging chip 2, it removes and suppresses the noise in the projected microscopic images through relevant image processing algorithms, and performs image enhancement, pseudo-color coloring, and image segmentation on image data with poor imaging effects, such as weak signals, blurred edges, and low signal-to-noise ratio.

[0295] The data transmission module 15 includes a WIFI module, a Bluetooth module, or a GSM module, which is used to transmit the processed projected microscopic images collected by the chip during the cell culture process to the image analysis and display module 16 and the data storage module 17.

[0296] The image analysis and display module 16 is used to receive the processed image data for further interactive analysis and display of the final imaging results. It can be a mobile phone, a tablet computer, a notebook computer, etc. The interactive analysis includes deleting, reducing, enlarging, rotating, selecting a specific area, and labeling a target of the image.

[0297] The data storage module 17 is used to establish an image database, and store image data after the data acquisition and processing module 14 or image data after the image analysis and display module 16. The data storage module 17 comprises a database, which can be stored locally or stored in a cloud server; the data storage module 17 saves the data after the data acquisition and processing module 14 or the data after the image analysis and display module 16 into the local database or uploads to the cloud server through the network, and can search, add or delete, modify and backup the image data in the database.

[0298] The process of monitoring the adherent cell culture by using the device of the embodiment is described as follows:

[0299] (1) The culture container 1 and the top cover 6 are sterilized, and the sterilization method can be ultraviolet irradiation for 10 min or immersion in a 75% alcohol solution for 15 min;

[0300] (2) 2 ml of culture medium (DMEM+10% FBS) is added to the culture groove 8 of the culture container 1, 10 μL of HCT116 cell suspension with good growth condition is taken and added to the culture medium, and the top cover 6 is covered;

[0301] (3) The culture container 1 is connected to the external control system, the culture device switch is turned on, and the whole culture device is placed in the incubator;

[0302] (4) The external tablet computer can be connected and communicated with the whole culture device through the WIFI module, and the image data collection time interval of the device is set through the tablet computer, and the global observation image data collected is viewed to understand the growth condition of the cells at the current time.

[0303] The above only describes the preferred embodiments of the present application, and does not limit the implementation and protection scope of the present application. For those skilled in the art, it should be realized that any equivalent replacement and obvious change made according to the content of the present application should be included in the protection scope of the present application.

Claims

1. A novel adherent cell culture device, characterized by, The application relates to a cell culture device. The device comprises: a PCB circuit board; an image acquisition device arranged on the upper surface of the PCB circuit board, the image acquisition device being connected to a controller; a cell culture container for providing a container for adherent cells, the cell culture container being arranged above the image acquisition device, and the bottom of the side wall of the cell culture container being attached to the upper surface of the image acquisition device, and the bottom of the cell culture container being provided with an opening for exposing the image acquisition device; the image acquisition device acquires images of the adherent cells through the opening, and outputs the acquired images to the controller; the controller processes the images to obtain growth data of the adherent cells, and transmits the growth data to an external display terminal; the image acquisition device comprises an image acquisition chip; the image acquisition chip comprises: a cell adhesion judgment unit for judging whether cells in the cell culture container adhere to the upper surface of the image acquisition chip; an image acquisition unit connected to the cell adhesion judgment unit, the image acquisition unit directly recording a projection microscopic image of the adherent cells after the cells adhere to the upper surface of the image acquisition chip; the image acquisition chip is packaged in a packaging tube, the electrodes of the packaged image acquisition chip are arranged on the back and / or side of the packaging tube, the packaging tube with the image acquisition chip is welded on the upper surface of the PCB circuit board, the middle of the upper surface of the packaging tube is exposed to the image acquisition chip, and the image acquisition chip is surrounded by the bottom of the side wall of the cell culture container; 2. The novel adherent cell culture device of claim 1, wherein, a groove for placing the packaging tube is arranged on the PCB circuit board, so that the upper surface of the packaging tube is flush with the upper surface of the PCB circuit board.

3. The novel adherent cell culture device of claim 1, wherein, UV glue is arranged at the joint of the image acquisition chip and the packaging tube.

4. The novel adherent cell culture device of claim 1, wherein, The image acquisition chip protrudes from the packaging tube.

5. The novel adherent cell culture device of claim 4, wherein, The image acquisition chip comprises a detector array composed of a plurality of detector units.

6. The novel adherent cell culture device of claim 4, wherein, The detector array adopts any one of a CMOS image sensor array, a half-floating gate transistor array, a composite dielectric gate photosensitive detector array, a double-device photosensitive detector unit array based on a composite dielectric gate, and a split-gate MOSFET imaging detector array.

7. The novel adherent cell culture device as claimed in claim 1, wherein, The size of the detector unit is less than or equal to 1 micrometer, and the number of the detector units in the detector array is greater than or equal to 100 million.

8. The novel adherent cell culture device of claim 7, wherein, The cell culture container comprises a cell culture tank and a top cover matched with the cell culture tank, the upper surface of the cell culture tank is provided with a top opening, the cell culture tank covers the top opening through the top cover, and the cell culture tank and the top cover are detachably arranged.

9. The novel adherent cell culture device of claim 7, wherein, The top cover is provided with a cover eave, an inner thread is arranged on the inner side wall of the cover eave, an outer thread matched with the inner thread is arranged on the outer side wall of the cell culture tank, and the top cover and the cell culture tank are detachably arranged through the inner thread and the outer thread. The top cover is provided with a cover eave, a protrusion is arranged on the inner side wall of the cover eave, and a gap is maintained between the top cover and the side wall of the cell culture tank through the protrusion.

10. The novel adherent cell culture device as claimed in claim 1, wherein, The shape of the cell culture container includes any one of a cylinder, a cuboid and a round-cornered cuboid.

11. The novel adherent cell culture device as claimed in claim 1, wherein, The shape of the cell culture container includes any one of a cylinder, a cuboid and a round-cornered cuboid.

12. The novel adherent cell culture device of claim 1, wherein, The shape of the opening includes any one of an ellipse, a circle, a rectangle or a round-cornered parallelogram.

13. The novel adherent cell culture device as claimed in claim 1, wherein, The shape of the cell culture container includes at least one of a culture dish shape and a culture bottle shape.

14. The novel adherent cell culture device as claimed in claim 1, wherein, The number of the cell culture containers is at least one, each of the cell culture containers corresponds to one of the image acquisition devices, and each of the cell culture containers is placed above the corresponding image acquisition device.

15. The novel adherent cell culture device of claim 14, wherein, The plurality of cell culture containers are arranged side by side, and the image acquisition devices corresponding to each of the cell culture containers are arranged side by side on the upper surface of the PCB circuit board, and each of the image acquisition devices is connected to the controller.

16. The novel adherent cell culture device of claim 14, wherein, When the plurality of cell culture containers are included, all the cell culture containers include a top cover, and the top cover covers all the cell culture containers.

17. The novel adherent cell culture device as claimed in claim 1, wherein, When the cell culture container is placed above the image acquisition device, the center of the opening is close to the center of the image acquisition device.

18. The novel adherent cell culture device as claimed in claim 1, wherein, The cell culture container is a transparent container made of glass or organic polymer.

19. The novel adherent cell culture device as claimed in claim 1, wherein, The controller outputs the growth data to the display terminal locally or remotely in a wired or wireless manner.

20. A novel adherent cell culture device, characterized by, The application relates to a cell culture device, which comprises at least one culture container (1) for culturing adherent cells and an imaging chip (2) for image acquisition, the top surface of the culture container (1) is open, and the bottom surface is provided with an imaging hole (3), the imaging chip (2) is located in the center of the imaging hole (3), the imaging chip (2) is packaged in a tube shell (4), the back surface or the side edge of the tube shell (4) is provided with an electrode after the imaging chip (2) is packaged, which is used for input and output between the imaging chip (2) and an external control system (9), and the upper surface of the tube shell (4) is attached to the lower surface of the culture container (1). The tube shell (4) packaged with the imaging chip (2) is welded to a PCB circuit board (5), and the PCB circuit board (5) is connected to the external control system (9). The PCB circuit board is provided with a groove for placing the tube shell, so that the upper surface of the tube shell is flush with the upper surface of the PCB circuit board.

21. A novel adherent cell culture device as claimed in claim 20, wherein, The culture container (1) comprises at least one culture groove (8), each culture groove (8) is provided with an imaging hole (3) with the same central axis on the bottom surface of the corresponding culture container (1), and each imaging hole (3) is provided with one imaging chip (2) in the center.

22. A novel adherent cell culture device as claimed in claim 21, wherein, The top surface of the culture container (1) is provided with a top cover (6), the inner side wall of the top cover (6) is uniformly distributed with a plurality of protrusions (7), and the top cover (6) is detachably matched with the side wall of the culture container (1) through the protrusions (7).

23. A novel adherent cell culture device as claimed in any one of claims 20 to 22, wherein, The detector array of the imaging chip (2) is one of CMOS image sensor array, semi-floating gate transistor array, composite dielectric gate photosensitive detector array, composite dielectric gate based dual-device photosensitive detector unit array or split-gate MOSFET imaging detector array.

24. A novel adherent cell culture device as claimed in claim 23, wherein, The single detector unit size of the imaging chip (2) is less than or equal to 1 micrometer, and the detector array scale is greater than or equal to 10 million.

25. A novel adherent cell culture device as claimed in claim 20, wherein, The shapes of the imaging hole (3) and the culture groove (8) are respectively selected from one of oval, circle, rectangle or round-cornered parallelogram.

26. A novel adherent cell culture device as claimed in claim 20, wherein, The culture container (1) and the top cover (6) are both completely transparent, and are both made of glass or organic polymer.

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