Cell culture detection equipment

Abstract

The embodiment of the utility model discloses cell culture detection equipment. The equipment comprises a control device, a base, and a pipetting device, a culture area, a functional area and a reagent area which are arranged on the base. The control device is electrically connected with the pipetting device; the culture area extends along a first direction, a culture plate is arranged in the culture area, and the culture plate is provided with a plurality of culture cavities for cell culture and / or chemical analysis; the reagent area and the culture area are adjacently arranged, the reagent area, the functional area and the culture area are adjacently arranged in the second direction, the second direction is perpendicular to the first direction, and the reagent area is used for containing a container for containing reagents. The cell culture detection equipment has the advantages of high automation degree and small size. Complex operation is integrated into the cell culture and detection equipment, meanwhile, operation which is long in occupied time and low in intelligent requirement is removed, the processing efficiency of the cell culture and detection equipment can be improved, and industrial production of cells or organoids is met.

Description

[0001] This application claims the priority of the prior application with application date of 2023-07-26, application number 2023219826662, and application name “Cell Culture Detection Equipment”, and introduces all the contents of the prior application into this application. Technical Field

[0002] The present application relates to the field of cell technology, and in particular to a cell culture detection device. Background Art

[0003] With the development of life sciences, in order to better overcome various diseases, we can no longer be satisfied with animal models. Replicating and reconstructing human organs has become one of the directions that scientists are trying to develop, and the culture technology of cells and organoids has become a top priority. The culture of cells and organoids is one of the most commonly used methods in biological and medical research. The cultured in vitro three-dimensional models such as organoids can be used in drug screening and precision medicine. The cultured cell types can include: epithelial cells, endothelial cells, fibroblasts, keratinocytes, melanocytes, neurons, astrocytes, hepatocytes, skeletal muscle cells, smooth muscle cells, osteoblasts, myocytes, chondrocytes, adipocytes, synovial cells, hair cells, blood cells, stem cells, etc. In the process of cell and organoid culture, for the purpose of sampling, proportioning, etc., it is often necessary to take out a small amount of liquid from a certain reagent and mix the taken out reagent with another reagent.

[0004] In the related art, liquids are pipetted by manual operation or liquid handling workstations. Manual operation often results in operator errors that seriously affect the credibility of sample preparation. Moreover, during the long sample preparation process, the operator's physical health will also be affected. For liquid handling, its main function is to perform operations such as liquid movement, separation, and drug screening in the fields of biochemistry, medicine, and pharmacy. In the experiment, the pipetting workstation can make the experimental operation more standardized by storing preset programs, automatically adjusting the aspiration depth, and minimizing capacity errors. However, the pipetting workstation has a single function and cannot implement the complex culture operation steps of complex in vitro organ models (such as organoid models). Moreover, the pipetting workstation is generally large in size and high in cost, and cannot meet the requirements of factors such as mobility and environmental changes when establishing and culturing in vitro organ models. Utility Model Content

[0005] The present application provides a cell culture detection device that can automatically complete the culture of cells and organoids, has high operating precision, can improve work efficiency and accuracy, reduce labor costs, and is smaller in size and can be placed in a clean bench for easy transfer, which is more convenient for experiments that require changing the culture environment.

[0006] The present application embodiment provides a cell culture detection device, the cell culture detection device comprising:

[0007] Base;

[0008] A liquid transfer device, disposed on the base;

[0009] A control device, electrically connected to the pipetting device;

[0010] A culture area is arranged on the base, the culture area extends along at least a first direction, a culture plate is arranged in the culture area, and the culture plate has a plurality of culture chambers for cell culture and / or chemical analysis;

[0011] A functional area is disposed on the base; and

[0012] The reagent area is arranged on the base. The reagent area, the functional area and the culture area are arranged adjacent to each other along a second direction. The second direction is perpendicular to the first direction. The reagent area is used to place a container containing reagents.

[0013] In some embodiments, it also includes:

[0014] A gun tip area is arranged on the base, a gun tip box for placing gun tips is arranged in the gun tip area, and the reagent area, the culture area and the gun tip area are arranged adjacent to each other along the second direction, and the gun tip area and the functional area are arranged along the first direction;

[0015] Wherein, controlled by the control device, the pipetting device can cooperate with the gun head to absorb the reagent in the container in the reagent area and transfer the reagent to the culture chamber.

[0016] In some embodiments, the functional area serves as another culture area, and in this case, the whole formed by the culture area and the another culture area also extends along the second direction; or

[0017] The functional area serves as another gun head area, and in this case, the entirety of the gun head area and the another gun head area extends along the first direction; or

[0018] The functional area is used as a dilution area and is arranged on the base. A dilution plate is arranged in the dilution area. The dilution plate has a plurality of dilution chambers for diluting reagents. The dilution area and the gun tip area are arranged adjacent to each other along the first direction. The reagent area, the culture area and the dilution area are arranged adjacent to each other along the second direction.

[0019] The liquid transfer device can cooperate with the gun tip in the gun tip area to absorb the reagent in the container in the reagent area and transfer the reagent to the dilution chamber for dilution.

[0020] In some embodiments, the tip area, the culture area, and the dilution area together form a rectangular area.

[0021] In some embodiments, it also includes:

[0022] A display area is arranged on the base, a display screen is arranged in the display area, and the display area, the reagent area, the culture area and the gun tip area are adjacently arranged along the second direction.

[0023] In some embodiments, it also includes:

[0024] A code scanning area is arranged on the base, a code scanner is arranged in the code scanning area, the display area and the code scanning area are arranged adjacent to each other along the first direction, and the code scanning area, the reagent area, the culture area and the dilution area are arranged adjacent to each other along the second direction.

[0025] In some embodiments, it also includes:

[0026] A waste liquid area is arranged on the base, a waste liquid box for collecting waste liquid is arranged in the waste liquid area, and the waste liquid area and the reagent area are adjacently arranged along the first direction;

[0027] Wherein, the pipetting device can be moved to the waste liquid area to release the waste liquid in the gun tip into the waste liquid box.

[0028] In some embodiments, it also includes:

[0029] A waste area is arranged on the base, wherein a waste box for collecting discarded gun tips is arranged in the waste area, the waste area and the culture area are arranged adjacent to each other along the first direction, and the waste area and the waste liquid area are arranged adjacent to each other along the second direction;

[0030] Wherein, the pipetting device can be moved to the waste area to release the discarded gun tips into the waste box.

[0031] In some embodiments, it also includes:

[0032] A position correction zone is arranged on the base, and a corrector for correcting the position of the pipetting device is arranged in the position correction zone. The position correction zone and the gun tip zone are arranged adjacent to each other along the first direction, and the waste liquid zone, the waste material zone and the position correction zone are arranged adjacent to each other along the second direction.

[0033] In some embodiments, the reagent zone comprises:

[0034] A refrigeration zone is arranged on the base, wherein a refrigeration device for refrigerating the reagent in the container is arranged in the refrigeration zone;

[0035] A heating zone is arranged on the base, wherein a heating device for heating the reagent in the container is arranged in the heating zone, and the heating zone and the cooling zone are arranged adjacent to each other along the first direction.

[0036] In some embodiments, it also includes:

[0037] a tilting drive device, disposed in the culture area, for supporting the culture plate and for driving one side of the culture plate to tilt up so that the liquid in the culture chamber gathers at a lower position; and / or

[0038] The anti-leakage device is directly or indirectly arranged on the pipetting device and can move with the pipetting device. After the pipetting device absorbs the liquid, the anti-leakage device can move to the bottom of the pipetting device to receive the liquid dripped by the pipetting device.

[0039] In some embodiments, the cell culture detection device has a third direction perpendicular to both the first direction and the second direction; the pipetting device further comprises:

[0040] A three-dimensional driving component is arranged on the base, and the pipetting device is arranged on the three-dimensional driving component. The three-dimensional driving component is used to drive the pipetting device to move in the first direction, the second direction and the third direction, so that the pipetting device moves at least between the reagent area and the culture area.

[0041] The cell culture detection device provided in this application has at least the following two technical effects:

[0042] First, the degree of automation is high: the pipetting device can automatically move to the gun tip area, cooperate with the gun tip of the required specifications in the gun tip box, and automatically move to the reagent area to absorb the reagent in the container, and then transfer the reagent to the culture chamber in the culture area to achieve cell culture. The entire process does not require manual operation. The required amount of reagent can be accurately absorbed through the pipetting device. The sample preparation after preparation has high consistency. The entire process is highly streamlined and standardized, and the credibility is also higher. It can also effectively ensure the health of the experimenters;

[0043] Second, the cell culture detection equipment is small in size: by dividing the reagent area and the culture area on the base, the reagent area and the culture area are arranged along the second direction, so that the container in the reagent area and the gun tip in the gun tip area and the culture plate in the culture area are all at a closer distance, making the container and the culture plate more compact in the second direction, which can not only shorten the stroke of the pipetting device and save energy, but also reduce the size of the cell culture detection equipment in the second direction.

[0044] Furthermore, since the culture area is longer and extends along the first direction instead of the second direction, the dimensions of the cell culture detection device in the first direction and the second direction are closer, and the cell culture detection device as a whole is more square. If the culture area extends along the second direction, and the reagent area and the culture area are arranged along the second direction, the dimension of the cell culture detection device in the second direction (i.e., the width) will be very large, and the entire cell culture detection device will be elongated, which is not conducive to reducing the volume of the cell culture detection device, nor is it conducive to transporting, handling, and packaging the cell culture detection device. In addition, the cell culture detection device can improve the processing efficiency of the cell culture detection device by integrating complex operations into the cell culture detection device and eliminating operations that take a long time and have low intelligence requirements, so as to meet the industrial production of cells or organoids. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings in the following description are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0046] Figure 1 is a schematic diagram of a top view of a cell culture detection device in an embodiment of the present application;

[0047] Figure 2 It is a three-dimensional structural schematic diagram of a cell culture detection device in one embodiment of the present application.

[0048] Explanation of the reference numerals: 100 - cell culture detection equipment; 10 - base; 11 - foot; 20 - pipetting assembly; 21 - pipetting pump; 22 - X-axis drive assembly; 23 - Y-axis drive assembly; 24 - Z-axis drive assembly; 30 - gun tip area; 31 - gun tip; 32 - gun tip box; 40 - culture area; 41 - culture plate; 41a - culture chamber; 50 - reagent area; 51 - refrigeration area; 511 - refrigeration device; 52 - heating area; 521 - heating device; 60 - dilution area; 61 - dilution plate; 61a - dilution chamber; 70 - display area; 71 - display screen; 80 - code scanning area; 81 - code scanner; 90 - waste liquid area; 91 - waste liquid box; 110 - waste area; 111 - waste box; 120 - position correction area; 121 - corrector. DETAILED DESCRIPTION

[0049] In order to make the objectives, technical solutions and advantages of the present application clearer, the following part will further describe the embodiments of the present application in detail in conjunction with the accompanying drawings.

[0050] When the following description refers to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Instead, they are only examples of devices and methods consistent with some aspects of the present application as detailed in the attached claims.

[0051] In the description of the present application, it should be understood that the terms "first", "second", etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to the specific circumstances. In addition, in the description of the present application, unless otherwise specified, "multiple" refers to two or more. "And / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. The character " / " generally indicates that the objects associated before and after are in an "or" relationship.

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used in this specification are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0053] See also Figure 1-2In a first aspect, an embodiment of the present application provides a cell culture detection device 100, wherein a culture chamber 41a is used for cell (including primary culture and subculture, etc.) or organoid culture, or for chemical analysis, wherein the chemical analysis includes drug sensitivity testing, drug screening, toxicity testing, staining testing, drug sensitivity culture, etc. The cell culture detection device 100 includes a control device, a base 10, a pipetting device 20, a gun tip area 30, a culture area 40, and a reagent area 50.

[0054] The base 10 is used to carry the pipetting device 20 and various devices in the gun tip area 30, the culture area 40 and the reagent area 50. The shape, size and material of the base 10 are not limited in this embodiment. Exemplarily, the bottom of the base 10 is provided with a foot 11 for carrying the base 10 to raise the base 10 to a certain height. The foot 11 can be made of elastic material to better place the base 10 stably; the foot 11 can also be connected to the base 10 in a threaded manner, so as to adjust the screw connection depth of the foot 11 and the base 10 through the thread, so as to adjust the support height of the foot 11 at various positions of the base 10 to the base 10, so that the base 10 can be placed more stably on the operating table.

[0055] The pipetting device 20 is arranged on the base 10 and is electrically connected to the control device. The pipetting device 20 can be a pipetting pump 21, an air pump or a piezoelectric drive device, etc. The following description takes the pipetting device as a pipetting pump 21. The pipetting pump 21 is a device for transferring liquid from one container to another container so as to transfer the liquid more efficiently and accurately. The pipetting pump 21 can be moved to the top of the gun head area 30 and cooperate with the gun head 31 in the gun head area 30 to realize the pipetting operation. It should be noted that the pipetting pump 21 can be a pneumatic pipetting pump 21 or an electric pipetting pump 21. The gun head 31 cooperating with the pipetting pump 21 can be disposable (discarded after one use) or reusable.

[0056] The gun tip area 30 is arranged on the base 10, specifically, it can be arranged on the upper surface of the base 10, and a gun tip box 32 for placing gun tips 31 is arranged in the gun tip area 30, and the gun tip box 32 is used to neatly place one or more gun tips 31, and the gun tips 31 are used to cooperate with the pipetting pump 21 to realize the pipetting operation. The gun tip box 32 can store large-sized (large-size) gun tips 31 and small-sized (small-size) gun tips 31 at the same time. For example, the gun tips 31 can include gun tips 31 of various specifications such as 10μL, 10μL extended, 20μL, 50μL, 100μL, 200μL, 300μL, 500μL, 1000μL, 1250μL, etc.

[0057] The culture area 40 is disposed on the base 10, and specifically can be disposed on the upper surface of the base 10. The culture area 40 is rectangular, and the culture area 40 extends at least along the first direction A, that is, the length direction of the culture area 40 is parallel to the first direction A. Exemplarily, the first direction A can be the length direction of the cell culture detection device 100. In other embodiments, the first direction A can also be the length direction of the cell culture detection device 100. The following description is made by taking the first direction A as the length direction of the cell culture detection device 100 as an example.

[0058] One or more culture plates 41 are arranged in the culture area 40, and the multiple culture plates 41 can be arranged along the first direction A. Each culture plate 41 has multiple culture chambers 41a, and the culture chambers 41a are used for cell or organoid culture, or for drug sensitivity testing, drug sensitivity culture, etc. This embodiment does not limit the specific function of the culture chambers 41a. Exemplarily, the culture chambers 41a can be arranged in an array.

[0059] In some embodiments, the cell culture detection device 100 further includes a tilting drive device, which is disposed in the culture area 40, for supporting the culture plate 41, and for driving one side of the culture plate 41 to tilt up, so that the liquid in the culture chamber 41a gathers at a lower position, so that the pipette pump 21 can absorb the liquid in the culture chamber 41a more cleanly and thoroughly. Exemplarily, the tilting drive device may include a motor, an eccentric wheel, and a lifting rod, wherein the motor is connected to one end of the lifting rod through the eccentric wheel, and the other end of the lifting rod is connected to one side of the culture plate 41, thereby driving one side of the culture plate to tilt up through the lifting rod.

[0060] The reagent area 50 is arranged on the base 10, and can be specifically arranged on the upper surface of the base 10. The reagent area 50 is used to place a container (not shown in the figure) containing a reagent. It should be noted that the container can also be replaced by a reagent bottle (not shown in the figure), or a container and a reagent bottle can be placed in the reagent area 50 at the same time. The reagent area 50 is arranged adjacent to the culture area 40, so that the container in the reagent area 50 and the culture plate 41 in the culture area 40 have a small distance. The reagent area 50, the culture area 40 and the gun tip area 30 are arranged adjacent to each other along the second direction B, and the positions of the three can be arbitrarily exchanged. For example, the reagent area 50, the culture area 40 and the gun tip area 30 are arranged adjacent to each other in sequence along the second direction B, that is, the culture area 40 is located between the gun tip area 30 and the reagent area 50, so that the culture plate 41 of the culture area 40 and the gun tip 31 of the gun tip area 30 and the container in the reagent area 50 are all at a close distance, so that the container, the culture plate 41 and the gun tip box 32 are more compact in the second direction B, and the size of the cell culture detection device 100 in the second direction B can be reduced. For example, the container can be a test tube or a reagent bottle.

[0061] The second direction B is perpendicular to the first direction A. When the first direction A is the length direction of the cell culture detection device 100, the second direction B may be the width direction of the cell culture detection device 100. The following description will take the example that the second direction B may be the width direction of the cell culture detection device 100.

[0062] Based on the above structure, in a feasible pipetting process, the pipetting pump 21 first moves to the top of the gun tip area 30, and descends to the height of the gun tip 31 of the required specification, and plugs and matches with the gun tip 31 in the gun tip area 30. Then, the pipetting pump 21 drives the gun tip 31 to move to the reagent area 50, and descends to a certain height so as to be able to absorb the reagent in the container (or reagent bottle) in the reagent area 50. Afterwards, the pipetting pump 21 moves to the top of the culture area 40 with the gun tip 31 and the reagent in the gun tip 31, and descends to a certain height to the top of the required culture chamber 41a, releases the reagent in the culture chamber 41a, and completes the pipetting process of the reagent in the container to the culture chamber 41a.

[0063] In some embodiments, the gun tip area 30 and the gun tip box 32 of the gun tip area 30 can be removed, and the pipetting device 20 can obtain the gun tip 31 from the outside of the cell culture detection equipment 100 to perform the pipetting operation.

[0064] In summary, the cell culture detection device 100 of this embodiment has at least the following two technical effects:

[0065] First, the degree of automation is high: the pipette pump 21 can automatically move to the gun tip area 30, cooperate with the gun tip 31 of the required specifications in the gun tip box 32, and automatically move to the reagent area 50 to absorb the reagent in the container, and then transfer the reagent to the culture chamber 41a of the culture area 40 to achieve cell culture. The whole process does not require manual operation. The required amount of reagent can be accurately absorbed by the pipette pump 21. The sample preparation after preparation has high consistency. The whole process is highly streamlined and standardized, and the credibility is also higher. And it can effectively ensure the health of the experimenters;

[0066] Second, the cell culture detection device 100 is small in size: by dividing the reagent area 50, the culture area 40 and the gun tip area 30 on the base 10, the reagent area 50, the culture area 40 and the gun tip area 30 are arranged along the second direction B, so that the container in the reagent area 50 and the gun tip 31 in the gun tip area 30 and the culture plate 41 in the culture area 40 are all at a close distance, so that the container, the culture plate 41 and the gun tip box 32 are more compact in the second direction B, which can not only shorten the stroke of the pipette pump 21 and save energy, but also reduce the size of the cell culture detection device 100 in the second direction B. Furthermore, since the culture area 40 is longer, the culture area 40 extends along the first direction A instead of the second direction B, so that the dimensions of the cell culture detection device 100 in the first direction A and the second direction B are closer, and the cell culture detection device 100 is more square as a whole. If the culture area 40 extends along the second direction B, and the reagent area 50, the culture area 40 and the gun tip area 30 are arranged along the second direction B, the size (i.e., width) of the cell culture detection device 100 in the second direction B will be very large, and the entire cell culture detection device 100 will be slender, which is not conducive to reducing the volume of the cell culture detection device 100, nor is it conducive to transporting, carrying and packaging the cell culture detection device 100.

[0067] Please continue reading Figure 1-2 In some embodiments, the cell culture detection device 100 further includes a dilution area 60, which is disposed on the base 10, and specifically can be disposed on the upper surface of the base 10. A dilution plate 61 is disposed in the dilution area 60, and the dilution plate 61 has a plurality of dilution chambers 61a for diluting the reagent. It should be noted that the dilution plate 61 can have the same or different structure as the culture plate 41, and the dilution chamber 61a can also have the same or different structure as the culture chamber 41a. Exemplarily, the dilution chambers 61a can be arranged in an array.

[0068] Further, the reagent area 50, the culture area 40 and the dilution area 60 are arranged adjacent to each other along the second direction B, and the positions of the three can be arbitrarily exchanged. For example, the reagent area 50, the culture area 40 and the dilution area 60 are arranged adjacent to each other in sequence along the second direction B, that is, the culture area 40 is located between the dilution area 60 and the reagent area 50, so that the culture plate 41 of the culture area 40 and the containers in the dilution area 60 and the reagent area 50 are all at a relatively close distance, so that the containers, the culture plate 41 and the dilution plate 61 are more compact in the second direction B, and the size of the cell culture detection device 100 in the second direction B is reduced. Further, the dilution area 60 and the gun tip area 30 are arranged adjacent to each other along the first direction A, and the size of the cell culture detection device 100 in the second direction B can be shortened compared to extending the dilution area 60 and the gun tip area 30 along the second direction B. And compared to arranging the dilution area 60 and the culture area 40 along the first direction A, the size of the cell culture detection device 100 in the first direction A can be shortened.

[0069] Based on the above structure, in another feasible liquid transfer process, the liquid transfer pump 21 can cooperate with the gun tip 31 in the gun tip area 30 to absorb the reagent in the container in the reagent area 50, and transfer the reagent to the dilution chamber 61a for dilution. Specifically, the liquid transfer pump 21 first moves to the top of the gun tip area 30, and descends to the height of the gun tip 31 of the required specification, and plugs and cooperates with the gun tip 31 in the gun tip area 30. Then, the liquid transfer pump 21 drives the gun tip 31 to move to the reagent area 50, and descends to a certain height so as to be able to absorb the reagent in the container (or reagent bottle) in the reagent area 50. Afterwards, the pipette pump 21 moves with the gun tip 31 and the reagent in the gun tip 31 to the top of the dilution area 60, and descends a certain height to the top of the required dilution chamber 61a, and releases the reagent into the first dilution chamber 61a, mixes the reagent with another reagent already in the original dilution chamber 61a, takes out part of the liquid, and adds it to the next dilution chamber 61a, and so on, until the last dilution chamber 61a, completing the pipetting process of the reagent in the container to the dilution chamber 61a and the reagent dilution process.

[0070] It should be noted that the dilution zone 60 and the dilution plate 61 are not necessary, and the dilution of the reagent can also be completed through the culture plate 41 in the culture zone 40. By setting up an independent dilution zone 60, the culture zone 40 can be relatively independent, and there is a larger area for setting up the culture plate 41, so as to complete a larger batch of cell culture, thereby improving the culture efficiency. In addition, in some experiments, for example, during drug sensitivity culture, the culture plate 41 is used for cell culture. At this time, the culture plate 41 cannot dilute the reagent. Therefore, it is necessary to dilute the reagent through the dilution plate 61 and pipette the diluted reagent into the culture chamber 41a of the culture plate 41 for cell culture. The dilution plate 61 and the culture plate 41 work together to further improve the culture efficiency.

[0071] The dilution area 60 can be further expanded into a functional area. In addition to being the dilution area 60, the functional area can also be used as an area with other functions, such as:

[0072] In some feasible embodiments, the functional area is used as another culture area. At this time, the whole formed by the culture area 40 and the other culture area also extends along the second direction B. In this way, this embodiment can not only achieve the effect of reducing the size of the cell culture detection device 100 in the second direction B when the functional area is used as the dilution area 60, but also the two culture areas (that is, the culture area 40, and the dilution area 60 is used as another culture area) can make the cell culture detection device 100 have a larger culture area and improve the culture efficiency. It can be understood that the culture area 40 and the other culture area can be set as a whole or separately.

[0073] In other feasible embodiments, the functional area is used as another gun tip area. In this case, the gun tip area 30 and the other gun tip area constitute a whole extending along the first direction A. In this way, this embodiment can not only achieve the effect of improving the automation degree of the cell culture detection device 100 and reducing the volume of the cell culture detection device 100 when the functional area is used as the dilution area 60, but also the two gun tip areas (i.e., the gun tip area 30, and the dilution area 60 as another gun tip area) can make the cell culture detection device 100 have a larger gun tip placement area, which can place more numbers and more specifications of gun tips 31, and reduce the frequency of users placing gun tips 31 in the gun tip area 30. It can be understood that the gun tip area 30 and the other culture area can be set as a whole or separately.

[0074] In some embodiments, the gun tip area 30, the culture area 40 and the dilution area 60 together form a rectangular area. Specifically, the area of ​​the culture area 40 is larger than the area of ​​the gun tip area 30 and also larger than the area of ​​the dilution area 60. For example, the area of ​​the culture area 40 is the sum of the area of ​​the gun tip area 30 and the area of ​​the dilution area 60. Therefore, more culture chambers 41a can be provided to culture cells in large quantities, thereby improving the culture efficiency. More specifically, the culture area 40 itself is arranged in a rectangular shape and covers two corner positions of the rectangular area formed by the gun tip area 30, the culture area 40 and the dilution area 60. The gun tip area 30 and the dilution area 60 respectively cover the other two corner positions of the rectangular area formed by the gun tip area 30, the culture area 40 and the dilution area 60. In this way, the distance between the gun tip box 32 in the gun tip area 30, the culture plate 41 in the culture area 40 and the dilution plate 61 in the dilution area 60 is shortened, the stroke of the pipette pump 21 is shortened, and the cell culture detection equipment 100 can have a smaller size in both the first direction A and the second direction B, thereby reducing the overall volume of the cell culture detection equipment 100.

[0075] Furthermore, the gun tip area 30 , the culture area 40 , the reagent area 50 and the dilution area 60 also form a rectangular area together, which can further reduce the overall volume of the cell culture detection device 100 .

[0076] Please continue reading Figure 1 In some embodiments, the cell culture detection device 100 further includes a display area 70, which is disposed on the base 10, and specifically can be disposed on the upper surface of the base 10. A display screen 71 is disposed in the display area 70, and the display area 70, the reagent area 50, the culture area 40 and the gun tip area 30 are arranged adjacent to each other in sequence along the second direction B. It should be noted that the positions of the reagent area 50, the culture area 40 and the gun tip area 30 can be arbitrarily swapped. In this way, on the one hand, the display screen 71 in the display area 70 is located at the front side of the cell culture detection device 100, which is convenient for the experimenter to watch the display screen 71. On the other hand, the display area 70, the reagent area 50, the culture area 40 and the gun tip area 30 are arranged adjacent to each other along the second direction B, which can reduce the size of the cell culture detection device 100 in the second direction B.

[0077] Specifically, the display screen 71 is used to display information such as the experimental process and the number of experiments, so that the experimenter can monitor the experimental process. Optionally, the display screen 71 can be a touch screen 71, so that the experimenter can control the experimental process through the touch screen 71. Optionally, the display screen 71 is tilted upward relative to the horizontal plane, so that the experimenter can look down at the display screen 71, check the experimental information, and control the experimental process.

[0078] In some embodiments, the cell culture detection device 100 further includes a code scanning area 80, which is disposed on the base 10, and can be specifically disposed on the upper surface of the base 10. A code scanner 81 is disposed in the code scanning area 80, and the code scanner 81 can be a two-dimensional code scanner 81, a bar code scanner 81, etc. The display area 70 and the code scanning area 80 are arranged adjacent to each other along the first direction A, so that the size of the cell culture detection device 100 in the second direction B can be reduced. The code scanning area 80, the reagent area 50, the culture area 40, and the dilution area 60 are arranged adjacent to each other in sequence along the second direction B, and the positions of the reagent area 50, the culture area 40, and the dilution area 60 can be arbitrarily exchanged. In this way, on the one hand, the code scanner 81 in the code scanning area 80 is located on the front side of the cell culture detection equipment 100, and is roughly arranged side by side with the display screen 71 along the first direction A, which is convenient for experimenters to perform code scanning operations. On the other hand, the code scanning area 80, the reagent area 50, the culture area 40 and the dilution area 60 are arranged adjacent to each other along the second direction B, which can reduce the size of the cell culture detection equipment 100 in the second direction B.

[0079] Specifically, the barcode scanner 81 is used to identify consumables and reagents used in experiments such as samples and culture media, so as to record the experimental process. Alternatively, the barcode scanning area 80 can also be replaced by a key area, and the barcode scanner 81 can also be replaced by a key, and the experimenter can input the identification information of consumables and reagents through the key to record the experimental process.

[0080] In some embodiments, the reagent area 50 includes a refrigeration area 51 and a heating area 52. The refrigeration area 51 is disposed on the base 10, and a refrigeration device 511 is disposed in the refrigeration area 51 for refrigerating the reagent in the container. The refrigeration device 511 can adjust the temperature in the refrigeration area 51 between 2 and 8 degrees, thereby achieving the preservation of biological tissues and reagents, or some reagents, such as hydrogels, have temperature-sensitive properties and need to be kept in liquid state at low temperature during early preparation for later preparation.

[0081] The heating area 52 is disposed on the base 10, and a heating device 521 for heating the reagent in the container is disposed in the heating area 52. When performing primary culture and subculture, the heating device 521 can quickly heat the low-temperature reagent or culture medium, for example, the culture medium is heated to about 37 degrees, and then added to the gel containing cells to culture the cells. Compared with natural heating, the heating device 521 heats the reagent faster, which can improve the heating efficiency and the experimental process.

[0082] Furthermore, the heating zone 52 and the refrigeration zone 51 are arranged adjacent to each other along the first direction A, and the positions of the display zone 70, the heating zone 52, the culture zone 40 and the gun tip zone 30 along the second direction B can be arbitrarily exchanged. For example, the display zone 70, the heating zone 52, the culture zone 40 and the gun tip zone 30 are arranged adjacent to each other in sequence along the second direction B, and the code scanning zone 80, the refrigeration zone 51, the culture zone 40 and the dilution zone 60 are arranged adjacent to each other along the second direction B. In this way, the layout of each zone is reasonable, and the device structure in each zone is compact, which can reduce the size of the cell culture detection equipment 100 in the first direction A and the second direction B.

[0083] See also Figure 1 In some embodiments, the cell culture detection device 100 further includes a waste liquid area 90, which is disposed on the base 10, and specifically can be disposed on the upper surface of the base 10. A waste liquid box 91 for collecting waste liquid is disposed in the waste liquid area 90, and the waste liquid area 90 and the reagent area 50 are adjacently arranged along the first direction A. In this way, while realizing the waste liquid recovery function, the size of the cell culture detection device 100 in the first direction A can be reduced.

[0084] Based on the above structure, in another feasible pipetting process, the pipetting pump 21 can move to the waste liquid area 90 to release the waste liquid in the gun tip 31 into the waste liquid box 91. Specifically, after the pipetting pump 21 drives the gun tip 31 to release the reagent into the culture chamber 41a or the dilution chamber 61a, some reagents still remain in the gun tip 31. In order to avoid cross contamination between different reagents or to facilitate the discharge and recovery of the liquid in the gun tip 31, as well as the recovery of the gun tip 31 itself, the pipetting pump 21 drives the gun tip 31 to move above the waste liquid area 90 and releases the residual liquid in the gun tip 31 into the waste liquid box 91.

[0085] In some embodiments, the cell culture detection device 100 further includes a waste area 110, which is disposed on the base 10, and specifically can be disposed on the upper surface of the base 10. A waste box 111 for collecting discarded gun tips 31 is disposed in the waste area 110, and the waste area 110 and the culture area 40 are arranged adjacent to each other along the first direction A to reduce the size of the cell culture detection device 100 in the first direction A, and the waste area 110 and the waste liquid area 90 are arranged adjacent to each other along the second direction B to reduce the size of the cell culture detection device 100 in the second direction B, thereby reducing the volume of the cell culture detection device 100 while realizing the gun tip 31 recovery function.

[0086] Based on the above structure, in another feasible pipetting process, the pipette pump 21 can move to the waste area 110 to release the discarded gun tip 31 into the waste box 111. Specifically, after the pipette pump 21 drives the gun tip 31 to release the residual reagent into the waste liquid box 91, the pipette pump 21 drives the gun tip 31 to move above the waste area 110 and releases the gun tip 31 into the waste liquid box 91, completing the recovery process of the discarded gun tip 31.

[0087] In some embodiments, the cell culture detection device 100 further includes a three-dimensional drive assembly, which includes, for example, an X-axis drive assembly 22, a Y-axis drive assembly 23, and a Z-axis drive assembly 24. The three-dimensional drive assembly is disposed on the base 10, specifically, on the upper surface of the base 10. The pipette pump 21 is arranged on the three-dimensional driving component. Specifically, the pipette pump 21 can be arranged on the Z-axis driving component 24, and the Z-axis driving component 24 drives the pipette pump 21 to perform lifting and lowering movements. The Z-axis driving component 24 can be arranged on the Y-axis driving component 23, and the Y-axis driving component 23 drives the Z-axis driving component 24 and the pipette pump 21 to move in the Y-axis direction. The Y-axis driving component 23 can be arranged on the X-axis driving component 22, and the X-axis driving component 22 drives the Y-axis driving component 23, the Z-axis driving component 24 and the pipette pump 21 to move in the Y-axis direction. That is, the three-dimensional driving component is used to drive the pipette pump 21 to move in a first direction A (for example, the X-axis direction), a second direction B (for example, the Y-axis direction) and a third direction C (for example, the Z-axis direction), so that the pipette pump 21 moves between the gun tip area 30, the reagent area 50, the culture area 40, the dilution area 60, the waste liquid area 90 and the waste area 110.

[0088] In some embodiments, the cell culture detection device 100 also includes a position correction area 120, and the position correction area 120 is arranged on the base 10, specifically, it can be arranged on the upper surface of the base 10. A corrector for correcting the zero position of the pipette pump 21 is arranged in the position correction area 120. The position correction area 120, the gun tip area 30 and the dilution area 60 are arranged adjacent to each other along the first direction A, and the waste liquid area 90, the waste area 110 and the position correction area 120 are arranged adjacent to each other along the second direction B, and the positions can be arbitrarily swapped. Exemplarily, the waste liquid area 90, the waste area 110 and the position correction area 120 are arranged adjacent to each other in sequence along the second direction B. In this way, the position correction area 120, the gun tip area 30, the dilution area 60, the waste area 110, the culture area 40, the waste liquid area 90, the heating area 52 and the refrigeration area 51 are located in the same rectangular area of ​​the nine-square grid, and the culture area 40 occupies two The grid area, that is, the grid area in the middle of the nine-square grid and the grid area in the middle of the left column, can, on the one hand, allow the culture area 40 to have a larger area to set the culture plate 41, so as to complete a larger batch of cell culture, thereby improving the culture efficiency; more importantly, it can make the layout of each area reasonable, and the structure of the devices in each area compact, which can not only reduce the travel distance of the pipette pump 21, but also reduce the size of the cell culture detection device 100 in the first direction A and the second direction B, thereby reducing the volume of the cell culture detection device 100. In addition, the gun tip area is close to the zero point position of the corrector in the position correction area 120, which is conducive to improving the stability of the pipette pump when taking the gun tip, and the sequential arrangement is conducive to preventing contamination.

[0089] Based on the above structure, in another feasible pipetting process, when it is necessary to perform zero-point correction on the position of the pipette pump 21, the three-dimensional driving component controls the pipette pump 21 to move to the position correction area 120 until the corrector in the position correction area 120 is aligned with the pipette pump 21. At this time, the corrector detects the pipette pump 21, and the cell culture detection equipment 100 uses the position of the pipette pump 21 at this time as the zero-point position, thereby realizing the zero-point correction function of the pipette pump 21, so that the pipette pump 21 can subsequently accurately move between the gun tip area 30, the culture area 40, the cooling area 51, the heating area 52, the dilution area 60, the waste liquid area 90, the waste area 110 and the position correction area 120.

[0090] In some embodiments, the cell culture detection device 100 further includes a liquid leakage prevention device, which is directly or indirectly arranged on the pipette pump 21. For example, the liquid leakage prevention device is fixed on the pipette pump 21 through a fixing plate, so that when the three-dimensional driving component drives the pipette pump 21 to move, the liquid leakage prevention device can follow the movement of the pipette pump 21. According to the foregoing content, the pipette pump 21 can be lifted and lowered along the third direction to absorb or release the reagent. When the pipette pump 21 is lifted and lowered, the liquid leakage prevention device avoids the lifting path of the pipette pump 21. After the pipette pump 21 descends to absorb liquid and rises, the liquid leakage prevention device moves to the bottom of the pipette pump 21 to receive the liquid that may drip from the pipette pump 21. Exemplarily, the liquid leakage prevention device includes a motor and a liquid leakage receiving plate, which is connected to the output shaft of the motor, and the motor drives the liquid leakage receiving plate to rotate to the bottom of the gun head carried by the pipette pump 21 to receive the leaked liquid, or the motor drives the liquid leakage receiving plate to rotate away from the bottom of the gun head so as not to affect the lifting and lowering movement of the pipette pump 21 and the gun head.

[0091] In some embodiments, the cell culture detection device 100 also has a shell (not shown in the figure), which is covered on the base 10, and the three-dimensional drive assembly, the gun head area 30, the culture area 40, the refrigeration area 51, the heating area 52, the dilution area 60, the waste liquid area 90, the waste area 110 and the position correction area 120 are all arranged in the shell, so that the devices in each area are protected by the shell, and the cleanliness of the environment in each area is ensured by the shell, so that the cell culture environment is free from external interference. The display area 70 and the code scanning area 80 are arranged outside the shell, so that the user can view the experimental information, perform experimental manipulation, and facilitate code scanning operations.

[0092] See also Figure 2In some embodiments, based on the cell culture detection device 100 having a gun tip area 30, a culture area 40, a refrigeration area 51, a heating area 52, a dilution area 60, a display area 70, a code scanning area 80, a waste liquid area 90, a waste area 110 and an embodiment with a position correction area 120, while realizing the corresponding functions of each area, along the first direction A, the length L of the cell culture detection device 100 is greater than or equal to 300 mm and less than or equal to 600 mm; along the second direction B, the width W of the cell culture detection device 100 is greater than or equal to 400 mm and less than or equal to 700 mm; along the third direction C, the height H of the cell culture detection device 100 is greater than or equal to 300 mm and less than or equal to 600 mm. It can be seen that the cell culture detection device 100 has a smaller size in the first direction A (e.g., length direction), the second direction B (e.g., width direction), and the third direction C (e.g., height direction). The cell culture detection device 100 has a higher degree of integration, automation, and intelligence, and is small in size. It can be operated in a small or medium-sized ultra-clean workbench, and can easily realize the industrial production of cells or organoids. And by accurately controlling the pipetting pump 21, the operation accuracy is high, and the complex operations in the experiment can be completed efficiently and accurately. The automated operation is effectively standardized, which can improve the success rate of organoid culture, ensure the uniformity of the culture preparation conditions, and thus control the uniformity of the cultured organoids.

[0093] A second aspect of the present application provides a cell culture detection method, which is applied to the cell culture detection device as described above. The cell culture detection method comprises the following steps:

[0094] Step S10, preparing a mixed suspension containing biological cells and hydrogel.

[0095] In step S10, the biological cells and the hydrogel can be extracted from the container of the reagent area 50 by the pipetting device 20, and the biological cells and the hydrogel can be moved to the dilution chamber 61a of the dilution area 60 for mixing to obtain a mixed suspension. It can be understood that the biological cells and the hydrogel can also be mixed outside the cell culture detection device 100 to obtain a mixed suspension.

[0096] Step S20 , injecting the mixed suspension into the culture chamber 41 a of the culture area 40 .

[0097] In step S20 , the mixed suspension is injected into the culture chamber 41 a of the culture area 40 by the pipetting device 20 .

[0098] Step S30, after the mixed suspension solidifies, culture medium is added for culturing.

[0099] In step S30, the culture medium is extracted from the container of the reagent area 50 by the pipetting device 20 and pipetted to the location of the culture chamber 41a with the mixed suspension, and the culture medium is added to the culture chamber 41a with the mixed suspension to culture the cells.

[0100] and / or

[0101] Step S40, adding a drug of a set concentration into the culture chamber 41a for culturing the biological model.

[0102] In step S40, the drug is extracted from the container of the reagent area 50 by the pipetting device 20, and the drug is moved to the dilution chamber 61a of the dilution area 60 for dilution treatment to obtain the drug of the set concentration, and then the drug of the set concentration is added to the culture chamber 41a of the culture biological model by the pipetting device 20.

[0103] Step S50, testing the biological model after the reaction to obtain a test result.

[0104] A third aspect of an embodiment of the present application provides an application of the cell culture detection device as described above in cell, cell model and organoid culture and chemical analysis.

[0105] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0106] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims.

Claims

1. A cell culture detection device, characterized in that: The cell culture detection equipment comprises: Base; A liquid transfer device, disposed on the base; A control device, electrically connected to the pipetting device; A culture area is arranged on the base, the culture area extends at least along a first direction, a culture plate is arranged in the culture area, and the culture plate has a plurality of culture cavities for cell culture and / or chemical analysis; A functional area is disposed on the base; and The reagent area is arranged on the base. The reagent area, the functional area and the culture area are arranged adjacent to each other along a second direction. The second direction is perpendicular to the first direction. The reagent area is used to place a container containing reagents.

2. The cell culture detection device according to claim 1, characterized in that: Also includes: A gun tip area is arranged on the base, a gun tip box for placing gun tips is arranged in the gun tip area, and the reagent area, the culture area and the gun tip area are arranged adjacent to each other along the second direction, and the gun tip area and the functional area are arranged along the first direction; Wherein, controlled by the control device, the pipetting device can cooperate with the gun head to absorb the reagent in the container in the reagent area and transfer the reagent to the culture chamber.

3. The cell culture detection device according to claim 2, characterized in that: The functional area serves as another culture area, and in this case, the whole formed by the culture area and the another culture area also extends along the second direction; or The functional area serves as another gun head area, and in this case, the entirety of the gun head area and the another gun head area extends along the first direction; or The functional area is used as a dilution area and is arranged on the base. A dilution plate is arranged in the dilution area. The dilution plate has a plurality of dilution chambers for diluting reagents. The dilution area and the gun tip area are arranged adjacent to each other along the first direction. The reagent area, the culture area and the dilution area are arranged adjacent to each other along the second direction. The liquid transfer device can cooperate with the gun tip in the gun tip area to absorb the reagent in the container in the reagent area and transfer the reagent to the dilution chamber for dilution.

4. The cell culture detection device according to claim 3, characterized in that: The gun tip area, the culture area and the dilution area together form a rectangular area.

5. The cell culture detection device according to claim 3, characterized in that: Also includes: A display area is arranged on the base, a display screen is arranged in the display area, and the display area, the reagent area, the culture area and the gun tip area are adjacently arranged along the second direction.

6. The cell culture detection device according to claim 5, characterized in that: Also includes: A code scanning area is arranged on the base, a code scanner is arranged in the code scanning area, the display area and the code scanning area are arranged adjacent to each other along the first direction, and the code scanning area, the reagent area, the culture area and the dilution area are arranged adjacent to each other along the second direction.

7. The cell culture detection device according to claim 2, characterized in that: Also includes: A waste liquid area is arranged on the base, a waste liquid box for collecting waste liquid is arranged in the waste liquid area, and the waste liquid area and the reagent area are adjacently arranged along the first direction; Wherein, the pipetting device can be moved to the waste liquid area to release the waste liquid in the gun tip into the waste liquid box.

8. The cell culture detection device according to claim 7, characterized in that: Also includes: A waste area is arranged on the base, wherein a waste box for collecting discarded gun tips is arranged in the waste area, the waste area and the culture area are arranged adjacent to each other along the first direction, and the waste area and the waste liquid area are arranged adjacent to each other along the second direction; Wherein, the pipetting device can be moved to the waste area to release the discarded gun tips into the waste box.

9. The cell culture detection device according to claim 8, characterized in that: Also includes: A position correction zone is arranged on the base, and a corrector for correcting the position of the pipetting device is arranged in the position correction zone. The position correction zone and the gun tip zone are arranged adjacent to each other along the first direction, and the waste liquid zone, the waste material zone and the position correction zone are arranged adjacent to each other along the second direction.

10. The cell culture detection device according to claim 1, characterized in that: The reagent area comprises: A refrigeration zone is arranged on the base, wherein a refrigeration device for refrigerating the reagent in the container is arranged in the refrigeration zone; A heating zone is arranged on the base, wherein a heating device for heating the reagent in the container is arranged in the heating zone, and the heating zone and the cooling zone are arranged adjacent to each other along the first direction.

11. The cell culture detection device according to claim 1, characterized in that: Also includes: a tilting drive device, disposed in the culture area, for supporting the culture plate and for driving one side of the culture plate to tilt up so that the liquid in the culture chamber gathers at a lower position; and / or The anti-leakage device is directly or indirectly arranged on the pipetting device and can move with the pipetting device. After the pipetting device absorbs the liquid, the anti-leakage device can move to the bottom of the pipetting device to receive the liquid dripped by the pipetting device.

12. The cell culture detection device according to any one of claims 1 to 11, characterized in that: The cell culture detection device has a third direction perpendicular to both the first direction and the second direction; the cell culture detection device further comprises: A three-dimensional driving component is arranged on the base, and the pipetting device is arranged on the three-dimensional driving component. The three-dimensional driving component is used to drive the pipetting device to move in the first direction, the second direction and the third direction, so that the pipetting device moves at least between the reagent area and the culture area.

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