Culture apparatus

By integrating the light source, gas supply components and optical observation components into the culture equipment, the status of the culture sample can be observed in a closed environment, which solves the negative impact of frequent sampling and testing on the culture process and improves the imaging quality and culture stability.

WO2025190088A1PCT designated stage Publication Date: 2025-09-18LOLMO INSTRUMENT CO LTD
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Patent Information

Application Number
PCT/CN2025/079733
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-03-15
Filing Date
2025-02-28
Publication Date
2025-09-18

AI Technical Summary

Technical Problem

Frequent opening of the incubator for sampling and testing during the culture process in existing culture equipment will have a negative impact on the culture process, and commonly used microscopes cannot observe culture samples for a long time in a closed environment.

Method used

A culture device was designed, which integrates a light source, an air supply component, and an optical observation component. The optical path structure enables observation of the status of the culture sample in a closed space, and optical components and a mobile mechanism are used to perform multi-angle imaging without affecting the culture environment.

Benefits of technology

It realizes the periodic observation of the state of the culture sample during the closed culture process, improves the imaging quality, avoids the interference with the culture environment, and ensures the stability of the culture process.

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Abstract

Provided in the present application is a culture apparatus. The culture apparatus comprises: a housing, inside which a closed culture space is formed, the direction from one end of the housing to the other end thereof being defined as a first direction. In the culture space, assemblies are provided in sequence in the first direction: a first assembly, which comprises a light source and a gas supply assembly, the gas supply assembly being configured to provide a gas required by the culture space; and an optical observation assembly, which comprises a shell and a functional portion, the functional portion being arranged inside the shell. A light path structure is provided by the culture apparatus, and by means of the light path structure, a light beam is emitted from the light source, penetrates cultured specimen and a light-transmitting area of the shell, and is received by the functional portion, such that an observation image of the cultured specimen is formed and the observed image is outputted.
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Description

Culture equipment Technical Field

[0001] The present application relates to a cultivation device. Background Art

[0002] Culture equipment, such as incubators, are box devices mainly used to culture microorganisms, plant and animal cells. They simulate the growth environment of microorganisms, tissues, cells, etc., provide stable temperature, humidity and gas concentration, and are widely used in cell and tissue culture and the reproduction and cultivation of certain special microorganisms.

[0003] During the culture process, there is a need to detect the growth status of the culture sample. However, the incubator is generally a closed space. If the incubator is frequently opened and samples are taken for testing during the culture process, it will have a negative impact on the culture process.

[0004] In this regard, in a comparative solution, the inventors tried to set up a commonly used microscope for observing biological samples in a closed space. However, due to its large size and the fact that it is not suitable for being placed in an incubator with a high temperature and high humidity environment, it is impossible to perform long-term observation of the cultured samples while culturing in a closed incubator. Summary of the Invention

[0005] The purpose of the present application is to realize that during the culture process in a closed culture device, the culture device can be kept closed during the culture process, and the state of the culture sample can be observed during the culture cycle.

[0006] According to the first aspect of the present application, a culture device includes: a shell, which provides a closed culture space, and the direction from one end to the other end of the shell is defined as a first direction; in the culture space, along the first direction, there are arranged in sequence: a first component, including a light source and a gas supply component, the gas supply component is used to provide the gas required for the culture space; an optical observation component, including an outer shell and a functional part, the functional part is arranged inside the outer shell; the light path structure provided by the culture device includes: a light beam is emitted from the light source, penetrates the culture sample, the light-transmitting area of ​​the outer shell, and is received by the functional part to form and output an observation image of the culture sample.

[0007] In one or more embodiments of the culture device, the light source and the gas supply component of the first component are arranged at one end of the closed culture space.

[0008] According to the second aspect of the present application, a culture device includes: a shell, which provides a closed culture space, and the direction from one end to the other end of the shell is defined as a first direction; in the culture space, along the first direction, there are arranged in sequence: a first component, including a light source; an optical observation component, including an outer shell and a functional part, and the functional part is arranged inside the outer shell; the light path structure provided by the culture device includes: a light beam is emitted from the light source, penetrates the culture sample, the light-transmitting area of ​​the outer shell, and is received by the functional part to form and output an observation image of the culture sample.

[0009] In one or more embodiments of the culture device, the boundary of the projection of the light source on the optical observation component along the first direction exceeds or coincides with the boundary of the light-transmitting area of ​​the optical observation component in the length direction and / or width direction.

[0010] In one or more embodiments of the cultivation device, the light source includes a plurality of light sources, and the plurality of light sources are arranged at intervals in the length direction and / or the width direction.

[0011] In one or more embodiments of the culture device, the functional part includes an optical component, a moving mechanism and an imaging mechanism, and the optical path structure includes: a light beam is emitted from the light source, penetrates the culture sample, penetrates the light-transmitting area, passes through the optical component, and reaches the imaging mechanism; wherein, the optical component is connected to the moving mechanism, so that the optical component is a moving part, and the optical component can be driven by the moving mechanism, so that the optical component and the light-transmitting area can move relative to each other.

[0012] In one or more embodiments of the culture device, the optical component includes an objective lens and one or more prisms, and the optical path structure includes: a light beam is emitted from the light source, penetrates the culture sample, penetrates the light-transmitting area, converges through the objective lens, and reaches the imaging chip of the imaging mechanism after being deflected by the prism.

[0013] In one or more embodiments of the culture device, the optical component includes multiple prisms, including at least a first prism and a second prism; the optical path structure includes: the light beam is converged by the objective lens, deflected 90° by the first prism, and then deflected 90° by the second prism to reach the imaging chip of the imaging mechanism.

[0014] In one or more embodiments of the culture device, the moving mechanism includes a first direction driving mechanism, a second direction driving mechanism, and a third direction driving mechanism, the first direction, the second direction, and the third direction are perpendicular to each other, and the second direction and the third direction constitute a plane parallel to the light-transmitting area; wherein the first direction driving mechanism, the second direction driving mechanism, and the third direction driving mechanism include linear motors, and the optical component is driven by the linear motors to move relative to the light-transmitting area in the first direction, the second direction, and the third direction.

[0015] In one or more embodiments of the culture device, the light-transmitting area, the second direction driving mechanism, and the third direction driving mechanism are integrated on a plate-like member, which provides the end cover of the shell, and the plate-like member is provided with a light-transmitting member to provide a light-transmitting area. The back side of the plate-like member is provided with a guide rail, a grating scale or a magnetic grating scale, an encoder, and a magnetic rod matching the linear motor, and the linear motor includes a magnetic axis linear motor supported by the magnetic rod.

[0016] In one or more embodiments of the culture device, the optical component and the imaging mechanism constitute a packaging module, and the packaging module is connected to the first direction driving mechanism, the second direction driving mechanism, and the third direction driving mechanism.

[0017] In one or more embodiments of the culture device, the optical observation component also includes an adapter plate, which is detachably arranged on the upper part of the outer shell, and the middle part of the adapter plate is hollowed out; optionally, the hollowed-out part in the middle of the adapter plate is a rectangle with a raised structure; optionally, a stepped annular surface is provided on the back of the adapter plate, and a groove matching the stepped annular surface is provided around the light-transmitting area on the upper part of the outer shell.

[0018] In one or more embodiments of the culture device, the culture device further comprises a control unit, which is disposed outside the optical observation component, and the optical observation component is electrically connected to the control unit.

[0019] In one or more embodiments of the culture device, the culture device also includes a control unit, which includes a processor and a memory of the first component and the optical observation component. The control unit is arranged outside the optical observation component, and the optical observation component and the first component are electrically connected to the control unit.

[0020] According to a third aspect of the present application, a culture method using the culture device described in the first aspect comprises the following steps:

[0021] S1. The culture sample is placed in the culture space of the culture device and is sealed and cultured during the culture cycle;

[0022] S2. During the culture cycle, the optical observation component photographs the culture sample during the set observation time period to obtain the observation image and output it; wherein, when photographing, the light source of the first component is turned on, and the gas supply component stops running; after the photographing is completed, the gas supply component continues to operate.

[0023] In one or more embodiments of the culture method, in S2, the observation time period is 1s to 10s. Preferably, the observation time period can also be 5s to 10s, 8s to 10s, 1s to 5s, or 1s to 3s.

[0024] In one or more embodiments of the culture method, in step S2, multiple observation cycles are set, each of which includes at least one observation time period. When multiple observation time periods are present in the same observation cycle, the optical observation assembly images different positions of the culture sample corresponding to different observation time periods. The frequency and duration of the observation cycles can be set based on actual experimental requirements. Preferably, the observation cycle duration does not exceed 5 minutes / hour, more preferably, the observation cycle duration does not exceed 3 minutes / hour, and more preferably, the observation cycle duration does not exceed 2 minutes / hour.

[0025] In one or more embodiments of the culture device, the device comprises: the memory for storing instructions executable by a processor; and the processor for executing the instructions to implement the steps of the culture method of the third aspect that can be implemented by a computer program.

[0026] According to a fourth aspect of the present application, a computer-readable storage medium has a computer program thereon, and the program is executed by a processor to implement the steps in the culture method described in the third aspect that can be implemented by a computer program.

[0027] A computer program product according to the fifth aspect of the present application includes a computer program, which, when executed by a processor, implements the steps in the culture method described in the third aspect that can be implemented by a computer program.

[0028] Summary of the Figures

[0029] In order to make the above-mentioned objects, features and advantages of the present application more clearly understood, the specific embodiments of the present application are described in detail below with reference to the accompanying drawings, wherein:

[0030] 1A and 1B are schematic structural diagrams of a culture device according to an embodiment.

[0031] FIG. 2 is a schematic diagram taken along the line AA of FIG. 1B .

[0032] FIG3 is a schematic diagram of the internal structure of an optical observation assembly of a culture device according to an embodiment.

[0033] FIG. 4 is a schematic structural diagram of the functional parts of the optical observation assembly of the culture apparatus according to one embodiment.

[0034] FIG5 is a schematic flow chart of a culture method according to an embodiment.

[0035] 6A and 6B are schematic structural diagrams of the front and back sides of a culture device according to an embodiment.

[0036] Preferred embodiments of the present invention

[0037] The following discloses a variety of different implementation methods or examples of the subject technical solutions. To simplify the disclosure, specific examples of the various elements and arrangements are described below. Of course, these are merely examples and are not intended to limit the scope of protection of the present invention. For example, a first feature described later in the specification is formed above or on a second feature, which may include an implementation method in which the first and second features are formed in a directly connected manner, or an implementation method in which an additional feature is formed between the first and second features, so that the first and second features may not be directly connected. In addition, the disclosures may repeat the figure marks and / or letters in different examples. This repetition is for brevity and clarity and does not in itself represent the relationship between the various implementation methods and / or structures to be discussed. Further, when a first element is described in a manner connected to or combined with a second element, the description includes an implementation method in which the first and second elements are directly connected or combined with each other, and also includes an implementation method in which one or more other intervening elements are added to indirectly connect or combine the first and second elements.

[0038] It will be appreciated that the following uses a flow chart to illustrate the steps performed by the culture method according to the embodiments of the present application. It should be understood that, depending on the actual situation, the preceding or following steps may not necessarily be performed in exact order. Other steps may also be added to these processes, or one or more steps may be removed from these processes.

[0039] 1A , 1B to 4 , the culture device 100 includes a housing 1 , a first component 2 , and an optical observation component 3 .

[0040] The housing 1 provides an enclosed culture space 10, and the direction from one end of the housing 1 to the other end is defined as a first direction. For example, referring to Figures 1A and 1B , the vertical direction from the top to the bottom of the housing 1 is defined as the first direction. The structure of the housing 1, such as the box structure shown in the figures, can be a cube / rectangular parallelepiped structure composed of multiple welded plates, and the material can be stainless steel, but this is not limiting.

[0041] In the culture space 10, vertically arranged from top to bottom are: a first component 2 and an optical observation component 3. The first component 2 includes a light source 21, which can emit a light beam to provide imaging to the optical observation component 3.

[0042] In some embodiments, the first assembly 2 further includes a gas supply assembly 22, which is used to provide the gas required by the culture space 10. For example, this may be a mixture of CO2, O2, and N2, but this is not limiting. The gas supply assembly 22 may specifically comprise an air duct structure disposed at the top of the culture apparatus 100. The air duct is used to promote air circulation within the culture space to improve gas uniformity within the culture space. A fan and a high-efficiency filter may also be provided within the air duct to filter and clean the gas. The light source 21 can emit a light beam to provide imaging to the optical observation assembly 3.

[0043] Here, the light source 21 and the air supply component 22 are classified as components of the first component 2, which means that the light source 21 and the air supply component 22 are arranged in an integrated manner. For example, as shown in Figure 1B and Figure 2, the light source 21 and the air supply component 22 of the first component 2 are arranged on the entire or partial top of the closed culture space. For example, as shown in Figure 2, the first component 2 occupies part of the space at the top, but this is not limited to it. It can also be the entire space. The light source 21 is arranged on the surface of the top, and the air duct of the air supply component 22 is arranged inside the top.

[0044] The optical observation assembly 3 includes a housing 31 and a functional portion 32, and the functional portion 32 is arranged inside the housing 31. The housing 31 has a light-transmitting area 311 at the top, so that the light beam emitted by the light source 21 can be received by the functional portion 32. The specific structure of the housing 31, for example, can be as shown in Figures 1A and 1B, and is composed of a lower box body 312, an upper cover body 313, and a light-transmitting area 311 (transparent stage) integrated in the upper cover body 313. The housing 31, except for the light-transmitting area 311, can be made of stainless steel, aluminum alloy, etc., so that the components inside the observation system will not be affected by the humidity and temperature in the culture space, and can work stably for a long time in an environment of high temperature, high humidity and a certain pressure. For example, the lower box body 312 can be stainless steel, the upper cover body 313 can be aluminum alloy, and the material of the light-transmitting area 311 can be ultra-clean glass, but all are not limited to this.

[0045] In other embodiments, ventilation holes can be provided in the housing 31 to dissipate heat from the functional portion 32. To protect the optical observation assembly 3 from the humidity within the culture space, when ventilation holes are provided in the housing 31, the internal components can be sealed with a sealant. In a preferred embodiment, such as that shown in Figure 4 , when ventilation holes are provided in the housing 31, a fan 33 can also be provided within the housing to assist in heat dissipation and ensure a constant temperature within the culture space.

[0046] In other embodiments, as shown in Figures 6A and 6B , the optical observation assembly 3 may further include an adapter plate 34, which is removably mounted on the upper portion of the housing 31. The middle portion of the adapter plate 34 is hollowed out, and the hollowed-out portion 341 may be a rectangle with a raised structure 3411. The hollowed-out portion 341 serves as a position limiter for different culture containers. The back of the adapter plate 34 is provided with a stepped annular surface 342, and the upper portion of the housing 31 is provided with a groove that matches the stepped annular surface 342, surrounding the light-transmitting area 311, for securing the position of the adapter plate 34. The culture container may include a 96-well plate, a 48-well plate, a 24-well plate, a T75 culture flask, a T300 culture flask, a cell factory, and the like.

[0047] For example, when observing a multi-well plate as a culture container, the multi-well plate is positioned against the upper left corner 3412 of the hollow portion, and the container to be observed is selected on the operating software interface. When observing multiple multi-well plates as multiple culture containers simultaneously, the first multi-well plate is positioned against the upper left corner 3412, and the second multi-well plate is positioned against the raised structure 3411, and the container to be observed is selected on the operating software interface. After selecting a multi-well plate of a certain specification as a culture container, during automatic observation, the imaging motion mechanism of the microscope stage will scan and photograph each well according to the preset program for the selected multi-well plate. For another example, when observing a culture bottle, the multi-well plate is positioned against the upper right corner 3413 of the hollow portion, and the container to be observed is selected on the operating software interface. After selecting a culture bottle as a culture container, different observation points can be selected within the observation range of the corresponding container, and then an automatic photography cycle is performed and the photos are saved.

[0048] Preferably, in some embodiments, as shown in Figure 1B, the structure of the light-transmitting area 311 and the light source 21 can be that the boundary of the projection of the light source 21 along the first direction (i.e., the vertical direction) on the optical observation component exceeds or coincides with the boundary of the light-transmitting area 311 of the optical observation component in the length direction and / or width direction. For example, as shown in Figure 1B, the boundary of the projection of the light source 21 along the first direction (i.e., the vertical direction) on the optical observation component basically coincides with or slightly exceeds the boundary of the upper cover body 313 in the length direction, then it must coincide with or exceed the boundary of the light-transmitting area 311 set on the upper cover body 313 in the length direction or width direction. The beneficial effect of this is that the inventors found that compared with the common practice in the art of setting the light source 21 at the center position corresponding to the light-transmitting area 311 to form an intermediate divergent optical path structure, the boundary of the light source 21 extends to exceed or overlap with the boundary of the light-transmitting area 311 of the optical observation component in the length direction and / or width direction, which significantly improves the imaging quality. In particular, for the structure of a compact culture device 100 that is in a sealed culture space and has an integrated air supply component 22 around it, the structure of the light source 21 shown in the figure is used, and compared with the centrally divergent optical path structure, the quality of the observed image obtained is higher, thereby ensuring the reliability of the observation results. Preferably, as shown in FIG2 , in some embodiments, the number of light sources 21 can be multiple, such as two as shown in FIG2 , and the multiple light sources are spaced apart in the length direction and / or width direction. This saves the cost of installing a light source while not affecting the gas circulation path of the culture device itself, compared to a single large light source. The illumination of the light source can be adjustable from 0 to 100,000. In addition, the distance between the light source 21 and the light-transmitting area 311 can also be adjustable, for example, by adjusting the vertical distance between the light source 21 and the light-transmitting area 311 as shown in FIG1B . This can accommodate different culture sample formats, such as culture dishes, multi-well plates, and multi-layer cell factories. It is understood that the culture sample format can also be a standard T25 cell culture flask, a T75 cell culture flask, a T300 cell culture flask, a multi-well culture plate, etc., without limitation.

[0049] As the name implies, the functional unit 32 is a mechanism capable of forming and outputting an observation image of the culture sample.

[0050] Thus, the optical path structure provided by the culture device 100 includes: a light beam emitted from the light source 21, passing through the culture sample, the light-transmitting area 311 of the housing 31, and being received by the functional portion 32 to form and output an observation image of the culture sample. It should be understood that the observation image here is not limited to a static image, but can also be a dynamic image of a short duration (e.g., 1 to 3 seconds).

[0051] In some embodiments, referring to Figures 3 and 4, the structure of the functional part 32 may include an optical component 321, a moving mechanism 322 and an imaging mechanism 323, and the corresponding optical path structure described above includes: a light beam is emitted from the light source 21, penetrates the culture sample, penetrates the light-transmitting area 311, passes through the optical component 321, and reaches the imaging mechanism 323; wherein, the optical component 321 is connected to the moving mechanism 322, so that the optical component 321 is a moving part, and the optical component 321 can be driven by the moving mechanism 322, so that the optical component 321 and the light-transmitting area 311 can move relative to each other, so that the optical component 321 can be adjusted to the ideal position for desired observation and imaging, and observation and imaging of the culture sample at multiple positions and multiple angles can be realized. In some embodiments, with continued reference to FIG4 , the optical assembly 321 may include an objective lens 3211 and one or more prisms 3212, and the corresponding optical path structure may be: a light beam is emitted from the light source 21, penetrates the culture sample, penetrates the light-transmitting area 311, converges through the objective lens 3211, and reaches the imaging chip of the imaging mechanism 323 after being deflected by the prism 3212. The meaning of the "objective lens" here is similar to that of the objective lens in a microscope, that is, a lens group composed of a plurality of lenses. The purpose of combined use is to overcome the imaging defects of a single lens and improve the optical quality of the objective lens. The magnifying effect of a microscope mainly depends on the objective lens. The meaning of "prism" is also similar to that in the art, that is, a transparent object surrounded by two intersecting but non-parallel planes, used to split light or disperse the light beam. The use of a combination of objective lens + prism can further improve the quality of imaging. Preferably, for multiple prisms, for example, including a first prism 32121 and a second prism 32122; the optical path structure includes: the light beam is converged by the objective lens, deflected 90° by the first prism, and then deflected 90° by the second prism to reach the imaging chip of the imaging mechanism, which can further improve the imaging quality.

[0052] Continuing to refer to Figures 3 and 4, in some embodiments, the structure of the moving mechanism 322 may include a first direction driving mechanism 3221, a second direction driving mechanism 3222, and a third direction driving mechanism 3223. The first direction, the second direction, and the third direction are perpendicular to each other, and the second direction and the third direction constitute a plane parallel to the light-transmitting area. For example, the first direction shown in the figure is the vertical direction, that is, the Z direction, and the second direction and the third direction are length and width directions, respectively, that is, the X and Y directions shown in the figure.

[0053] Among them, the first direction drive mechanism 3221, the second direction drive mechanism 3222, and the third direction drive mechanism 3223 include linear motors 3224. The linear motors 3224 drive the optical component 321 to move relative to the light-transmitting area 311 in the first, second, and third directions to adjust the optical component 321 to the ideal position for desired observation and imaging, and also to enable observation and imaging of cultured samples at multiple positions and angles. Specifically, the second direction drive mechanism 3222 and the third direction drive mechanism 3223 can drive the optical component 321 to move within a plane, thereby enabling observation of samples at any position on the light-transmitting area 311 (transparent stage), while the first direction drive mechanism 3221 drives the optical component 321 to move in a vertical direction, which can achieve clearer imaging. The optical component 321 can move in the first, second, and third directions, avoiding the impact of disturbances on cells or microorganisms and their culture fluid when adjusting the observation position. Without affecting the growth and movement environment of cells or microorganisms, in-situ observation can be performed at multiple points in a large area. Furthermore, the structure of the linear motor 3224 is easy to control and has high position repeatability, which can accurately realize observation of the same position at different times.

[0054] Preferably, in some embodiments, with continued reference to Figures 3 and 4 , the arrangement of the moving mechanism 322 can be such that the light-transmitting region 311, the second directional drive mechanism 3222, and the third directional drive mechanism 3223 are integrated into an upper cover 313, which is a plate-like member. The upper cover 313 of the plate-like member serves as an end cap for the housing 31. The upper cover 313 is provided with a light-transmitting member to provide the light-transmitting region 311. The back side of the upper cover 313 is provided with a guide rail 3225, a grating scale 3226, an encoder 3227, and a magnetic rod 3228, which are compatible with the linear motor 3224. The linear motor 3224 is a magnetic axis linear motor supported by the magnetic rod 3228. This arrangement allows the moving mechanism to be compactly integrated into the upper cover 313, resulting in a more compact structure for the optical observation assembly 3. In another embodiment, a magnetic rod can be used in place of the grating scale 3226 to improve the linear motor's resistance to high humidity. Preferably, as shown in Figures 3 and 4, the optical assembly 321 and imaging mechanism 323 form a packaging module 320, which is encapsulated by an outer layer of wrapping, thereby protecting the optical assembly 321 and imaging mechanism 323. The packaging module 320 is connected to the first direction drive mechanism 3221, the second direction drive mechanism 3222, and the third direction drive mechanism 3223. This improves the integration and compactness of the optical observation assembly 3, further protects the optical assembly 321 and imaging mechanism 323, and further improves imaging quality. The packaging mentioned here simply refers to the integration of the optical assembly and imaging mechanism into a space and their packaging by the outer layer of wrapping. This can include complete sealing by the outer layer of wrapping or incomplete sealing by providing ventilation holes in the outer layer of wrapping.

[0055] In some embodiments, the culture device 100 may further include a control unit 4, which includes a processor 41 and a memory 42 of the integrated first component 2 and the optical observation component 3 to achieve centralized control. The control unit 4 is arranged outside the optical observation component 3. The optical observation component 3 can be electrically connected to the control unit 4 to achieve driving and control of the functional part 32. For example, the power line of the linear motor 3224 in the optical observation component 3, the connecting line of the encoder 3227, and the cable of the imaging mechanism 323 are respectively connected to the processor 41 of the control unit through a multi-core aviation through-board plug and a USB through-board plug. Such an arrangement can greatly reduce the number of heat-generating components inside the optical observation component 3, which is more conducive to temperature control. At the same time, due to the reduction of components inside the optical observation component 3, the area of ​​the light-transmitting area is correspondingly increased, and the observable range is increased.

[0056] In summary, the beneficial effect of the culture device 100 introduced in the above embodiment is that it enables the culture device to observe the status of the culture sample during the culture cycle while maintaining the closure during the culture process.

[0057] As shown in FIG5 , as described above, the present application further provides a culture method, using the culture device 100 described in the above embodiment, the culture method includes the following steps:

[0058] S1. The culture sample is set in the culture space 10 of the culture device 100 and is sealed for culture during the culture cycle; for example, as recorded above, the culture sample can be placed in a standard T25 cell culture flask, T75 cell culture flask, T300 cell culture flask, multi-well culture plate, cell factory, etc., and is set in the culture space 10. It can be understood that the position of the culture sample is set in the vertical direction between the first component 2 and the optical observation component 3; in one embodiment, the culture sample can be placed directly on the light-transmitting area (transparent stage), and the culture cycle can be set according to the needs of the experiment.

[0059] S2. During the culture cycle, the optical observation component 3 photographs the culture sample during the set observation time period to obtain an observation image and output it; wherein, when photographing, the light source 21 of the first component 2 is turned on, and the gas supply component 22 stops running; after the photographing is completed, the gas supply component 22 continues to run. Preferably, the light source 21 is turned off when the gas supply component 22 is running to avoid interfering with the culture process.

[0060] That is, the first component 2 can be electrically connected to the control unit 4 and controlled to realize the control of stopping or running the light source 21 and the gas supply component 22. The control unit 4 generally includes a processor 41 and a memory 42. The memory 42 is used to store instructions that can be executed by the processor 41; the processor 41 is used to execute the instructions to realize the steps executed by the program in the culture method introduced in this application. It should be noted that the above-mentioned memory and processor are not limited to a specific memory or processor. For example, in some cases, both the memory and the processor can have a distributed structure. For example, it can include a memory and a processor respectively located at the culture device end and the background cloud, and the culture device end and the background cloud jointly implement the above-mentioned culture method. Furthermore, in an embodiment adopting a distributed structure, the specific execution terminal of each step can be adjusted according to actual conditions, and the specific scheme of each step implemented at a specific terminal should not limit the scope of protection of the present invention.

[0061] This beneficial effect is that it can significantly improve the imaging quality of observed images. This is likely due to the inventor's accidental discovery in practice that a significant factor affecting imaging quality may be the compact structure of the first component 2, which integrates the light source 21 and the air supply component 22. When the observation system takes a picture, the controller temporarily shuts down the fan, air circuit, and other devices in the air supply component 22 that would disturb the sample. This ensures stable airflow within the culture space 10 and prevents vibration, thereby improving imaging quality. After the picture is taken, the power supply to the motor of the fan in the air supply component 22 and the power supply to the air circuit solenoid valve are restored almost immediately. Since the picture taking time itself is relatively short, it does not affect the cultured sample.

[0062] In some embodiments, the above-mentioned observation time period is 1s to 10s. Preferably, the observation time period can also be 5s to 10s, 8s to 10s, 1s to 5s, or 1s to 3s. This can ensure imaging quality while avoiding adverse effects on the culture process. It can be understood that for multiple observation time periods, different observation time periods can correspond to different times. For example, the observation time period mentioned above can also be 5s to 10s or 8s to 10s. This is generally the first observation time period, and time for adjusting the photosensitivity and focusing needs to be reserved. The observation time periods thereafter are generally shorter, such as 1s to 5s or 1s to 3s. Preferably, for situations where observation images need to be obtained for multiple positions and / or multiple angles of the culture sample, multiple observation cycles can be set, each of which includes at least one observation time period. When there are multiple observation time periods in the same observation cycle, the optical observation component photographs different positions of the culture sample corresponding to different observation time periods. Specifically, for the experimenter operating the culture device 100, the following operations can be performed: first, the shooting interval time, shooting position and / or shooting angle within the same observation cycle are set on the software interface corresponding to the culture device 100. The specific shooting interval time, shooting position and / or shooting angle can be set according to the experimental requirements. Before shooting, the imaging of the optical observation component 3 can be pre-adjusted to make the imaging clear. For example, the second direction driving mechanism 3222 and the third direction driving mechanism 3223 are energized to generate magnetic force to drive the optical component on the magnetic rod 3228 to move frictionlessly. At the same time, the encoder 3227 reads the full real-time position data of the grating scale or magnetic scale 3226 as the mover moves and feeds it back to the control unit 4, thereby accurately locating the horizontal position. After the optical component 321 reaches the shooting position, the first direction driving mechanism 3221 is energized to generate magnetic force to drive the optical component 321 to move frictionlessly, driving the optical component 321 to move in the vertical direction to achieve focusing, so that the imaging is clear. When photography is required, light source 21 is turned on, and air supply assembly 22 is shut down to stop operation. For example, the fan, gas circuit solenoid valve, and / or optical observation assembly fan in the culture device are shut down. This completes the photography at the first photography position and / or photography angle (hereinafter referred to as the "photographing point") within the observation cycle. Immediately after the photography is complete, light source 21 is turned off, and air supply assembly 22 is restored to resume operation. Subsequently, the second directional drive mechanism 3222 and the third directional drive mechanism 3223 are used to sequentially move to the remaining photography points within the observation cycle, photographing each point one by one. After completing the first round of point-by-point scanning, the system enters standby mode according to a set interval. After the waiting time expires, the second observation cycle begins. This cycle repeats itself, performing long-term automatic observation and photography. Simultaneously, the observation images are continuously transmitted to the control mechanism.For the distribution of standby and shooting time, it can be adjusted according to actual needs. For example, preferably, the duration of the observation cycle is no more than 5min / h, that is, in the culture cycle, every 1 hour, the duration of the observation cycle is no more than 5 minutes. It is also preferred that the duration of the observation cycle is no more than 3min / h. More preferably, the duration of the observation cycle is no more than 2min / h. But it will be understood that the duration of the observation cycle needs to meet the requirement of not affecting the normal culture process. The upper limit of the specific duration can be adjusted according to different culture objects and culture processes. For example, the upper limit of the duration of the observation cycle corresponding to different culture objects and culture processes can be obtained through experiments. In addition, if you need to stop the automatic cycle, you can stop it by the stop button on the software interface, or you can perform manual operation by the button on the interface of the culture device itself.

[0063] According to another aspect of the present application, the present application also provides a computer-readable medium.

[0064] The computer-readable medium provided herein has computer instructions thereon. When the computer instructions are executed by a processor, the program can be executed by the processor to implement the steps performed by the program in the culture method described in the above embodiment.

[0065] According to yet another aspect of the present application, the present application also provides a computer program product.

[0066] The computer-readable medium provided in the present application includes a computer program, which, when executed by a processor, can implement the steps executed by the program in the culture method described in the above embodiment.

[0067] In summary, the beneficial effect of the culture equipment, culture method, computer-readable storage medium, and computer program product introduced above is that, during the culture process in a closed culture equipment, the culture equipment can observe the status of the culture sample during the culture cycle while maintaining the closure during the culture process.

[0068] The steps of the methods described in conjunction with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. The software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art. An exemplary storage medium is coupled to the processor so that the processor can read and write information from / to the storage medium. In an alternative, the storage medium may be integrated into the processor. The processor and storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In an alternative, the processor and storage medium may reside in a user terminal as discrete components.

[0069] In one or more exemplary embodiments, the functions described may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software as a computer program product, the functions may be stored on or transmitted via a computer-readable medium as one or more instructions or code. Computer-readable media include both computer storage media and communication media, including any media that facilitates the transfer of a computer program from one location to another. A storage medium may be any available medium that can be accessed by a computer. By way of example and not limitation, such computer-readable media may include RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to carry or store desired program code in the form of instructions or data structures and that can be accessed by a computer. Any connection is also properly referred to as a computer-readable medium. For example, if the software is transmitted from a website, server, or other remote source using a coaxial cable, fiber optic cable, twisted pair, digital subscriber line (DSL), or wireless technologies such as infrared, radio, and microwave, then the coaxial cable, fiber optic cable, twisted pair, DSL, or wireless technologies such as infrared, radio, and microwave are included in the definition of medium. As used herein, disk and disc include compact disc (CD), laser disc, optical disc, digital versatile disc (DVD), floppy disk and Blu-ray disc, where disks typically reproduce data magnetically, while discs reproduce data optically with lasers. Combinations of the above should also be included within the scope of computer-readable media.

[0070] Although the present application is disclosed above with reference to preferred embodiments, this is not intended to limit the present application. Any person skilled in the art may make possible changes and modifications without departing from the spirit and scope of the present application. Therefore, any modifications, equivalent variations, and modifications made to the above embodiments based on the technical essence of the present application without departing from the content of the technical solution of the present application shall fall within the scope of protection defined by the claims of the present application.

Claims

1. A culture device, characterized in that include: a housing, wherein the housing provides a closed culture space, and a direction from one end to the other end of the housing is defined as a first direction; In the culture space, arranged in sequence along the first direction are: The first component includes a light source and a gas supply component, wherein the gas supply component is used to provide the gas required by the culture space; An optical observation assembly includes a housing and a functional portion, wherein the functional portion is disposed inside the housing; The light path structure provided by the culture device includes: a light beam emitted from the light source, penetrating the culture sample, the light-transmitting area of ​​the shell, and being received by the functional part to form and output an observation image of the culture sample.

2. The culture device according to claim 1, wherein The light source and the gas supply component of the first component are arranged at one end of the closed culture space.

3. A culture device, characterized in that include: a housing, wherein the housing provides a closed culture space, and a direction from one end to the other end of the housing is defined as a first direction; In the culture space, arranged in sequence along the first direction are: A first component includes a light source; An optical observation assembly includes a housing and a functional portion, wherein the functional portion is disposed inside the housing; The light path structure provided by the culture device includes: a light beam emitted from the light source, penetrating the culture sample, the light-transmitting area of ​​the shell, and being received by the functional part to form and output an observation image of the culture sample.

4. The culture device according to claim 2 or 3, characterized in that The boundary of the projection of the light source on the optical observation component along the first direction exceeds or coincides with the boundary of the light-transmitting area of ​​the optical observation component in the length direction and / or width direction.

5. The culture device according to claim 4, wherein The light source includes a plurality of light sources, and the plurality of light sources are arranged at intervals in the length direction and / or the width direction.

6. The culture device according to claim 1 or 3, wherein: The functional part includes an optical component, a moving mechanism and an imaging mechanism. The optical path structure includes: a light beam is emitted from the light source, penetrates the culture sample, penetrates the light-transmitting area, passes through the optical component, and reaches the imaging mechanism; wherein, the optical component is connected to the moving mechanism, so that the optical component is a moving part, and the optical component can be driven by the moving mechanism, so that the optical component and the light-transmitting area can move relative to each other.

7. The culture device according to claim 6, wherein The optical component includes an objective lens and one or more prisms, and the optical path structure includes: a light beam is emitted from the light source, penetrates the culture sample, penetrates the light-transmitting area, converges through the objective lens, and reaches the imaging chip of the imaging mechanism after being deflected by the prism.

8. The culture device according to claim 7, wherein The optical component includes multiple prisms, including at least a first prism and a second prism; the optical path structure includes: the light beam is converged by the objective lens, deflected 90° by the first prism, and then deflected 90° by the second prism to reach the imaging chip of the imaging mechanism.

9. The culture device according to claim 6, wherein: The moving mechanism includes a first direction driving mechanism, a second direction driving mechanism, and a third direction driving mechanism. The first direction, the second direction, and the third direction are perpendicular to each other, and the second direction and the third direction constitute a plane parallel to the light-transmitting area; wherein the first direction driving mechanism, the second direction driving mechanism, and the third direction driving mechanism include linear motors, and the optical component is driven by the linear motors to move relative to the light-transmitting area in the first direction, the second direction, and the third direction.

10. The culture device according to claim 9, wherein The light-transmitting area, the second direction driving mechanism, and the third direction driving mechanism are integrated on a plate-like member, which provides the end cover of the shell. The plate-like member is provided with a light-transmitting member to provide a light-transmitting area. The back side of the plate-like member is provided with a guide rail, a grating scale or a magnetic grating scale, an encoder, and a magnetic bar that match the linear motor. The linear motor includes a magnetic axis linear motor supported by the magnetic bar.

11. The culture device according to claim 9, wherein The optical assembly and the imaging mechanism constitute a packaging module, and the packaging module is connected to the first direction driving mechanism, the second direction driving mechanism, and the third direction driving mechanism.

12. The culture device according to claim 1 or 3, wherein: The optical observation assembly further includes an adapter plate, which is detachably arranged on the upper portion of the housing, and the middle portion of the adapter plate is hollowed out; Optionally, the hollowed-out portion in the middle of the adapter plate is a rectangle with a raised structure; Optionally, a stepped annular surface is provided on the back of the adapter plate, and a groove matching the stepped annular surface is provided on the upper portion of the housing surrounding the light-transmitting area.

13. The culture device according to claim 1 or 3, wherein: The culture device further includes a control unit, which is disposed outside the optical observation component and is electrically connected to the control unit.

14. The culture device according to claim 1 or 3, wherein: The culture device further includes a control unit, which includes a processor and a memory of the first component and the optical observation component. The control unit is arranged outside the optical observation component, and the optical observation component and the first component are electrically connected to the control unit.

15. A culture method, using the culture device according to claim 1, comprising the following steps: S1. The culture sample is placed in the culture space of the culture device and is sealed and cultured during the culture cycle; S2. During the culture cycle, the optical observation component photographs the culture sample during the set observation time period to obtain the observation image and output it; wherein, when photographing, the light source of the first component is turned on, and the gas supply component stops running; after the photographing is completed, the gas supply component continues to operate.

16. The culture method according to claim 15, wherein In S2, the observation period is from 1s to 10s. Preferably, the observation time period may also be 5s to 10s, 8s to 10s, 1s to 5s, or 1s to 3s.

17. The culture method according to claim 15, wherein In S2, multiple observation cycles are set, each of which includes at least one observation time period. When there are multiple observation time periods in the same observation cycle, the optical observation component photographs different positions of the culture sample corresponding to different observation time periods. Preferably, the duration of the observation cycle does not exceed 5 min / h; Also preferably, the duration of the observation cycle does not exceed 3 min / h; More preferably, the duration of the observation cycle does not exceed 2 min / h.

18. The culture device according to claim 14, wherein the memory is used to store instructions executable by a processor; and the processor is used to execute the instructions to implement the steps of the culture method according to any one of claims 15 to 17 that can be implemented by a computer program.

19. A computer-readable storage medium having a computer program thereon, wherein the program is executed by a processor to implement the steps of the culture method according to any one of claims 15 to 17 that can be implemented by a computer program.

20. A computer program product, comprising a computer program, wherein when the computer program is executed by a processor, the computer program implements the steps of the culture method according to any one of claims 15 to 17 that can be implemented by a computer program.