Organ-like sample preparation system

Abstract

The invention discloses an organ-like sample preparation system. The system comprises a liquid drop preparation subsystem, the liquid drop preparation subsystem comprises a glue drop preparation cold chamber and a power device; the power device is connected with the glue drop preparation cold chamber; the glue droplet preparation cold chamber comprises a refrigeration module and a preparation module, the refrigeration module is arranged at any position around the preparation module, and the refrigeration module is used for adjusting a temperature parameter corresponding to a to-be-treated organ sample in the preparation module; the power device is used for driving an oil phase and a to-be-treated organ-like sample to enter the glue drop preparation cold chamber, so that the glue drop preparation cold chamber generates first glue drops for the to-be-treated organ-like sample; a detection subsystem; the detection subsystem is connected with the liquid drop preparation subsystem, and the problem of pre-coagulation in the preparation process of the organ-like sample is avoided through the organ-like sample preparation system, so that the preparation efficiency of the organ-like sample is improved.

Description

Technical Field

[0001] The embodiments of the present application relate to the field of biomanufacturing technology, and in particular to an organoid sample preparation system. Background Art

[0002] As a three-dimensional in vitro culture model, organoids have demonstrated significant application value in drug development, drug sensitivity testing, and precision medicine. Their technological implementation relies on the large-scale production of highly uniform organoid units.

[0003] Currently, laboratories routinely use manual dispensing with a pipette to prepare organoid-matrigel mixed droplets. In recent years, some general dispensing equipment has also appeared on the market for organoid sample preparation.

[0004] However, since organoid culture requires matrix gel as a substrate, which is very sensitive to temperature, the above-mentioned technology needs to be performed on ice throughout the entire organoid sample preparation process, resulting in poor consistency, large sample loss, and low operational tolerance during droplet plating. Summary of the Invention

[0005] The problem to be solved by the embodiments of the present invention is to provide an organoid sample preparation system to avoid the problem of pre-coagulation during the organoid sample preparation process, thereby improving the efficiency of organoid sample preparation.

[0006] In order to solve the above problems, according to one aspect of an embodiment of the present invention, a system for preparing an organoid sample is provided, comprising:

[0007] droplet preparation subsystem;

[0008] The droplet preparation subsystem includes a droplet preparation cold chamber and a power device; the power device is connected to the droplet preparation cold chamber;

[0009] The droplet preparation cold chamber includes a refrigeration module and a preparation module, wherein the refrigeration module is arranged at any position around the preparation module, and the refrigeration module is used to adjust the temperature parameters corresponding to the organoid samples to be processed in the preparation module;

[0010] The power device is used to drive the oil phase and the organoid sample to be processed into the gel droplet preparation cold chamber, so that the gel droplet preparation cold chamber generates a first gel droplet for the organoid sample to be processed;

[0011] Detection subsystem;

[0012] The detection subsystem is connected to the droplet preparation subsystem, and is used to perform fluorescence detection on the first gel droplet corresponding to the organoid sample to be processed generated by the droplet preparation subsystem, and to sort and collect the target organoid gel droplets according to a preset sampling interval to obtain the target organoid gel droplets, and distribute the target organoid gel droplets to a preset well plate.

[0013] Optionally, the preparation module includes a first preparation module, the first preparation module includes a droplet preparation integrated chip, and the droplet preparation integrated chip is provided with an integrated sample tank.

[0014] Optionally, the power device includes a syringe pump; the sample tank includes a first sample tank;

[0015] When the power device is a syringe pump, the droplet preparation integrated chip is a first droplet preparation integrated chip; the first droplet preparation integrated chip is integrated with the first sample slot at a first preset position.

[0016] Optionally, a first sample tank is provided on one side of the first droplet preparation integrated chip, and a sample spotting port is provided at one end of the first sample tank, and the sample spotting port is used to obtain the organoid sample to be processed transmitted by the power device, and the other end is connected to the sample mixing pipeline, and the sample mixing pipeline forms a first preset interface at the other end. The first preset interface includes a T-shaped, cross-shaped or coaxial laying pipeline interface and an oil phase interface, the laying pipeline interface is connected to the detection subsystem, and the oil phase interface is used to obtain the oil phase transmitted by the power device.

[0017] Optionally, the power device includes a pressure pump; the sample tank includes a second sample tank;

[0018] When the power device is a pressure pump, the droplet preparation integrated chip is a second droplet preparation integrated chip; the second droplet preparation integrated chip is integrated with at least two second sample slots at a second preset position.

[0019] Optionally, at least two second sample slots are provided on the second droplet preparation integrated chip, each of the second sample slots is provided with a sample point port at one end, and a first preset interface is formed at the other end, the first preset interface includes a T-shaped, cross-shaped or coaxial laying pipeline interface and an oil phase interface, the laying pipeline interface is connected to the detection subsystem, and the oil phase interface is used to obtain the oil phase transmitted by the power device.

[0020] Optionally, the glue drop preparation cold chamber further comprises:

[0021] Sealing cover;

[0022] The sealing cover is provided with a sealing structure, and the sealing cover is used to seal the preparation module. The sealing cover is provided with a plurality of interfaces, and the plurality of interfaces respectively correspond to the corresponding interfaces on the droplet preparation integrated chip in the first preparation module.

[0023] Optionally, the preparation module includes a second preparation module;

[0024] The second preparation module includes a droplet preparation chip and a sample injection unit;

[0025] The injection unit is a tubular injection bottle or an injection ring.

[0026] Optionally, the power device is used to drive the oil phase and the organoid sample to be processed into the injection unit and the droplet preparation chip in the droplet preparation cold chamber.

[0027] Optionally, the system further includes a shell, which is a closed or non-closed cavity composed of multiple preset polygons, the power device and the droplet preparation cold chamber are arranged on any surface or any position inside the shell, and the detection subsystem is arranged inside the shell.

[0028] The technical solution provided by the present invention brings at least the following beneficial effects:

[0029] In the present invention, a power device drives the continuous generation of microfluidic droplets, and the droplet preparation cold chamber maintains a low temperature to avoid damaging the preparation of organoid samples, that is, to avoid pre-condensation of organoid samples. Combined with real-time fluorescence detection and sorting, the processing speed is significantly improved; based on the preset fluorescence signal of the detection subsystem, the target droplets are accurately sorted to ensure that the number, activity and size of organoids in each well plate are highly uniform; droplet encapsulation is combined with an invalid sample disposal mechanism to reduce the amount of organoids, so that precious samples can be efficiently utilized. The entire organoid sample preparation system is designed to operate continuously in an assembly line, with seamless connection between generation-detection-sorting, breaking through the bottleneck of traditional batch processing. Through the collaborative innovation of the droplet preparation subsystem and the detection subsystem, the fully automated and efficient preparation of high-throughput organoid microsphere samples is achieved.

[0030] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application, it can be implemented in accordance with the contents of the specification. In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a system block diagram of an organoid sample preparation system provided in an embodiment of the present application;

[0032] Figure 2is an exemplary structural diagram of an organoid sample preparation system provided in an embodiment of the present application;

[0033] Figure 3 This is a schematic structural diagram of a first droplet preparation integrated chip in an organoid sample preparation system provided in an embodiment of the present application;

[0034] Figure 4 This is a schematic structural diagram of a second droplet preparation integrated chip in an organoid sample preparation system provided in an embodiment of the present application;

[0035] Figure 5 1 is a schematic diagram of the cover closing structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system provided in an embodiment of the present application;

[0036] Figure 6 Schematic diagram of the cover connection structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system provided in an embodiment of the present application;

[0037] Figure 7 This is a schematic diagram of the open cover structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system provided in an embodiment of the present application.

[0038] Explanation of the accompanying drawings: 1-droplet preparation subsystem; 11-power device; 12-droplet preparation cold chamber; 121-first droplet preparation integrated chip; 1211-first sample tank; 1212-sample spotting port; 1213-sample mixing pipeline; 1214-plate pipeline interface; 1215-oil phase interface; 122-second droplet preparation integrated chip; 1221-second sample tank; 123-chip card slot; 124-refrigeration module; 1241-cold block; 125-preparation module; 126-sealing structure; 127-cover plate oil phase interface; 128-cover plate plate pipeline interface; 129-cover plate sample interface; 130-sealing cover; 2-detection subsystem; 3-radiator; 4-waste liquid pump; 5-housing. DETAILED DESCRIPTION

[0039] The following describes exemplary embodiments of the present application in more detail with reference to the accompanying drawings. Although exemplary embodiments of the present application are shown in the accompanying drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.

[0040] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of embodiments of the present invention. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known structures and technologies are omitted to avoid unnecessary confusion of the concept of the present invention.

[0041] It should be noted that the directional terms mentioned in the embodiments, such as "up", "down", "front", "back", "left", "right", etc., are only reference to the directions of the drawings. When the orientation of the elements / components changes, the "up" in the corresponding structure may change to "down". Therefore, the above description should not be understood as an absolute meaning in order to clearly describe the relative positions, and the above description is not intended to limit the scope of protection of the present invention. Throughout the drawings, the same elements are represented by the same or similar figure marks. Conventional structures or constructions will be omitted when they may cause confusion in the understanding of the present invention. The shapes and sizes of the components in the drawings do not reflect the actual size and proportion, but only illustrate the contents of the embodiments of the present invention. In addition, in the claims, any reference symbols placed between brackets should not be constructed as limitations on the claims.

[0042] The organoid sample preparation system provided by the present invention has a power device that drives the continuous generation of microfluidic droplets, and the droplet preparation cold chamber maintains a low temperature to avoid damaging the preparation of organoid samples, that is, to avoid pre-condensation of organoid samples. Combined with real-time fluorescence detection and sorting, the processing speed is significantly improved; based on the preset fluorescence signal of the detection subsystem, the target droplets are accurately sorted to ensure that the number, activity and size of organoids in each well plate are highly uniform; droplet encapsulation is combined with an invalid sample discard mechanism to reduce the amount of organoids, so that precious samples can be efficiently utilized. The entire organoid sample preparation system is designed for continuous operation in an assembly line, with seamless connection between generation, detection and sorting, breaking through the bottleneck of traditional batch processing. Through the collaborative innovation of the droplet preparation subsystem and the detection subsystem, the fully automated and efficient preparation of high-throughput organoid microsphere samples is achieved.

[0043] Figure 1 is a system block diagram of an organoid sample preparation system according to an embodiment of the present invention. Figure 2 is an exemplary structural diagram of an organoid sample preparation system according to an embodiment of the present invention. Figure 3 This is a schematic diagram of the structure of the first droplet preparation integrated chip in the organoid sample preparation system according to one embodiment of the present invention. Figure 4 This is a schematic diagram of the structure of the second droplet preparation integrated chip in the organoid sample preparation system according to one embodiment of the present invention. Figure 51 is a schematic diagram of the cover closing structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system according to one embodiment of the present invention. Figure 6 1 is a schematic diagram of the cover connection structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system according to one embodiment of the present invention. Figure 7 Schematic diagram of the open cover structure of an exemplary droplet preparation cold chamber in an organoid sample preparation system according to one embodiment of the present invention.

[0044] In the embodiment of the present invention, referring to Figure 1-Figure 7 , 1-droplet preparation subsystem; 11-power device; 12-gel droplet preparation cold chamber; 121-first droplet preparation integrated chip; 1211-first sample slot; 1212-sample point port; 1213-sample mixing pipeline; 1214-plate pipeline interface; 1215-oil phase interface; 122-second droplet preparation integrated chip; 1221-second sample slot; 123-chip card slot; 124-refrigeration module; 1241-cold block; 125-preparation module; 126-sealing structure; 127-cover plate oil phase interface; 128-cover plate plate pipeline interface; 129-cover plate sample interface; 130-sealing cover; 2-detection subsystem; 3-radiator; 4-waste liquid pump; 5-shell.

[0045] It should be noted that since organoid culture requires matrix gel as a substrate, it is very sensitive to temperature. However, related technologies still have problems such as poor consistency, large sample loss, and low operational tolerance during droplet plating.

[0046] Therefore, in an embodiment of the present invention, an organoid sample preparation system is provided, which includes: a droplet preparation subsystem 1 and a detection subsystem 2, wherein the droplet preparation subsystem 1 includes a droplet preparation cold chamber 12 and a power device 11, and the power device 11 is connected to the droplet preparation cold chamber 12.

[0047] The droplet preparation cold chamber 12 includes a refrigeration module 124 and a preparation module 125, wherein the refrigeration module 124 is arranged at any position around the preparation module 125, and the refrigeration module 124 is used to adjust the temperature parameters corresponding to the organoid samples to be processed in the preparation module 125;

[0048] The power device 11 is used to drive the oil phase and the organoid sample to be processed into the gel droplet preparation cold chamber, so that the gel droplet preparation cold chamber generates a first gel droplet for the organoid sample to be processed;

[0049] Specifically, the power device 11 can be connected to the corresponding receiving interfaces in the droplet preparation cold chamber 12 through the liquid circulation pipeline, thereby driving the oil phase and the sample into the droplet preparation cold chamber 12 for preparing the droplets.

[0050] Specifically, the detection subsystem 2 is connected to the droplet preparation subsystem 1, and is used to perform fluorescence detection on the first gel droplet corresponding to the organoid sample to be processed generated by the droplet preparation subsystem 1, and to sort and collect it according to the preset sampling interval to obtain the target organoid gel droplet, and then distribute the target organoid gel droplet to the preset well plate.

[0051] It should be noted that the above-mentioned fluorescence detection is to detect the fluorescence value corresponding to each first gel droplet through the detection subsystem 2, record the fluorescence value, and divide the first gel droplet according to the preset sampling interval to ensure its consistency. Specifically, based on the fluorescence value, more consistent organoid gel droplets are allocated to the 96-well plate for subsequent culture and detection, for example, drug sensitivity testing.

[0052] Furthermore, in an embodiment of the present invention, the preparation module 125 includes a first preparation module, and the first preparation module includes a droplet preparation integrated chip, and the droplet preparation integrated chip is provided with an integrated sample tank.

[0053] It should be noted that in the embodiment of the present application, the preparation module 125 has two structural forms, one is the first preparation module, which is composed of a droplet preparation integrated chip, and the other is the second preparation module, which is composed of a droplet preparation chip and a sampling unit.

[0054] First, for the first preparation module, the automated preparation process of droplets is realized by designing an integrated droplet preparation integrated chip. Different from the second preparation module composed of a droplet preparation chip and an injection unit, this method can fully close the flow channel to prevent the sample from being exposed to the air, prevent microbial contamination or aerosol interference, and the ultra-short flow channel almost does not generate bubbles. Even if bubbles are generated, they can be quickly discharged through the chip design. In the subsequent operation of the system, only the sample needs to be injected into the injection slot, reducing the use of pipelines.

[0055] Specifically, in an embodiment of the present invention, the droplet preparation integrated chip will be equipped with different droplet preparation integrated chips according to the specific configuration of the power device.

[0056] The power device may include but is not limited to an injection pump and a pressure pump. Figure 2 In the specific exemplary structural diagram given, the power device 11 is a specific structure of a double injection pump.

[0057] It should be noted that one side of the dual syringe pump can accurately push the oil phase as the continuous phase, and the other side of the pump can push the aqueous phase of the organoid sample as the dispersed phase. Then, when the two phases intersect in the first droplet preparation integrated chip 121 or the T-shaped or flow focusing channel of the droplet preparation chip, the shear force will cause the organoid sample to break into monodisperse droplets.

[0058] Therefore, in an embodiment of the present invention, when the power device 11 equipped in the organoid sample preparation system is a syringe pump, the droplet preparation integrated chip is the first droplet preparation integrated chip 121 .

[0059] The first droplet preparation integrated chip 121 is integrated with a first sample tank at a first preset position.

[0060] Further, refer to Figure 3 A first sample tank 1211 is provided on one side of the first droplet preparation integrated chip 121, and a sample spotting port 1212 is provided at one end of the first sample tank 1211. The sample spotting port 1212 is used to obtain the organoid sample to be processed transmitted by the power device 11, and the other end is connected to the sample mixing pipe 1213. The sample mixing pipe 1213 forms a first preset interface at the other end. The first preset interface includes a T-shaped, cross-shaped or coaxial laying pipeline interface 1214 and an oil phase interface 1215. The laying pipeline interface 1214 is connected to the detection subsystem 2, and the oil phase interface 1215 is used to obtain the oil phase transmitted by the power device 11.

[0061] Specifically, the first droplet preparation integrated chip 121 achieves precise mixing of organoid samples and oil phase and droplet generation through a three-dimensional flow channel integrated design. The sample spotting port 1212 is directly connected to the power device. The power device 11 (syringe pump / pressure pump) injects the organoid sample suspension directly into the sample spotting port. The pipeline is reduced to avoid excessive sample residue. The sample is subjected to mild shear force through the sample mixing pipeline 1213 to evenly disperse the organoids while maintaining cell activity.

[0062] Specifically, Figure 3 The above is an exemplary structure of a T-type interface. In addition, there are cross-type and coaxial types. Furthermore, through the T-type / cross-type interface, the oil phase is vertically cut into the sample flow from the oil phase interface 1215, and monodisperse droplets are generated by shear fracture.

[0063] Furthermore, a coaxial interface is used to allow the oil phase to wrap around the sample to form a sheath flow, achieving gentle wrapping droplet generation and reducing the organoid damage rate.

[0064] The slab pipeline interface 1214 is seamlessly connected to the detection subsystem 2, and the generated droplets pass directly to the fluorescence detection area through this interface. The temperature throughout the process can be adjusted to the bottom or surrounding of the chip through the cooling module 124 to prevent the hydrogel from pre-solidifying.

[0065] Therefore, in an embodiment of the present invention, the three steps of "injection-mixing-droplet generation" are compressed into a single chip, the total length of the flow path is reduced, the path is shortened compared to the traditional split system, and the risk of contamination and sample loss are reduced.

[0066] In an embodiment of the present invention, when the power device 11 equipped in the organoid sample preparation system is a pressure pump, the droplet preparation integrated chip is the second droplet preparation integrated chip 122 .

[0067] It should be noted that the pressure pump introduces compressed gas into the top space of the oil phase storage tank and the organoid sample storage tank through a proportional valve, applying a constant pressure on the liquid surface. The pressure difference drives the oil phase and the organoid sample to flow through independent pipelines to the second droplet preparation integrated chip 122 or the droplet preparation chip. The two phases intersect in the second droplet preparation integrated chip 122 or the droplet preparation chip flow focusing structure, and the organoid sample is broken into uniform droplets under the shear of the oil phase.

[0068] The two-phase gas pressure drive driven by the pressure pump is gentler and reduces the damage rate of the organoid sample. Since the pressure pump is driven by pressure difference, two second sample tanks 1221 are included.

[0069] Specifically, refer to Figure 4 At least two second sample slots 1221 are provided on the second droplet preparation integrated chip 122. A sample port 1212 is provided at one end of each second sample slot 1221, and a first preset interface is formed at the other end. The first preset interface includes a T-shaped, cross-shaped or coaxial laying pipeline interface 1214 and an oil phase interface 1215. The laying pipeline interface 1214 is connected to the detection subsystem 2, and the oil phase interface 1215 is used to obtain the oil phase transmitted by the power device 11.

[0070] In addition, in an embodiment of the present invention, the preparation module includes a second preparation module;

[0071] The second preparation module includes a droplet preparation chip and a sample injection unit;

[0072] The injection unit is a tubular injection bottle or an injection ring.

[0073] Use a tubular vial or sampling loop to avoid air bubbles.

[0074] It should be noted that the materials of the first droplet preparation integrated chip 121 and the second droplet preparation integrated chip 122 and the corresponding droplet preparation chips can be any one of PMMA, PC, PDMS or PP, and the present invention does not impose specific limitations.

[0075] Furthermore, if the second preparation module is configured in the organoid sample preparation system, the power device is used to drive the oil phase and the organoid sample to be processed into the sampling unit and the droplet preparation chip in the droplet preparation cold chamber. Then, at the T-shaped interface / cross-shaped interface / coaxial interface corresponding to the droplet preparation chip, shear force is used to form droplets, and a certain amount of organoids are wrapped therein, forming a 3D culture structure after room temperature.

[0076] Furthermore, the glue drop preparation cold chamber also includes:

[0077] Radiator 3;

[0078] The radiator 3 is arranged at any position around the preparation module and / or the refrigeration module 124 .

[0079] It should be noted that the radiator can be in the form of a heat dissipation hole or other device form, and the present invention does not make specific restrictions. The radiator can ensure the normal operation of the first droplet preparation integrated chip 121 and the second droplet preparation integrated chip 122 as well as the droplet preparation chip and the refrigeration module 124.

[0080] Furthermore, the refrigeration module 124 in the present invention can be a semiconductor refrigeration device or other refrigeration device. The refrigeration module can effectively solve the problem of pre-coagulation of organoid samples and realize overall automation in the organoid sample preparation system without a lot of manpower and time costs.

[0081] Furthermore, the droplet preparation cold chamber also includes: a sealing cover 130; a sealing structure 126 is provided on the sealing cover, the sealing cover 130 is used to seal the preparation module, and a plurality of interfaces are provided on the sealing cover 130, and the plurality of interfaces respectively correspond to the corresponding interfaces on the droplet preparation integrated chip in the first preparation module.

[0082] Specifically, refer to Figure 7 , a schematic diagram of an exemplary open cover structure of a droplet preparation cold chamber, the droplet preparation cold chamber 12 includes a refrigeration module 124, which can include a semiconductor refrigerator and a cold block 1241 disposed below any type of preparation module, and a corresponding interface is provided on the sealing cover 130 corresponding to the first droplet preparation integrated chip 121 or the second droplet preparation integrated chip 122. Taking the first droplet preparation integrated chip as an example, the sealing cover 130 is provided with a sealing structure 126, wherein, Figure 7 The example given in the text can be a magnetic strip. In addition, it can also be a clip, a screw, etc. There are corresponding interfaces on the sealing cover. The cover plate pipeline interface 128, the cover plate oil phase interface 127 and the cover plate sample interface 129 correspond one by one to the plate pipeline interface 1214, the oil phase interface 1215 and the sample port 1212 respectively.

[0083] It should be noted that the chip is sealed by a sealing cover, and the corresponding interface and sealing structure on the sealing cover can be precisely aligned with the interface on the droplet preparation integrated chip, so as to better realize the integration and prepare the cold chamber through the completely sealed droplet. While ensuring that the temperature is controllable, the risk of contamination in the process of preparing organoid samples can be reduced.

[0084] Furthermore, the organoid sample preparation system also includes a detection subsystem 2, which can be found in Figure 2 , the detection subsystem may include a pipeline and a detection bracket, a hole plate displacement platform and a planking cabin.

[0085] Specifically, the detection subsystem 2 performs fluorescence detection on the first gel droplet corresponding to the organoid sample to be processed generated by the droplet preparation subsystem through the above structure, and sorts and collects it according to the preset sampling interval to obtain the target organoid gel droplet, and distributes the target organoid gel droplet to the preset well plate, that is, automatically spreads it to the spreading chamber through the well plate displacement platform.

[0086] Furthermore, the organoid sample preparation system also includes a waste liquid pump 4, which is used to collect droplets that fail to meet the standards after detection by the detection subsystem.

[0087] Furthermore, the organoid sample preparation system also includes a shell 5, which is a closed or non-closed cavity composed of multiple preset polygons. The power device 11 and the droplet preparation cold chamber 12 are arranged on any surface or at any position inside the shell 5, and the detection subsystem 2 is arranged inside the shell 5.

[0088] It should be noted that in the above structure, for the automation of the system, each module, such as the modules in the droplet preparation subsystem 1 and the detection subsystem 2, will be encapsulated. Specifically, it can be a cube or a cuboid or other regular or irregular graphics encapsulated based on actual needs. It can be a closed cavity with a built-in camera and an external display to view the operation process, or it can be a non-closed cavity, such as Figure 2 As shown, the opening is located on the surface of the shell directly facing the detection subsystem, and the specific position and shape are not specifically limited in the present invention.

[0089] It should be noted that, in the embodiments of the present application, the above-mentioned organoid sample preparation system corresponds to a specific method embodiment, an organoid sample preparation method, and the organoid sample preparation method includes:

[0090] In step 101, a power device drives the oil phase and the organoid sample to be processed into the droplet preparation cold chamber, so that the droplet preparation cold chamber generates a first droplet for the organoid sample to be processed through the preparation module and controls the temperature of the organoid sample to be processed during the generation process through the refrigeration module.

[0091] It should be noted that in the embodiment of the present application, a power device (in this embodiment, a syringe pump) drives the oil phase and sample (cells / organoids) into the droplet preparation chip. Specifically, shear force is used to form droplets at the T-shaped / cross-shaped / coaxial opening of the droplet preparation chip, and a certain amount of organoids are wrapped therein, forming a 3D culture structure at room temperature.

[0092] In step 102, the detection subsystem performs fluorescence detection on the first gel droplet corresponding to the organoid sample to be processed generated by the droplet preparation subsystem, and sorts and collects the droplets according to a preset sampling interval to obtain target organoid gel droplets, and distributes the target organoid gel droplets to a preset well plate.

[0093] It should be noted that in the embodiments of the present application, the fluorescence value is judged to distribute more consistent organoid droplets into a preset well plate. Specifically, the above-mentioned preset well plate can be a 96-well plate, and then used for subsequent culture and testing, such as drug sensitivity testing.

[0094] Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all modifications and variations that fall within the scope of the present invention.

[0095] The embodiments of the present application are described above in conjunction with the accompanying drawings, but the present application is not limited to the above-mentioned specific implementation methods. The above-mentioned specific implementation methods are merely illustrative and not restrictive. Under the guidance of this application, ordinary technicians in this field can also make many forms without departing from the purpose of this application and the scope of protection of the claims, all of which are within the protection of this application.

[0096] Obviously, those skilled in the art may make various modifications and variations to the present invention without departing from the spirit and scope of the present invention. Thus, if such modifications and variations fall within the scope of the claims and their equivalents, the present invention is intended to include such modifications and variations.

Claims

1. An organoid sample preparation system, characterized in that: The system comprises: droplet preparation subsystem; The droplet preparation subsystem includes a droplet preparation cold chamber and a power device; the power device is connected to the droplet preparation cold chamber; The droplet preparation cold chamber includes a refrigeration module and a preparation module, wherein the refrigeration module is arranged at any position around the preparation module, and the refrigeration module is used to adjust the temperature parameters corresponding to the organoid samples to be processed in the preparation module; The power device is used to drive the oil phase and the organoid sample to be processed into the gel droplet preparation cold chamber, so that the gel droplet preparation cold chamber generates a first gel droplet for the organoid sample to be processed; Detection subsystem; The detection subsystem is connected to the droplet preparation subsystem, and is used to perform fluorescence detection on the first gel droplet corresponding to the organoid sample to be processed generated by the droplet preparation subsystem, and to sort and collect the target organoid gel droplets according to a preset sampling interval to obtain the target organoid gel droplets, and distribute the target organoid gel droplets to a preset well plate.

2. The system according to claim 1, wherein: The preparation module includes a first preparation module, the first preparation module includes a droplet preparation integrated chip, and the droplet preparation integrated chip is provided with an integrated sample tank.

3. The system according to claim 2, characterized in that The power device includes a syringe pump; the sample tank includes a first sample tank; When the power device is a syringe pump, the droplet preparation integrated chip is a first droplet preparation integrated chip; the first droplet preparation integrated chip is integrated with the first sample slot at a first preset position.

4. The system according to claim 3, characterized in that A first sample tank is provided on one side of the first droplet preparation integrated chip, and a sample spotting port is provided at one end of the first sample tank, and the sample spotting port is used to obtain the organoid sample to be processed transmitted by the power device, and the other end is connected to the sample mixing pipeline, and the sample mixing pipeline forms a first preset interface at the other end. The first preset interface includes a T-shaped, cross-shaped or coaxial laying pipeline interface and an oil phase interface. The laying pipeline interface is connected to the detection subsystem, and the oil phase interface is used to obtain the oil phase transmitted by the power device.

5. The system according to claim 2, wherein: The power device includes a pressure pump; the sample tank includes a second sample tank; When the power device is a pressure pump, the droplet preparation integrated chip is a second droplet preparation integrated chip; the second droplet preparation integrated chip is integrated with at least two second sample slots at a second preset position.

6. The system according to claim 5, characterized in that At least two second sample slots are provided on the second droplet preparation integrated chip, each of which is provided with a sample point port at one end and a first preset interface at the other end. The first preset interface includes a T-shaped, cross-shaped or coaxial plate pipeline interface and an oil phase interface. The plate pipeline interface is connected to the detection subsystem, and the oil phase interface is used to obtain the oil phase transmitted by the power device.

7. The system according to claim 2, wherein: The glue drop preparation cold chamber also includes: Sealing cover; The sealing cover is provided with a sealing structure, and the sealing cover is used to seal the preparation module. The sealing cover is provided with a plurality of interfaces, and the plurality of interfaces respectively correspond to the corresponding interfaces on the droplet preparation integrated chip in the first preparation module.

8. The system according to claim 1, wherein: The preparation module includes a second preparation module; The second preparation module includes a droplet preparation chip and a sample injection unit; The injection unit is a tubular injection bottle or an injection ring.

9. The system according to claim 8, characterized in that The power device is used to drive the oil phase and the organoid sample to be processed into the injection unit and the droplet preparation chip in the droplet preparation cold chamber.

10. The system according to any one of claims 1 to 9, characterized in that: The system also includes a shell, which is a closed or non-closed cavity composed of multiple preset polygons. The power device and the droplet preparation cold chamber are arranged on any surface or any position inside the shell, and the detection subsystem is arranged inside the shell.

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