Integrated device for generating decellularized organ patch

Abstract

The invention belongs to the field of medical instruments, and discloses an integrated device for generating a decellularized organ patch, which is characterized in that a decellularized chip is designed and comprises a decellularized processing module and an oscillator, and the decellularized processing module is arranged above the oscillator and is fixedly connected with the oscillator; the decellularization processing module comprises a middle layer and a cell filtering layer, wherein the middle layer comprises an open cavity formed in the central area of the middle layer and a cell filtering net covering the open cavity; the bottom plate is bonded on the lower layer of the middle layer, a concave flow channel is arranged on one surface, facing the middle layer, of the bottom plate, and the concave flow channel is positioned in an orthographic projection area of the cell filter screen on the bottom plate; the upper cover is bonded on the upper layer of the middle layer and is provided with a liquid inlet communicated with the head end of the concave flow channel and a liquid outlet communicated with the tail end of the concave flow channel; and integrating the control unit, the decellularization chip and the fluid module to form an integrated device. Based on the device, decellularization can be controlled and adjusted to be completed in a stable and accurate environment.

Description

Technical Field

[0001] The technical field of the present invention related to medical devices, more specifically, relates to an integrated device for generating a decellularized organ patch. Background Art

[0002] In recent years, with the rapid development of regenerative medicine and tissue engineering, decellularization technology has received increasing attention. Decellularized scaffolds are often used to replace damaged or diseased organs, which can effectively restore organ function and improve the quality of life of patients. However, traditional decellularization methods often have problems such as low efficiency, complex operation, and unstable quality. These problems limit the popularization and promotion of decellularization in clinical applications.

[0003] Currently, many studies focus on using biomaterials and cell technology to generate functional tissues or organs. Although some laboratories have successfully produced simple tissue structures, there are still certain technical challenges in large-scale production and high-throughput culture. In addition, most existing equipment is a single functional module and lacks integrated design, which leads to the need to frequently replace equipment during the experiment, increasing the complexity and time cost of the operation.

[0004] Therefore, there is an urgent need for an efficient, intelligent and integrated automated device to solve the many technical challenges currently faced in the process of generating complete organ patches. Summary of the invention

[0005] In view of the above defects or improvement needs of the prior art, the present invention provides an integrated device for generating decellularized organ patches. The device is designed with a decellularized chip with an oscillator and a circulation channel, and integrates a control unit, a decellularized chip, a fluid module and a temperature control module in a box, thereby solving the technical problems of the prior art in that the generation of decellularized organ patches is not efficient enough and the reliability is not high.

[0006] To achieve the above-mentioned object, according to one aspect of the present invention, an integrated device for generating a decellularized organ patch is provided, comprising a detachable housing, a control unit, a decellularization chip and a fluid module, wherein the decellularization chip and the fluid module are arranged in the housing;

[0007] The decellularization chip comprises a decellularization processing module and an oscillator. The decellularization processing module is arranged above the oscillator and is fixedly connected to the oscillator, so that the decellularization chip resonates through the oscillation of the oscillator. The decellularization processing module comprises:

[0008] The middle layer comprises an opening arranged in the central area of ​​the middle layer, and a cell filter covering the opening;

[0009] A bottom plate bonded to the lower layer of the middle layer, with a concave flow channel disposed on a side facing the middle layer and located in the orthographic projection area of ​​the cell filter on the bottom plate;

[0010] An upper cover bonded to the upper layer of the middle layer, which is provided with a liquid inlet communicated with the head end of the concave flow channel, and a liquid outlet communicated with the end of the concave flow channel;

[0011] Wherein, the decellularization chip is electrically connected to the control unit via an oscillator, the decellularization chip is respectively connected to the fluid module via the liquid inlet and the liquid outlet, and the fluid module is electrically connected to the control unit.

[0012] As a preferred embodiment of the present invention, the middle layer comprises at least one opening, and is provided with an equal number of cell filters, and each of the openings is communicated with each other at the upper part of the flow channel to form a microfluidic channel.

[0013] As a preferred embodiment of the present invention, the integrated device includes at least one cellular processing module, and each of the modules is independently connected to the fluid module.

[0014] The integrated device includes at least one cellular processing module, and is independently connected to the fluid module.

[0015] As a preferred embodiment of the present invention, the decellularization chip further comprises a chip fixing frame, and the chip fixing frame is used for fixing and supporting the decellularization chip.

[0016] As a preferred embodiment of the present invention, the fluid module includes a liquid pump, an external pipe and a plurality of liquid storage tanks, the liquid pump is arranged in the liquid storage tank, and the liquid pump is respectively connected to the liquid inlet and the liquid outlet of the decellularization chip through the external pipe.

[0017] As a preferred embodiment of the present invention, the integrated device further comprises a temperature module electrically connected to the control unit;

[0018] The temperature module includes a refrigeration element, a temperature sensor and a refrigeration and heat dissipation fan; the refrigeration element and the temperature sensor are both arranged inside the box; the refrigeration and heat dissipation fan is nested on the side shell of the box, and the air outlet of the refrigeration and heat dissipation fan faces outside the box.

[0019] As a preferred embodiment of the present invention, the integrated device also includes a liquid valve control, which is arranged on the side wall of the box body, communicated with the liquid storage tank, and electrically connected to the control unit to control the inflow or discharge of liquid in the decellularization chip.

[0020] As a preferred embodiment of the present invention, a hatch is provided on the top surface of the box body.

[0021] As a preferred embodiment of the present invention, the control unit includes a control panel, which is arranged on the box body and is used to display and adjust the execution parameters of each module in the integrated device through the control panel.

[0022] As a preferred embodiment of the present invention, the integrated device further comprises a main power switch, which is respectively connected to the control unit, the decellularization chip and the fluid module, and is used to control the switch of the integrated device.

[0023] In general, the above technical solution conceived by the present invention has the following technical advantages compared with the prior art:

[0024] (1) The integrated device of the present invention is designed with a decellularization chip driven by an oscillator, and the decellularization chip includes a middle layer with a cell filter and a bottom plate with a flow channel, so that during the decellularization process, the tissue sample is fixed in a relatively stable position by the cell filter to reduce damage to the extracellular matrix, the oscillator promotes full contact between the cleaning solution and the tissue sample, the cell fragments enter the lower layer flow channel, and the cell fragments are taken away by the flow channel to complete continuous liquid replacement, thereby improving the decellularization effect, thereby jointly optimizing the decellularization process; at the same time, the device integrates the decellularization chip, the control unit and the fluid module, and relies on the connection between each module and the control unit to achieve intelligent control of the decellularization environment. Specifically, by connecting the oscillator to the control unit, the decellularization process is effectively regulated, and by connecting the decellularization chip to the fluid module, the liquid flow in the decellularization chip is driven to achieve automatic liquid replacement of the cleaning solution. Therefore, the device uses a control module to uniformly control and regulate decellularization in a more stable and precise environment.

[0025] (2) Preferably, the present invention arranges multiple open cavities and the same number of cell filters at intervals in the middle layer of a decellularization treatment module, which are connected by microfluidic channels, so that the same organ patches can be generated in batches using a batch of decellularization processes, or different types of organ patches can be generated at one time.

[0026] (3) Preferably, multiple decellularization processing modules can be integrated into the integrated device of the present invention for simultaneous operation and cultivation, and each unit can be independently connected to and driven by the liquid circulation pump in the fluid module, so as to realize large-scale generation of the same organ patch by integrating a batch of decellularization processes, or to generate different types of organ patches at one time.

[0027] (4) Preferably, the integrated device of the present invention also includes a temperature module to meet the requirement of low temperature for maintaining the activity of extracellular mechanism proteins during the decellularization process. Specifically, the environment inside the box is cooled by the temperature control module, and the temperature sensor inside the box is used to feedback and control the above-mentioned refrigeration equipment, thereby maintaining the stability of the decellularization environment inside the cabin.

[0028] In summary, the device of the present invention improves the efficiency and quality of decellularized organ patch generation by designing a decellularization chip with an oscillator and a cell filter, and integrating a control unit, a decellularization chip, a fluid module and a temperature control module in one box. The use of an automated system can not only improve the efficiency and consistency of organ patch generation, but also reduce the errors caused by human operation, thereby improving the quality of the final product. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 A schematic diagram of an integrated device for generating a decellularized organ patch according to an example of the present invention;

[0030] Figure 2 A schematic diagram of a decellularized chip structure according to an example of the present invention;

[0031] Figure 3 Schematic diagram of the structure of the decellularization processing module in the decellularization chip according to an example of the present invention.

[0032] In all the drawings, the same figure marks are used to represent the same elements or structures, including: 1. hatch; 2. refrigeration chamber; 3. liquid storage chamber; 4. liquid circulation pump; 5. cooling fan; 6. oscillator; 7. liquid valve control; 8. control panel; 9. chip fixing frame; 10. temperature sensor; 11. decellularization processing module; 12. liquid inlet; 13. cell filter; 14. concave flow channel, 15-liquid outlet. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0034] In the present invention, Figure 1 As shown, an integrated device for generating a decellularized organ patch is provided, comprising a detachable housing, a control unit, a decellularization chip and a fluid module, wherein the decellularization chip and the fluid module are arranged in the housing;

[0035] Specifically, Figure 2As shown, the decellularization chip includes a decellularization processing module 11 and an oscillator 6. The decellularization processing module 11 is arranged above the oscillator 6 and is fixedly connected to the oscillator 6, so that the decellularization chip resonates through the oscillation of the oscillator;

[0036] Further, such as Figure 3 As shown, the decellularization processing module 11 includes:

[0037] The middle layer comprises an opening arranged in the central area of ​​the middle layer, and a cell filter 13 covering the opening;

[0038] A bottom plate bonded to the lower layer of the middle layer, with a concave flow channel 14 disposed on a side facing the middle layer and located in the orthographic projection area of ​​the cell filter on the bottom plate;

[0039] The upper cover bonded to the upper layer of the middle layer is provided with a liquid inlet 12 connected to the head end of the concave flow channel 14, and a liquid outlet 15 connected to the end of the concave flow channel;

[0040] The intermediate layer is bonded to the bottom plate by a sealant, but the intermediate layer and the upper cover are not required to be sealed and bonded.

[0041] The decellularization chip is electrically connected to the control unit through an oscillator, the decellularization chip is respectively connected to the fluid module through a liquid inlet and a liquid outlet, and the fluid module is electrically connected to the control unit.

[0042] Preferably, a plurality of isolated openings are designed in the middle layer of a specific decellularization processing module, and a corresponding number of cell filters are provided, so that the same organ patches can be produced in batches using a decellularization process, or different types of organ patches can be produced at one time.

[0043] Preferably, in the design of a specific decellularization chip, a plurality of decellularization processing modules can be provided, which are arranged in a flat surface and fixed on a chip fixing bracket, thereby achieving high-throughput decellularization processing in a stable and precise environment.

[0044] Preferably, a chip holder 9 is fixed above the oscillator 6, such as Figure 2 The chip holder shown in the figure is in the shape of a tray and is used for different types of decellularization processing modules.

[0045] Preferably, the fluid module includes a liquid pump, an external pipe and a plurality of liquid storage tanks. The liquid pump is connected to the liquid inlet and the liquid outlet of the decellularization chip through the external pipe, and the liquid pump drives the liquid storage tanks corresponding to the cleaning liquid or washing liquid to circulate the fluid. More than two cleaning liquid or washing liquid storage tanks can be controlled by one or more liquid pumps to release in sequence.

[0046] Preferably, the integrated device of the present invention also includes a temperature module, which also includes a refrigeration element, a temperature sensor and a refrigeration and heat dissipation module. The temperature control system is used to cool the environment inside the equipment chamber, and the temperature detector in the equipment cavity is used to feedback and regulate the above-mentioned refrigeration equipment, thereby maintaining the stability of the decellularization environment in the cabin.

[0047] Preferably, the side wall of the box body is provided with a liquid valve control, which is communicated with the liquid storage tank and connected with the control unit to control the inflow and discharge of liquid in the decellularization chip.

[0048] Preferably, there is a hatch on the top of the box body, and the hatch can be opened separately.

[0049] Preferably, the control unit includes a control panel, which is arranged on the box body. The control panel contains a vibrator control, a liquid pump flow rate, a flow control setting area, and a temperature switch and setting area, that is, the temperature of the temperature module, the liquid circulation pump flow rate and flow, the vibration time and frequency of the oscillator, etc. can be displayed and adjusted through the control panel.

[0050] Preferably, the device has a main power switch outside the box and supports wireless control

[0051] The device of the present invention is applicable to different species, such as pigs, humans, monkeys, etc., to various tissues, such as intestines, livers, lungs, etc., and to different types of tissues, such as normal or pathological.

[0052] The preparation of the relevant structures of the present invention and the application of the device of the present invention are further explained below through specific examples.

[0053] Example 1: Combining laser engraving technology and 3D printing technology to illustrate the process of making a decellularized chip. The following are the steps for making a decellularized chip with a single filter structure:

[0054] (1) Prepare polymethyl methacrylate sheets (sheets are 1mm, 2mm, 5mm, and 1mm from bottom to top), peel off the film on one side, stick on special double-sided tape, and use a laser engraving machine to engrave as follows Figure 3 The sheet-like structure shown in the figure serves as the overall framework structure of the decellularized chip;

[0055] (2) The top layer is a pressure-sensitive adhesive layer, which is directly engraved using a laser engraving machine Figure 3 The top structure is cut and set aside;

[0056] (3) Place the carved overall frame structure as follows: Figure 3 The structures shown are aligned in sequence and bonded through the double-sided adhesive layer, and the top layer is not bonded temporarily;

[0057] (4) Put the bonded whole structure into a hot press together, with the upper and lower pressing surfaces at 60°C for 5 minutes;

[0058] (5) Use a 3D printer to print out Figure 3 The cell filter structure is buckled into the assembled overall frame;

[0059] (6) Place in pure water and ultrasonicate for 24 h, then blow dry with a nitrogen gun.

[0060] Example 2: The use process of automatic sampling of the automated integrated device for generating a complete decellularized organ patch is described in conjunction with a pig heart patch. The specific steps are as follows:

[0061] (1) Prepare the decellularized chip, prepare the pig heart, and slice it to fit the cell filter size;

[0062] (2) Place the tissue sheet into the cell filter of the decellularization chip and seal the chip with a top layer of pressure-sensitive adhesive;

[0063] (3) Place the chip into the device slot and manually connect the tubing to the chip;

[0064] (4) Add cleaning fluid and washing fluid to the liquid storage tank;

[0065] (5) Close the door and control the decellularization process through the control panel or wireless device.

[0066] Example 3: The use process of automatic sampling of the automated integrated device for generating a complete decellularized organ patch is described in conjunction with porcine intestinal tissue. The specific steps are as follows:

[0067] (1) Prepare a decellularization chip with an interface on the side, prepare porcine intestine, and cut it into segments to fit the size of the cell filter;

[0068] (2) A columnar structure is installed horizontally in the cell filter of the decellularization chip, a small segment of pig intestine is put on the columnar structure to fix it, and the chip is encapsulated with a top layer of pressure-sensitive adhesive;

[0069] (3) The pipeline inside the device is directly connected to the card slot, and the external interface is supported by a spring column. The chip is placed in the device card slot, which is directly connected to the pipeline;

[0070] (4) Add cleaning fluid and washing fluid to the liquid storage tank;

[0071] (5) Close the door and control the decellularization process through the control panel or wireless device.

[0072] Example 4: The use of the automated integrated device for generating a complete decellularized organ patch to generate a decellularized gel is described in conjunction with pig skin tissue. The specific steps are as follows:

[0073] (1) Prepare a decellularized chip and pig skin;

[0074] (2) Place the pig skin in liquid nitrogen overnight and take it out and break it the next day;

[0075] (3) Replace the cell filter with a cell filter, put the skin powder in, and seal the chip using a top layer of pressure-sensitive adhesive;

[0076] (4) Place the chip into the device slot and manually connect the tubing to the chip;

[0077] (5) Add cleaning fluid and washing fluid to the liquid storage tank;

[0078] (6) Close the door and control the decellularization process through the control panel or wireless device;

[0079] (7) The decellularized powder is taken out and freeze-dried, digested, and the pH value is adjusted to obtain a decellularized biogel.

[0080] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the present invention and its equivalent technologies, the present invention is also intended to include these changes and variations. The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and their protection scope is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are all within the protection scope of the present invention.

Claims

1. An integrated device for generating a decellularized organ patch, characterized in that: It comprises a detachable box, a control unit, a decellularization chip and a fluid module, wherein the decellularization chip and the fluid module are arranged in the box; The decellularization chip comprises a decellularization processing module and an oscillator. The decellularization processing module is arranged above the oscillator and is fixedly connected to the oscillator, so that the decellularization chip resonates through the oscillation of the oscillator. The decellularization processing module comprises: The middle layer comprises an opening arranged in the central area of ​​the middle layer, and a cell filter covering the opening; A bottom plate bonded to the lower layer of the middle layer, with a concave flow channel disposed on a side facing the middle layer and located in the orthographic projection area of ​​the cell filter on the bottom plate; An upper cover bonded to the upper layer of the middle layer, which is provided with a liquid inlet communicated with the head end of the concave flow channel, and a liquid outlet communicated with the end of the concave flow channel; Wherein, the decellularization chip is electrically connected to the control unit via an oscillator, the decellularization chip is respectively connected to the fluid module via the liquid inlet and the liquid outlet, and the fluid module is electrically connected to the control unit.

2. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The middle layer comprises at least one opening cavity, and is provided with an equal number of cell filters, and each of the opening cavities is communicated with each other at the upper part of the flow channel to form a microfluidic channel.

3. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The integrated device includes at least one cellular processing module, and each of the modules is independently connected to the fluid module.

4. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The decellularization chip further comprises a chip fixing frame, and the chip fixing frame is used for fixing and supporting the decellularization chip.

5. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The fluid module includes a liquid pump, an external pipe and a plurality of liquid storage tanks. The liquid pump is arranged in the liquid storage tanks, and the liquid pump is respectively connected to the liquid inlet and the liquid outlet of the decellularization chip through the external pipe.

6. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The integrated device further comprises a temperature module electrically connected to the control unit; The temperature module includes a refrigeration element, a temperature sensor and a refrigeration and heat dissipation fan; the refrigeration element and the temperature sensor are both arranged inside the box; the refrigeration and heat dissipation fan is nested on the side shell of the box, and the air outlet of the refrigeration and heat dissipation fan faces outside the box.

7. The integrated device for generating a decellularized organ patch according to claim 5, characterized in that: The integrated device also includes a liquid valve control, which is arranged on the side wall of the box body, communicated with the liquid storage tank, and electrically connected to the control unit to control the inflow or discharge of liquid in the decellularization chip.

8. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The top surface of the box body is provided with a hatch.

9. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The control unit includes a control panel, which is arranged on the box and is used to display and adjust the execution parameters of each module in the integrated device through the control panel.

10. The integrated device for generating a decellularized organ patch according to claim 1, characterized in that: The integrated device also includes a main power switch, which is respectively connected to the control unit, the decellularization chip and the fluid module, and is used to control the switch of the integrated device.

Images