An integrated device for generating decellularized organ patches

Abstract

The application belongs to the field of medical instruments, and discloses an integrated device for generating a decellularized organ patch, which is designed as a decellularization chip, which comprises a decellularization processing module and an oscillator, the decellularization processing module is arranged above the oscillator and is fixedly connected with the oscillator; the decellularization processing module comprises: a middle layer, which comprises an open cavity arranged in the central region of the middle layer and a cell filter screen arranged on the open cavity; a bottom plate bonded to the lower layer of the middle layer, which is provided with a concave flow channel on the side facing the middle layer and is located in the orthographic projection region of the cell filter screen on the bottom plate; an upper cover bonded to the upper layer of the middle layer, which is provided with a liquid inlet in communication with the initial end of the concave flow channel and a liquid outlet in communication with the terminal end of the concave flow channel; and an integrated device formed by integrating a control unit, the decellularization chip and a fluid module. Based on the device, the decellularization can be controlled and adjusted to be completed in a stable and accurate environment.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, and more particularly to an integrated device for generating decellularized organ patches. BACKGROUND

[0002] In recent years, with the rapid development of regenerative medicine and tissue engineering, decellularization technology has attracted more and more attention. The scaffold formed by decellularization is usually 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 low efficiency, complex operation, unstable quality and other problems. 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 manufactured simple tissue structures, there are still certain technical challenges in large-scale production and high-throughput culture. In addition, existing equipment is mostly single-function modules, lacking integrated design, resulting in the need to frequently change equipment during experiments, increasing the complexity and time cost of operation.

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

[0005] In view of the above defects or improvement needs of the prior art, the present application provides an integrated device for generating decellularized organ patches. The device solves the technical problems of insufficient efficiency and low reliability in generating decellularized organ patches in the prior art by designing a decellularization chip with an oscillator and a circulating flow channel, and integrating a control unit, a decellularization chip, a fluid module and a temperature control module in a box.

[0006] To achieve the above-mentioned purpose, according to one aspect of the present application, an integrated device for generating decellularized organ patches is provided, comprising a detachable box, a control unit, a decellularization chip and a fluid module, and the decellularization chip and the fluid module are arranged in the box.

[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 with the oscillator, so that the decellularization chip causes resonance through the oscillation of the oscillator; the decellularization processing module comprises:

[0008] The intermediate layer comprises an open cavity arranged in the central region of the intermediate layer and a cell filter screen covering the open cavity.

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

[0010] an upper cover bonded to the upper layer of the intermediate layer, provided with a liquid inlet communicating with the initial end of the concave flow channel, and a liquid outlet communicating with the terminal end of the concave flow channel;

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

[0012] As a preferred embodiment of the present application, the intermediate layer comprises at least one open cavity, and an equal number of cell filter screens are arranged, and each open cavity is communicated with the upper part of the flow channel to form a microfluidic channel.

[0013] As a preferred embodiment of the present application, the integrated device comprises at least one cell processing module, and is independently connected to the fluid module.

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

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

[0016] As a preferred embodiment of the present application, the fluid module comprises 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 connected to the liquid inlet and the liquid outlet of the decellularization chip through the external pipe respectively.

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

[0018] The temperature module comprises a refrigeration element, a temperature sensor and a refrigeration and heat dissipation fan; the refrigeration element and the temperature sensor are 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 the outside of the box.

[0019] As a preferred embodiment of the present application, the integrated device further comprises a liquid valve control arranged on the side wall of the box, in communication with the liquid storage tank, and electrically connected to the control unit to control the inflow or outflow of liquid in the decellularization chip.

[0020] As a preferred embodiment of the present application, the top surface of the box is provided with a hatch.

[0021] As a preferred embodiment of the present application, the control unit comprises a control panel arranged on the box for displaying and adjusting the execution parameters of each module in the integrated device through the control panel.

[0022] As a preferred embodiment of the present application, the integrated device further comprises a power supply master switch connected with the control unit, the decellularization chip and the fluid module respectively for controlling the switch of the integrated device.

[0023] Overall, compared with the prior art, the above technical scheme conceived by the present application mainly has the following technical advantages:

[0024] (1) The integrated device of the present application is driven by an oscillator, and the decellularization chip contains 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 through the cell filter to reduce the damage to the extracellular matrix, the oscillator promotes the full contact of the washing liquid with the tissue sample, the cell fragments enter the lower flow channel, and the cell fragments are carried away by the flow channel to complete continuous liquid exchange, thereby improving the decellularization effect and 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 with each module and the control unit to realize intelligent control of the decellularization environment. Specifically, by connecting the oscillator with the control unit, the decellularization process is effectively regulated, and by connecting the decellularization chip with the fluid module, the liquid flow in the decellularization chip is driven to realize automatic liquid exchange of the washing liquid, so that the device can be uniformly controlled and regulated by one control module to complete the decellularization in a more stable and precise environment.

[0025] (2) Preferably, a plurality of open cavities and the same number of cell filters are arranged in the middle layer of a decellularization processing module and are connected through a microfluidic channel, which can generate the same organ patch in batches or generate different types of organ patches at one time.

[0026] (3) Preferably, the integrated device of the present application can integrate multiple decellularization processing modules for simultaneous operation and culture, and each unit can be individually connected with a liquid circulating pump in the fluid module for driving, which can generate the same organ patch in large scale or 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 need for maintaining the activity of extracellular mechanism proteins at low temperatures during the decellularization process. Specifically, the temperature control module cools the environment inside the chamber, and the temperature sensor inside the chamber provides feedback to regulate the cooling equipment, thereby maintaining the stability of the decellularization environment inside the chamber.

[0028] In summary, the device of this 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, the decellularization chip, a fluid module, and a temperature control module within a single enclosure. The use of an automated system not only improves the efficiency and consistency of organ patch generation but also reduces errors caused by human operation, thereby improving the quality of the final product. Attached Figure Description

[0029] Figure 1 This is a schematic diagram of an integrated device for generating decellularized organ patches, as exemplified by the present invention.

[0030] Figure 2 This is a schematic diagram of the decellularized chip structure as an example of the present invention;

[0031] Figure 3 This is a schematic diagram of the decellularization processing module in the decellularization chip of the present invention.

[0032] In all the accompanying drawings, the same reference numerals are used to denote 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 holder; 10. temperature sensor; 11. decellularization module; 12. liquid inlet; 13. cell filter; 14. concave flow channel; 15. liquid outlet. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0034] In this invention, such as Figure 1 As shown, an integrated device for generating decellularized organ patches is provided, including a detachable housing, a control unit, a decellularization chip, and a fluid module, wherein the decellularization chip and the fluid module are disposed within the housing;

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

[0036] Further, as shown in the specific design of the decellularization chip, Figure 3 As shown, the decellularization processing module 11 comprises:

[0037] The intermediate layer comprises an open cavity arranged in the central region of the intermediate layer and a cell filter 13 covering the open cavity;

[0038] The bottom plate bonded to the lower layer of the intermediate layer is provided with a concave flow channel 14 on the side facing the intermediate layer, and is 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 intermediate layer is provided with a liquid inlet 12 communicating with the leading end of the concave flow channel 14, and a liquid outlet 15 communicating with the trailing end of the concave flow channel;

[0040] And the intermediate layer and the bottom plate are bonded by sealing glue, and the intermediate layer and the upper cover are not required to be bonded by sealing.

[0041] Wherein, the decellularization chip is electrically connected with the control unit through the oscillator, and the decellularization chip is connected with the fluid module through the liquid inlet and the liquid outlet, and the fluid module is electrically connected with the control unit.

[0042] Preferably, in the intermediate layer of a specific decellularization processing module, a plurality of isolated open cavities corresponding to the number of cell filters can be designed to generate the same organ patch in batches or generate different types of organ patch at a time.

[0043] Preferably, in the design of a specific decellularization chip, a plurality of decellularization processing modules can be arranged by flat laying and fixed on the chip fixing support, so that high-throughput decellularization processing can be realized in a stable and precise environment.

[0044] Preferably, the chip fixing support 9 is fixedly designed above the oscillator 6, as shown in Figure 2 The chip fixing support is in the form of a tray and is used for different types of decellularization processing modules.

[0045] Preferably, the fluid module comprises a liquid pump, an external pipe and a plurality of liquid storage tanks, the liquid pump is connected with the liquid inlet and the liquid outlet of the decellularization chip through the external pipe, and the liquid pump drives the corresponding liquid storage tank of the cleaning liquid or the washing liquid to circulate.

[0046] Preferably, the integrated device of the present application further comprises a temperature module, which further comprises a refrigeration element, a temperature sensor and a refrigeration heat dissipation module. The refrigeration device is controlled by a temperature control system to cool the environment in the device chamber, and the temperature detector in the device chamber feeds back to control the refrigeration device, so as to maintain the stability of the decellularization environment in the cabin.

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

[0048] Preferably, the box has a hatch on the top, and the hatch can be opened separately.

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

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

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

[0052] The preparation of the related structure of the present application and the application of the device of the present application will be further explained and described below through specific examples.

[0053] Example 1: The decellularization chip manufacturing process is described by combining laser engraving technology and 3D printing technology. The following is the manufacturing steps of the single filter screen structure decellularization chip:

[0054] (1) Prepare polymethyl methacrylate plate (the plate is 1mm, 2mm, 5mm, 1mm from bottom to top), after single-sided film is removed, special double-sided adhesive is pasted, and laser engraving machine is used to engrave the sheet structure as shown in Figure 3 , as the overall framework structure of the decellularization chip;

[0055] (2) The top layer is a pressure-sensitive adhesive layer, which is directly engraved by a laser engraving machine Figure Three , and the cut part is reserved;

[0056] (3) Align the engraved overall framework structure according to the structure as shown in Figure 3 , bond through the double-sided adhesive layer, and temporarily do not bond the top layer;

[0057] (4) Put the whole structure together into the hot press, the temperature of the upper and lower pressing surface is 60℃, 5 min;

[0058] (5) Use 3D printer to print the cell filter structure as shown in Figure 3 , and buckle it into the whole frame that has been assembled;

[0059] (6) Put into pure water for 24 h ultrasonic, and dry with nitrogen gun.

[0060] Example 2: The use process of automatic feeding of the automatic integrated device for generating complete decellularized organ patch is explained in combination with pig heart patch, and the specific steps are as follows:

[0061] (1) Prepare the decellularization chip, prepare the pig heart, and cut the slices to adapt to the size of the cell filter;

[0062] (2) Put the sheet-shaped tissue into the cell filter of the decellularization chip, and use the top layer of pressure sensitive adhesive to package the chip;

[0063] (3) Put the chip into the equipment card slot, and manually connect the pipeline to the chip;

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

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

[0066] Example 3: The use process of automatic feeding of the automatic integrated device for generating complete decellularized organ patch is explained in combination with pig intestine tissue, and the specific steps are as follows:

[0067] (1) Prepare the decellularization chip with the interface on the side, prepare the pig intestine, and cut the sections to adapt to the size of the cell filter;

[0068] (2) Horizontally install the columnar structure in the cell filter of the decellularization chip, and fix the pig intestine section on the columnar structure, and use the top layer of pressure sensitive adhesive to package the chip;

[0069] (3) The pipeline in the equipment directly connects with the card slot, and the external interface is supported by the spring column, and the chip is put into the equipment card slot, that is, directly connected with the pipeline;

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

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

[0072] Example 4: The use mode of the automatic integrated device for generating complete decellularized organ patch is explained in combination with pig skin tissue, and the specific steps are as follows:

[0073] (1) Prepare the decellularization chip, prepare the pig skin;

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

[0075] (3) Replace the cell filter with a cell filter, put the skin powder into it, and use the top layer of pressure-sensitive adhesive to package the chip;

[0076] (4) Place the chip into the equipment card slot, and manually connect the pipeline to the chip;

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

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

[0079] (7) Take out the decellularized powder, freeze-dry it, digest it, adjust the pH value, and obtain the decellularized biological gel.

[0080] Obviously, those skilled in the art can make various modifications and variations to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application belong to the scope of the present application and its equivalent technology, the present application also intends to include these modifications and variations. The above-described embodiments are only preferred embodiments for fully illustrating the present application, and the protection scope is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present application are within the protection scope of the present application.

Claims

1. An integrated device for generating decellularized organ patches, characterized in that, It includes a detachable housing, a control unit, a decellularized chip, and a fluid module, wherein the decellularized chip and the fluid module are disposed within the housing; The decellularized chip includes a decellularization processing module and an oscillator. The decellularization processing module is disposed above the oscillator and fixedly connected to it, so that the decellularized chip resonates through the oscillation of the oscillator. The decellularization processing module includes: The intermediate layer includes an opening disposed in the central region of the intermediate layer and a cell filter covering the opening; The bottom plate bonded to the lower layer of the intermediate layer has a concave flow channel on the side facing the intermediate layer, and is located in the orthogonal projection area of ​​the cell filter on the bottom plate; The top cover bonded to the upper layer of the intermediate layer is provided with an inlet communicating with the first end of the concave flow channel and an outlet communicating with the end of the concave flow channel. The decellularization chip is electrically connected to the control unit via an oscillator, and the decellularization chip is connected to the fluid module via the liquid inlet and the liquid outlet, respectively. The fluid module is electrically connected to the control unit. The fluid module includes a liquid pump, an external pipe, and multiple liquid storage tanks. The liquid pump is located in the liquid storage tanks and is connected to the inlet and outlet of the decellularized chip via the external pipes.

2. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The intermediate layer includes at least one cavity, each configured with an equal number of cell filters, and each cavity is connected to the upper portion of the concave flow channel to form a microfluidic channel.

3. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The integrated device includes at least one of the decellularization processing modules, each independently connected to the fluid module.

4. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The decellularized chip also includes a chip holder for fixing and supporting the decellularized chip.

5. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The integrated device also includes a temperature module, which is electrically connected to the control unit; The temperature module includes a cooling element, a temperature sensor, and a cooling fan; the cooling element and the temperature sensor are both located inside the housing; the cooling fan is nested on the side shell of the housing, and the air outlet of the cooling fan faces outward from the housing.

6. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The integrated device also includes a liquid valve control, which is disposed on the side wall of the housing, communicates with the liquid storage tank, and is electrically connected to the control unit to control the inflow or outflow of liquid in the decellularized chip.

7. The integrated device for generating decellularized organ patches according to claim 1, characterized in that, The top surface of the container is equipped with a hatch.

8. The integrated apparatus for generating decellularized organ patches according to claim 1, characterized in that, The control unit includes a control panel, which is mounted on the housing, and is used to display and adjust the execution parameters of each module in the integrated device through the control panel.

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

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