CN107012085B

CN107012085B - Automatic fluid infusion type cell removal system and method

Info

Publication number: CN107012085B
Application number: CN201710401386.0A
Authority: CN
Inventors: 雷文诚; 王红刚; 韩卫东; 米维
Original assignee: SHAANXI RUISHENG BIOLOGICAL SCIENCE AND TECHNOLOGY Co Ltd
Current assignee: SHAANXI RUISHENG BIOLOGICAL SCIENCE AND TECHNOLOGY Co Ltd
Priority date: 2017-05-31
Filing date: 2017-05-31
Publication date: 2020-01-03
Anticipated expiration: 2037-05-31
Also published as: CN107012085A

Abstract

The invention relates to the technical field of decellularization, in particular to an automatic fluid infusion type decellularization system and method. Through automated control, can carry out real-time detection to the liquid level height of taking off the cell reagent in taking off the cell container to in time supply taking off the cell reagent according to the testing result, can practice thrift the human cost, be favorable to the large-scale production and the application of biomaterial. The embodiment of the invention provides an automatic fluid infusion type decellularization system, which comprises: the cell removing equipment comprises a cell removing container and oscillating equipment, the oscillating equipment is positioned below the cell removing container, and a liquid level meter is arranged in the cell removing container; the fluid infusion equipment is communicated with the acellular container; and the control equipment is electrically connected with the oscillation equipment, the liquid level meter and the liquid supplementing equipment.

Description

Automatic fluid infusion type cell removal system and method

Technical Field

The invention relates to the technical field of decellularization, in particular to an automatic fluid infusion type decellularization system and method.

Background

In recent years, with intensive research on a cell removal technology of a biomaterial, a biomaterial substitute which has good biocompatibility, low immunogenicity, and a good repair effect after implantation is provided, wherein a three-dimensional structure of an original tissue is retained after cell removal of a biomaterial such as an animal membrane tissue of a porcine small intestine, a bovine pericardium, and the like, and a collagen protein with low immunogenicity is a main component, and becomes an optimal substitute for human tissue transplantation.

The existing cell removing technology is mainly completed in a reaction container through shaking table oscillation, when biological materials are subjected to large-scale cell removing, a large amount of foam can be generated, the generated foam is discharged in time, a good cell removing environment can be provided for the biological materials, however, the cell removing reagent can be reduced along with continuous discharge of the foam, the cell removing reagent needs to be continuously added into the reaction container, the labor cost is high, and the large-scale production and application of the biological materials are not facilitated.

Disclosure of Invention

The embodiment of the invention provides an automatic liquid supplementing type decellularization system and method, which can detect the liquid level height of a decellularization reagent in a decellularization container in real time through automatic control, supplement the decellularization reagent in time according to a detection result, save labor cost and be beneficial to large-scale production and application of biological materials.

In order to achieve the above purpose, the embodiment of the invention adopts the following technical scheme:

in one aspect, an embodiment of the present invention provides an automatic fluid infusion type decellularization system, including:

the cell removing equipment comprises a cell removing container and oscillating equipment, wherein the oscillating equipment is positioned below the cell removing container, and a liquid level meter is arranged in the cell removing container;

the fluid infusion device is communicated with the acellular container;

and the control equipment is electrically connected with the oscillation equipment, the liquid level meter and the liquid supplementing equipment, is used for controlling the oscillation equipment to be opened and closed, controls the liquid level meter to detect the liquid level height in the acellular container, and controls the liquid supplementing equipment to supply the acellular reagent into the acellular container or stop supplying the acellular reagent into the acellular container according to a liquid level signal sent by the liquid level meter.

Optionally, the decellularization container comprises at least two decellularization grooves, and two adjacent decellularization grooves are communicated through a communication hole.

Optionally, a foam sensor is arranged in at least one decellularization groove;

the system still includes row's foam equipment, arrange the foam equipment including row's foam pump and row's foam pipe, arrange the one end one-to-one of foam pipe with the acellular groove intercommunication, the other end with arrange the input intercommunication of foam pump, arrange the foam pump with the foam sensor all with the controlgear electricity is connected.

Optionally, the decellularization container comprises a first box body and a second box body, and the first box body is arranged in the second box body; a partition plate is arranged in the first box body and divides the first box body into at least two decellularization grooves, and the communication hole is formed in the partition plate between every two adjacent decellularization grooves;

the second box body is provided with a liquid outlet communicated with the bottom space of the second box body, a liquid outlet valve is arranged at the liquid outlet, and the first box body is provided with a liquid outlet hole communicated with the bottom space of the second box body; the drain valve is electrically connected with the control equipment.

Optionally, the number of the liquid discharge holes is at least two, and the liquid discharge holes are respectively formed in the bottom plate and the side plate of the first box body, the bottom plate of the second box body and the bottom plate of the first box body enclose a cavity, and the cavity communicates the liquid discharge holes with the liquid discharge port.

In another aspect, an embodiment of the present invention provides an automatic fluid infusion type decellularization method, which is applied to the system described above, and includes:

placing a biological material in a decellularization container, decellularizing the biological material, and discharging the generated foam out of the decellularization container;

control through controlgear the level gauge is right the liquid level height in the decellularization container detects, if the liquid level height in the decellularization container is less than preset height, then the level gauge to controlgear sends first instruction signal, controlgear according to first instruction signal control fluid infusion equipment to supply to in the decellularization container and take off cell reagent, if the liquid level height in the decellularization container reaches preset height, then the level gauge to controlgear sends second instruction signal, controlgear according to second instruction signal control fluid infusion equipment stop to supply to in the decellularization container take off cell reagent.

Optionally, the decellularization container comprises at least two decellularization grooves, and the two adjacent decellularization grooves are communicated through a communication hole;

placing the biological material in a decellularized container specifically comprises:

at least two biological materials are placed in different decellularization tanks.

Optionally, a foam sensor is arranged in at least one decellularization groove; the system also comprises a foam discharging device, the foam discharging device comprises a foam discharging pump and foam discharging pipes, one end of each foam discharging pipe is communicated with the acellular groove in a one-to-one correspondence mode, the other end of each foam discharging pipe is communicated with the input end of the foam discharging pump, and the foam discharging pump and the foam sensor are both electrically connected with the control device;

expelling the generated foam out of the decellularization vessel specifically comprises:

controlling the foam sensor to detect foam in the acellular container through a control device, if the foam sensor detects foam, sending a first indication signal to the control device, and controlling the foam discharge pump to be started by the control device according to the first indication signal to discharge the foam out of the acellular container; and if the foam sensor does not detect foam, sending a second indication signal to the control equipment, and controlling the foam discharging pump to be closed by the control equipment according to the second indication signal.

the second box body is provided with a liquid outlet communicated with the bottom space of the second box body, a liquid outlet valve is arranged at the liquid outlet, and the first box body is provided with a liquid outlet hole communicated with the bottom space of the second box body; the liquid discharge valve is electrically connected with the control equipment;

the method further comprises the following steps: after the preset time, the control device controls the drainage valve to open, and the liquid in the acellular container is drained through the drainage port.

The embodiment of the invention provides an automatic liquid supplementing type decellularization system and method, because a great amount of foam is generated in a decellularization reagent when the decellularization is carried out under oscillation, and the foam is required to be continuously discharged to the outside of the acellular container, therefore, by arranging the liquid supplementing device and the control device and arranging the liquid level meter in the acellular container, in the whole cell removing process, the liquid level meter and the liquid supplementing device are automatically controlled by the control device, so that the liquid level height in the cell removing container can be detected in real time, and controlling the liquid supplementing device to supplement the decellularization reagent into the decellularization container in time or stopping supplementing the decellularization reagent according to the detection result, compared with the prior art in which the cell removal reagent needs to be continuously supplemented by manpower, the method can save the labor cost and is beneficial to large-scale production and application of the biological material.

Drawings

FIG. 1 is a schematic structural diagram of an automatic fluid infusion type decellularization system according to an embodiment of the present invention;

FIG. 2 is a schematic structural diagram of another automatic fluid infusion type decellularization system according to an embodiment of the present invention;

fig. 3 is a schematic structural diagram of a first box according to an embodiment of the present invention;

FIG. 4 is a schematic structural diagram of a decellularization vessel according to an embodiment of the invention;

FIG. 5 is a schematic structural diagram of another decellularization vessel according to an embodiment of the invention;

FIG. 6 is a schematic structural diagram of a bottom of a first box according to an embodiment of the present invention;

fig. 7 is a schematic structural diagram of an automatic foam discharging apparatus according to an embodiment of the present invention;

FIG. 8 is a schematic structural diagram of another automatic defoaming device provided in the embodiment of the present invention;

fig. 9 is a schematic structural diagram of a first cover according to an embodiment of the present invention;

fig. 10 is a schematic flow chart of an automatic fluid infusion type decellularization method according to an embodiment of the present invention.

Detailed Description

An automatic fluid infusion type decellularization system and method provided by the embodiments of the present invention are described in detail below with reference to the accompanying drawings.

In one aspect, an embodiment of the present invention provides an automatic fluid infusion type decellularization system, referring to fig. 1, including:

the cell removing device comprises a cell removing container 1 and an oscillating device 2, wherein the oscillating device 2 is arranged below the cell removing container 1, and a liquid level meter a is arranged in the cell removing container 1;

the fluid infusion device 3 is communicated with the decellularization container 1;

and the control device 4 is used for controlling the oscillation device 2 to be opened and closed and controlling the liquid level meter a to detect the liquid level height in the decellularization container 1 and controlling the liquid supplementing device 3 to supply a decellularization reagent into the decellularization container 1 or stop supplying the decellularization reagent into the decellularization container 1 according to a liquid level signal sent by the liquid level meter a.

The embodiment of the invention provides an automatic liquid supplementing type decellularization system, because a great amount of foam is generated in a decellularization reagent when the decellularization is carried out under oscillation, and it is necessary to continuously discharge the bubbles to the outside of the decellularization vessel 1, by providing the solution supplementing apparatus 2 and the control apparatus 3, and providing the level gauge a in the decellularization vessel 1, in the whole cell removing process, the liquid level meter a and the liquid supplementing device 2 are automatically controlled by the control device 3, the liquid level height in the cell removing container 1 can be detected in real time, and controls the fluid infusion device 3 to timely supplement the decellularization reagent into the decellularization container 1 or stop supplementing the decellularization reagent according to the detection result, compared with the prior art in which the cell removal reagent needs to be continuously supplemented by manpower, the method can save the labor cost and is beneficial to large-scale production and application of the biological material.

The control device 4 may include one or more processors, memory, user interfaces, network interfaces, and a communication bus, among others.

The communication bus is used for communication between the respective constituent elements in the control device 4. The user interface is used for plugging external equipment, such as a touch screen, a mouse, a keyboard and the like, so as to receive information input by a user. The network interface is used for the control device 4 to communicate with the outside, and mainly includes a wired interface and a wireless interface.

The memory may be used to store software programs and modules, databases, and program instructions/modules corresponding to the methods for decellularizing biological materials as described in the embodiments of the invention. The memory may include high speed random access memory, and may also include non-volatile memory, such as one or more magnetic storage devices, flash memory, or other non-volatile solid-state memory. In some examples, the memory may further include memory remotely located from the processor, and these remote memories may be connected to the control device via a network. Examples of such networks include, but are not limited to, the internet, intranets, local area networks, mobile communication networks, and combinations thereof.

The processor executes various functional applications and data processing by executing software programs and modules stored in the memory, for example, the processor calls a decellularized application program in the memory to realize a rapid and accurate decellularization process.

The specific structure of the fluid infusion device 3 is not limited as long as the decellularization reagent can be supplied into the decellularization container 1.

In one embodiment of the present invention, referring to fig. 2, the fluid infusion apparatus 3 includes a decellularization reagent storage tank 31 and a fluid infusion pump 32, an input end of the fluid infusion pump 32 is communicated with the decellularization reagent storage tank 31, an output end of the fluid infusion pump 32 is communicated with the decellularization container 1, and the fluid infusion pump 32 is electrically connected with the control apparatus 4. When fluid replacement is needed, the control device 4 may control the fluid replacement pump 32 to be turned on, so as to input the decellularization reagent in the decellularization reagent storage tank 31 into the decellularization container 1, and perform fluid replacement in time.

The decellularization container 1 may be a reaction tank or a large-sized reaction tank, and the specific structure thereof is not limited.

In one embodiment of the present invention, referring to fig. 3, the decellularization container 1 includes at least two decellularization grooves 11, and two adjacent decellularization grooves 11 are communicated through a communication hole 5.

In the embodiment of the invention, by adopting the decellularization container 1 with the structure, when the cell of the biological material is removed, at least two biological materials can be respectively placed in different decellularization grooves 11, when the biological material is subjected to the cell removal under the oscillation, the biological materials can be prevented from being wound, so that the biological materials can be fully contacted with a decellularization reagent, the size of the decellularization grooves 11 can be reasonably set, the biological materials can be conveniently flapped with the walls of the decellularization grooves 11 under the oscillation, the decellularization effect can be improved, compared with the use of one decellularization groove, the large-scale batch treatment can be realized, and after the cell removal is finished, the separation and the subsequent treatment are facilitated, so that the finished product quality of the cell removal of the biological materials can be improved. Further, since the two adjacent decellularization tanks 11 are communicated with each other through the communication hole 5, when the decellularization reagent is supplied into any one of the decellularization tanks 11 by the decellularization reagent supplying apparatus 3, the decellularization reagent can flow into the other decellularization tanks 11 through the communication hole 5, so that the flow of the decellularization reagent during the decellularization process can be ensured, and a stable and uniform decellularization environment can be provided for the biological material in each of the decellularization tanks 11.

The level gauge a may be disposed in any one of the decellularization tanks 11.

The specific structure of the decellularization container 1 is not limited, and the decellularization container 1 comprises at least two decellularization tanks 11, so that at least one partition plate can be arranged in one tank body or the tank body, and the tank body or the tank body is divided into the at least two decellularization tanks 11 by the partition plate; at least two reaction tanks can be spliced together to form the decellularization container 1.

In one embodiment of the present invention, referring to fig. 3 and 4, the decellularization container 1 comprises a first case 12 and a second case 13, wherein the first case 12 is disposed in the second case 13; a partition plate 14 is arranged in the first box body 12, the partition plate 14 divides the first box body 12 into at least two decellularization grooves 11, and the communication hole 5 is formed in the partition plate 14 between every two adjacent decellularization grooves 11;

a liquid outlet communicated with the bottom space of the second box body 13 is formed in the second box body 13, a liquid outlet valve b is arranged at the liquid outlet, and a liquid outlet hole 6 communicated with the bottom space of the second box body 13 is formed in the first box body 12; the drain valve b is electrically connected to the control device 4.

In the embodiment of the present invention, the first casing 12 is disposed in the second casing 13, the first casing 12 is provided with the drain hole 6, and the second casing 13 is provided with the drain port, so that both the drain hole 6 and the drain port communicate with the bottom space of the second casing 13, and when the drain valve b is opened, the waste liquid after decellularization in the first casing 12 can be discharged through the drain hole 6 and the drain port. In the process, the fluid movement rule is complied, so that the labor can be saved, and the energy consumption caused by discharging the waste liquid through the waste liquid pump can be reduced.

The first housing 12 may have a circular or square horizontal cross-sectional shape, and the partition 14 may have an arc-shaped or straight plate as long as the first housing 12 can be divided into at least two decellularization cells 11, and accordingly, the decellularization cells 11 may have a circular or square horizontal cross-sectional shape depending on the shape of the first housing 12 and the partition 14.

In an embodiment of the present invention, the largest dimension of the decellularization tank 11 in the horizontal direction is less than or equal to 300 mm, and the height of the decellularization tank 11 in the vertical direction is greater than or equal to 100 mm. Can adapt to the oscillation amplitude of the oscillating shaking table 2, can provide enough movement space for at least three biological materials and prepare for the cell removal of the biological materials.

Illustratively, when the horizontal cross-sectional shape of the decellularization tank 11 is a square, the width of the decellularization tank 11 may be 140 mm, and the length may be 230 mm.

To prevent the liquid in the decellularization tank 11 from splashing out when it is shaken. Preferably, the height of the decellularization tank 11 in the vertical direction should be greater than or equal to 250 mm.

The arrangement of the decellularization grooves 11 may be various, and for example, the decellularization grooves 11 may be arranged in a row along the same linear array, or the decellularization grooves 11 may be arranged in a rectangular array. The whole structure of the decellularization tank 11 in a rectangular array is more compact than that in a linear array. Illustratively, as shown in FIG. 3, the partition 14 divides the space in the first housing 11 into 16 decellularization cells 11, and the 16 decellularization cells 11 are arranged in 4 rows and 4 columns. Of course, the partition 14 may also divide the space in the first housing 12 into 9 decellularization tanks 11, which is not limited herein.

It should be noted that, during the decellularization process, the decellularization reagent is usually a corrosive solvent, and therefore, the first tank 12 and the partition 14 may be made of a corrosion-resistant material, and preferably, the first tank and the partition 14 are made of a stainless steel material. The stainless steel material is adopted, so that the strength of the acellular container 1 can be effectively improved, and acid-base corrosion can be prevented.

In practical applications, in order to avoid scratches on the biological material caused by the communication holes 5 and affect the quality of the finished product, it is preferable that the communication holes 5 are circular or elliptical.

In order to ensure the smooth flow of the decellularization reagent and effectively block the biological materials, the diameter of the communication hole 5 is preferably 3 mm, so that the cell can be effectively blocked by various biological materials and the cell can be smoothly flowed.

Preferably, referring to fig. 3, the communication holes 5 are opened at the lower end of the partition 14, and the communication holes 5 are arranged in two rows in the vertical direction. Thus, the circulation of the decellularization reagent is facilitated, and the beating force of the partition plate 14 at the time of oscillation can be secured.

The drain hole 6 may be formed in a bottom plate or a side plate of the first casing 12. When the liquid discharge holes 6 are formed in the side plates, the liquid discharge holes 6 are formed in the lower ends of the side plates, and the two rows of liquid discharge holes 6 are arranged in the vertical direction. This facilitates the flow of the cell-free waste liquid in each of the cell-free tanks 12.

Further, the drain hole 6 is circular or elliptical. Likewise, the circular or elliptical through holes can prevent the biological material from being easily scratched by the edges of the drainage holes 6 or scratches during the oscillation process due to the sharp corners of the drainage holes 7, thereby causing defects that affect the quality of the finished biological material.

Preferably, the drain hole 6 has a diameter of 3 mm. Also can be convenient for blocking the biological material to lead the cell-free reagent to flow smoothly.

In another embodiment of the present invention, referring to fig. 5 and 6, the number of the drain holes 6 is at least two, and the drain holes are respectively opened on the bottom plate and the side plate of the first casing 12, and the bottom plate of the first casing 12 and the bottom plate of the second casing 13 enclose a cavity a for communicating the drain port and the drain holes 6. Like this, be favorable to the all-round discharge of outage on cell waste liquid through curb plate and the bottom plate to, through setting up cavity A, liquid in the first box 11 can pass through outage 6 is arranged to in the cavity A, then pass through the leakage fluid dram is discharged, can guarantee the smooth and easy discharge of waste liquid.

In order to completely discharge the waste liquid in the second tank 13 and reduce the residual, it is preferable that a bottom plate of the second tank 13 is disposed to be inclined, and a lowest portion of the bottom plate is disposed near the liquid discharge port.

In an embodiment of the present invention, the liquid discharge opening is further provided with a filter (not shown in the figure) for filtering the discharged waste liquid. After the decellularization is completed, cell debris and fibrous impurities are dispersed in the decellularization reagent to form a decellularized waste liquid, and when the decellularized waste liquid is discharged through the liquid discharge port, the waste liquid is filtered by the filter, so that the liquid discharge valve can be prevented from being clogged by the impurities.

Referring to fig. 5, the first casing 12 may be disposed in the second casing 13 through a bracket 7, such that the bottom plate of the first casing 12 and the bottom plate of the second casing 13 enclose the cavity a. A suspension structure may be provided in the second casing 12 to suspend the first casing 12 from the second casing 13, and the cavity a may be formed.

In order to completely discharge the waste cell-free liquid and avoid the residue, it is preferable that the bottom plate of the second casing 13 is inclined and the lowest part of the bottom plate is disposed near the liquid discharge port.

In another embodiment of the present invention, the side wall of the first box 12 is attached to the side wall of the second box 13. In this way, during the oscillation, the first casing 12 can be prevented from slipping with respect to the second casing 13, and the space inside the second casing 13 can be fully utilized.

In actual operation, if the decellularized container 1 is placed on the oscillating tray, slippage between the decellularized container 1 and the oscillating tray is likely to occur, which is disadvantageous to stable operation of the system.

In view of this, in an embodiment of the present invention, a connecting portion extends outwardly from a bottom edge of the second casing 13, and the connecting portion is detachably connected to the oscillating tray. Thus, the connecting part can be detached from the oscillation tray to replace the decellularization vessel 1 while preventing the decellularization vessel 1 from slipping with respect to the oscillation tray.

Here, the connection part and the oscillating tray may be in a snap connection or a screw connection.

It should be noted that the whole cell removing process is performed in a sterile environment, which can ensure the quality of the finished product of the biological material, and the first box 12 needs to be cleaned and sterilized after each cell removing process, so that, preferably, referring to fig. 4, the handle 8 is disposed on the upper end surface of the first box 12. In this way, when it is desired to sterilize the first casing 12, it can be lifted out of the second casing 13.

In one embodiment of the present invention, referring to fig. 7, a foam sensor c is disposed in at least one of the decellularization cells 11; the system still includes row's foam equipment 6, row's foam equipment 6 includes row's foam pump 61 and row's foam pipe 62, row's foam pipe 62 one end one-to-one with the acellular groove 11 intercommunication, the other end with row's foam pump 61's input intercommunication, row's foam pump 61 with foam sensor c all with controlgear 4 electricity is connected.

In the embodiment of the present invention, by providing the foam sensor c in the acellular container 1 and providing the foam discharging device 6, the control device 4 can control the foam sensor c to detect the foam in the acellular container 1 in real time, and control the foam discharging pump 61 to discharge the foam in time according to the detection result, so as to further improve the automation degree of acellular.

Specifically, as the cell removal progresses, if the foam sensor c detects foam, a first indication signal is sent to the control device 4, the control device controls the foam discharging pump to be turned on according to the first indication signal to discharge the foam to the outside, and as the foam is discharged, if the foam sensor c does not detect the foam, a second indication signal is sent to the control device 4, and the control device 4 controls the foam discharging pump 61 to be turned off according to the second indication signal.

In a possible implementation manner, referring to fig. 7, the other ends of the foam discharging pipes 62 can be integrally connected together through a multi-pipeline joint 63 and then are communicated with the input end of the foam discharging pump 61; in another possible implementation manner, referring to fig. 8, the other ends of the foam discharging pipes 62 are in one-to-one correspondence with the input ends of the plurality of foam discharging pumps 61.

In an embodiment of the present invention, referring to fig. 9, the decellularization container 1 further includes a first cover 15 that is matched and covered with the upper end surface of the first case 12. By providing the first lid member 15, it is possible to prevent the reagent from splashing when the decellularization reagent is injected into the decellularization tank 11.

Further preferably, in order to prevent the biological materials in the different decellularization tanks 11 from being thrown against the upper end of the partition plate 13 during the oscillation process, referring to fig. 5 and 9, it is preferable that the first cover 15 is a flat plate-shaped structure, the upper edges of the side plate and the partition plate 13 are located in the same plane, and the first cover 15 covers the side plate and the partition plate 13.

Referring to fig. 9, a handle 9 may be further disposed on the upper surface of the first cover 15, and the handle 9 is grasped to open the first cover 15, which is convenient for operation.

Of course, when the upper end surface of the first box 12 is matched and covered with the first cover 15, referring to fig. 7, one end of each foam discharging pipe 62 may penetrate through the first cover 15 and extend into the decellularization tank 13.

Further, in order to facilitate observation of the decellularization process, a transparent observation window may be formed on the first cover body 15, and the transparent observation window may be made of a corrosion-resistant transparent material, or the first cover body 15 may be directly made of a corrosion-resistant transparent material.

Similarly, referring to FIG. 4, a second cover 16 may be provided at the opening of the second casing 14 to prevent contamination of the decellularized reagent.

In another aspect, an embodiment of the present invention provides an automatic fluid infusion type decellularization method applied to the decellularization system described above, with reference to fig. 10, including:

step 1) placing a biological material in a decellularization container, decellularizing the biological material, and discharging generated foam to the outside of the decellularization container;

step 2) the liquid level meter is controlled by a control device to detect the liquid level height in the acellular container, if the liquid level height in the acellular container is lower than a preset height, the liquid level meter sends a first indicating signal to the control device, the control device controls the liquid supplementing device to supply the acellular reagent into the acellular container according to the first indicating signal, if the liquid level height in the acellular container reaches the preset height, the liquid level meter sends a second indicating signal to the control device, and the control device controls the liquid supplementing device to stop supplying the acellular reagent into the acellular container according to the second indicating signal.

The embodiment of the invention provides an automatic liquid supplementing type decellularization method, which is characterized in that generated foam is discharged to the outside of a decellularization container in the process of decellularizing biological materials, a control device is used for controlling a liquid level meter to detect the liquid level height in the decellularization container, the liquid supplementing device is controlled to supplement a decellularization reagent into the decellularization container or stop supplementing the decellularization reagent into the decellularization container according to a detection result, the liquid level height in the decellularization container can be automatically controlled, compared with the prior art that the decellularization reagent needs to be continuously supplemented manually, the labor cost can be saved, and the large-scale production and application of the biological materials are facilitated.

In an embodiment of the present invention, the decellularization container includes at least two decellularization grooves, and two adjacent decellularization grooves are communicated through a communication hole;

The at least two means that the two are not connected and separated in space, but do not limit the whole number of the bovine pericardium or the porcine small intestine, for example, one bovine pericardium may be cut into two biological materials.

Through placing a plurality of biological materials in different acellular tanks, the acellular reagent can avoid winding among the biological materials in different acellular tanks while continuously circulating among the acellular tanks, so that the biological materials are fully contacted with the acellular reagent and fully slapped with the walls of the acellular tanks, the acellular effect of the biological materials can be improved, and after the acellular process is completed, the subsequent separation steps can be reduced, the acellular efficiency is improved, and the large-scale production and application of the biological materials are facilitated.

In another embodiment of the present invention, a foam sensor is disposed in at least one of the decellularization cells; the system also comprises a foam discharging device, the foam discharging device comprises a foam discharging pump and a foam discharging pipe, one end of the foam discharging pipe is communicated with the acellular groove in a one-to-one correspondence mode, the other end of the foam discharging pipe is communicated with the input end of the foam discharging pump, and the foam discharging pump and the foam sensor are both electrically connected with the control device;

In the embodiment of the invention, foam generated in the cell removing container is automatically discharged, so that the automation degree of the system can be further improved, errors caused by manual operation can be reduced, the cell removing reagent is kept at a preset height, and the cell removing effect is improved.

In a preferred embodiment of the present invention, the acellular container comprises a first box and a second box, wherein the first box is arranged in the second box; a partition plate is arranged in the first box body and divides the first box body into at least two decellularization grooves, and the communication hole is formed in the partition plate between every two adjacent decellularization grooves;

In the embodiment of the invention, the first box body is provided with the liquid discharge hole communicated with the bottom space of the second box body, the first box body is arranged in the second box body, the second box body is provided with the liquid discharge port communicated with the bottom space of the second box body, the liquid discharge port is provided with the liquid discharge valve, and after the decellularization is finished, the liquid discharge valve is directly controlled to be opened, so that the waste liquid generated by the decellularization can be discharged to the outside of the decellularization container, and the large energy consumption caused by discharging the waste liquid by using a waste liquid pump and the labor cost caused by manually discharging the waste liquid can be avoided.

The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention, and all the changes or substitutions should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.

Claims

1. An automatic fluid infusion type decellularization system, comprising:

the fluid infusion device is communicated with the acellular container;

the control device is electrically connected with the oscillation device, the liquid level meter and the liquid supplementing device, and is used for controlling the oscillation device to be turned on and turned off, controlling the liquid level meter to detect the liquid level height in the decellularization container, and controlling the liquid supplementing device to supply the decellularization reagent into the decellularization container or stop supplying the decellularization reagent into the decellularization container according to a liquid level signal sent by the liquid level meter; wherein

The acellular container comprises a first box body and a second box body, and the first box body is arranged in the second box body; a partition plate is arranged in the first box body and divides the first box body into at least two decellularization grooves, and a communication hole which allows a decellularization reagent to pass through and prevents biological materials from passing through is formed in the partition plate between every two adjacent decellularization grooves; the second box body is provided with a liquid outlet communicated with the bottom space of the second box body, a liquid outlet valve is arranged at the liquid outlet, the first box body is provided with a liquid outlet communicated with the bottom space of the second box body, and the liquid outlet allows the cell-removing reagent to pass and prevents the biological material from passing; the drain valve is electrically connected with the control equipment.

2. The system of claim 1,

a foam sensor is arranged in at least one cell removing groove;

3. The system of claim 1,

the liquid discharge holes are at least two and are respectively arranged on the bottom plate and the side plate of the first box body, the bottom plate of the second box body and the bottom plate of the first box body enclose a cavity, and the cavity communicates the liquid discharge holes with the liquid discharge port.

4. An automatic fluid replacement type decellularization method, which is applied to the system according to any one of claims 1 to 3, comprising:

placing at least two biological materials in different decellularization tanks, decellularizing the biological materials, and discharging generated foams out of the decellularization container;

the liquid level meter is controlled by a control device to detect the liquid level height in the acellular container, if the liquid level height in the acellular container is lower than a preset height, the liquid level meter sends a first indicating signal to the control device, the control device controls the liquid supplementing device to supply the acellular reagent into the acellular container according to the first indicating signal, if the liquid level height in the acellular container reaches the preset height, the liquid level meter sends a second indicating signal to the control device, and the control device controls the liquid supplementing device to stop supplying the acellular reagent into the acellular container according to the second indicating signal;

after the preset time, the control device controls the drainage valve to open, and the liquid in the acellular container is drained through the drainage port.

5. The method of claim 4, wherein a foam sensor is disposed within at least one decellularization cell; the system also comprises a foam discharging device, the foam discharging device comprises a foam discharging pump and foam discharging pipes, one end of each foam discharging pipe is communicated with the acellular groove in a one-to-one correspondence mode, the other end of each foam discharging pipe is communicated with the input end of the foam discharging pump, and the foam discharging pump and the foam sensor are both electrically connected with the control device;