CN111909829A - A bioartificial liver perfusion bioreactor - Google Patents

Abstract

The invention provides a bioartificial liver perfusion bioreactor, which is characterized by comprising a cylindrical shell, a plasma inlet and a sealing cover at the lower end of the shell, a plasma outlet and a sealing cover at the upper end of the shell, and a cell filling port and a sealing cover on the side. , and two upper and lower filter screens protruding from the center of the reactor near the two ends to the outside. The advantages of the bioartificial liver perfusion bioreactor of the present invention are: 1. An independent cell filling port is provided, which is convenient for filling cells into the reactor; 2. The center of the filter screen on the plasma inlet side inside the reactor supplies the plasma The inlet side is convex, which is beneficial for the plasma to be dispersed after entering the reactor; 3. The center of the filter screen on the plasma outlet side of the reactor is convex to the plasma outlet side, which is conducive to the discharge of air bubbles during pre-flushing; 4. The internal structure is simple, as The full contact between cells and plasma provides enough space to facilitate material exchange, thereby effectively exerting the function of the bioartificial liver reactor.

Description

A bioartificial liver perfusion bioreactor

technical field

The invention belongs to the field of biology, in particular to a biological artificial liver perfusion bioreactor.

Background technique

At present, the most effective way to treat liver disease in the world is liver transplantation, but the shortage of liver donors makes patients need to wait for a liver source, and some patients eventually die because of waiting for a liver source. Therefore, artificial liver support systems have emerged as "bridges" that allow patients to wait until liver transplantation or the recovery of their own liver.

The traditional artificial liver system (non-biological artificial liver) can physically reduce plasma toxins in the short term through measures such as hemodialysis, plasma exchange and activated carbon adsorption, but it does not have the normal detoxification, metabolism and secretion of the liver. Function. The bioartificial liver support system established with in vitro cultured hepatocytes, because the active human hepatocytes are used in vitro to replace the patient's liver for detoxification, metabolism and secretion functions, thereby reducing the burden on the patient's liver and allowing it to recover on its own. The development of bioartificial liver support system has become the focus.

The structural part containing hepatocytes in the bioartificial liver is the place where the hepatocytes perform the functions of detoxification, metabolism and secretion, and is called a bioreactor. At present, the bioreactors of the more common bioartificial liver support systems mainly include hollow fiber bioreactors, plate bioreactors and perfusion bioreactors. Among them, the hollow fiber reactor is safe, but there is a semi-permeable membrane between the plasma and cells, which is not conducive to material exchange and detoxification, so the treatment effect is poor; if the plate bioreactor needs to achieve an effective number of cells, it is necessary to continuously increase the number of culture plates. Although the number of layers is easy to enlarge, the volume of the reactor also increases, which is not conducive to use; in the perfusion bioreactor, the plasma is in direct contact with the hepatocytes, which is easier to exert its physiological function.

Bio-artificial liver perfusion bioreactors are generally used when there is clinical demand, before filling the hepatocyte suspension or microcarrier suspension with hepatocytes into the reactor, and then pre-washing and removing air bubbles. In order to maintain the viability and function of the cells in the bioartificial liver perfusion bioreactor, the structure of the perfusion bioreactor should be easy to operate, so as to ensure that the time-consuming of cell filling, pre-flushing and debubbling is short.

SUMMARY OF THE INVENTION

Aiming at the functional requirements of the bioartificial liver perfusion bioreactor, the purpose of the present invention is to provide a perfusion bioreactor for the bioartificial liver.

In order to achieve this purpose, the present invention adopts the following design scheme: comprising a cylindrical shell 1, a plasma inlet 2 and a sealing cover 3 at the lower end of the shell, a plasma outlet 4 and a sealing cover 5 at the upper end of the shell, a cell filling port 6 and a sealing cover on the side. 7. The filter screen 8 inside the reactor near the plasma inlet side and the filter screen 9 inside the reactor near the plasma outlet side.

In the bioartificial liver perfusion bioreactor, the cell filling port 6 on the side is located between the filter screen 8 and the filter screen 9, that is, the cell filling port communicates with the interior of the perfusion bioreactor. When filling the cells, open the sealing cover 7 and the sealing cover 5, respectively connect the pipelines, and put the cell suspension into the perfusion bioreactor from the cell filling port 6, and the excess liquid flows out from the plasma outlet 4, and the filling is completed. Then cover the sealing cover 5 and the sealing cover 7.

In the bio-artificial liver perfusion bioreactor, the center of the filter screen 8 and the filter screen 9 are both convex to the outside.

In the bio-artificial liver perfusion bioreactor, the purpose of the filter screen 8 and the filter screen 9 is to intercept the microcarriers and prevent the microcarriers from leaking out of the reactor. The diameter of the commonly used microcarriers is 50-300 μm. Therefore, the pore size of the filter screen 8 and the filter screen 9 in the perfusion bioreactor of the present invention is 25-300 μm, preferably 50-200 μm, more preferably 100-150 μm.

In the bio-artificial liver perfusion bioreactor, the filter screen is made of medical materials, including but not limited to alloys, polytetrafluoroethylene, polyester, and nylon. The alloy itself has good hardness, and when used in the filter screen near the plasma inlet end in the reactor, it can maintain the shape of the center convex. If other softer mesh cloth is used, alloy or medical plastic support bars are added to the filter screen.

In the bio-artificial liver perfusion bioreactor, the materials other than the filter screen are all medical plastics.

The advantages of the present invention are:

1. There is an independent cell filling port, which is convenient for filling cells into the reactor;

2. The center of the filter screen on the plasma inlet side inside the reactor bulges toward the plasma inlet side, which is beneficial for the plasma to be dispersed after entering the reactor;

3. The center of the filter screen on the plasma outlet side inside the reactor bulges toward the plasma outlet side, which is conducive to the discharge of air bubbles during pre-flushing;

4. The internal structure is simple, providing enough space for the cells and plasma to fully contact, which is conducive to the exchange of substances, so as to effectively exert the function of the bioartificial liver.

Description of drawings

Figure 1: Schematic diagram of the structure of the bioartificial liver perfusion bioreactor.

Figure 2: Schematic diagram of the filter holder.

Reference numerals: 1: Housing; 2: Plasma inlet; 3: Plasma inlet sealing cap; 4: Plasma outlet; 5: Plasma outlet sealing cap; 6: Cell filling port; 7: Cell filling port sealing cap; 8: Plasma inlet side filter; 9: plasma outlet side filter; 10: filter holder.

Detailed ways

In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined practical purpose, the present invention will be further described in detail below in conjunction with the specific embodiments and with reference to the accompanying drawings. It should be understood that these descriptions are given by way of example only, and are not intended to limit the scope of the present invention. Also, in the following description, descriptions of structures and techniques known to those skilled in the art are omitted.

As shown in Figure 1, the bioartificial liver perfusion bioreactor of the present invention comprises a cylindrical shell 1, a plasma inlet 2 and a sealing cover 3 at the lower end of the shell, a plasma outlet 4 and a sealing cover 5 at the upper end of the shell, and a cell perfusion on the side. The filling port 6 and the sealing cover 7, the filter screen 8 inside the reactor near the plasma inlet side, and the filter screen 9 inside the reactor near the plasma outlet side.

In this specific embodiment, the filter screen 8 and the filter screen 9 are made of nylon material, and the filter screen is provided with a filter screen support 10 shown in FIG. 2 , the filter screen support, the cylindrical shell and the sealing cover are made of medical plastic, and the filter screen support The rim is sealed integrally with the cylindrical housing.

When in use, turn the plasma outlet end of the bioartificial liver perfusion bioreactor of the present invention upward, open the sealing cap of the plasma outlet, connect the plasma outlet to the waste liquid bottle through a medical silicone tube, and then open the seal of the cell filling port. Cover, connect the cell filling port to the storage bottle containing the microcarrier cell suspension through a medical silicone tube, and then use a peristaltic pump to fill the microcarrier cell suspension into the reactor from bottom to top, and the excess liquid flows from the plasma outlet into the waste bottle.

The present invention has been described above with reference to preferred embodiments, but the scope of protection of the present invention is not limited thereto, and various improvements may be made and equivalents may be substituted therein without departing from the scope of the present invention. As long as there is no structural conflict, the technical features mentioned in the embodiments can be combined in any manner, and any reference signs in the claims should not be construed as limiting the related claims. Therefore, any technical solutions falling within the scope of the claims are within the protection scope of the present invention.

A schematic cross-sectional view of the structure of the present invention is shown in the accompanying drawings, which are not drawn to scale, in which details are exaggerated for clarity of description of certain structures, and some readily conceivable details may be omitted. The shapes of various regions and details shown in the figures, as well as their relative sizes and positional relationships are only examples, and there may be slight deviations due to production errors or technical limitations during actual manufacturing, and those skilled in the art may design additionally according to actual needs. Regions with different shapes, sizes, relative positions.

Claims (7)

1. A bio-artificial liver perfusion bioreactor, characterized in that it comprises a cylindrical shell (1), a plasma inlet (2) at the lower end of the shell and a sealing cover (3), a plasma outlet (4) at the upper end of the shell and a sealing cover (5), the cell filling port (6) and sealing cover (7) on the side, the filter screen (8) inside the reactor near the plasma inlet side, and the filter screen (9) inside the reactor near the plasma outlet side. 2. A bio-artificial liver perfusion bioreactor according to claim 1, wherein the cell filling port (6) on the side is located between the filter screen (8) and the filter screen (9). 3. A bio-artificial liver perfusion bioreactor according to claim 1, wherein the center of the filter screen (8) and the filter screen (9) both protrude to the outside. 4. A bio-artificial liver perfusion bioreactor according to claim 1, wherein the pore size of the filter screen (8) and the filter screen (9) is 25-300 μm, preferably 50-200 μm, more preferably 100-150 μm. 5. A kind of bioartificial liver perfusion bioreactor according to claim 1, wherein the used material of filter screen (8) and filter screen (9) is medical material, including but not limited to alloy, polytetrafluoroethylene, Polyester, nylon. 6. a kind of bioartificial liver perfusion bioreactor according to claim 1, when wherein filter screen (8) and filter screen (9) adopt the mesh cloth with soft texture, this filter screen is provided with alloy or medical plastic Material filter holder (10). 7 . The bio-artificial liver perfusion bioreactor according to claim 1 , wherein the materials other than the filter screen are all medical plastics. 8 .

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