JP2020028819A - Pore diffusion flat membrane separation module using fluidizing fractionation and membrane separation device applied with the same - Google Patents

Abstract

To provide a design of a pore diffusion membrane module embodying performances predicted by pore diffusion membrane separation techniques and to provide a device taking advantages of the module.MEANS FOR SOLVING THE PROBLEM: A module where a primary side flow passage is designed so that dynamic pressure loaded to a porous membrane constituting the wall part of the primary side flow passage of a pore diffusion membrane module becomes zero (a design such that a cloth-like material showing the roll of a valve in a flow passage in which a liquid is flown from a laminar flow preparation region to a pore diffusion region is added, and the like) and the laminar flow preparation region and the pore diffusion region are connected from the lower part of the flow passage in series and a device stably applying hydrostatic pressure to the module as transmembrane pressure difference are provided.SELECTED DRAWING: Figure 1

Description

The module of the present invention and the membrane separation device of the present invention to which the module is applied make the most of the flow separation effect and separate / fractionate / particulate components including macromolecules and microorganisms dissolved or dispersed in an aqueous solution. The present invention relates to a membrane module for removing and concentrating and a membrane separation device. Flow separation in the present invention means that when an aqueous solution flows in a laminar state along a smooth membrane surface, the particle components present in the aqueous solution are distributed toward the center of the flow depending on the size thereof. Means that. This phenomenon is caused by (a) drag from the membrane due to collision with the membrane surface (see Non-Patent Document 1, where it is expressed as a steric factor due to collision with the membrane wall) and (b) rotation of particles in the fluid. The effect of the axial concentration toward the center of the flow of the particles inside the laminar flow resulting from the action of the accompanying lift, and the effect of the uniformization of the particle density distribution accompanying the diffusion of the particles (Non-Patent Document 1 discloses these effects) The effects are collectively expressed as flow fractionation factors).

The pore diffusion flat membrane separation module intended in the present invention is a membrane separation module that satisfies the following requirements for causing pore diffusion membrane separation, and the membrane is a hollow fiber membrane or a tubular membrane. Means a porous membrane with no planar shape. Porous membrane has an average pore size of 10 nm
As described above, it means a film having a porosity of 30% or more, a bubble point in ethanol of 0.1 atm or more, and the presence of pores can be confirmed by a transmission electron microscope. The necessary conditions for the shape of the primary side flow path in order for the module to realize hole diffusion are as follows. The primary side flow path in the module has a smooth wall that forms a flow path such that the flow of the liquid in the primary side flow path (hereinafter, abbreviated as the primary side liquid) is laminar. The unevenness of the film surface of the formed flat film is 10 μm or less. The flow line drawn by the flow path is a smooth straight line or a gentle curve. The primary flow path is connected to the liquid inlet, and then to the laminar flow preparation area and the hole diffusion area. The length (L) between the laminar flow preparation area and the pore diffusion area is 50 mm or more.
When the thickness is 1500 mm or less, the thickness (D) of the flow channel is 4 mm or less and 1 mm or more.

The flat membrane that can be loaded into the pore diffusion flat membrane separation module intended in the present invention must satisfy the following requirements. That is, the smoothness of the membrane surface of the outer membrane (the membrane surface forming the primary channel is defined as the membrane surface) is 10 μm or less, and the flat membrane in the module has no pinhole with a diameter of 10 μm or more. is there. The requirement for the smoothness of the film surface is to ensure that the flow of the primary liquid flowing on the film surface on the film surface is laminar. The denial of the existence of the pinhole is to prevent disturbance of the collision angle of the particle component colliding with the film surface. The requirement of a bubble point in ethanol also ensures that the pore structure of the flat membrane is not destroyed even at the maximum transmembrane pressure of 0.1 atm applied to the pore diffusion membrane separation process.

In the membrane separation apparatus to which the pore diffusion flat membrane module intended in the present invention is applied, it is necessary that the environment of the module can be operated under the following operating conditions. In other words, the transmembrane pressure is always within 0.2 atm during operation over the entire flat membrane in the module. This condition must be satisfied when starting or stopping operation. In normal operation, the transmembrane pressure is 0.1 atm or less,
The strain rate of the primary liquid on the membrane surface becomes 10 / sec or more, and at the same time, it becomes laminar. Furthermore, in order to confirm that these operating conditions simultaneously satisfy the necessary conditions, the ratio of the velocity of the primary liquid passing through the flat membrane to the flow velocity of the primary liquid also needs to be 0.2 or less. It is.

In the membrane separation module and the membrane separation device of the present invention, the transmembrane pressure as a normal low hydrostatic pressure (positional head difference) of 0.1 atm or less is almost evenly applied to the entire surface of the membrane, and the liquid to be treated (primary liquid) Side liquid) flows over the membrane surface in a laminar flow. As for the lift exerted by the rotational motion of the particles generated by this flow, the rotational motion and the viscosity, which are the causes thereof, have a particle size dependence. Therefore, the particles are localized at a distance from the membrane surface corresponding to the size by balancing the flow fractionation effect, which reflects the lift dependent on the particle diameter toward the center of the flow, and the diffusion based on the Brownian motion of the particles. Let it. Focusing on this localization, if it is possible to sequentially recover the localized particles using a membrane,
Particle separation by the membrane becomes possible. That is, the present invention provides a membrane separation module and a membrane separation apparatus as a practical example of a pore diffusion membrane separation technique which is a membrane separation technique emphasizing a flow separation effect which is an operation effect which cannot be imagined by a conventional membrane filtration technique.

The current state of separation and purification technology for substances using membranes is the separation of substances according to their size by a sieving mechanism using pores in the membrane when transporting substances through the membrane using the transmembrane pressure as a driving force.
That is, membrane filtration is the majority. Membrane filtration is suitable for solid-liquid separation, which separates and purifies substances that are unstable and easily denatured by heat and chemicals. However, the membrane filtration method is not suitable for a technique for continuously fractionating and separating three or more component materials. A membrane filtration method based on a mechanism for trapping a substance to be removed in the pores of a membrane is not suitable for fractionation. In addition to membrane filtration, methods for separating and purifying biologically active substances such as proteins and glycoproteins include centrifugation, various types of chromatography, adsorption, dialysis,
Precipitation / dissolution method and asymmetric field flow fractionation method exist. The purpose is achieved by these techniques because a small amount of sample is sufficient for analysis purposes. However, when a large amount of treatment is required, it cannot be dealt with other than the precipitation / dissolution method. In the membrane separation module and the membrane separation apparatus of the present invention, a spatial dimensional effect (Steric factor) that is covered by a broad concept is used without using a sieving mechanism of the membrane. This effect is theoretically predicted in Non-Patent Document 1.
The spatial dimensional effect considers particles as flying objects, and is described by the movement of the particles due to collision with the holes and the surface of the film on the flying objects. The main contents of the difference between the spatial size effect and the sieving effect are summarized in the following two points according to the theory of Non-Patent Document 1.
1. The diameter of the particles that can enter the pores of the membrane is equal to the pore diameter in the sieving effect, but is 1/5 to 1/10 of the pore diameter in the dimensional effect.
2. In the particle removal performance of the film, the effect of the pinhole is very large in the sieving effect, but is hardly recognized in the size effect.
If the above two points can be confirmed, it is possible to determine whether the membrane module and the membrane separation apparatus in question are the pore diffusion of the present invention or the membrane filtration.

      A problem with the membrane filtration method is the clogging of pores. This phenomenon necessarily occurs as long as a sieving mechanism is used as a separation mechanism by a membrane. A dialysis method has conventionally been employed as a membrane separation method for preventing clogging. In the dialysis method, only dissolution of a permeated substance in a membrane and subsequent diffusion in a substantial part of the membrane (this diffusion is abbreviated as a dissolution / diffusion mechanism) is used. The dissolution / diffusion mechanism is not used for continuous mass processing because the diffusion coefficient inside the film is extremely small. In the pore diffusion membrane separation, membrane permeation is performed using a diffusion mechanism in a solvent (usually water in an aqueous solution) in pores inside the membrane. Therefore, in the pore diffusion membrane separation method, the membrane permeation rate of the low molecular substance is about 10,000 times that of the dissolution / diffusion mechanism (Non-Patent Document 2 and Patent Document 1). The present invention was developed as a membrane separation technique which eliminates the above-mentioned drawbacks of the membrane filtration method and the dialysis method. The diffusion method is now called the steady hole diffusion method).

      The pore diffusion method introduced in Patent Literature 1 and Non-Patent Literature 2 is a steady pore diffusion method. This method has a feature that both the solution medium (usually water) and the solute move in the pores by a diffusion mechanism, and the problem of pore clogging caused by solute molecules of any size is completely eliminated. Will be resolved. Since the separation speed between substances based on the difference in diffusion coefficient is about 10,000 times that in the case of the dissolution / diffusion mechanism, the problem of low separation speed is also solved. However, the steady pore diffusion method cannot concentrate the component molecules. In steady-state pore diffusion, the transmembrane pressure is practically zero.Therefore, in the steady-pore diffusion module, the liquid feed pump for flowing the primary fluid flows at the inlet and outlet of the primary fluid in the module. The alignment forces the conditions under which membrane filtration does not occur. In steady-state pore diffusion, both flat membranes and hollow fiber membranes can be used. When the membrane used is a hollow fiber membrane, the pressure on the inlet side is always higher than the pressure on the outlet side in order to allow the liquid on the primary side to flow inside the hollow fiber, and the steady hole diffusion is 30 cm or longer. It is difficult to carry out with a thread membrane. For example, in the case of a hollow fiber membrane having an inner diameter of 0.5 mm, if the length of the hollow fiber is not less than 7 cm, the transport by filtration by pressure for flowing the liquid on the primary side (transport by viscous flow) is 10% of the transport amount of all components. %, The clogging proceeds and the particle removability is extremely reduced.

Of particular importance in the pore diffusion flat membrane separation module using flow separation is the design of the primary flow path. The definition of the language related to the channel is shown below.
Primary side; side in contact with the surface of the flat membrane; secondary side; side in contact with the back side of the flat membrane.
Primary liquid; liquid filling the primary flow path,
Primary side flow path: A path in a module in which the liquid to be treated flows along a circuit (primary side circuit) having a flat membrane surface as a wall surface of the flow path.
Primary circuit: A continuous body of space that defines the flow of the primary liquid, and is a circuit that is directly connected to the primary flow path of the module in the flow of the liquid that connects the various operation units that constitute the membrane separation device.
Secondary liquid, secondary flow path, and secondary circuit; the contents defined on the primary side are defined on the side in contact with the back surface of the flat membrane.

      The flow separation type pore diffusion method has begun to be studied as a pore diffusion method for eliminating the problem of the stationary pore diffusion membrane separation technology and removing or concentrating fine particles in the liquid to be treated (see Patent Document 2). ). In this technique, a liquid on the primary side flows in parallel along the membrane surface while applying a slight transmembrane pressure (differential pressure as a hydrostatic pressure difference). The liquid solvent flows out to the back side of the membrane. The outflowing liquid solvent (consisting essentially of the solvent in the solution without any particulate components dispersed in the liquid, defined as the recovered secondary liquid) is defined as the particle-removing liquid. The primary liquid after the treatment is used as the particle concentrated liquid. The feature of this technique is that the transmembrane pressure is indirectly controlled to be 0.1 atm or less by controlling the flow velocity of the liquid on the primary side and the secondary side. Theoretically, the effectiveness of this control method is that the distance y from the film surface of the primary liquid that can flow into the hole and the collision angle α of the particles with the film surface in Non-Patent Document 1 are determined by the primary liquid. It was clarified by being determined by the ratio of the flow velocity (equal to the membrane permeation rate) and the membrane permeation rate of the liquid on the secondary side. The advantage of this technology is that the transmembrane pressure is not controlled by the pump pressure of the primary liquid flow rate pump, but is controlled indirectly by controlling the flow rate of the secondary liquid. Controlling. Since the flow speed of the secondary fluid can be easily controlled with a cock or the like, this type of control is suitable when the amount of the liquid to be processed is large. On the other hand, it is a necessary condition for this system to function that the secondary flow path forms a closed system (the volume in the secondary flow path is constant). Therefore, a time delay occurs between the operation with the cock or the like and the response of the transmembrane pressure difference. Common requirements are given to the modules of the flow separation type pore diffusion method in addition to the transmembrane pressure difference. That is, laminating the primary liquid and securing the flow velocity of the secondary liquid. For laminarization, a unique design for laminarization of the primary flow path and a unique porous support of the flat membrane must be secured to ensure the flow velocity of the secondary liquid .

K. Kamide, S. Manabe, “Mechanism of Permselectivity of Porous Polymeric Membranes in Ultrafiltration Process, Polymer J., 13 (No. 5), pp459-479 (1981). Rumiko Fujioka, Masako Yoshida, Tomoko Yoshimura, Tomoko Yamamura, Seiichi Manabe, Bulletin of the Faculty of Human Environmental Studies, Fukuoka Women's University, Vol. 29, pp. 13-20, 1998. Patent publication 2006-055780 Patent publication 2015-10074

The following items are theoretically predicted in the pore diffusion membrane separation module in which the flow separation effect is sufficiently utilized (disclosed in Non-Patent Document 1).
(1) Particles having a diameter of 1/5 (at a strain rate of 10 / sec) to 1/10 (at a strain rate of 100 / sec) or more of the average pore diameter of the flat membrane are used for flow separation effects. Can not pass. In the display of the particle logarithm removal coefficient LRV, when the strain rate of the primary liquid on the film surface is 10 / sec, LRV is 2-3, and when the strain rate is 100 / sec, LRV is 3-4.
(2) The collision angle α of the particles on the membrane surface is the ratio of the average flow velocity of the primary liquid to the average flow velocity from the primary side to the secondary side through the membrane (so-called membrane permeation velocity), and the empty space of the membrane. It has the characteristic of an average value (an average value that does not depend on the shape of the pore size distribution) almost uniquely determined by the porosity. If α is increased (for example, 70 degrees or more), particles cannot pass through the pores even if the particle diameter is 1/2 or more of the pore diameter.

Either of two types of regenerated cellulose porous membranes (two types with average pore diameters of 500 nm and 80 nm) are loaded into a pore diffusion membrane module with an effective membrane area of 0.2 square meters and 0.0057 square meters, and a transmembrane pressure difference of 0.05 atm is applied. The following experimental results were obtained when the strain rate of the primary liquid on the surface was 10 / sec. The liquid to be treated was a culture containing a retrovirus.
(A) The removal performance against bacteria (expressed as logarithmic removal performance LRV) was always LRV ≧ 6 for a module with a membrane area of 0.2 square meters (abbreviated as a large module) for a membrane with an average pore diameter of 500 nm, but a module of 0.0057 square meters ( (Small module), there was also a module with LRV <5. That is, the performance of removing bacteria is close to the theoretical prediction described above.
(B) Virus removal performance (retrovirus as a virus type, 70 to 80 nm in diameter) LRV is 2.0 (large module) to 0.5 (small module) when a flat membrane with an average pore diameter of 500 nm is loaded, and average For a flat membrane with a pore size of 80 nm, the number was 4 or more (large module) to 2.5 (small module).
The experimental results of (a) and (b) were qualitatively consistent with the theoretical predictions (1) and (2). However, quantitatively, the deviation from the theory is large, and the practical application of the pore diffusion membrane separation technology (for practical use, the reproducibility of this technology and the validity of the particle separation mechanism can be confirmed theoretically and empirically. The following specific issues remain.

      Problems to be solved by the present invention can be summarized as follows from the above examination. That is, (a) As shown in (a) and (b) above, the cause of the deviation from the actually measured value is clarified, and a method for solving the problem is shown. (B) To clarify the basics of the design of the primary flow path that realizes the function expected as the hole diffusion membrane module, (c) To perform an appropriate design for the structure on the back side of the flat membrane, (d) ) To show the basic requirements for the structure of the secondary flow path, (e) To clarify the components that make up the device that makes use of the characteristics of the hole diffusion membrane module, and to clarify the connection method and arrangement characteristics of each component. To

      The most significant feature of the membrane module and apparatus of the present invention is that the primary side flow path is designed so as to exhibit the feature of pore diffusion membrane separation, and the contribution of the membrane permeation phenomenon by filtration is minimized. Flat membranes with the same pore characteristics were loaded into two types of membrane modules with different effective membrane areas, and the particle removal performance was examined. As a result, a phenomenon that is opposite to the removal performance of the membrane filtration module, in which a module having a large membrane area has a higher particle removal performance than a small module, occurs. It has been clarified that the reverse phenomenon is caused by the dynamic pressure of the pressure applied to the flat membrane. That is, there are two types of pressure applied to the flat membrane: hydrostatic pressure and dynamic pressure, and the present inventors have found a phenomenon that the greater the contribution of the dynamic pressure, the smaller the particle removal performance becomes. The most important feature of the present invention is that the primary flow path is designed so that the dynamic pressure is substantially zero at all points of the flat membrane constituting about half of the primary flow path. The area of the membrane where the dynamic pressure is generated on the membrane surface must be less than 1 / 10,000 of the membrane area of the membrane surface where the pore diffusion membrane separation is performed.

      In order to reduce the dynamic pressure applied to the flat membrane surface to zero, the stream line of the primary liquid must be parallel along the flat membrane surface. In particular, the direction of the liquid inlet to the module must be set as parallel as possible to the membrane plane. It is premised that the flow of the primary liquid is laminar, and if the direction of the streamline of the laminar flow is parallel to the membrane surface, the dynamic pressure is necessarily zero. When the dynamic pressure becomes zero at all points on the surface of the flat membrane, the performance of removing fine particles (indicated by LRV) becomes close to the LRV in the case of membrane filtration using particles having a particle diameter ten times larger than the fine particles. As a specific measure for making the dynamic pressure substantially zero at any point on the membrane surface, there is a method of lowering the kinetic energy of the fluid by vertically colliding the fluid with the membrane. For example, if there is a location where the direction of the streamline of the primary liquid changes on the membrane surface, the velocity in the flow direction is reduced to zero by collision with a flexible membrane such as a nonwoven fabric at that location (see FIG. 1). Nonwoven fabric (illustrated as 9 in the figure)).

      A second feature of the present invention resides in that the flow path on the primary side in the membrane module is directly connected in series with the laminar flow preparation area and subsequently the hole diffusion area along the flow path. A part of the primary-side channel is constituted by the surface of the flat membrane. The flat membrane surface is present only in the pore diffusion region, and no material permeates in the laminar flow preparation region. The laminar flow preparation region plays an important role only in guiding the primary liquid flowing into the membrane module to the pore diffusion region in a laminar flow state. In other words, the cross-sectional shape of the liquid flow at the inlet of the laminar flow preparation region is usually circular or elliptical, but the cross-sectional shape is a band shape in the hole diffusion region of the module of the present invention which is the outlet of the preparation region. It is. In the laminar flow preparation region, it has a role of changing the cross-sectional shape by K. If the module is installed so that the laminar flow preparation area has the same liquid level as the inlet of the module or lower, the change in the cross-sectional shape of the primary liquid flow is the same under the influence of gravity. This can be performed at the liquid level. Also, the volume of the laminar flow preparation area is preferably as small as possible because it provides a space unrelated to the separation of the module.

    The third feature of the module of the present invention resides in that it has a unique flow path (ie, a secondary flow path) on the back side of the flat membrane. The space for the secondary flow path is provided by the unevenness if the flat film has a structure in which the back surface has unevenness. Alternatively, the back surface of the flat membrane is secured by adding a porous flat support. Since the hydrostatic pressure on the back side of the flat membrane fluctuates the transmembrane pressure, the design of the secondary flow path is usually simplified by setting it to atmospheric pressure. By setting the hydrostatic pressure at the back of the flat membrane to atmospheric pressure, the pore diffusion is performed only by controlling the pressure of the primary flow path. The pressure in the primary flow path can be prevented from generating static on the primary side.

      As a method of providing irregularities on the back surface of the flat film, there is a method of loading a nonwoven fabric as a support on the back surface of the flat film. With this method, deformation of the flat membrane due to hydrostatic pressure can be prevented. As a method of providing the unevenness, there is a method of securing a part of the flow path on the back side of the flat membrane with a solid flat plate. In this case, it is possible to design the secondary channel at the same time as providing the surface of the flat plate with irregularities.

      A fourth feature of the present invention is that, when the module of the present invention is incorporated into an apparatus, a component for exhibiting the pore diffusion membrane separation characteristics of the membrane module and an apparatus composed of a combination of the components make the pore diffusion membrane separation possible. The point is that the apparatus has good reproducibility and the properties of the recovered liquid are predicted. That is, as components for the primary circuit, (a) a liquid level control unit connected to an inlet or an outlet of the primary channel of the module, (b) a liquid transport unit for giving a position head difference of the liquid to be treated, (C) a receiving tank for storing the primary liquid, and (d) connecting to the outlet of the primary flow path of the module. The secondary side circuit passing through the back side of the membrane is (e) the outlet of the secondary side flow path in the module, a part of which is open to the atmosphere through (f) the sterilization or virus removal membrane, and the other part is (G) The liquid is passed to the recovery tank for the liquid that has passed through the flat membrane.

      The above liquid level control unit is set in the primary circuit. The liquid level is controlled by providing a part that is open to the atmosphere at the required height. However, by setting the volume of the control unit in the membrane module to 以下 or less of the volume of the primary side channel in the membrane module, membrane filtration does not occur even under troubles such as failure of the liquid transport unit. The pore diffusion membrane separation automatically stops. In addition, the portion that is open to the atmosphere communicates with the atmosphere only through a sterilization or virus removal membrane. The liquid to be treated in the receiving tank is sent to the inlet of the primary flow path of the module. A liquid pump is used as the liquid transport unit. Alternatively, the liquid in the receiving tank section can be transported to the liquid level control section by other physical means (including human power), and then the inlet section of the primary flow path of the module can be connected. Gravity is used for transportation from the liquid level control unit to the module entrance.

      The use of the module and the device of the present invention makes it possible to remove infectious microorganisms such as viruses and bacteria in an aqueous solution and to recover a polymer substance while maintaining physiological activity. Microorganisms to be removed include viruses, mycoplasmas, and bacteria. It is also possible to remove cells or aggregates of a plurality of cells. By determining the average pore size of the polymer porous membrane loaded in the module according to the object to be removed, it becomes possible to remove only specific infectious microorganisms. The average pore size upon removal is set to about 5 times the size of the microorganism of interest. Unlike the case of the membrane filtration method, the removal of the microorganisms is not a mechanism of capturing the microorganisms by the pores of the membrane (this mechanism is applied to the case of the membrane filtration method). In the pore diffusion method, particles to be removed are removed without clogging pores of the membrane. That is, this is a separation technique for removing particles without clogging the membrane. The particles to be removed are also particles to be concentrated. The method of the present invention provides a literal membrane separation method different from the membrane filtration method, and embodies the principle features of the pore diffusion method. Since there is no clogging of the pores of the membrane, the processing capacity is more than twice that of the membrane filtration method.

      The method of the present invention enables not only removal of infectious microorganisms but also separation, concentration and fractionation. Pharmaceutical raw materials and cosmetics in a raw state in which only infectious microorganisms are removed from biological raw materials containing many types of physiologically active substances (eg, body fluids such as blood and lymph, intracellular fluids, extracellular fluids, placenta, etc.) as the solution to be separated Raw materials, food raw materials, etc. can be produced.

      This technology will be applied in the future for removing infectious microorganisms as a basic technology for safety measures in the production of products such as regenerative medicine. It can be used for cell separation / purification and also for exosome purification / concentration / removal, and can be separated over a wide range of particle sizes. The pressure required for separation is 0.1 atm or less, which means separation under energy saving. Therefore, it can be said that it can be replaced with a conventional separation technique based on affinity, such as extraction separation, adsorption separation, and chromatography. For example, pore diffusion separation using the affinity between a membrane material and particles as an example incorporating separation based on affinity or separation of a target substance into a large particle by adding a substance having a high affinity with a target substance to be separated to form a pore diffusion membrane. It can be used as particles to be separated in the separation method. For example, the arsenic compound can be made larger by adding ferric hydroxide colloid particles to the arsenic compound dissolved in the aqueous solution. These particles can be removed by a pore diffusion membrane separation method.

A cellulose nonwoven fabric having an average pore size of 370 nm is used as the flat membrane loaded in the module of the present invention. The nonwoven fabric has a thickness of 100 μm, a porosity of 70%, the surface of the nonwoven fabric has a roughness of 200 nm or less (this surface is defined as a flat film surface), the roughness of the back surface is 50 μm, and the dimensional change when immersed in water is 2 μm. % Or less. The nonwoven fabric is tightly adhered to the support by a 0-ring packing material (11 in the figure) between two plate-like supports (2 and 7 in the figure) as indicated by 1 in FIG. I do. Two types of support plates (each support has two O-ring grooves and a primary flow channel or a secondary flow channel and a laminar flow preparation area flow channel or secondary The space portions 2 and 6 of the flat membrane 1 which have an outlet connected to the circuit from the side flow path to the recovery tank) serve as a liquid flow path. The primary liquid 4 and the secondary liquid 5 flow in the flow path. Since the flow of the primary liquid 4 flows in a laminar flow, the wall surfaces of the space 6 are all smooth. The film surface of the flat film 1 is defined as a surface in contact with the primary liquid.

      FIG. 1 shows two types of plate-shaped supports. One of them has a primary flow path 8 having a circular cross-section serving as a laminar flow preparation area as shown in FIG. It is guided to the side channel 6. The channel 8 is connected to the inlet of the primary channel of the module. The support is preferably made of polypropylene, polycarbonate, or acrylic resin. Each of the supports may be a primary channel or a secondary channel. The channel provided by this support is the secondary channel 3. Cloth 9 acting as a valve is fused to the support. As the cloth-like material, a non-woven fabric such as nylon or polyester is suitable. These nonwoven fabrics are fused at predetermined positions on the support. The two types of supports are manufactured by cutting a plastic plate or by an injection molding method using a mold.

      FIG. 2 shows an example of an apparatus for exerting the function of the hole diffusion membrane module of the present invention. Two methods are adopted: a method in which the strain rate of the primary liquid on the flat membrane surface is controlled by the liquid feed pump (Figure A) and a method in which the strain rate is controlled by the hydrostatic pressure difference (Figure B). When the module of FIG. 1 is used for the transmembrane pressure applied to the membrane surface, the dynamic pressure becomes zero. Operate at a hydrostatic pressure difference of 0.05 atm or less. The strain rate is operated under a constant condition of 10 to 100 / sec. In Fig. A, the tank is open to the atmosphere (connected to the filter F3 for opening), the secondary side flow path (F2) of the pore diffusion membrane module M, and the liquid level L (through the F1 filter). Open). In this method, stable operation in the liquid transport section is important. On the other hand, in the method shown in FIG. B, the transmembrane pressure and the strain rate can be controlled stably by setting the liquid level L.

A pore diffusion membrane module loaded with a regenerated cellulose porous membrane having an average pore diameter of 300 nm (film thickness: 150 μm, porosity: 80%) was assembled. An effective membrane area was 140 cm 2, and a membrane module was produced so that two porous membranes were sandwiched between three plate-like supports as in FIG. The cross-sectional shape of the primary flow path was a 3 mm-thick strip, and the secondary flow path was provided with a copper regenerated cellulose nonwoven fabric on the back side of the porous membrane. Using the module, the apparatus shown in FIG. 2B was assembled. A commercially available expanded polystyrene product was pulverized with a mixer in water at 20 ° C. to prepare a flaky (about 10 μm thick) aqueous dispersion solution having various areas. An aqueous solution (pH = 2.7, particle concentration: 1000 ppm) in which ferric hydroxide colloid particles having a particle size of 50 nm were dispersed was mixed with this aqueous solution to prepare an aqueous solution having a pH of 4. This aqueous solution was used as a model test solution for an aqueous solution in which a mixture of virus / bacteria / cells was dispersed. The test solution was subjected to a pore diffusion treatment in the apparatus shown in FIG.
Average transmembrane pressure: 0.05 atm, strain rate on membrane surface; 50 / sec treatment rate: 1.5 LMH (liter / square meter / hour). All concentrations were below the detection limit (ie, 1 ppm or less). The treatment rate decreased slightly over time but remained approximately constant for 24 hours.

      It can be applied in a wide range of fields as a technique for separating, removing, concentrating, and fractionating molecules and particles without heating. Typically, it can be used for safety measures in the manufacture of biopharmaceuticals (for example, for process validation of virus removal and inactivation) and for safety measures in the manufacture of products such as regenerative medicine. . Used as a safety measure in the manufacture of other health foods and cosmetics. In the field of safety measures, the environmental industry (eg, water recycling as an example of the recycling industry) is a field to be considered for application in the future.

      The feature of the hole diffusion membrane separation technology is that components are separated using a membrane. There is a difference in principle from a membrane filtration method that uses a sieving effect to capture a large-sized component such as particles inside the membrane. Therefore, the technology of the present invention can be used in fields where conventional membrane filtration technology cannot be applied. For example, application to a fractionation and recovery step of a component having biological activity from biological resources such as a plasma fractionation step or a fractionation and recovery step of a body fluid component is considered. It is also applied to fields such as concentration and recovery of fresh ingredients in agriculture, and ingredient concentration and long-term storage in liquid fertilizers. It can be applied to the removal of microorganisms instead of heat sterilization in the fermentation industry, and can be used for the production of new raw products (eg, production of raw placenta).

Sectional view of the lower part of the hole diffusion membrane module loaded with two flat membranes: the laminar flow preparation area and the part where the hole diffusion area is present. Example of a device that makes use of the features of the hole diffusion membrane module: device. B: An apparatus of a system for controlling the strain rate by the hydrostatic pressure difference.

DESCRIPTION OF SYMBOLS 1: Flat membrane 2: Support plate which constitutes a skeleton of module 3: Secondary flow path in module 4: Flow direction of liquid to be treated flowing in primary flow path in laminar flow state, 5: Secondary flow path Flow direction of membrane permeate flowing through the membrane 6; primary flow path in module 7; support plate with built-in laminar flow preparation area
8: Laminar flow preparation area existing inside the support plate 9; Cloth-like material having a role of a valve for reducing dynamic pressure to zero 10; Liquid inlet 11 toward the outlet of module for membrane permeate 11: Flat membrane O-ring-shaped packing M for bringing the substrate and the support into close contact with each other; a hole diffusion membrane module T of the present invention T; a receiving tank section L; a liquid level control section R; a collecting tank P; a liquid transport pump G; a pressure gauge F1 / F2. / F3: Air inlet / outlet for opening to the atmosphere, sterilization or virus removal filter installed at the entrance / exit

Claims (3)

      In the flat membrane separation module, the primary flow path is designed such that the dynamic pressure applied to the porous flat membrane constituting the wall of the primary flow path is substantially zero at all places of the membrane. And the secondary flow path, which is a flow path of the recovered liquid permeated through the membrane and whose primary flow path is parallel to the membrane surface from the inlet of the liquid to be treated, has a space of the flow path. A module having a porous flat plate-shaped support that provides a space portion, or a space portion provided by providing an unevenness on the back surface of the flat membrane serving as a wall portion of the flow channel, and A pore diffusion type flat membrane separation module characterized in that a laminar flow preparation area and a pore diffusion area are directly connected in series from the lower side of the flow path.       2. An apparatus which is assembled with parts essential to realize all the pore diffusion membrane separation mechanisms of the membrane separation module according to claim 1, wherein (1) the membrane surface of the porous flat membrane loaded in the module is The module is installed vertically, (2) a liquid level control unit connected to the inlet of the primary side flow path of the module, (3) a liquid transport unit for giving a head difference, and (4) a primary unit. And (5) a primary circuit connected to an outlet of a primary channel of the module, and an outlet of a secondary channel of the module and a part connected to the primary circuit. A pore diffusion membrane separation device comprising: (6) a part to be released to the atmosphere via a bacteria-eliminating or virus-eliminating membrane; and (7) a secondary circuit connected to a recovery tank at the other part. 3. The pore diffusion type flat membrane separation module according to claim 1, wherein the laminar flow preparation area has a liquid level equal to or lower than the inlet level of the module, and the volume of the preparation area is the pore diffusion area. Module and device having a volume of not more than.