Apparatus for forming hollow fibers and said fibers.

Description: TECHNICAL FIELD [Detailed description of the invention]

Background of the invention Hollow fiber membranes are hollow capillaries whose walls function as permeable, impermeable or semi-permeable membranes, depending on the application. Hollow fibers are often used as cylindrical membranes that allow the selective exchange of material through the wall. They are also used as containers for controlled release of specific materials, or as reactors that chemically modify the permeation that diffuses through the chemically activated hollow fiber walls. Hollow fiber technology has recently become beneficial for the production of osmotic selectivity, biocompatibility, and immunostaining mediators. These hollow fiber mediators contain materials such as living cells, proteins, or drugs. They are designed so that the material within the hollow fibers penetrates the walls of the hollow fiber mediator. In use, hollow fiber mediators are delivered to specific parts of the body when special materials need to be present in the core of the hollow fibers. Specific applications in which such hollow fibers are used include the treatment of neurotransmitter deficiencies such as Parkinson's disease by regenerating insulin production and delivering special neurotransmitters to specific parts of the body. Whatever the special application of the hollow fiber medium, the morphology and thickness of the fiber membrane must be controlled to obtain the desired mechanical and transport properties suitable for the special application. Conventionally, four synthetic fiber spinning methods have been used to produce hollow fiber membranes. That is, it is a combination of (1) melt spinning, (2) dry spinning, (3) wet spinning and (4) dry and wet spinning. In each of these methods, the tubular cross section of the hollow fiber is formed by delivering a spinning material, such as a polymer, copolymer, cellulose material, etc., through a spinneret nozzle and at the same time delivering a material that is housed in the fiber core. Spinner nozzle assemblies are US Pat. Nos. 4,035,459, 4,127,625, 4,229,154, 4,322,381, 4,323,627,4. , 342, 711, 4, 380, 520 and 4, 744, 932, as shown in various designs. Problems related to these prior art nozzle assemblies and hollow fiber forming techniques include the inability to form fibers from highly viscous thermoplastic polymers due to nozzle clogging, and nozzle assembly to produce variable film thickness and morphology. The conformation cannot be adjusted, the nozzle type or nozzle cap cannot be changed in the assembly to allow the production of hollow fibers of various types and shapes, and the inside of the fiber wall is oriented almost vertically and within the fiber wall. It is not possible to produce Z fibers having rod-like structures that are substantially interconnected with each other. U.S. Pat. Nos. 3, 871, 950 discloses hollow fiber membranes with pore-sized gradients on the outer or outer and inner surfaces. There is no interconnection between the perforated regions along the long axis of the fiber. As such, the fiber is a series of closed voids oriented along the long axis of the fiber. However, the membranes of the present invention have different morphologies, the rod-like structures within the fiber walls are substantially interconnected with each other, and some or all are continuous with the outside of the fibers. General background information in the field of the present invention is described in US No. 4, 385, 017, European Application 0 277 619 and JP-A 57 106. Found in 708. Therefore, it is an object of the present invention to produce nozzle assemblies that are used in a variety of entities with a variety of highly variable viscosities. It is another object of the present invention to provide a nozzle assembly with a modular configuration, in which the parts of the assembly facilitate the production of hollow fibers of various sizes, shapes, film thicknesses and surface forms. Easily replaced and substituted to do so. Abstract of the invention Therefore, one aspect of the invention is directed to nozzle assemblies used in making hollow fibers that are impermeable, semi-permeable or permeable. The voids in the fiber wall are left as voids. Alternatively, when semi-permeable or permeable, it is filled with a material such as a drug or a biological material such as a living cell or protein. The nozzle assembly generally comprises an extension bore or tube passing through the housing and a second outer bore or tube concentrically disposed on the inner base. The inner bore is movable and is retracted and extended with respect to the stationary outer bore and housing in such a way as to provide precise and reproducible adjustment of the bore with respect to the extrusion cap and housing. The output end of the outer bore is equipped with a removable nozzle cap, and the output end of the inner bore is equipped with a removable seal guide. These can be replaced with other caps and seal guides to allow the production of hollow fibers of different shapes and different film thicknesses and forms. The medial bore is also interchangeable with other medial bores to change the central canal diameter or fiber wall morphology. The nozzle assembly of the present invention is particularly useful in making hollow fibers containing living cells or biomaterials. Furthermore, the present invention is directed to a novel fibrous structure here referred to as "Z fiber". The Z fibers contain a rod-like structure within the fiber wall, and each of these rod-like structures (i) extends outward from the central axis of the fiber, that is, approximately in the radial direction, and (ii) connects to each other. It has a portion and (iii) is partially or completely connected to the outer surface of the fiber. In addition, Z fibers have a semi-permeable inner thin film that defines the fiber lumen and are used to provide immunoseparation function. A brief description of the drawing FIG. 1 is a cross-sectional plan view of the nozzle assembly of the present invention showing a fully extended inner bore. FIG. 2 is a cross-sectional plan view of the nozzle assembly of the present invention showing the retracted inner bore. FIG. 3a is a cross-sectional plan view of the nozzle cap used in the nozzles of FIG. 1, except for the different nozzle caps and seal guides, and the bottom cross section of the seal guides for the inner bore, which is different from FIG. Further includes a partial plan view. FIG. 3b is a detailed cross-sectional enlarged plan view of the nozzle cap and the outlet end of the seal guide shown in FIG. 3a. Figure 4 shows a series of three photographs of a single Z fiber membrane at various magnifications, namely (i) 100X, (ii) 200X and (iii) 500X, to better show the rod-like structure and longitudinal relationship. Is. Detailed description of preferred embodiments As best shown in the drawings, the nozzle assembly 10 according to the invention comprises a housing 12 made of a solvent resistant material. An extension hollow inner bore or a pipe 14 is arranged in the housing 12. Further, in the housing 12, an outer bore 16 concentric with the inner bore 14 is arranged to define an annular space or a conduit 18. The inner bore 14 is pierced and fixed and attached to a threaded pipe joint 20 screwed into the housing 12 including the matching thread at the upper portion 22 of the outer bore 16. The inclusion material in the core hollow fiber membrane is fed into the nozzle assembly at the input end 23 of the inner bore 14. The inner bore 14 also passes through a seal 24 that prevents the fluid present in the conduit 18 from flowing upwards and out of the top of the housing. The seal 24 is held in place by the spring 46. In the lower portion of the housing, the inner bore 14 passes through a seal guide 26 removably attached to the housing 12 by the compressive force generated by the attachment of the nozzle cap 28. The seal guide 26 includes one or more holes for aligning and maintaining the inner bore 14 during extension and retractation, and directing fluid present in the conduit 18 to penetrate the outer region of the conduit 19. .. The nozzle cap 28 is removably attached to the housing 12 by fastening means 30 like screws, bolts or equivalents. The nozzle cap 28 serves to extend the conduit 18 to the outlet end 36 of the nozzle assembly. As shown, the contours of the seal guide 26 and the bottom of the nozzle cap 28 define the dimensions and paths of the conduit 19. Just in front of the intersection with the bore 14, the conduit 19 makes an angle of about 45 °, as shown in Figures 1 and 2. The outer bore 18 is connected to a fluid source used in the production of hollow fiber membranes using a pipe joint 32 such as a conventional lure pipe joint. As shown, the pipe fitting 32 includes a tubular inlet 34 through which fluid flows into the nozzle assembly and conduit 16. The seal 33 provides a fluid seal to prevent fluid flow outward through the pipe joint. The extension and pull-in of the inner bore 14 is achieved by the rotation of the inner bore adjusting means 38 attached to the threaded pipe joint 20. And form a bore adjustment assembly that is threaded to the matching thread of the outer bore 16. The bore adjustment assembly rotates as a single unit and, depending on the direction of rotation, moves the inner bore 14 vertically up and down. Pin 42 is secured and intervened by the inner bore adjusting means 38 or pipe joint 40 (not shown) shown in FIG. 2 to rotate both together. The pipe joint 40 rotates in combination with the adjusting means 38, which is vertically sealed by the tension applied by the spring 44. The reproducibility of extension or pull-in between subsequent extrusions is improved using a measuring tool such as a vernier ruler attached to the pipe joint 40. Stretching and pulling in is done manually or mechanically under computer control (not shown). FIG. 1 shows a cross-sectional plan view of a nozzle assembly with an inner bore 14 at an intermediate position between full retract and full extension. All components of the nozzle assembly, including the housing, are made from stainless steel, glass, and organic solvent resistant materials such as Teflon®, Delrin® or polypropylene polymers. Seals that must be compatible and must not be adversely affected by the solvents used during the extrusion process are preferably made from Teflon polymers, but also from materials such as polypropylene, nitrile polymers. In operation, the fluid used to form the hollow fiber membrane flows through the pipe joint 32 to the outer bore 16 and the conduit 18 and then through one or more holes through the seal guide 26 to the conduit 19. Is pushed by a pump (not shown). The type of fluid used depends, of course, on the desired specific hollow fiber membrane. Suitable materials used as hollow fiber membranes include thermoplastic polymers, thermosetting polymers, gels, and hydrogels. Specific materials used include cellulose, acrylic copolymers, polyvinylidene fluoride, polyurethane isocyanates, arginates, polysulfones, polyvinyl alcohols, polyacrylonitrile, and mixtures thereof. Also, the material used as the core material is used to form the film. The film-forming material is a melt, which is preferably a solution. Suitable solvents used in forming the solution include water-soluble organic solvents such as dimethylacetamide, dimethylformamide, acetone, dimethyl sulfoxide, N-methylpyrrolidone, acetonitrile, and mixtures thereof, and hexane, diethyl ether, chloride. There are other solvents such as methylene and mixtures thereof. In many applications, hollow fibers formed using the apparatus of the invention, if not all, are terrible, such as core materials and / or drugs, biological materials, such as living cells or proteins, or described herein. There are other similar materials. The core material and / or terrible is generally a fluid medium, generally water, to form a core material composition. Compositions often include one or more cross-linking agents, gel-forming agents, or viscosity-enhancing substances. Other materials present in the core material composition include Ficol, saline, ethanol, tissue culture medium, serous fluid, and methanol. The core material composition also comprises a biocompatible hydrogel used to immobilize cells or provide a growth substrate. The specific core material is an anion [arginate], a cation [collagen], an omnidirectional [poly (phosphazene) optionally having an ionic side chain], or a neutral [poly (ethylene oxide)]. Arginate is in liquid form or CaCl₂Is extruded and then crosslinked by diffusing into a liquid core. The core material composition is supplied through the inner bore 14. The film material and the core material composition are in contact with each other at or near the nozzle output end 36. When forming unfilled hollow fibers, a fluid, such as water, solvent, or a mixture thereof, is provided through the inner bore 14. Thus, the core material composition comprises a fluid and optionally contains a core material, deliverables, or both. By adjusting the position of the inner bore 14 with respect to the nozzle output end 36, clogging of conduits 18 and 19 especially at the nozzle cap portion is controlled and substantially cleared. Clogs are a special problem when the film-forming material is a highly viscous or fast-precipitating material, such as a thermoplastic polymer in solution. In some cases during fiber film formation, two materials were found to be beneficial in expansion time in controlling the fluid flow direction in the nozzle to generate specific wall dimensions and fiber wall morphology. Prior to exiting the nozzle, the film-forming material should be in contact with the core material composition within the nozzle assembly for as long as possible. As a result, it is often preferable to maintain the inner bore 14 in a nearly perfect retracted position that allows long contact before the two materials leave the nozzle assembly. However, the initial long contact causes clogging, especially in the nozzle cap, because the fibrous film forming material precipitates and hardens when in contact with the aqueous core material. This usually slows the flow of material in conduits 18 and 19 and causes clogging. However, clogging is overcome by the apparatus of the present invention by projecting the inner bore so that the core material composition and the film forming composition do not come into contact with each other until they exit the nozzle. The inner bore is then generally gradually retracted, increasing the amount of time the two materials are in contact before leaving the nozzle. Usually, once the phase inversion, i.e., the transition from liquid to solid, begins at a particular flow rate, the flow is substantially constant, even with long contacts between the materials. The flow rates of the two materials are maintained by an external pump (not shown). This technique for avoiding clogging is preferred over prior art techniques that use polymeric solvents such as dimethyl sulfoxide (DMSO). Solvents, such as DMSO, cannot be used due to their toxicity in many applications, such as those relating to the production of hollow fiber membranes used in the human body to administer drugs or equivalents. Another benefit of the device of the present invention is the use of removable and replaceable nozzle caps 28 and seal guides 26. By replacing the nozzle cap with another nozzle cap and / or replacing the seal guide with another seal guide, the size and configuration of the annular conduit is changed near the output end of the assembly, changing the synthetic membrane. .. Furthermore, the flow direction of the film-forming material is changed. For example, as shown in FIGS. 1 and 2, the flow direction of the conduit 18 in the region 19 of the conduit is at an angle of about 45 ° with respect to the flow of material exiting the inner bore 14. On the other hand, FIGS. 3a and 3b show the cap 28 and the seal guide 26, in which case the flow direction at portion 21 of the conduit 19 is 90 ° with respect to the flow of material exiting the inner bore 14. Various other nozzle caps and seal guides that provide other flow angles are used. By changing the angle at which the film-forming material contacts the core material composition, the morphology of the film wall is changed. Further, the thickness of the synthetic film is changed by changing the diameter and / or height 21 of the conduit 19 of the conduit portion of the nozzle cap 28 in particular. The nozzle caps of FIGS. 3a and 3b further include a sleeve 50 inside the nozzle cap housing 28 to reduce the diameter of the conduit 19 and change the opening size or affect the fiber size and / or morphology. Facilitates changes in the giving orifice plate 52. The sleeve 50 also serves to transmit the force generated when the nozzle cap fastening means 30 is fastened to the housing 12. When the fastening means 30 is tightened, the seal guide 26 and the seal 54 located below the orifice plate 52 are compressed to achieve a valid seal. The sleeve 50 terminates at an orifice plate 52 that is generally held in place between the sleeve 50 and the seal 54 by compression, but can be physically attached to the sleeve 50. The orifice plate 52 changes the flow direction or angle of the membrane material and the outer diameter of the formed membrane. The morphology of the fiber walls and the formation of rod-like structures produced in the anisotropic membrane can be controlled by the nozzles of the present invention. The formation of rod-like tissue is partly a phase separation phenomenon. In general terms, the polymer used to form the fiber wall is the most non-polar component of the overall system, but the solvent in which the polymer is generally dissolved is more polar and water soluble than the polymer. During extrusion, the water or water component of the core material composition in the inner bore contacts the polymer and / or solvent fiber forming material when mating near the nozzle orifice. In this regard, the water diffuses into the polymer and the solvent / polymer / water mixture is partitioned into solvent / polymer and solvent / water phases. The solvent / water phase creates voids in the polymer. The sum of these voids gives rise to a rod-like tissue network within the fiber wall. Normally, the rod-like structure of hollow fibers is oriented perpendicular to the fiber wall, as it occurs when 45 ° caps (shown in Figures 1 and 2) are used. Many factors, such as the relative flow rates of the two materials, are changed to change the orientation of the rod-like structure. The nozzle is provided with additional means for changing and controlling the morphology of the rod-shaped structure. When 90 ° caps and seal guides (as in Figure 3) are used, they direct the polymer flow path perpendicular to the flow from the inner bore, and as a result, the void formation is probably this flow. It begins while being oriented in the direction. A sudden 90 ° orientation change then distorts the shape of the initial rod-like structure at an angle diagonally or parallel to the fiber wall, thereby forming fibers here called "Z fibers". The Z-fibers include a rod-like structure within the fiber wall, the rod-like structure (i) oriented approximately longitudinally with respect to each other, (ii) substantially interconnected with each other within the fiber wall, and (iii) portion. Targetly or completely continuous with the outside of the fiber. In addition, the Z fiber has a semi-permeable inner thin film that defines the fiber lumen and provides immunoisolation. Z-fibers are considered to be even more beneficial than other fiber morphologies in inducing and improving intracapillary growth into the fiber wall when used as a transplant device in living animals. It was found that the Z-fiber morphology did not depend on the chemical composition of the membrane, the dimensions, or the composition flowing through the inner bore. In order to make the fibers sensitive to the irregularity of material flow in the outer bore, the traditional non-retractable coaxial nozzle tends to have substantially free play in the central bore, so this nozzle is also synthetic. Generally increases the uniformity of hollow fibers. This sensitivity is manifested by the movement of the central bore, which leads to the production of irregular asymmetric fibers during the extrusion process. The seal guide 26 in this nozzle minimizes the free play of the central bore due to its position close to the orifice of the inner bore, which leads to more uniform fiber preparation. The seal guide 26 also reduces the need for frequent recentering of the inner bore, allowing the inner bore to be retracted and stretched without shifting and concentric changes. The fibers prepared using the nozzles of the present invention are non-permeable, permeable or semi-permeable. Preferably, they are semi-permeable fibers used in filtration devices, biological reactors or as cell encapsulation mediators. Example The following examples show the formation of unfilled Z fibers. The nozzle assembly of Figure 3 was used with a 90 ° cap and seal guide. This assembly directs the flow path of the film-forming polymer perpendicular to the flow from the inner bore. Fiber membranes were prepared from a pouring solution of 12.5% w / w poly (acrylonitrile-vinyl chloride) copolymer in dimethyl sulfoxide. The inner bore contained distilled water. The pouring solution was pumped at a rate of 1 ml / min and the water was pumped at a rate of 5 ml / min. The nozzle was maintained at a distance of 7 cm above the settling bath containing 10 liters of distilled water at ambient temperature and pressure. The inner bore was positioned about 0.5-3 mm above the outer tip of the nozzle, preferably about 1 mm above. The two solutions were then pumped simultaneously through the hollow fiber nozzle assembly, and synthetic hollow fibers were collected in the settling bath. Synthetic fibers have shown the following dimensions. It has an outer diameter of 1,000 to 1,200 microns and a film wall thickness of 80 to 100 microns. FIG. 4 is a set of three scanning electron micrographs at various magnifications showing the vertical bar-like tissue orientation of synthetic Z fibers. In synthetic Z fibers, cells used to induce and improve intracapillary growth can be introduced into the fiber wall, but an easier technique to achieve the same result is through the inner bore. By replacing the pumped distilled water with cells in a suitable aqueous growth medium and crimping the fibrous membrane immediately after disclosure of its formation.