BLENDED FIBER DIALYZERS

Abstract: A method of blending two different sizes or two different types of hollow fiber membranes provides hemodialyzers with specifiable characteristics utilizing standardized housings. The system can blend two different fiber sizes of the same type to achieve a desired ultrafilteration rate in a standard housing. This system can also blend two different types of fibers to be used in a standardized housing to provide a desired ultrafiltration rate.

Description: Technical Field The invention pertains to methods of manufacture of and to particular types of hollow fiber fluid filtration devices. More particularly, the invention pertains to a method making hemodialyzers which incorporate at least two different fiber members. Background of the Invention It has been generally known to make hemodialyzers by utilizing hollow membrane filter elements supported axially within a cylindrical housing. Such housings usually have fluid flow input port and an output port. Fluid injected into the input port flows through the hollow membrane filter elements. The housings also include dialysate input and output ports. The dialysate flows around the exterior surfaces of the hollow membrane filter elements. The filter elements can be formed from a variety of natural as well as synthetic materials. For example, hollow membrane fibers can be formed of polysulfone, polyethylene, cellulose or cuprammonium. A common form of cuprammonium is available from Enka under the trade name CUPROPHAN. It is also known that use of these differing materials results in dialyzers with substantially different characteristics. Dialyzers of polysulfone and polyethylene are known to be more biocompatible then dialyzers of cuprammonium. On the other hand, polysulfone dialyzers are more expensive than cuprammonium dialyzes. Also, cuprammonium dialyzers have better ultrafiltration performance characteristics than do polysulfone dialyzers. Whatever the selected hollow fiber material or size, it is necessary to encase the appropriate numbers of fibers in a housing. In the past, dialyzers have been manufactured by arriving at a particular number of fibers, of certain type and size. These fibers can then be encased to provide a dialyzer with the appropriate ultrafiltration perameter. Casings or housings can be injection or blow molded. A particular housing can be used with only a few different selected number and type of ultrafiltration fibers. In part, this is due to the internal crossection of the housing. In addition, space must be provided around the fibers so that the dialysate can freely flow around same to effect filtration. Hence, if the number, type, or size of the ultrafiltration fibers is to be altered due to a desire to change the ultrafiltration perameter, or any other characteristic of the dialyzer it may be necessary to create molds to make a new case. This is a very expensive process. It would be desirable to be able to vary the contents of a hemodialyzer in order to alter the dialyzer parameters while continuing to use existing housings. For example, combining polysulfone with cuprammonium might result in a lower cost dialyzer, than a completely polysulfone dialyzer. Such a dialyzer could still be adequately biocompatible but with greater ultrafiltration performance characteristics than would be the case of a dialyzer having only polysufone fibers. Cuprammonium could also be combined with cellulose acetate or polyethylene. Similarly, it would be desirable to blend fibers of the same type having different radii. However, the prior art does not disclose how to carryout such blending and still use an existing housing. Hence there is a need for a method of making hemodialyzers which is substantially more flexible and less expensive than known methods. Medical and Biological Engineering & Computing, vol 18, no 4, July 1978, pages 369 to 378 discloses a method of fabricating capillary membrane oxygenators in which hollow fibres are accurately spaced in potted end sections. The present invention provides a method of making a blended fiber filtration device having a housing (12) with a predetermined cross-section, the method comprising:- (a) specifying at least first and second fiber members (26) having first and second filtration factors respectively, (b) specifying a range for the desired filtration factor of the device, (c) selecting predetermined quantities of each of the first and second fiber members, which combined quantities will fit into the housing, (d) determining the expected filtration factor of a device having said combined quantities of first and second fiber members, (e) comparing the expected filtration factor with the specified range, (f) if the expected filtration factor falls outside the specified range, reducing or increasing by a predetermined quantity the number of fiber members having the higher filtration factor, depending on whether the expected filtration factor exceeds or falls below, respectively, the specified range, (g) repeating step (e) if step (f) is carried out and repeating step (g), if necessary, until the expected filtration factor falls within the specified range, (h) determining that the combined quantities of fiber members after carrying out steps (f) and (g) still fit into the housing, and (i) assembling the fiber members in the housing. The invention also provides a blended fiber dialyzer made by the method. Preferably, characteristics of hollow fiber dialyzers incorporating the two preferred sizes can be determined. The number of fibers of each size which will fit into the known housing is also determined. The smaller of these two numbers, usually associtated with the larger diameter fiber, is selected. The percentage that this smaller number of fibers is to the larger number is determined. In an initial trial, a predetermined quantity, N1 of the larger number of fibers is selected. For example, in a preferred embodiment of the method, this number N1 can be set equal to one-half the total number of the smaller diameter fibers which can be used in the housing. Using the predetermined percentage, the corresponding quantity of the smaller number N2 of fibers, which would be the larger diameter fibers, can be determined. The two determined quantities of different size fibers N1, N2 can then be compared to the available cross-section of the housing to determine if this total number of fibers, N1 + N2 will fit within the housing. This determination takes into account a packing factor. This packing factor limits the number of fibers to provide flow space for the dialysate. Assuming that the fibers will fit within the housing, the filtration factor of the filtration device using this particular combination of hollow fiber filter elements can be determined. The determined filtration factor can then be compared to the range of the specified filtration factor. Assuming that the determined filtration factor falls within the range of this specified filtration factor, the filter can then be assembled using the two quantities of fibers N1 and N2 as previously determined. In the event that the determined quantity N1 + N2 of the two fiber sizes will not fit within the available cross-section of the housing, the number N1 of the smaller diameter fibers can be increased a predetermined amount, for example 2%, and the method repeated. The percentage factor can also be reduced a predetermined amount, for example 2%. In the event that the determined filtration factor has a value which exceeds the range of the specified filtration factor, the number N1 of fibers having a higher ultrafiltration parameter can be reduced a predetermined amount, for example 2%, and the process can be repeated. In the event that the determined filtration factor has a value which falls below the range of the specified filtration factor, the quantity N1 of fibers having a higher filtration characteristic can be increased a predetermined amount, for example 2%, and the process can be repeated. Also in accordance with the present invention, the method can be used either with two different fiber sizes or with two different fiber materials each having a predetermined size. Numerous other advantages and features of the present invention will become readily apparent from the following detailed description of the invention and the embodiments thereof, from the claims and from the accompanying drawings in which the details of the invention are fully and completely disclosed as a part of this specification. Brief Description of the Drawings Figure 1 is a side plan view of a hemodialyzer in accordance with the present invention partly broken away to show the internal structure; Figure 2 is an overall block diagram illustrating a method of making a hemodialyzer in accordance with the present invention; and Figure 3 is a block diagram of a system for making a hemodialyzer in accordance with the present invention. Detailed Description of the Preferred Embodiment While this invention is susceptible of embodiment in many different forms, there is shown in the drawing and will be described herein in detail a specific embodiment thereof with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the invention to the specific embodiment illustrated. With respect to Figure 1, a hemodialyzer 10 is illustrated having a generally cylindrical housing 12 defining an internal volume 14 therein. Affixed to the housing 12 is an input fluid port 16 and an output fluid port 18. Fluid to be filtered, such as blood, is passed through the dialyzer 10 between the ports 16 and 18. The dialyzer 10 also includes a dialysate input port 20 and a dialysate output port 22. The input fluid port 16 and the output fluid port 18 are in fluid flow communication by means of a plurality of hollow membrane filter elements 26. The filter elements 26 are generally hollow and cylindrical in shape and extend axially between the input fluid port 16 and the output fluid port 18. The hollow membrane fibers 26 are packed in the housing 12 with a preselected packing density. The packing density limits the number of fibers to permit the flow of dialysate solution around and past the exterior surfaces of the fibers 26. Known hemodialyzers have been made with one type of fiber having a single internal diameter. For example, one known hemodialyzer makes use of an existing cylindrical housing having an internal diameter on the order of 1.125 inches (28 mm), hereafter called the "1.125 diameter case". The internal diameter of one known fiber type is on the order of 8 microns. It has been found that 6500 of the 8 micron fibers can be incorporated into a 1.125 diameter case. The ultrafiltration parameter of this dialyzer is 4.2. It is also been known that 11 micron hollow fibers can be used in the same case. In this instance, 6100 of the 11 micron fibers can be incorporated into the 1.125 diameter case. The ultrafiltration parameter of this dialyzer is 3.0. Figure 2 illustrates in block diagram form a method of making a new hemodialyzer using a blend of 8 micron and 11 micron fibers to provide an ultrafiltration rate between 3.0 and 4.2. The present invention offers a number of important advantages. Blended dialyzers can be expected to cost less then dialyzers which utilize only 8 micron fibers. Further, by being able to blend various fiber sizes, it will be possible to use the same housing size with new or different fiber sizes. A family of dialyzers could be created. By blending 8 and 11 micron fibers, it will be possible to reduce the patient's extracorporeal blood volume. Additionally, it is known that dialyzers using 11 micron fibers may be reused more extensively than dialyzers using only 8 micron fibers. Hence, it is expected that blended dialyzers would have improved reuse when compared to dialyzers using only 8 micron fibers. Finally, its expected that the compliment reaction rate can be reduced from that of a single type of fiber by blending a synthetic with a cellulosic fiber. In accordance with the method of Figure 2, the internal diameter of an available dialyzer housing is specified. For example, the above-noted 1.125 diameter case could be utilized. Further, ultrafiltration rates of the two known fiber dialyzers and the desired ultrafiltration range can be specified. For example, from the known dialyzers, 6500 eight micron fibers will fit into the desired housing. However, only 6100 of the 11 micron fibers will fit into that housing. In accordance with the method of Figure 2, the percentage of the number of larger diameter fibers with respect to the number of smaller diameter fibers is determined. This percentage can be utilized to establish the relationship of the blended fibers in the dialyzer. As an initial trial, one-half, N1, of the known number of smaller diameter fibers can be selected. By means of the percentage factor the number N2 of larger diameter dialyzer fibers can also be determined. The total number of dialyzer fibers of both sizes N1+N2 can then be compared to the case size to determine whether or not they will properly fit within the existing housing. This comparison utilizes the following equation: The factor .3714 is a packing factor reflecting permitted density of fiber to housing inner diameter. The factor 2.54 is a conversion factor to convert case internal diameter to inches. In the equation I.D. = internal diameter and OD = outer diameter. If, based on the above noted equation including the packing density which has been empirically derived, the total number of fibers will fit into the desired case, the ultrafiltration rate for the blended dialyzer can then be determined. Determining the ultrafiltration rate depends first on deriving the ultrafiltration rate per individual fiber of the above two known dialyzers. In the case of the 8 micron dialyzer, the ultra filtration rate is .000631/fiber. The ultrafiltration rate fiber of the 11 micron fibers is .000492/fiber. The ultrafiltration rate for the blended dialyzer fiber can then be determined. This determined ultrafiltration rate can then be compared to the specified ultrafiltration range. For example, if it is desired to make a blended fiber dialyzer having an ultrafiltration rate of 3.5 ± 7%, the present method can be utilized to determine the number of 8 and 11 micron fibers needed. In an initial step, the number of 11 micron fibers, 6100, in the known product is divided by the number of 8 micron fibers, 6500, in the known product to determine a relative percentage. This corresponds to 93.85%. In the initial trial, one-half of the number of 8 micron fibers is selected. N1 equals 3250 eight micron fibers. The number of 11 micron fibers can be initially determined by multiplying the pecentage, 93.85, by N1 resulting in N2 = 3050 eleven micron fibers. The number of 8 micron fibers and the number of 11 micron fibers can then be compared to the housing capacity using the above-noted equation. The ultrafiltration rate of the dialyzer can then be determined by taking the ultrafiltration rate for each fiber size and multiplying by the corresponding number of fibers. For the 8 micron fibers, this would correspond to an ultrafiltration rate of 2.05. For the 11 micron fibers, this would correspond to an ultrafiltration rate of 1.50. The total ultrafiltration rate is the sum of these two corresponding to 3.55 for the new dialyzer. Hence, the new blended fiber dialyzer will fall within the range of the specified ultrafiltration rate. The blended fibers can then be positioned in the housing, sealed and the dialyzer sterilized. A system 30 for determining parameters of and assembling blended fiber hemodialyzers is illustrated in block diagram form in Figure 3. A manually operable display terminal 32 can be used to enter the performance characteristics and constraints through a keyboard. The display terminal is coupled to programmable control unit 34, such as a Hewlet-Packard Model 9836. A disk storage unit 36, coupled to the control unit 34, can be used to store a control program for determining the numbers of each fiber size in accordance with the above-noted method. A control program could be written in BASIC to carry out various of the above noted steps. This control program can be stored on the disk storage unit 36. The values of N1 and N2 of each fiber size generated by the control unit 34 can be transferred to a housing forming system 38 and a fiber forming system 40. The housing forming system 38 could be an injection molding system. Housing 12 of a predetermined length and internal diameter can be formed as a molded plastic member. Housings can also be formed by blow molding. Alternately, an extruded rod having a cross section that is circular or in the shape of a parallogram can be cut to the desired length. The fiber forming system 40 can provide a plurality 42 of hollow membrane fibers having first and second predetermined diameters. The process of fabrication of hollow membrane fibers with a selected internal diameter D usable for separation of a fluid component is well known. The fiber forming system can also cut the fibers to the correct length and collect the desired number N1 and N2 of such fibers. For example, an effective length of 21 cm could be used for all dialyzers in the family. A dialyzer assembly system 44 can assemble the fibers 42 within the housing 12. In a preferred form of practicing the invention, the fibers are assembled axially in a cylindrical housing. The assembly system can also provide end caps such as caps 48 to seal the fibers 42 within the housing 12 thereby forming the assembled dialyze 10. In addition to blending two different sizes of fibers, it is also possible, in accordance with the above method, to blend two different types of fibers. For example, using the above method cuprammonium fibers could be blended with polysulfone fibers or polyethlylene fibers. This would result in a lower cost dialyzer for the same or improved ultrafiltration performance then could be realized with the use of only polysulfone fibers. In view of the increased ultrafiltration characteristic of cuprammonium fibers, less surface area would be required to acheive the same ultrafiltration rate. This results in a lower excorporeal blood volume with respect to the patient. This also results in less of the patient's blood being exposed to the device. Further, lower surface area results in a lower priming volume also. Such a blended fiber dialyzer should also cost less then a fully synthetic dialyzer. From the foregoing, it will be observed that numerous variations and modifications may be effected without departing from the true spirit and scope of the novel concept of the invention. It is to be understood that no limitation with respect to the specific apparatus illustrated herein is intended or should be inferred. It is, of course, intended to cover by the appended claims all such modifications as fall within the scope of the claims.

Claims: A method of making a blended fiber filtration device having a housing (12) with a predetermined cross-section, the method comprising:- (a) specifying at least first and second fiber members (26) having first and second filtration factors respectively, (b) specifying a range for the desired filtration factor of the device, (c) selecting predetermined quantities of each of the first and second fiber members, which combined quantities will fit into the housing, (d) determining the expected filtration factor of a device having said combined quantities of first and second fiber members, (e) comparing the expected filtration factor with the specified range, (f) if the expected filtration factor falls outside the specified range, reducing or increasing by a predetermined quantity the number of fiber members having the higher filtration factor, depending on whether the expected filtration factor exceeds or falls below, respectively, the specified range, (g) repeating step (e) if step (f) is carried out and repeating step (g), if necessary, until the expected filtration factor falls within the specified range, (h) determining that the combined quantities of fiber members after carrying out steps (f) and (g) still fit into the housing, and (i) assembling the fiber members in the housing. A method according to Claim 1, wherein step (a) includes specifying different materials for the first and second fiber members (26). A method according to Claim 2, wherein the materials are selected from polysulfone, polyethylene, cellulose acetate and cuprammonium. A method according to Claim 1, 2 or 3, wherein the first and second fiber members (26) have different diameters. A method according to Claim 4, wherein step (c) includes the steps of:- (i) determining the number of fiber members (26) of each diameter which will fit into the housing (12), (ii) selecting the smaller of the determined numbers, (iii) determining the percent value of the smaller number relative to the larger number, (iv) selecting a predetermined quantity of fiber members from the group giving the larger number, (v) determining the corresponding quantity of fiber members from the group giving the smaller number, the determination being based on the percent value, (vi) comparing the combined two determined quantities of fiber members to the available cross-section of the housing, (vii) if the combined fiber members will fit into the housing, continuing with step (d) and, if the combined fiber members will not fit into the housing, reducing the quantity of fiber members in the group giving the larger number by a predetermined amount and repeating steps (v) and (vi) until the combined fiber members will fit into the housing before continuing with step (d). A method according to Claim 5, wherein step (vii) includes reducing the percent value a predetermined amount before repeating steps (v) and (vi). A method according to any preceding claim, wherein filtration factor range is ±7% of a desired center value. A method according to any preceding claim, wherein the housing and the fiber members (26) are suitable for filtration of blood. A blended fiber hemodialyzer comprising: a housing defining an internal volume; a first plurality of hollow fiber members (26) oriented within said housing, each having a first predetermined filtration factor; and a second plurality of hollow fiber members oriented within said housing each having a second predetermined filtration factor wherein said dialyzer has a selected composite filtration factor achieved by carrying out the method of any one of Claims 1 to 8.

Inventors: FISHER, JERRY D., MOLTHOP, SUSAN C.
Applicants: BAXTER INTERNATIONAL INC. (A DELAWARE CORPORATION)
Application year: 1988
Main classification: A61M1
IPC codes: B01D63, A61M1, B01D61