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CN-116322956-B - Tangential flow box-HF simulation

CN116322956BCN 116322956 BCN116322956 BCN 116322956BCN-116322956-B

Abstract

The biocompatible polymer film comprises a hole (106) defined between two material layers, wherein the first film material layer (101) comprises strips and the second film material (104) is bonded to each of the plurality of first film material layer strips (101) comprising a plurality of windows (105) exposing each first film material strip (101). The biocompatible polymer filtration membrane comprises a hole (106) defined by uniform channels defined by the first membrane material layer strip (101) and the second membrane material layer (104) within each window (105).

Inventors

  • W. A. Hennessy
  • D. Albagri
  • R. Stankovsky

Assignees

  • 环球生命科技咨询美国有限责任公司

Dates

Publication Date
20260508
Application Date
20211005
Priority Date
20201009

Claims (8)

  1. 1. A method of making a biocompatible polymeric filtration membrane comprising the steps of: (a) Depositing a first layer of film material (101) on a substrate (100); (b) Patterning the first layer of film material (101) into a plurality of strips; (c) Depositing a sacrificial layer (103) defining a hole on the first strip of film material; (d) Patterning a sacrificial layer (103) defining a hole into strips orthogonal to the strips of first film material; (e) Depositing a second layer of film material (104) on the substrate (100); (f) Etching a window (105) in the second film material layer (104) to expose the sacrificial layer (103) defining the aperture, and (G) The sacrificial layer (103) defining the apertures is selectively etched to produce apertures (106) defined by uniform channels defined by the first and second strips of film material (104) within each window (105).
  2. 2. The method of claim 1, wherein the step (b) of patterning the first film material layer (101) into a plurality of strips comprises depositing a hard mask layer on the first film material layer (101).
  3. 3. A method according to claim 1 or 2, wherein the step (f) of etching a window (105) in the second layer of film material (104) to expose the sacrificial layer (103) defining the aperture comprises depositing a hard mask layer over the second layer of film material (104).
  4. 4. The method of claim 1 or 2, wherein the first film material and the second film material comprise polyimide.
  5. 5. The method of claim 1 or 2, wherein the holes (106) have a thickness of 20-1000 nm.
  6. 6. The method of claim 1 or 2, wherein the biocompatible polymer filtration membrane has a thickness in the range of 2-10 microns.
  7. 7. The method according to claim 1 or 2, wherein the first layer of film material (101) has a thickness in the range of 1-5 micrometers.
  8. 8. The method according to claim 1 or 2, wherein the second layer of film material (104) has a thickness in the range of 2.5-20 micrometers.

Description

Tangential flow box-HF simulation Background Tangential flow filtration is widely used in biological process technology to remove liquid from a mixture of particles and liquid, and can be used, for example, to concentrate cells or to remove liquid from a mixture of liquid and cells, cell debris, or other particulate matter. Tangential flow devices are complex three-dimensional devices, fundamentally different from normal flow (dead-end) devices. Hollow fiber devices and most tangential flow devices have very small holes that are prone to fouling. Dead-end devices with very small holes are almost immediately fouled by many large solids that are larger than the holes. Tangential flow equipment recirculates "feed" in a loop. The "permeate" typically has a much lower flow rate, so the larger suspended solids continue to travel in the direction of the "retentate". If the retentate is recycled to the feed tank, the process is a batch process, and if the retentate is withdrawn without being recycled, it is a single pass tangential flow process, as shown in FIG. 1A. One type of tangential flow filtration device is known as a hollow fiber membrane device and is shown in FIGS. 1B-C. The hollow fibers are packed into tubes ("canned") so that feed is pumped through the hollow fibers and permeate is collected outside the fibers within the tubes. Fig. 1B shows the bare end of the fiber as it emerges at the end of the tube. Figure 1C shows several tubes housing hollow fiber membranes. Hollow fiber devices have several disadvantages. The pore size of the film itself is a function of the extrusion process and the material properties of the fiber itself and can only be controlled to produce a range of pore sizes. Furthermore, there is variability in the effectiveness of each device due to the variability of the somewhat manual process of embedding hollow fibers into the tube, which can make process design more difficult. Another type of tangential flow device is a stacked plate device that uses flat plate membranes stacked between plates, as shown in fig. 1D-E. The porosity of flat sheet devices like hollow fiber devices is typically dependent on the process of making the membrane and typically results in a range of pore sizes due to the variability of the process of making the pores. Furthermore, the process of manufacturing flat sheet membranes may limit the size of the available pores. Micromachined particulate filters are described in U.S. entitled "micromachined particulate filters". 5,651,900. The process disclosed in the' 900 patent allows for the preparation of pore sizes that are determined by the thickness of the deposited material layer. However, these devices utilize standard microprocessor technology to produce particulate filters made of semiconductor materials such as silicon and silicon dioxide. The' 900 patent discloses an embodiment that uses a polyimide matrix to hold "islands" with holes created using conventional semiconductor construction methods that utilize silicon and silicon dioxide. These filters have not been employed in the bioprocess industry because they include rigid components and rely on complex manufacturing processes. These components are fragile and cannot withstand the typical conditions required for membrane filters. In addition, polyimide substrates are used with holes that include horizontal channels that may deform when pressure is applied to the membrane. The present inventors have recognized that the need for a biocompatible particulate filter with a uniform pore size distribution is particularly desirable for tangential flow filtration applications. SUMMARY In one aspect, the present invention is directed to a biocompatible polymer filtration membrane comprising a plurality of strips of a first membrane material layer, a second membrane material associated with each of the plurality of strips of the first membrane material layer, the second membrane material comprising a plurality of windows exposing each of the strips of the first membrane material, wherein the biocompatible polymer filtration membrane comprises pores defined within each window by uniform channels defined by the strips of the first membrane material layer and the second membrane material layer. The first and second film materials may comprise polyimide. The pores may have a thickness of 20-1000nm and the film may have a thickness in the range of 2-10 microns. In one aspect, the film may have a thickness of 2-10 microns, the first film has a thickness in the range of 1-5 microns, and the second film layer has a thickness in the range of 2.5-20 microns. In another aspect, the invention relates to a method of making a biocompatible polymeric filtration membrane comprising the steps of (a) depositing a first layer of membrane material on a substrate, (b) patterning the first layer of membrane material into a plurality of strips, (c) depositing a sacrificial layer defining apertures on the first strip of membrane mate