BIOCOMPATIBLE COMPOSITE ELEMENTS AND METHODS FOR PRODUCING

Abstract

A biocompatible composite element for a bioreactor is provided that includes an outer frame and an inner component. The outer frame is a polymeric material. The outer frame can be inseparably attached to a wall of the bioreactor. The inner component is a transparent material selected from a group consisting of glass, sapphire, and glass ceramic. The inner component is secured in the outer component in an inseparable hermetically tight manner. The inner component is configured for a spectral process control through the transparent material of the inner component.

Claims

1. A biocompatible composite element for a bioreactor, comprising: an outer frame comprising a polymeric material, the outer frame being configured for inseparable attachment to a wall of the bioreactor; and an inner component comprising a transparent material selected from a group consisting of glass, sapphire, and glass ceramic, wherein the inner component is secured in the outer component in an inseparable hermetically tight manner, and wherein the inner component is configured for a spectral process control through the transparent material of the inner component.

2. The biocompatible composite element of claim 1, wherein the transparent material exhibits a transmittance that is selected from a group consisting of: greater than 75% in a spectral range with a wavelength of 190 to 5500 nm; greater than 90% in a spectral range with a wavelength of 190 to 5500 nm; greater than 75% in a spectral range with a wavelength of 190 to 2800 nm; greater than 80% in a spectral range with a wavelength of 190 to 2800 nm; greater than 90% in a spectral range with a wavelength of 190 to 2800 nm; greater than 75% in a spectral range with a wavelength of 190 to 2700 nm; greater than 90% in a spectral range with a wavelength of 190 to 2700 nm; and any combinations thereof.

3. The biocompatible composite element of claim 1, wherein the outer frame has a structure selected from a group consisting of: an annular cross section so that the outer frame surrounds the inner component; a tubular having a first end and a second end with the first end being configured for inseparable attachment to the wall of the bioreactor; a flange being configured for inseparable attachment to the wall of the bioreactor; an outer thread configured for inseparable attachment to the wall of the bioreactor; and any combinations thereof.

4. The biocompatible composite element of claim 1, wherein the inner component is a single component having a plate or disc-shape.

5. The biocompatible composite element of claim 1, wherein the inner component comprises with a transparent structural part and a tubular connecting part, the tubular connecting part is directly or indirectly joined both to the transparent structural part and to the outer frame.

6. The biocompatible composite element of claim 5, wherein the tubular connecting part comprises a plurality of projections that increase a contact surface area with the outer frame.

7. The biocompatible composite element of claim 5, wherein the transparent structural part is arranged at a second end of the tubular connecting part.

8. The biocompatible composite element of claim 5, wherein the tubular connecting part surrounds the transparent structural part in such a way that the transparent structural part is fitted in the connecting part in a hermetically tight manner.

9. The biocompatible composite element of claim 5, wherein the tubular connecting part is made from a material selected from a group consisting of metal, stainless steel, and austenitic-ferritic duplex steel.

10. The biocompatible composite element of claim 5, wherein the tubular connecting part and transparent structural part are each fitted in the outer frame.

11. The biocompatible composite element of claim 5, wherein the tubular connecting part is made from a common transparent material as the transparent structural part.

12. The biocompatible composite element of claim 5, wherein the tubular connecting part is made from a non-transparent material selected from a group consisting of ceramic, metal, oxidizable metal, and aluminum.

13. The biocompatible composite element of claim 12, wherein the tubular connecting part has an oxide layer on a surface that adjoins the transparent structural part.

14. The biocompatible composite element of claim 5, wherein the inner component projects, at least partially, out of the outer frame.

15. The biocompatible composite element of claim 1, wherein the connecting part is laser-welded to the transparent structural part.

16. The biocompatible composite element of claim 1, wherein the inner component is fitted vertically under compressive stress in the outer frame.

17. The biocompatible composite element of claim 1, wherein the outer frame comprises a material selected from a group consisting of polyether ether ketone (PEEK), polyethylene (PE), and a material having a wetting angle of contact that is less than 90 with a material of the inner component.

18. The biocompatible composite element of claim 1, wherein the inner component is fitted in the outer frame in a stress-neutral manner.

19. A method for producing a biocompatible composite element, comprising: providing an outer frame comprising a polymeric material; providing an inner component comprising a transparent structural part comprising a material selected from a group consisting of glass, sapphire, and glass ceramic; causing a relative expansion of the outer frame with respect to the inner component; inserting the inner component in the outer frame; and causing a relative contraction of the outer frame with respect to the inner component so that the inner component is fitted in the outer frame in a hermetically tight manner.

20. The method of claim 19, wherein the relative expansion and contraction comprise the steps of heating and cooling the outer frame and the inner component with respect to one another.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0092] In the following, a number of special exemplary embodiments of the invention, which are not to be understood as conclusive, in particular glass-to-polymer seals (GTPS), are explained with reference to the appended drawings. Shown are:

[0093] FIG. 1 a sectional view of a composite element in accordance with a first embodiment;

[0094] FIG. 2 a sectional view of a composite element in accordance with a second embodiment;

[0095] FIG. 3 a sectional view of a composite element in accordance with a third embodiment;

[0096] FIG. 4 a sectional view of a composite element in accordance with a fourth embodiment;

[0097] FIG. 5 a sectional view of a composite element in accordance with a fifth embodiment;

[0098] FIGS. 6 and 7 sectional views of composite elements in accordance with a seventh embodiment;

[0099] FIGS. 8 and 9 a sectional view and a detail view of a composite element in accordance with a sixth embodiment;

[0100] FIGS. 10 and 11 a sectional view and a detail view of a composite element in accordance with an eighth embodiment;

[0101] FIGS. 12 and 13 a sectional view and a detail view of a composite element in accordance with a ninth embodiment;

[0102] FIGS. 14 and 15 a perspective view and a view from the top of a surface of a connecting part having a microstructure;

[0103] FIGS. 16 and 17 perspective views of a composite element mounted on a bioreactor in accordance with the first embodiment;

[0104] FIG. 18 a sectional view of a composite element mounted on a bioreactor in accordance with the first embodiment; and

[0105] FIG. 19 a perspective detail view of a composite element in accordance with the first embodiment.

DETAILED DESCRIPTION

[0106] The composite element (10) shown in FIG. 1 and FIG. 19 comprises an outer frame (20), which is made of a polymer, such as, for example, polyether ether ketone (PEEK), and an inner component (30), which is designed as a one-piece transparent structural part (32) made of transparent material, such as, for example, glass.

[0107] In this embodiment, what is involved is a pressure polymerization incorporation, which, for example, can be carried out as follows: The transparent structural part (32), in particular glass, is inserted under compressive stress in the polymer outer frame (20).

[0108] For this purpose, the outer frame (20),which is designed as a polymer molding, is heated (for example, PEEK to 200 C.), the transparent structural part (32), which, in this example, is designed as a disc, is inserted with a greater diameter than the inner diameter of the port and then cooled. This results in an autoclavable and sterilely tight pressure polymerization incorporation.

[0109] The polymer outer frame (20) has a flange (22), with the flange (22) being arranged at the first (proximal) end of the tube (20p). However, a flange (22) can also be provided at another point, in particular between the first end of the tube (20p) and the second end of the tube (20d), as illustrated in FIG. 5.

[0110] The composite element (10) shown in FIG. 2 comprises an outer frame (20) made from a polymer, such as, for example, polyethylene (PE), and a two-part inner component (30) that has a disc-shaped transparent structural part (32) made of glass, for example, and a tubular connecting part (34), made of metal, for instance, such as, for example, 1.4404 stainless steel. In this example, the connecting part (34) surrounds the transparent structural part (32).

[0111] In this embodiment, what is involved is a glass/metal/polymer composite, which can be produced, for example, as follows: The pressure sealing of the transparent structural part (32) is conducted in a sterilely tight manner and/or in a hermetically tight manner in the connecting part (34), which, in this example, is designed as a profiled hollow metal cylinder. The connecting part (34) or the thus formed inner component (30) is coated in a sterilely tight manner with a polymer, such as, for example, polyethylene (PE), polypropylene (PP), polyamide (PA), polyethylene terephthalate (PET), ethylene vinyl alcohol (EVOH), polyether ether ketone (PEEK), polyaryl ether ketone (PAEK), polysulfone (PSU), polyphenylene sulfide (PPS), or a multimaterial molding containing a number of polymers, to create the desired dimension of the structural part, inclusive of a flange (22). Accordingly, the outer frame (20) can comprise one or a plurality of the previously mentioned materials or be composed thereof or be produced or be producible from them.

[0112] The polymer outer frame (20) has a flange (22) at the first end of the tube (20p). Alternatively, however, a flange (22) can also be provided at another point, in particular between the first end of the tube (20p) and the second end of the tube (20d), as illustrated in FIG. 6 and FIG. 7.

[0113] The composite elements shown in FIG. 6 and FIG. 7 have, in addition, a multipart (here: three-part) inner component (30), with the connecting part (34) being joined both directly to the outer frame (20) and indirectly to the transparent structural part (32). At its front end, the connecting part (34) is joined to a frame (33) that surrounds the transparent structural part (32) in such a way that the transparent structural part (32) is fitted in the frame (33) in a sterilely tight manner, preferably in a hermetically tight manner; the frame (33), in turn, is joined to the connecting part (34) in a sterilely tight manner, preferably in a hermetically tight manner; and the connecting part (34), in turn, is fitted in the outer frame (20) in a sterilely tight manner, preferably in a hermetically tight manner.

[0114] The composite element (10) shown in FIG. 3 comprises, in turn, a polymer outer frame (20) and a two-part inner component (30) having a transparent structural part (32) and a tubular connecting part (34), whereby, in this example, the connecting part (34) is designed as a hollow cylinder made of a transparent material, especially glass. Furthermore, in this case, the connecting part (34) abuts, at its front end, the transparent structural part (32).

[0115] In this embodiment, what is involved is a glass/glass/polymer composite, which, for example, can be produced as follows: The connecting part (34), which, in particular, is designed as a glass cylinder, is ground and polished at its front end; in addition, the transparent structural part (32), which is designed, for example, as a disc, is ground and polished and, namely, these connecting parts are ground and polished such that coherent surface areas are created.

[0116] Afterwards, the two parts are joined such that they adhere to each other through intermolecular forces (that is, the disc is pushed onto the glass cylinder). Subsequently, the two parts can be joined in a fixed manner by laser welding, for example, in order to produce in this way a permanently sterilely tight connection. The inner component (30) thus formed is, in turn, coated with a polymer, such as, for example, polyethylene (PE), in a sterilely tight manner to create the desired dimension of the structural part, inclusive of a flange (22).

[0117] The coating results in formation of the polymer outer frame (20), which, in this example, has a flange (22) at the first (proximal) end of the tube (20p). However, a flange (22) can also be formed at another point, in particular between the first end of the tube (20p) and the second end of the tube (20d), as illustrated in FIG. 8.

[0118] Beyond this, FIG. 9 shows a detail view of the connecting element (10) shown in FIG. 8. The transparent structural part (32) here projects out of the outer frame (20), so that an overhang U is formed. Because the wetting angle of contact of the material of the outer frame on the material of the transparent structural part (20) is less than 90, an angle a of less than 90 is correspondingly formed between the outer frame (20) and the transparent structural part (32).

[0119] The composite element (10) shown in FIG. 4 comprises a polymer outer frame (20) and a multipart component (30) having a transparent structural part (32), a frame (33) that surrounds the transparent structural part (32), and a tubular connecting part (34). At its front end, the connecting part (34) is joined to the frame (33) that surrounds the transparent structural part (32) in such a way that the transparent structural part (32) is fitted in the frame (33) in a sterilely tight manner, preferably in a hermetically tight manner; the frame (33), in turn, is joined to the connecting part (34) in a sterilely tight manner, preferably in a hermetically tight manner; and the connecting part (34), in turn, is fitted in the outer frame (20) in a sterilely tight manner, preferably in a hermetically tight manner.

[0120] In this example, the inner component (30) projects at least partially out of the outer frame (20), in particular by the transparent structural part (32) and the frame (33). Alternatively, however, it can also be provided that the outer frame (20) completely surrounds the inner component (30) along its length.

[0121] In this example, the outer frame (20) has, in turn, a flange (22) at the first end of the tube (20p). However, a flange (22) can also be provided at another point, in particular between the first end of the tube (20p) and the second end of the tube (20d), as illustrated in FIG. 10 and FIG. 12.

[0122] Beyond this, FIG. 11 and FIG. 13 show detail views of the connecting element (10) shown in FIG. 10 and FIG. 12. Between the outer frame (20) and the inner component (30), an angle a of less than 90 is provided. For this purpose, an arched-shape recess (23) is introduced in the outer frame (20). This recess (23) is found in the polymeric material at the material transition to the inner component (30).

[0123] FIGS. 14 and 15 show a surface of a connecting part in which a microstructure in the form of numerous projections (36) is introduced. The majority of projections (36) between the grooves are formed by way of a bunch of grooves (37) that is crossed by a second bunch of grooves (37).

[0124] FIGS. 16, 17, and 18 show a bioreactor wall (40) as a part of a bioreactor with a through passage (42), also referred to as a port (42), situated in it, which forms an opening into the interior of the bioreactor, whereby a composite element (10) extends at least partially into the opening formed by the through passage (42). In this example, the composite element (10) is designed in accordance with the composite element (10) shown in FIG. 1. Obviously, however, any previously described composite element (10) can extend through the through passage (42) illustrated here.

[0125] Installed in the interior of the composite element (10) is a measuring probe (50), which makes it possible to carry out measurements in the interior of the bioreactor, whereby the measurement is produced through the transparent structural part (32) of the composite element (10). By means of a sealing element (44), such as, for example, an O-ring, the composite element (10) is preferably fluidtight and is held most preferably in a sterilely tight manner and/or in a hermetically tight manner with respect to the through passage (42) of the bioreactor wall (40), in particular in a form-fitting and friction-fitting manner. The measuring probe (50) engages, in turn, by means of a friction element (46), preferably an O-ring, in a friction-fitting connection with the composite element (10), whereby the friction element (46) is held in a cylindrical recess of the composite element by way of a compression element (compression ring) (48), which, in particular, is essentially annular in shape and which exerts a definably adjustable force on the friction element (46) in the axial direction of the composite element (10).

[0126] By means of a union nut (52), which is formed, in particular, as a cap nut, the composite element (10) can be detached, but held in fixed position at the through passage (42) of the bioreactor wall (40). By means of a retaining ring or snap ring (54), the union nut (52) is held in a rotatable manner, although with only slight axial play, at the composite element (10).

[0127]