UV-sterilizable bioprocess ports and systems using the same

Abstract

UV-sterilizable bioprocess ports are described and enabled. A bioprocess system may utilize one or more of the disclosed UV-sterilizable bioprocess ports. Some variations provide a bioprocess system comprising: a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer that is substantially translucent or transparent to ultraviolet light; a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer that is substantially translucent or transparent to ultraviolet light; a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber; and one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

Description

UV-STERILIZABLE BIOPROCESS PORTS AND SYSTEMS USING THE SAMEPRIORITY DATA

[0001] This Patent Cooperation Treaty patent application claims priority to U.S. Provisional Patent App. No. 63 / 710,625, filed on October 23, 2024, which is hereby incorporated by reference.FIELD

[0002] The present invention generally relates to sterilization within bioprocesses. More particularly, the present invention relates to the design of bioprocess ports for efficient sterilization, and methods of sterilizing bioprocess ports.BACKGROUND

[0003] Biological production of products typically requires the elimination to the greatest extent possible of contaminating microorganisms, otherwise known as adventitious agents or non-host contaminants. Contamination can cause conversion of nutrients into undesirable products, change the conditions of the broth, or degrade or otherwise adversely affect the product(s). In modem bioprocess facilities, the presence of adventitious agents is reduced by thorough cleaning, most commonly by steam. This process is referred to as sterilization. In some cases, a fraction of the contaminating organisms remains active within the system.

[0004] In bioprocess facilities, the sterile transfer of fluids from one component or piece of equipment to another in a process is highly desirable. Air or other gaseous materials are frequently supplied to modem bioreactors to enable, for example, aerobic fermentation. Sterile liquid media is supplied to a sterile bioreactorin advance of a fermentation process, or during a fermentation process to enable further growth and product formation. Culture is also often transferred from a seed bioreactor to a production bioreactor. Such transfers can be a major source of contamination in bioprocesses. Transfer of material from one vessel to another vessel usually involves a bioprocess port, which generally is a connection point on a bioprocess container that allows tubing or piping to be attached.

[0005] See Junker et al., “Sustainable Reduction of Bioreactor Contamination in an Industrial Fermentation Pilot Plant”, Journal of Bioscience and Bioengineering, Vol. 102, No. 4, Pages 251-268, 2006 (hereinafter, “Junker”), which is hereby incorporated by reference. According to Junker, contaminated media transfer is a commonly suspected cause of contamination in industrial bioprocessing facilities.

[0006] Steam sterilization is widely utilized in bioprocess facilities. However, steam sterilization suffers from several problems. Steam sterilization process failures are well-known and can be caused not only by human errors, but also by steam quality problems, such as incorrect temperature or pressure, insufficient air removal from steam, etc. Steam sterilization process failures can also be caused by incorrect design or placement of process components to be sterilized. Steam by nature is dangerous and can cause severe bums to a human if there is a steam leak.

[0007] In addition, repeated sterilizations cycles can cause undesirable changes in the material properties of process piping and components. Possible changes include corrosion that alters the chemical composition of the metal or polymer; and erosion, pipe thinning, surface pitting, or phase changes that alter the mechanical properties of the metal or polymer. One example in the case of polymers is embrittlement caused by repeated sterilizations cycles. For both metals and polymers, steam leakage or even catastrophic failures of process piping and components can occur. Even stainless steel is not immune to problems from repeated sterilizations cycles. During a sterilization cycle, there is heating, sterilizing and cooling. During each of these phases, alloy stresses or metal oxidation can result from temperature and pressure changes. Steam corrosion in stainless steel can be reduced with a corrosion inhibitor, such as cyclohexylamine, but usually such additives cannot be used in a bioprocess for safety reasons.

[0008] Steam sterilization is also energy-intensive. Conventional autoclaves utilize steam generated by burning natural gas, resulting in non-renewable CO2 emissions and therefore adding to the overall carbon intensity of the particular bioprocess.

[0009] In view of the need for sterilization during bioprocessing, and the challenges posed by steam sterilization, there is a tremendous need for an alternative means of sterilizing bioprocess ports.SUMMARY

[0010] The present invention addresses the aforementioned needs in the art, as will now be summarized and then further described in detail below.

[0011] Some variations provide a bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

[0012] In some embodiments, the bioprocess fitting is selected from the group consisting of a valve, a filter, an adapter, a sanitary flange, a Luer lock, a Luer slip, a cap, a stopcock, and combinations thereof.

[0013] In some embodiments, the first fluoropolymer is selected from the group consisting of PF A, FEP, PTFE, ETFE, ECTFE, PCTFE, THV, HFP, PVDF, and combinations thereof. In these or other embodiments, the second fluoropolymer is selected from the group consisting of PF A, FEP, PTFE, ETFE, ECTFE, PCTFE, THV, HFP, PVDF, and combinations thereof. The first fluoropolymer and the second fluoropolymer may be chemically the same or different.

[0014] In some embodiments, the bioprocess tube and the bioprocess fitting are permanently joined. For example, the bioprocess tube and the bioprocess fitting may be permanently joined via chemical welding, melt processing, additive manufacturing, mechanical fasteners, or a combination thereof.

[0015] In some embodiments, the bioprocess tube and the bioprocess fitting are non-permanently joined via a sanitary connection. The sanitary connection may be a threaded connection or a compression connection, for example.

[0016] In some embodiments, the chamber conduit is a sanitary conduit.

[0017] In some embodiments, the one or more UV light sources are configured to expose ultraviolet light to 100% of the wettable surfaces of the bioprocess tube and the bioprocess fitting.

[0018] In some embodiments, a mechanical support structure is disposed within the bioprocess tube. The mechanical support structure may be fabricated from a support material selected from the group consisting of metals, metal alloys, ceramics, polymers, quartz, borosilicate glass, carbon fibers, and combinations thereof. Preferably, the support material is substantially chemically inert to the ultraviolet light. The mechanical support structure may contain macroporosity.

[0019] In some embodiments, a mechanical support structure is disposed outside the bioprocess tube, and the mechanical support structure and the bioprocess tube are reversibly or non-reversibly joined.

[0020] In some embodiments employing a mechanical support structure within the bioprocess tube, that structure is a structural element than spans between inner walls of the bioprocess tube.

[0021] In some embodiments employing a mechanical support structure within the bioprocess tube, that structure is disposed on inner walls of the bioprocess tube.

[0022] In some embodiments, the second tube terminus is configured to direct a material into the bioprocess chamber from the bioprocess tube.

[0023] In some embodiments, the second tube terminus is configured to direct a gas into the bioprocess chamber via a bioprocess sparger that is connected to the second tube terminus.

[0024] In some embodiments, the second tube terminus is configured to direct a material from the bioprocess chamber, through the bioprocess tube, and into or through the bioprocess fitting.

[0025] In some bioprocess systems, the bioprocess chamber is a tank. In some bioprocess systems, the bioprocess chamber is a bioreactor.

[0026] Other variations provide a bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light; (b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light; and(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber.

[0027] Certain variations provide a bioprocess system comprising:(a) multiple bioprocess tubes each having a first tube terminus and a second tube terminus, wherein the bioprocess tubes are each fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) multiple bioprocess fittings fitted to the multiple bioprocess tubes respectively, wherein each of the bioprocess fittings are sealably positioned on the first tube terminus, wherein the bioprocess fittings are each fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tubes are sealably connected to the bioprocess chamber, wherein the first tube terminus of each of the bioprocess tubes is disposed outside the bioprocess chamber, and wherein the second tube terminus of each of the bioprocess tubes is contained within the bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tubes and the bioprocess fittings, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

[0028] In some bioprocess systems using multiple bioprocess tubes and multiple bioprocess fittings, there are at least three of the bioprocess tubes and at least three of the bioprocess fittings. In certain bioprocess systems, there are at least five of the bioprocess tubes and at least five of the bioprocess fittings. In specific bioprocess systems, there are at least eight of the bioprocess tubes and at least eight of the bioprocess fittings.BRIEF DESCRIPTION OF THE DRAWINGS

[0029] FIG. 1 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube having a first tube terminus and a second tube terminus. The bioprocess fitting is sealably positioned on the first tube terminus. In FIG. 1, the bioprocess fitting is a cap.

[0030] FIG. 2 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. In FIG. 2, the bioprocess fitting is a stopcock.

[0031] FIG. 3 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. In FIG. 3, the bioprocess fitting is a check valve.

[0032] FIG. 4 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positionedon the bioprocess tube. In FIG. 4, the bioprocess fitting is a generic fitting which may be a Luer lock, a sanitary flange, a filter, or an adapter, for example.

[0033] FIG. 5 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube, in which a heat shrink is wrapped around a region where the bioprocess fitting is attached to the bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube using the heat shrink.

[0034] FIG. 6 (plan view and side view) depicts an exemplary mechanical support structure disposed within a bioprocess tube. In FIG. 6, the mechanical support structure is a structural element that spans between inner walls of the bioprocess tube.

[0035] FIG. 7 (plan view and side view) depicts an exemplary porous mechanical support structure disposed within a bioprocess tube. In FIG. 7, the porous mechanical support structure contains macroporosity, as shown in the side view.

[0036] FIG. 8 (plan view and side view) depicts an exemplary mechanical support structure disposed within a bioprocess tube. In FIG. 8, the mechanical support structure is disposed on inner walls of the bioprocess tube.

[0037] FIG. 9 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube that has a mechanical support structure disposed within, forming a structurally supported bioprocess tube. In addition, a heat shrink is wrapped around a region where the bioprocess fitting is attached to the structurally supported bioprocess tube, and / or a region in which the bioprocess tube adjoins the mechanical support structure.

[0038] FIG. 10 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube, as well as a UV light source configured to expose ultraviolet light onto wettable surfaces within the bioprocess fitting and possibly also the bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube.

[0039] FIG. 11 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus inside the bioprocess chamber, and a bioprocess fitting that is sealably positioned on the bioprocess tube.

[0040] FIG. 12 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus inside the bioprocess chamber, and a bioprocess fitting that is sealably positioned on the bioprocess tube.

[0041] FIG. 13 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, bioprocess tubes inside the bioprocess chamber, a mechanical support structure that is perpendicularly disposed relative to the bioprocess tubes, and a bioprocess fitting.

[0042] FIG. 14 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus also outside the bioprocess chamber.

[0043] FIG. 15 is a photograph of an exemplary bioprocess system comprising a bioprocess chamber and eight bioprocess ports. Each bioprocess port comprises a bioprocess fitting sealably positioned on a bioprocess tube. Each bioprocess tube has a first tube terminus outside the bioprocess chamber, and a second tube terminus inside the bioprocess chamber. The eight first-tube termini are explicitly shown in FIG. 15, while the eight second-tube termini are hidden from view. Each bioprocess tube enters into the bioprocess chamber via its own sanitary chamber conduit. UV light sources are configured to expose ultraviolet light onto wettable surfaces within all bioprocess tubes and all bioprocess fittings.DETAILED DESCRIPTION OF EMBODIMENTS

[0044] The apparatus, structures, systems, and methods of the present invention will be described in detail by reference to various non-limiting embodiments.

[0045] This description will enable one skilled in the art to make and use the invention, and it describes several embodiments, adaptations, variations, alternatives, and uses of the invention. These and other embodiments, features, and advantages of the present invention will become more apparent to those skilled in the art when takenwith reference to the following detailed description of the invention in conjunction with any accompanying figures.

[0046] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this invention belongs.

[0047] Unless otherwise indicated, all numbers expressing conditions, concentrations, dimensions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending at least upon a specific analytical technique.

[0048] The term “comprising,” which is synonymous with “including,” “containing,” or “characterized by” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. “Comprising” is a term of art used in claim language which means that the named claim elements are essential, but other claim elements may be added and still form a construct within the scope of the claim.

[0049] As used herein, the phrase “consisting of’ excludes any element, step, or ingredient not specified in the claim. When the phrase “consists of’ (or variations thereof) appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. As used herein, the phrase “consisting essentially of’ limits the scope of a claim to the specified elements or method steps, plus those that do not materially affect the basis and novel characteristic(s) of the claimed subject matter.

[0050] With respect to the terms “comprising,” “consisting of,” and “consisting essentially of,” where one of these three terms is used herein, the presently disclosed and claimed subject matter may include the use of either of the other two terms, except when used in a Markush group. Thus in some embodiments not otherwise explicitly recited, any instance of “comprising” may be replaced by “consisting of’ or, alternatively, by “consisting essentially of.”

[0051] The present invention is predicated on the discovery of particularly effective combinations of components and chemical materials for sterilizing bioprocess ports. The discovery and the claimed invention required dedicated research, development, and experimentation that was necessary because the prior art did not provide an effective solution.

[0052] Some variations provide a bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

[0053] In this specification, by “sealably positioned” it is meant that a gastight seal is formed. A gas-tight seal, in turn, means that very little gas will flow through the seal under normal operating conditions in the bioprocess system. The quality of the gas-tight seal can be quantified using the following test. Air at 10 psig is added to a sub-system that contains the bioprocess tube and the bioprocess fitting. After 15 minutes, the sub-system pressure is measured. The final sub-system pressure is preferably at least 9 psig, more preferably at least 9.5 psig, even more preferably at least 9.9 psig, and most preferably at least 9.99 psig (possibly 10 psig, with no detectible air loss under pressure).

[0054] In some embodiments, the bioprocess fitting is selected from the group consisting of a valve, a filter, an adapter, a sanitary flange, a Luer lock, a Luer slip, a cap, a stopcock, and combinations thereof. The fitting may also be a sensor input, orpossibly a fitting with an integrated sensor. In the case of a valve, the valve may be selected from the group consisting of a butterfly valve, a diaphragm valve, a ball valve, a globe valve, a gate valve, and a check valve, for example.

[0055] In this specification, a “fluoropolymer” is an organic polymer containing fluorine atoms. Note that there can be various degrees of substitution of H with F in a polymer. In the extreme, all H atoms can be replaced with F atoms, such as in polytetrafluoroethylene, (C2F4 Also note that H atoms need not all be replaced by F atoms; other halogens, notably chlorine (Cl) but also potentially bromine (Br) or iodine (I) can be used for some of the H substitutions in a fluoropolymer.Additionally, other chemical functional groups may be present, such as alkyl groups, hydroxyl groups, aromatic groups, etc.

[0056] In some embodiments, the first fluoropolymer is selected from the group consisting of PF A (perfluoroalkoxy alkanes, a co-polymer of tetrafluoroethylene and perfluoroether), FEP (fluorinated ethylene propylene, a copolymer of hexafluoropropylene and tetrafluoroethylene), PTFE (polytetrafluoroethylene), ETFE (ethylene tetrafluoroethylene polymer), ECTFE (ethylene-chlorotrifluoroethylene co-polymer), PCTFE (polychlorotrifluoroethylene), THV (co-polymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride), HFP (polyhexafluoropropylene), PVDF (polyvinylidene fluoride), and combinations thereof. An example of a combination is PVDF-HFP, poly(vinylidene fluoride-co-hexafluoropropylene), which is a hydrophobic, crystalline copolymer.

[0057] In these or other embodiments, the second fluoropolymer is selected from the group consisting of PF A, FEP, PTFE, ETFE, ECTFE, PCTFE, THV, HFP, PVDF, and combinations thereof. The second fluoropolymer is independently selected from the first fluoropolymer.

[0058] The first fluoropolymer and the second fluoropolymer may be chemically the same or different. It can be beneficial to choose different polymers for the first fluoropolymer and the second fluoropolymer, so that one is more rigid (e.g., higher tensile strength or higher flexural modulus) than the other, for example.

[0059] The first fluoropolymer and the second fluoropolymer can also be chemically the same but have different mechanical properties, such as when one of the fluoropolymers has a higher polymer molecular weight, a different degree ofcrosslinking, a different heat treatment (e.g., annealing), or a different mechanical treatment (e.g., strain hardening), for example.

[0060] When the first and second fluoropolymer have different mechanical properties (whether due to chemical differences or differences in chemical treatment and / or mechanical treatment), the connection and seal between the bioprocess tube and the bioprocess fitting may be improved. An improved seal may mean a better gas-tight seal (lower air leak rate in the above-described test) as well as a more sanitary connection.

[0061] In some embodiments, the bioprocess tube and the bioprocess fitting are permanently joined. For example, the bioprocess tube and the bioprocess fitting may be permanently joined via chemical welding, melt processing, additive manufacturing, mechanical fasteners, or a combination thereof. Note that even a “permanent” connection could be physically cut if desired. In certain embodiments, such as melt processing or additive manufacturing, a single integrated piece is fabricated such that the single integrated piece structurally contains the bioprocess tube and the bioprocess fitting, which may collectively be referred to as a continuous bioprocess port.

[0062] In some embodiments, the bioprocess tube and the bioprocess fitting are non-permanently joined via a sanitary connection. The sanitary connection may be a threaded connection or a compression connection, for example. A sanitary connection may utilize a sanitary flange, an O-ring seal, a hose barb, or another type of connection. A sanitary connection may be compliant with American Society of Mechanical Engineers (ASME) standards for sanitary fittings, for example. In certain embodiments, a sanitary connection utilizes a tri-clamp fitting.

[0063] In some embodiments, the chamber conduit is a sanitary conduit, so that adventitious microorganisms do not enter into the bioprocess chamber at the chamber conduit despite the bioprocess fitting and bioprocess tube (and optionally, the bioprocess chamber) all being UV-sterilized.

[0064] In some embodiments, the one or more UV light sources are configured to expose ultraviolet light to 100% of the wettable surfaces of the bioprocess tube and the bioprocess fitting. Optionally, one or more UV light sources (typically, distinct UV light sources from those for the bioprocess tube and fitting) areconfigured to expose ultraviolet light to internal surfaces of the bioprocess chamber. Optionally, one of these UV light sources, or potentially a different UV light source, is configured to expose the chamber conduit to ultraviolet light as well.

[0065] In some embodiments, a mechanical support structure is disposed within the bioprocess tube. The mechanical support structure may be fabricated from a support material selected from the group consisting of metals, metal alloys (e.g., stainless steel), ceramics (e.g., alumina), polymers (e.g., high-density polyethylene or a polycarbonate), quartz, borosilicate glass, carbon fibers, and combinations thereof. Preferably, the support material is substantially chemically inert to ultraviolet light. The mechanical support structure may contain macroporosity.

[0066] In some embodiments, a mechanical support structure is disposed outside the bioprocess tube, and the mechanical support structure and the bioprocess tube are reversibly or non-reversibly joined.

[0067] In some embodiments employing a mechanical support structure, that structure is a structural element than spans between inner walls of the bioprocess tube. See FIG. 6, for example. Unless it contains macroporosity, the structural element should not span the entire volume within the bioprocess tube, since material (e.g., liquid media or air) needs to be able to flow through the tube.

[0068] In some embodiments employing a mechanical support structure, that structure contains macroporosity. See FIG. 7, for example. The mechanical support structure may contain from about 1 vol% to about 50 vol% porosity, such as from about 5 vol% to about 25 vol% porosity, for example. The average pore size may be selected from about 0.0 Ir to about r, where r is the inner radius of the bioprocess tube. In some embodiments, the average pore size is selected from about 0.05r to about 0.5r.

[0069] In some embodiments employing a mechanical support structure, that structure is disposed on inner walls of the bioprocess tube. See FIG. 8, for example. The thickness of the mechanical support structure may be selected from about 0.00 Ir to about 0.9r, where r is the inner radius of the bioprocess tube in the absence of the mechanical support structure. In some embodiments, the mechanical support structure thickness is selected from about 0. Ir to about 0.5r. The value of r may vary widely, from about 0.1 millimeter to about 5 centimeters, for example. Typically, thethickness of the mechanical support structure is constant along the length of the bioprocess tube, but the thickness could vary along the length.

[0070] In some embodiments, the second tube terminus is configured to direct a material into the bioprocess chamber from the bioprocess tube.

[0071] In some embodiments, the second tube terminus is configured to direct a gas into the bioprocess chamber via a bioprocess sparger that is connected to the second tube terminus.

[0072] In some embodiments, the second tube terminus is configured to direct a material from the bioprocess chamber, through the bioprocess tube, and into or through the bioprocess fitting.

[0073] In some bioprocess systems, the bioprocess chamber is a tank. In some bioprocess systems, the bioprocess chamber is a bioreactor.

[0074] Other variations provide a bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light; (b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light; and(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber.

[0075] Certain variations provide a bioprocess system comprising:(a) multiple bioprocess tubes each having a first tube terminus and a second tube terminus, wherein the bioprocess tubes are each fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) multiple bioprocess fittings fitted to the multiple bioprocess tubes respectively, wherein each of the bioprocess fittings are sealably positioned on the first tube terminus, wherein the bioprocess fittings are each fabricated from a secondfluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tubes are sealably connected to the bioprocess chamber, wherein the first tube terminus of each of the bioprocess tubes is disposed outside the bioprocess chamber, and wherein the second tube terminus of each of the bioprocess tubes is contained within the bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tubes and the bioprocess fittings, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

[0076] In some bioprocess systems using multiple bioprocess tubes and multiple bioprocess fittings, there are at least three of the bioprocess tubes and at least three of the bioprocess fittings. In certain bioprocess systems, there are at least five of the bioprocess tubes and at least five of the bioprocess fittings. In specific bioprocess systems, there are at least eight of the bioprocess tubes and at least eight of the bioprocess fittings.

[0077] A bioprocess tube and a bioprocess fitting sealably positioned (or positionable) on the bioprocess tube may be referred to as a “bioprocess port”. Thus when there are for example four bioprocess tubes and each bioprocess tube is fitted with a bioprocess fitting, there are four bioprocess ports. In various embodiments, the number of bioprocess ports within a bioprocess system is at least, or is at most, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0078] Typically a bioprocess port is configured as single bioprocess tube and a single bioprocess fitting sealably positioned on the tube. However, a bioprocess port may utilize a single bioprocess tube and multiple bioprocess fittings each sealably positioned on the same tube. Also, multiple bioprocess tubes may join into a single bioprocess fitting. Therefore, the ratio of number of bioprocess tubes and number of bioprocess fittings is not necessarily 1, for a given number of bioprocess ports.

[0079] FIG. 1 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube having a first tube terminus and a second tubeterminus. The bioprocess fitting is sealably positioned on the first tube terminus. In FIG. 1, the bioprocess fitting is a cap.

[0080] FIG. 2 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. In FIG. 2, the bioprocess fitting is a stopcock.

[0081] FIG. 3 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. In FIG. 3, the bioprocess fitting is a check valve.

[0082] FIG. 4 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. In FIG. 4, the bioprocess fitting is a generic fitting which may be a Luer lock, a sanitary flange, a filter, or an adapter, for example.

[0083] FIG. 5 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube, in which a heat shrink is wrapped around a region where the bioprocess fitting is attached to the bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube using the heat shrink.

[0084] FIG. 6 (plan view and side view) depicts an exemplary mechanical support structure disposed within a bioprocess tube. In FIG. 6, the mechanical support structure is a structural element that spans between inner walls of the bioprocess tube.

[0085] FIG. 7 (plan view and side view) depicts an exemplary porous mechanical support structure disposed within a bioprocess tube. In FIG. 7, the porous mechanical support structure contains macroporosity, as shown in the side view.

[0086] FIG. 8 (plan view and side view) depicts an exemplary mechanical support structure disposed within a bioprocess tube. In FIG. 8, the mechanical support structure is disposed on inner walls of the bioprocess tube.

[0087] FIG. 9 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube that has a mechanical support structure disposed within, forming a structurally supported bioprocess tube. In addition, a heat shrink is wrapped around a region where the bioprocess fitting is attached to the structurally supported bioprocess tube, and / or a region in which the bioprocess tube adjoins the mechanical support structure.

[0088] FIG. 10 (side view) depicts an exemplary bioprocess port comprising a bioprocess fitting and a bioprocess tube, as well as a UV light source configured to expose ultraviolet light onto wettable surfaces within the bioprocess fitting and possibly also the bioprocess tube. The bioprocess fitting is sealably positioned on the bioprocess tube. An external UV light source (not shown) may be configured to expose ultraviolet light onto wettable surfaces within the bioprocess tube. In this embodiment, the bioprocess fitting does not need to be fabricated from a fluoropolymer (e.g., stainless steel may be used for the fitting). While the bioprocess fitting in FIG. 10 is shown as a valve, other bioprocess fittings may be used.

[0089] FIG. 11 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus inside the bioprocess chamber, and a bioprocess fitting that is sealably positioned on the bioprocess tube. The bioprocess tube enters into the bioprocess chamber via a chamber conduit (preferably a sanitary conduit). One or more UV light sources (not shown) may be configured to expose ultraviolet light onto wettable surfaces within the bioprocess tube and the bioprocess fitting.

[0090] FIG. 12 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus inside the bioprocess chamber, and a bioprocess fitting that is sealably positioned on the bioprocess tube. The bioprocess tube enters into the bioprocess chamber via a chamber conduit (preferably a sanitary conduit). The second tube terminus is configured to direct a gas into the bioprocess chamber via a bioprocess sparger connected to the bioprocess tube. One or more UV light sources (not shown) may be configured to expose ultraviolet light onto wettable surfaces within the bioprocess tube and the bioprocess fitting.

[0091] FIG. 13 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, bioprocess tubes inside the bioprocess chamber, a mechanical support structure that is perpendicularly disposed relative to the bioprocess tubes, and a bioprocess fitting. One or more UV light sources (not shown)may be configured to expose ultraviolet light onto wettable surfaces within the bioprocess tube and the bioprocess fitting.

[0092] FIG. 14 (side view) depicts an exemplary bioprocess system comprising a bioprocess chamber, a bioprocess tube having a first tube terminus outside the bioprocess chamber and a second tube terminus also outside the bioprocess chamber. One of the first tube terminus and the second tube terminus may be fitted with a bioprocess fitting, or both termini may be fitted with bioprocess fittings. Each bioprocess fitting is sealably positioned on the bioprocess tube. One or more UV light sources (not shown) may be configured to expose ultraviolet light onto wettable surfaces within the bioprocess tube.

[0093] FIG. 15 is a photograph of an exemplary bioprocess system comprising a bioprocess chamber and eight bioprocess ports. Each bioprocess port comprises a bioprocess fitting sealably positioned on a bioprocess tube. Each bioprocess tube has a first tube terminus outside the bioprocess chamber, and a second tube terminus inside the bioprocess chamber. The eight first-tube termini are explicitly shown in FIG. 15, while the eight second-tube termini are hidden from view. Each bioprocess tube enters into the bioprocess chamber via its own sanitary chamber conduit. UV light sources are configured to expose ultraviolet light onto wettable surfaces within all bioprocess tubes and all bioprocess fittings.

[0094] Some variations provide a bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a fluoropolymer, and wherein the fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on the first tube terminus;(c) a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the fluoropolymer is substantially chemically inert to the ultraviolet light.

[0095] In some embodiments, the bioprocess fitting has its own UV light source contained within the fitting. This would be a separate UV light source from the UV light source(s) that are configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube. In such a configuration, the bioprocess fitting need not be fabricated from a polymer that is substantially translucent or transparent to ultraviolet light, since the UV light source is inside the fitting. The material of the bioprocess fitting should still be substantially chemically inert to the ultraviolet light.

[0096] Other variations of the invention provide bioprocess ports that can be used in various bioprocess systems.

[0097] In some embodiments, a bioprocess port comprises:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light; and(c) one or more UV light sources configured to expose ultraviolet light to 100% of wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to the ultraviolet light.

[0098] In some embodiments, a bioprocess port comprises:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, and wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light; and (b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, and wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light, wherein the first fluoropolymer and the second fluoropolymer are substantially chemically inert to ultraviolet light.

[0099] In some embodiments, a bioprocess port comprises:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a fluoropolymer, and wherein the fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on the first tube terminus; and (c) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of the bioprocess tube and the bioprocess fitting, wherein the fluoropolymer is substantially chemically inert to the ultraviolet light.

[0100] In certain embodiments, a bioprocess port comprises:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a fluoropolymer, and wherein the fluoropolymer is substantially translucent or transparent to ultraviolet light; and (b) a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is made from a material that is substantially chemically inert to the ultraviolet light.

[0101] A bioprocess port is preferably designed such that the UV dose exposed to the wettable surfaces, delivered by the UV light source(s), is sufficient to accomplish the desired reduction of the contaminant (e.g., adventitious microorganisms) suitable for the process, in a reasonable amount of time. For example, if it is determined that a UV dose of 300 mJ / cm2is desirable to substantially eliminate all adventitious microorganisms, this UV dose may be accomplished by providing a UV light intensity at a target wavelength of at least 0.1 mW / cm2to all wettable surfaces for at least 3000 seconds, or a light intensity of 1 mW / cm2to all wettable surfaces for at least 300 seconds, or a light intensity of at least 10 mW / cm2for at least 30 seconds, or any other combination of UV light intensity and UV time sufficient to achieve the desired UV dose. The units of mW / cm2are milliwatts UV light power divided by bioprocess-port wettable surface area in square centimeters.

[0102] In some embodiments, a UV light source is located inside a bioprocess port, such as inside a bioprocess fitting. In some embodiments, a UV light source is positioned outside the bioprocess port.

[0103] In some embodiments, the one or more UV light sources are configured to expose ultraviolet light to at least 90% of the wettable surface area within the bioprocess port. In certain embodiments, the one or more UV light sourcesare configured to expose ultraviolet light to at least 95% of the wettable surface area within the bioprocess port. In certain embodiments, the one or more UV light sources are configured to expose ultraviolet light to at least 99% of the wettable surface area within the bioprocess port. In certain preferred embodiments, the one or more UV light sources are configured to expose ultraviolet light to 100% of the wettable surface area within the bioprocess port.

[0104] The present invention, in various embodiments, is characterized by a number of important advantages.

[0105] 1. The disclosed UV-sterilizable bioprocess port avoids thermal stress on process ports that ordinarily, over time, cause corrosion, pitting, cracking, wear, and buildup of contaminants.

[0106] 2 The disclosed UV-sterilizable bioprocess port enables effectively complete sterilization in preparation for process fluid transfer (or during transfer in the case of media sterilization), which has heretofore not been achievable.

[0107] 3. The disclosed UV-sterilizable bioprocess port enables the use of alternative materials that are not conducive to traditional sterilization methods, including thermoplastics that soften, melt, or decompose when exposed to sterilizing steam or heat.

[0108] 4. The disclosed UV-sterilizable bioprocess port potentially reduces the cost and time required to sterilize process ports relative to traditional methods, by (i) eliminating the need for additional piping to deliver steam to a process port, (ii) eliminating the need for steam traps in process systems, and / or (iii) reducing the contact time required for sterilization.

[0109] The disclosed bioprocess ports may be contained in a system configured to carry out a biological process. Alternatively, the bioprocess ports may be contained in a system configured to carry out a non-biological process. A “biological process” means a process that utilizes at least one biological reaction involving a living microorganism, to convert a substrate into a product. A “non-biological process” means a process that does not utilizes a biological reaction involving a living microorganism, to convert a substrate into a product. A non-biological process may employ chemical catalysts, for example. Even in a non-biological process, contamination by microorganisms can occur and can be prevented using the disclosed bioprocess ports.

[0110] There are many methods that may utilize the disclosed bioprocess ports. Methods may involve sterile material transfer into a process unit, sterile material transfer out of a process unit, sterilization of a material while being conveyed into a process unit, sterilization of a material following by storage in a tank, the creation of a sterile boundary within a process unit, the creation of a sterile boundary around a process unit, and combinations of the foregoing.[OHl] In this disclosure, a “material” shall be broadly construed and may be a vapor / gas, a liquid, a slurry, a paste, or a solid. An example of a vapor is air. An example of a liquid is a liquid media. An example of a slurry is a broth with an insoluble product. An example of a paste is a thick broth with cells and an insoluble product. An example of a solid is sucrose powder being conveyed pneumatically into a bioreactor.

[0112] Some variations provide a method of sterilizing a bioprocess system, the method comprising:(i) providing a bioprocess tube having a first tube terminus and a second tube terminus, wherein the bioprocess tube is fabricated from a first fluoropolymer, wherein the first fluoropolymer is substantially translucent or transparent to ultraviolet light, and wherein the first fluoropolymer is substantially chemically inert to ultraviolet light;(ii) providing a bioprocess fitting sealably positioned on the first tube terminus, wherein the bioprocess fitting is fabricated from a second fluoropolymer, wherein the second fluoropolymer is substantially translucent or transparent to ultraviolet light, and wherein the second fluoropolymer is substantially chemically inert to ultraviolet light;(iii) providing a bioprocess chamber configured with a chamber conduit at which the bioprocess tube is sealably connected to the bioprocess chamber, wherein the first tube terminus is disposed outside the bioprocess chamber, and wherein the second tube terminus is contained within the bioprocess chamber; and(iv) using one or more UV light sources to expose ultraviolet light onto wettable area in the bioprocess tube and the bioprocess fitting, using a UV dose that is effective to sterilize the bioprocess tube and the bioprocess fitting.

[0113] The “wettable area” means the area that can be wetted by the material being processed within or through the bioprocess port, and which area is actually wetted during process operation.

[0114] In some method embodiments, the UV dose is at least 100 mJ / cm2(sterilization energy per unit total wettable area in the bioprocess tube and the bioprocess fitting). In certain methods, the UV dose is at least 200 mJ / cm2or at least 300 mJ / cm2. When there are multiple bioprocess ports, different UV doses may be used for different bioprocess ports, if desired, even if the same UV light source is used.

[0115] In some methods, step (iv) utilizes a total UV power capacity from about 0.1 W / m3to about 10 W / m3.

[0116] In some methods, step (iv) utilizes a UV sterilization time from about 10 seconds to about 2 hours.

[0117] In some methods, the one or more UV light sources each have a UV wavelength selected from about 100 nm to about 400 nm.

[0118] In some methods, step (iv) utilizes a total UV power output from about 0.1 mW / cm2to about 100 mW / cm2.

[0119] In some method embodiments, the one or more UV light sources are configured to expose ultraviolet light to at least 90% of the wettable area in the bioprocess tube and the bioprocess fitting. In certain methods, the one or more UV light sources are configured to expose ultraviolet light to 100% of the wettable area in the bioprocess tube and the bioprocess fitting.

[0120] In some method embodiments, step (iv) is effective to reach a 6-log reduction in the adventitious microorganisms present prior to step (iv). In certain embodiments, step (iv) is effective to reach an 8-log reduction in the adventitious microorganisms present prior to step (iv). In certain preferred embodiments, step (iv) is effective to reach a 10-log reduction in the adventitious microorganisms present prior to step (iv).

[0121] In some methods, a media passes into or through a bioprocess port. The media may be selected from the group consisting of a sugar, a salt, a vitamin, a mineral, a pH buffer, an antifoam, an alcohol, an acid, a base, water, a solution of any one of the foregoing, and combinations thereof.

[0122] In some methods, a gas passes into or through a bioprocess port. The gas be a reactant, such as in aerobic or microaerobic fermentation, or may be a catalyst, promoter, reaction-rate moderator, or other reaction agent. The gas introduced to the process chamber may be air, oxygen, syngas, hydrogen, carbon monoxide, methane, natural gas, or a combination thereof. In typical embodiments, the gas is oxygen, air, oxygen-enriched air, or oxygen-depleted air.

[0123] Various options, embodiments, features, and alternatives will now be further described.

[0124] The use of UV light, or other forms of non-ionizing radiation, effectively sterilize surfaces within bioprocess ports. The bioprocess ports may incorporate materials that are expressly incompatible with steam sterilization, which allows for the use of lower-cost materials, among many other benefits arising from UV sterilization.

[0125] Conventionally, sterile conditions are generated within bioprocess components (including ports) using steam sterilization. Such bioprocess components are evacuated and subsequently pressurized with typically 121°C steam. The steam environment is maintained until the adventitious microorganisms are inactivated, at which point the steam is removed from the system and bioprocess operation can begin. This process of steam sterilization introduces significant costs to the system operator. First, a significant amount of energy is required to generate the steam, which is both expensive as well as highly carbon-intensive unless renewable energy is used to generate the steam, which adds more cost. Also, designing the bioprocess port for steam compatibility introduces additional costs and complexities.

[0126] It is known that ultraviolet light can kill or deactivate living organisms. Ultraviolet radiation, mainly UV-C is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers, 6-4 photoproducts, and DNA strand breaks by interfering the genome integrity. See Rastogi et al., “Molecular Mechanisms ofUltraviolet Radiation-Induced DNA Damage and Repair”, Journal of Nucleic Acids, Volume 2010, Article ID 592980, Pages 1-32 (2010), which is hereby incorporated by reference.

[0127] In some variations, the disclosed bioprocess port is connected to a UV-sterilizable bioreactor system comprising:(a) a chamber configured to carry out a reaction;(b) a component configured for introducing a gas into the chamber; and (c) one or more UV light sources configured to expose ultraviolet light to surfaces within the chamber.

[0128] In this specification, “UV-sterilizable” means that a system or component is capable of being sterilized by UV light, at least to some extent. In this specification, “sterilized”, “sterilize”, “sterilization”, and the like refer to the killing, deactivation, or removal of microorganism to various extents. Sterilization does not mean that absolutely all microorganisms have been killed, deactivated, or removed (which may be referred to as “aseptic”). Certain embodiments may provide aseptic conditions for the system or component being sterilized.

[0129] In some embodiments, the chamber is a bioreactor chamber configured to carry out a bioreaction, such as fermentation or enzymatic conversion. In this specification, a “bioreactor” is a fermentor that utilizes at least one gas (typically air or oxygen) in the fermentation reaction(s). In other embodiments, the process chamber is a reactor chamber configured to carry out an anaerobic bioreaction or a non-biological reaction that does not utilize microorganisms or enzymes.

[0130] In preferred embodiments, the bioprocess chamber is configured to maintain a sterile boundary with the environment. A sterile boundary means that adventitious microorganisms do not penetrate into the process chamber from the environment. An “adventitious microorganism” is any microorganism (e.g., yeast, bacteria, fungi, or mold) that is not the desired microorganism (biocatalyst) for catalyzing the intended reaction in the process chamber. Adventitious microorganisms may be referred to as contaminant microorganisms. Adventitious microorganisms can compete with the biocatalyst for resources, introduce undesirable properties, or generate side products within the bioreactor environment.

[0131] A gas may be introduced to the bioprocess chamber. The gas be a reactant, such as in aerobic or microaerobic fermentation, or may be a catalyst, promoter, reaction-rate moderator, or other reaction agent. The gas introduced to the process chamber may be air, oxygen, syngas, hydrogen, carbon monoxide, methane, natural gas, or a combination thereof. In typical embodiments, the gas is oxygen, air, oxygen-enriched air, or oxygen-depleted air.

[0132] An external oxygen concentration may be utilized to increase the oxygen content of air beyond the normal 21 vol% O2 concentration. In various embodiments employing O2 in fermentation, the O2 concentration in the gas stream fed to the process chamber (e.g., through a sparger) is about, at least about, or at most about 1 vol%, 2 vol%, 5 vol%, 10 vol%, 15 vol%, 20 vol%, 21 vol%, 22 vol%, 25 vol%, 30 vol%, 40 vol%, 50 vol%, 60 vol%, 70 vol%, 80 vol%, 90 vol%, 95 vol%, or 100 vol%, including all intervening ranges.

[0133] In some embodiments, the component for introducing a gas is a gas sparger. A sparger may be defined as a component for introducing a gas into the liquid within a bioreactor. Three basic types of spargers are porous spargers, orifice spargers, and nozzle spargers. Spargers are tailored to introduce the desired gas in a controlled manner, resulting in mass transfer between the liquid phase and gas phase, while also introducing mechanical energy into the system.

[0134] In some embodiments, the component for introducing a gas is a membrane. These components serve to introduce the gaseous substrate via a semi-permeable membrane, allowing for selective mass transfer of desired components between a gaseous phase and a liquid phase. In some cases, this mass transfer occurs via diffusion within a polymeric matrix, while in other cases this mass transfer occurs via diffusion within pores that are within the membrane itself. In certain embodiments, the gaseous component being transported across the membrane is oxygen.

[0135] In some embodiments, the component for introducing a gas is a pipe or tube that is disposed in the volume of the bioreactor and that directly injects a gas into the liquid phase. The pipe or tube may have a single outlet, such as near the bottom of the chamber, near the top of the chamber, or anywhere else in the chamber. Thepipe or tube may have multiple outlets, such as a perforated pipe with a plurality of holes, out of which a gas enters the liquid phase.

[0136] In some embodiments, the component for introducing a gas is a plate sparger. A plate sparger is typically located at the bottom of the chamber and has a plurality of holes, out of which a gas enters the liquid phase.

[0137] In some embodiments, the component for introducing a gas is UV-sterilizable. The component (e.g., sparger) for introducing a gas may be UV-sterilizable by being exposed to a UV light source that is external to the component (and internal or external to the process chamber). Alternatively, or additionally, the component may be UV-sterilizable by incorporating a UV light source within the component itself.

[0138] In this specification, a “UV-transparent material” is not necessarily completely UV-transparent; some absorption of UV radiation may occur. In particular, “UV-transparent” means a sheet of material with 1 -millimeter thickness absorbs less than 50%, preferably about 25% or less, more preferably about 10% or less, most preferably about 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less, of incident (perpendicular) UV light at a wavelength of interest. The actual material or component need not be 1 millimeter; that thickness is only specified when measuring the UV transmission for purposes of this paragraph. If a wavelength range is used, the UV transmission is averaged over that range. UV transmission can be determined experimentally, for example, using a Perkin Elmer UV-Vis-IR spectrometer. It is noted that UV transmission generally can include regular UV transmission and diffuse UV transmission, both of which can contribute to total UV transmission.

[0139] A UV-transparent material may contain a UV-transparent polymer, a UV-transparent ceramic, a UV-transparent glass, or a combination thereof. A UV-transparent polymer may be selected from the group consisting of polyacrylates, silicones, fluoropolymers, and combinations thereof. A UV-transparent ceramic may be selected from the group consisting of quartz, fused silica, borosilicates, and combinations thereof. Silica or borosilicates may be doped to modify their UV transparency.

[0140] The number of UV light sources may vary widely. In some embodiments, there is a single UV light source configured to expose ultraviolet lightto surfaces within the process chamber, and optionally surfaces within the bioprocess port(s). The number of individual UV light sources can vary widely, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 25, 50, 100, or more. In certain embodiments employing one or more micro-arrays of UV LED light sources, the number of individual UV light sources can be many hundreds or thousands.

[0141] In some embodiments, one or more UV light sources are situated within the bioprocess chamber. One or more UV light sources may be permanently situated within the bioprocess chamber. Alternatively, or additionally, one or more UV light sources may be reversibly situated within the bioprocess chamber. The UV light source(s) may be removed from the bioprocess chamber in such a manner that sterile conditions are maintained within the bioprocess chamber.

[0142] In some embodiments, one or more UV light sources are situated within UV-transparent wells that are disposed within the bioprocess chamber. The UV-transparent wells may be fabricated from a UV-transparent material containing a UV-transparent polymer, a UV-transparent ceramic, a UV-transparent glass, or a combination thereof. A UV-transparent polymer may be selected from the group consisting of polyacrylates, silicones, fluoropolymers, and combinations thereof. Fluoropolymers may be selected from the group consisting of polyvinylidene fluoride, polytetrafluoroethylene, perfluoroalkoxy alkanes, and combinations thereof. A UV-transparent ceramic may be quartz. A UV-transparent glass may be fused silica, borosilicates, or a combination thereof. Silica or borosilicates may be doped to modify their UV transparency.

[0143] In some embodiments, at least some (including at least one) of the one or more UV light sources are external to the bioprocess chamber. In certain embodiments, all of the one or more UV light sources are external to the bioprocess chamber.

[0144] Typically, the bioprocess chamber walls facing the inside of the bioprocess chamber need to be sterilized, but the outside chamber walls exposed to the environment do not need to be sterilized. If desired, the outside chamber walls may be sterilized as well.

[0145] In some embodiments, one or more UV light sources are configured to provide radiant UV flux to a corner of a bioprocess chamber, such as a corner definedby part of the chamber wall and an internal component (e.g., static mixer or agitator shaft). In certain embodiments, discrete UV LED fixtures are utilized for specific components that would otherwise be inaccessible to a primary UV light source, such as a UV mercury lamp.

[0146] In some embodiments, the bioprocess chamber has walls fabricated from a metal, a metal alloy, a polymer, a ceramic, a composite material, glass, concrete, or a combination thereof. In certain embodiments, the metal is aluminum. In certain embodiments, the metal alloy is carbon steel or stainless steel. In certain embodiments, the polymer is selected from the group consisting of polyolefins, polyacrylates, polycarbonates, fluoropolymers, silicones, and combinations thereof. In certain embodiments, the composite material is a polymer reinforced with glass fibers. In certain embodiments, the polymer is selected from high-density polyethylene, polypropylene, polycarbonate, or a combination thereof. The polymer may be selected from the group consisting of poly(methyl methacrylate), polyvinylidene fluoride, hexafluoropropylene-tetrafluoroethylene copolymers, perfluoroether-tetrafluoroethylene copolymers, and combinations thereof.

[0147] In some embodiments, the bioprocess chamber has UV-transparent chamber walls containing a UV-transparent material. The UV-transparent material may contain a UV-transparent polymer, a UV-transparent ceramic (e.g., quartz), a UV-transparent glass (e.g., fused silica and / or borosilicates), or a combination thereof. A UV-transparent polymer may be selected from the group consisting of polyacrylates (e.g., poly(m ethyl methacrylate)), silicones, fluoropolymers, and combinations thereof. Fluoropolymers may be selected from the group consisting of polyvinylidene fluoride, hexafluoropropylene-tetrafluoroethylene copolymers, perfluoroether-tetrafluoroethylene copolymers, poly(ethene-co-tetrafluoroethene), or a combination thereof.

[0148] In certain embodiments, the bioprocess chamber has UV-reflective chamber walls containing, or internally coated with, a UV-reflective material. The UV-reflective material may be selected from aluminum, stainless steel, polytetrafluoroethylene, or a combination thereof, for example.

[0149] The bioprocess chamber volume may vary widely for a given system, including laboratory scale, pilot scale, demonstration scale, and commercial scale. Invarious embodiments, the chamber volume is about, at least about, or at most about 10 mL, 50 mL, 100 mL, 250 mL, 1 L, 2 L, 5 L, 10 L, 25 L, 50 L, 100 L, 500 L, 1,000 L, or greater.

[0150] The bioprocess chamber geometry may also vary. A typical bioprocess chamber is cylindrical with rounded walls (circular with respect to the horizontal axis). A bioprocess chamber may have rounded walls, flat walls, or a combination thereof. Chamber geometries may generally include cylindrical, tubular, conical, spherical, or rectangular. The aspect ratio of the bioprocess chamber may vary, such as tall (longer in the vertical dimension than the horizontal dimension) or short (longer in the horizontal dimension than the vertical dimension). The bioprocess chamber orientation may be vertical, horizontal, or slanted. The bioprocess chamber may be designed to have a flow pattern that is plug flow, continuously stirred, or flow distribution between these extremes.

[0151] One or more UV light sources may be configured to expose ultraviolet light to at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the total wettable surface area within the bioprocess chamber including its internal components. Internal components that are counted towards the chamber surface area may include a static mixer, a heat-exchange element, a sparger, an impeller, an impeller shaft, or a sensor, for example.

[0152] The one or more UV light sources may be configured to expose ultraviolet light to at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the total volume of the bioprocess chamber. The total volume of the bioprocess chamber is calculated from the nominal volume, based on the internal diameter and height / length, rather than the working volume.

[0153] The UV light source for sterilizing the bioprocess ports may be the same UV light source as that which sterilizes the bioprocess chamber, or they may be different.

[0154] In some embodiments, the one or more UV light sources each have a UV wavelength selected from about 100 nm to about 400 nm. In certain embodiments, the UV wavelength is selected from about 220 nm to about 300 nm, for at least one of the one or more UV light sources, such as for all of the UV light sources. In various embodiments, the UV wavelength is about, at least about, or atmost about 100, 110, 120, 125, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, or 400 nm, including all intervening ranges, and inclusive of each 1 -nanometer increment within each sub-range (e.g., including 227-304 nm, 188-242 nm, etc.). In some embodiments, such as (but not limited to) those utilizing pulsed light, multiple radiation wavelengths may be provided by the light source, some of which fall in the 100-400 nm range and some of which are higher than 400 nm, such as in the visible or infrared range in the electromagnetic spectrum. In certain embodiments, the one or more UV light sources each have a UV wavelength selected from 125 nm to 400 nm.

[0155] In certain embodiments, the one or more UV light sources each have a UV wavelength selected from UV-C wavelengths, which for purposes of this specification are 200-290 nm. In certain embodiments, the one or more UV light sources each have a UV wavelength selected from UV-B wavelengths, which for purposes of this specification are 291-320 nm. In certain embodiments, the one or more UV light sources each have a UV wavelength selected from UV-A wavelengths, which for purposes of this specification are 321-400 nm.

[0156] With respect to wavelength, while 100-400 nm is a preferred range of radiation wavelengths, it will be recognized that higher wavelengths can also be effective in certain embodiments, depending on the specific adventitious microorganism and the radiation parameters other than wavelength (e.g., time, light intensity, total power, or absorbed energy). Wavelengths in the visible band (about 400-700 nm) and / or infrared band (about 700 nm-1 mm) may be capable of inactivating adventitious microorganisms, such as by inducing DNA lesions.

[0157] The one or more UV light sources may each be selected from the group consisting of UV light-emitting diodes, UV mercury lamps, UV xenon lamps, and UV krypton lamps, for example. In certain embodiments, all UV light sources are UV light-emitting diodes (UV LEDs). A UV light source may be configured to generate pulsed UV light. For example, a pulsed-UV light source may be pulsed several times per second, with each pulse lasting between about 100 nanoseconds and 10 milliseconds.

[0158] In some embodiments, the UV-sterilizable bioprocess chamber contains a biosensor situated within the chamber. The biosensor may be configured todetect or measure a parameter selected from the group consisting of pH, temperature, oxygen, carbon dioxide, foaming, mixing, cell density, feed-substrate concentration, reaction-intermediate concentration, and product concentration, for example. There may be multiple biosensors situated within the bioprocess chamber. In some embodiments, the biosensor is configured to transmit a wireless signal to a computer for monitoring and control of the system.

[0159] In some embodiments, the biosensor is UV-sterilizable. The biosensor may be configured with a UV optical waveguide for sterilizing the biosensor. The UV optical waveguide may be a UV optical fiber, for example.

[0160] In some embodiments, the biosensor is disposed within or through a probe port, wherein the probe port is UV-sterilizable. In some embodiments, the biosensor is contained in a UV-sterilizable housing that is situated within the process chamber. The UV-sterilizable housing may contain a UV-transparent material, such as a UV-transparent polymer, a UV-transparent ceramic, a UV-transparent glass, or a combination thereof. A UV-transparent polymer may be selected from the group consisting of polyacrylates, silicones, fluoropolymers, and combinations thereof. An exemplary polyacrylate is poly(methyl methacrylate). Fluoropolymers may be selected from the group consisting of polyvinylidene fluoride, hexafluoropropylene-tetrafluoroethylene copolymers, perfluoroether-tetrafluoroethylene copolymers, poly(ethene-co-tetrafluoroethene), and combinations thereof. An exemplary UV-transparent ceramic is quartz. Exemplary UV-transparent glasses include fused silica, borosilicates, or a combination thereof. Silica or borosilicates may be doped to modify their UV transparency.

[0161] In certain embodiments, the UV-sterilizable bioprocess port contains a biosensor situated within the bioprocess fitting. The biosensor may be configured to detect or measure a parameter selected from the group consisting of pH, temperature, oxygen, carbon dioxide, foaming, cell density, and chemical concentration, for example. In some embodiments, the biosensor is configured to transmit a wireless signal to a computer for monitoring and control of the system that uses the bioprocess port.

[0162] In some embodiments, aeration is accomplished using a gas-input component configured for introducing a gas into the bioprocess chamber. The gas-input component may be a sparger, a membrane, or another means of effectively distributing a gas into the chamber. While it is possible to feed a gas through a port into the bioprocess chamber, this may lead to highly non-uniform gas concentrations within the chamber. In some embodiments, a gas input is sterilized via UV sterilization, filtration, or a combination thereof. In some embodiments, the gas-input component may have UV-light sources mounted within the component, such that sterile conditions are generated within the interior of the gas-input component.

[0163] In some embodiments, an agitation component facilitates mixing of the internal constituents of the bioprocess chamber. In some embodiments, the agitation component is a static mixer. In some embodiments, the agitation component is an impeller that achieves mixing by rotating around within the bioprocess chamber, transferring kinetic energy to the chamber contents (usually in turbulent flow, although can be laminar flow). The power to the impeller typically comes from an electric motor, i.e. powered by electricity, although in principle the impeller may be powered by magnetic induction or even compressed air. When an electrical motor is used, the motor is preferably mounted outside the process chamber, and the motor may be sealed using a mechanical seal, a lip seal, or a magnetic seal, any of which may be UV-sterilized.

[0164] A thermal-management component may introduce or remove thermal energy (heat) from the bioprocess chamber. In some embodiments, heat transfer may occur through the chamber walls, using a heat-transfer fluid, a steam jacket, heating coils, cooling coils, another thermal-management component, or a combination thereof. In some embodiments, internal baffles and / or internal coils are used to heat or cool the chamber contents. An external flow loop may be used to heat or cool the chamber contents.

[0165] Various components for sensing within the system may be used, such as bioreactor sensors. In various embodiments, a bioreactor sensor detects or measures a bioreactor parameter selected from the group consisting of pH, temperature, dissolved oxygen, dissolved air, dissolved hydrogen, dissolved carbon monoxide, dissolved carbon dioxide, dissolved methane, foaming, mixing, cell density, feed-substrate concentration, reaction-intermediate concentration, product concentration, density, or weight, for example. The bioreactor sensor may measurevarious spectrophotometric characteristics. A bioreactor sensor may be configured with an optical microscope, camera, or IR scope to take a picture of the mass distribution and / or the heat distribution at certain locations in the bioreactor, such as near the sparger. In some embodiments, the bioreactor sensor is configured to transmit a wireless signal to a computer for monitoring and control.

[0166] Sensors may also be used for measuring a property within a product stream, a property of a sample that is withdrawn from the process chamber, a property of a sample that is withdrawn from a vessel that is connected to the bioprocess chamber, or a property of a sample that is withdrawn from, contained in, or has flowed through a bioprocess port. Product sensors or sample sensors may detect or measure a parameter selected from the group consisting of pH, temperature, dissolved oxygen, dissolved air, dissolved hydrogen, dissolved carbon monoxide, dissolved carbon dioxide, dissolved methane, cell density, product concentration, density, or weight, for example.

[0167] The measurement that is made with a sensor may be used to make process adjustments dynamically or in the future. The process adjustments may utilize well-known principles of process control, including proportional feedback control, proportional-integral-derivative (PID) feedback control, feedforward control, etc. A computer may be employed to automatically make adjustments to the process and system based on one or more measurements from sensors.

[0168] A step of UV sterilization may utilize a sterilization energy per unit total wettable area in the bioprocess chamber (and optionally, the wettable area in the bioprocess port) of about 50, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, or 5000 mJ / cm2, or more, including all intervening ranges. The sterilization energy per unit total area is also known as the light intensity. The light intensity may be constant, or it may vary over time.

[0169] A total UV power output as power per unit total wettable area in the bioprocess chamber (and optionally, the wettable area in the bioprocess port) may vary from about 0.5 mW / cm2to about 1000 mW / cm2. The total UV power may be about, at least about, or at most about 0.5, 1, 2, 3, 4, 5, 10, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 mW / cm2, including all intervening ranges. The total UV power output may be constant, or it may vary over time.

[0170] A step of UV sterilization may utilize a total UV power capacity from about 0.1 W / m3to about 5000 W / m3. The total UV power capacity is calculated as input UV power divided by volume of the bioprocess chamber (and optionally, the wettable volume in the bioprocess port). The total UV power capacity may be about, or at most about 5000, 4000, 3000, 2000, 1000, 500, 400, 300, 200, 100, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.4, 0.3, 0.2, or 0.1 W / m3, including all intervening ranges.

[0171] A step of UV sterilization may utilize a UV sterilization time from about 1 minute to about 24 hours. The UV sterilization time is the time that the UV light source is illuminated. In various embodiments, the UV sterilization time is about, at least about, or at most about 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 12 hours, 16 hours, 20 hours, or 24 hours, including all intervening ranges.

[0172] A step of UV sterilization may be conducted at a sterilization temperature from about 10°C to about 95°C. In various embodiments, the sterilization temperature is about, at least about, or at most about 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, or 95 °C, including any intervening range. In some embodiments, the sterilization temperature is not controlled and is at or about the ambient temperature, such as about 25°C. In other embodiments, it is desirable to increase the temperature to assist in the sterilization.

[0173] In some methods, UV sterilization is conducted in an atmosphere that consists essentially of air, which may be dry air or humid air. In typical methods, UV sterilization is conducted in an atmosphere that does not contain steam, although water vapor may be present, due to humidity in air, for example. In some methods, UV sterilization is conducted in an inert-gas atmosphere, using N2, Ar, or CO2, for example.

[0174] In certain methods, UV sterilization is conducted in an atmosphere that contains a sterilization-enhancing vapor or gas, such as ethylene oxide, chlorine dioxide, hydrogen peroxide, ozone, formaldehyde, peracetic acid, or glutaraldehyde.Ozone may be generated in situ from photolysis of oxygen (e.g., from air), creating O3 from O2, such as when a sterilizing UV wavelength is in the 160-240 nm range.

[0175] In various methods, UV sterilization is effective to reach a 4-log reduction in adventitious microorganisms present prior to the UV sterilization. In this specification, “log” refers to the common base- 10 logarithm. Thus, a 4-log reduction is a 99.99% reduction in population of adventitious microorganisms because the fraction of adventitious microorganisms remaining is 104, and log (1CH) = -4. In some methods, UV sterilization is effective to reach a 6-log reduction in adventitious microorganisms present prior to the UV sterilization. In certain methods, UV sterilization is effective to reach an 8-log reduction in adventitious microorganisms present prior to the UV sterilization. In specific methods, UV sterilization is effective to reach a 10-log reduction in adventitious microorganisms present prior to the UV sterilization. In various embodiments, UV sterilization is effective to reach a reduction in adventitious microorganisms, present initially prior to such UV sterilization, that is about, or at least about, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 logs. In certain embodiments, UV sterilization is effective to reach a complete elimination of adventitious microorganisms, present initially prior to the UV sterilization, i.e. 100% reduction which may be referred to as achieving aseptic conditions. Generally speaking, different microorganisms have different vulnerabilities to UV light. When there are multiple species of adventitious microorganisms present, the kill rates of the different species may differ.

[0176] In bioreactor facilities, adventitious microorganisms can include spore¬ forming gram-positive or gram-negative rods; non-spore-forming bacteria; fungal contaminations; or cocci, for example. The microorganism for the desired fermentation may or may not be more UV-tolerant than adventitious microorganisms. If the adventitious microorganisms are especially UV-tolerant and survive the UV sterilization, this may pose no problem for the eventual fermentation in the bioreactor.

[0177] Generally speaking, the principles of the invention can be applied to a wide variety of commercial bioprocesses and products, including (but not limited to) industrial chemicals, biochemicals, biofuels, pharmaceuticals, nutraceuticals, vitamins, food ingredients, protein products, enzymes, and cells.

[0178] A typical bioprocess involves fermentation. To carry out a desired fermentation, there will generally be several inputs such as, but not limited to, media, a feedstock acting as a carbon source, acid input, base input, anti-foaming agent, buffer, vitamins, gaseous input, or any bolus of materials intended to influence the biochemical process. The fermentation may include introducing gas to the reaction chamber. The gas may be air, oxygen, syngas, hydrogen, carbon monoxide, methane, natural gas, or a combination thereof, for example. The gas may be a mixture of O2 and N2 in various concentrations of O2, above or below 21 vol% O2. The gas may be a reactant, such as in aerobic or microaerobic fermentation, or may be a catalyst, promoter, reaction-rate moderator, or other reaction agent. The gas may be first sterilized, prior to being fed to the chamber, via filtration, exposure to UV light, or a combination thereof (e.g., by filtering through a UV-sterilized filter).

[0179] Following production of a fermentation product, the product will typically be present in a dilute solution or broth. Product recovery may be performed using known techniques, such as (but not limited to) evaporation, distillation, centrifuge, liquid-liquid extraction, to generate a concentrated form of a desired product. In certain embodiments, no product concentration is necessary because the as-is fermentation broth is the product which may be stored, shipped, or used elsewhere at a plant site.

[0180] In some embodiments, one or more materials recovered from a dilute solution a recovered for reuse at a plant site or an adjacent site. For example, water may be recovered and reused, to improve the water balance. Vitamins and minerals may be recovered and reused in another fermentation. Any recovered materials may be subjected to UV sterilization prior to reuse, or UV sterilization at the point of reentry into a process, such as via UV-sterilized filters. In some embodiments, biological material is inactivated upon removal from the bioreactor system via UV sterilization.

[0181] In this detailed description, reference has been made to multiple embodiments which show by way of illustration specific exemplary embodiments of the invention. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that modifications to the various disclosed embodiments may be made by a skilled artisan.

[0182] Where methods and steps described above indicate certain events occurring in certain order, those of ordinary skill in the art will recognize that the ordering of certain steps may be modified and that such modifications are in accordance with the variations of the invention. Additionally, certain steps may be performed concurrently in a parallel process when possible, as well as performed sequentially.

[0183] All publications, patents, and patent applications cited in this specification are herein incorporated by reference in their entirety as if each publication, patent, or patent application were specifically and individually put forth herein. This specification hereby incorporates by reference commonly owned Heligman, “Bioreactors configured for UV sterilization, and methods of using UV sterilization in bioprocesses”, U.S. Patent App. Pub. No. 2023 / 0313111 Al, published on October 5, 2023. This specification also hereby incorporates by reference Stanbury et al., Principles of Fermentation Technology, 3rdEdition, Elsevier, 2017.

[0184] The embodiments and variations described above should provide an indication of the utility and versatility of the present invention. Other embodiments that do not provide all of the features and advantages set forth herein may also be utilized, without departing from the spirit and scope of the present invention. Such modifications and variations are considered to be within the scope of the invention defined by the claims.

Claims

CLAIMSWhat is claimed is:

1. A bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein said bioprocess tube is fabricated from a first fluoropolymer, and wherein said first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on said first tube terminus, wherein said bioprocess fitting is fabricated from a second fluoropolymer, and wherein said second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which said bioprocess tube is sealably connected to said bioprocess chamber, wherein said first tube terminus is disposed outside said bioprocess chamber, and wherein said second tube terminus is contained within said bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of said bioprocess tube and said bioprocess fitting, wherein said first fluoropolymer and said second fluoropolymer are substantially chemically inert to said ultraviolet light.

2. The bioprocess system of claim 1, wherein said bioprocess fitting is selected from the group consisting of a valve, a filter, an adapter, a sanitary flange, a Luer lock, a Luer slip, a cap, a stopcock, and combinations thereof.

3. The bioprocess system of claim 1, wherein said first fluoropolymer is selected from the group consisting of PF A, FEP, PTFE, ETFE, ECTFE, PCTFE, THV, HFP, PVDF, and combinations thereof.

4. The bioprocess system of claim 1, wherein said second fluoropolymer is selected from the group consisting of PF A, FEP, PTFE, ETFE, ECTFE, PCTFE, THV, HFP, PVDF, and combinations thereof.

5. The bioprocess system of claim 1, wherein said first fluoropolymer and said second fluoropolymer are chemically the same.

6. The bioprocess system of claim 1, wherein said first fluoropolymer and said second fluoropolymer are chemically different.

7. The bioprocess system of claim 1, wherein said bioprocess tube and said bioprocess fitting are permanently joined.

8. The bioprocess system of claim 7, wherein said bioprocess tube and said bioprocess fitting are permanently joined via chemical welding, melt processing, additive manufacturing, mechanical fasteners, or a combination thereof.

9. The bioprocess system of claim 1, wherein said bioprocess tube and said bioprocess fitting are non-permanently joined via a sanitary connection.

10. The bioprocess system of claim 9, wherein said sanitary connection is a threaded connection.

11. The bioprocess system of claim 9, wherein said sanitary connection is a compression connection.

12. The bioprocess system of claim 1, wherein said chamber conduit is a sanitary conduit.

13. The bioprocess system of claim 1, wherein said one or more UV light sources are configured to expose ultraviolet light to 100% of said wettable surfaces of said bioprocess tube and said bioprocess fitting.

14. The bioprocess system of claim 1, wherein a mechanical support structure is disposed within said bioprocess tube.

15. The bioprocess system of claim 1, wherein a mechanical support structure is disposed outside said bioprocess tube, and wherein said mechanical support structure and said bioprocess tube are reversibly or non-reversibly joined.

16. The bioprocess system of either one of claims 14 or 15, wherein said mechanical support structure is fabricated from a support material selected from the group consisting of metals, metal alloys, ceramics, polymers, quartz, borosilicate glass, carbon fibers, and combinations thereof.

17. The bioprocess system of either one of claims 14 or 15, wherein said support material is substantially chemically inert to said ultraviolet light.

18. The bioprocess system of claim 14, wherein said mechanical support structure is a structural element than spans between inner walls of said bioprocess tube.

19. The bioprocess system of claim 14, wherein said mechanical support structure is disposed on inner walls of said bioprocess tube.

20. The bioprocess system of either one of claims 14 or 15, wherein said mechanical support structure contains macroporosity.

21. The bioprocess system of claim 1, wherein said second tube terminus is configured to direct a material into said bioprocess chamber from said bioprocess tube.

22. The bioprocess system of claim 1, wherein said second tube terminus is configured to direct a gas into said bioprocess chamber via a bioprocess sparger that is connected to said second tube terminus.

23. The bioprocess system of claim 1, wherein said second tube terminus is configured to direct a material from said bioprocess chamber, through said bioprocess tube, and into or through said bioprocess fitting.

24. The bioprocess system of claim 1, wherein said bioprocess chamber is a tank.

25. The bioprocess system of claim 1, wherein said bioprocess chamber is a bioreactor.

26. A bioprocess system comprising:(a) a bioprocess tube having a first tube terminus and a second tube terminus, wherein said bioprocess tube is fabricated from a first fluoropolymer, and wherein said first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) a bioprocess fitting sealably positioned on said first tube terminus, wherein said bioprocess fitting is fabricated from a second fluoropolymer, and wherein said second fluoropolymer is substantially translucent or transparent to ultraviolet light; and(c) a bioprocess chamber configured with a chamber conduit at which said bioprocess tube is sealably connected to said bioprocess chamber, wherein said first tube terminus is disposed outside said bioprocess chamber, and wherein said second tube terminus is contained within said bioprocess chamber.

27. A bioprocess system comprising:(a) multiple bioprocess tubes each having a first tube terminus and a second tube terminus, wherein said bioprocess tubes are each fabricated from a first fluoropolymer, and wherein said first fluoropolymer is substantially translucent or transparent to ultraviolet light;(b) multiple bioprocess fittings fitted to said multiple bioprocess tubes respectively, wherein each of said bioprocess fittings are sealably positioned on said first tube terminus, wherein said bioprocess fittings are each fabricated from a second fluoropolymer, and wherein said second fluoropolymer is substantially translucent or transparent to ultraviolet light;(c) a bioprocess chamber configured with a chamber conduit at which said bioprocess tubes are sealably connected to said bioprocess chamber, wherein said first tube terminus of each of said bioprocess tubes is disposed outside said bioprocesschamber, and wherein said second tube terminus of each of said bioprocess tubes is contained within said bioprocess chamber; and(d) one or more UV light sources configured to expose ultraviolet light onto wettable surfaces of said bioprocess tubes and said bioprocess fittings, wherein said first fluoropolymer and said second fluoropolymer are substantially chemically inert to said ultraviolet light.

28. The bioprocess system of claim 27, wherein there are at least three of said bioprocess tubes and at least three of said bioprocess fittings.

29. The bioprocess system of claim 27, wherein there are at least five of said bioprocess tubes and at least five of said bioprocess fittings.

30. The bioprocess system of claim 27, wherein there are at least eight of said bioprocess tubes and at least eight of said bioprocess fittings.

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