Apparatus and Method for Optical Sampling in Miniature Bioprocessing Vessels
An optical sampling apparatus for miniature-scale bioprocessing vessels includes features for optical interrogation of the bioprocessing vessel contents by means of transmission or transflection spectroscopy. This optical interrogation allows for the determination of quantities and parameters of substances in fluids contained within the bioprocessing vessels during bioprocesses. Multiple such bioprocessing vessels with the optical interrogation features may be mounted in a receiver for conducting multiple bioprocesses simultaneously. A translatable probe may be used to interact with each of the bioprocessing vessels in the receiver.
This application claims the benefit of U.S. provisional patent application No. 61/992,735, filed May 13, 2014, for “Optical Interfaces for Bioprocessing Vessels.” Such application is incorporated herein by reference in its entirety.
BACKGROUNDThe present invention relates to optical sampling means for providing optical communication between an optical instrument and a disposable vessel of polymeric construction for applications including, but not limited to, pharmaceutical, food processing, and chemical manufacturing as well as other laboratory and industrial processes.
The use of optical and electronic instrumentation to monitor and control the contents of vessels and changes taking place therein is well known in the art. Processing and storage of, for example, food, beverage, chemical, agricultural, fuel, and pharmaceutical products have historically taken place primarily in multiple-use vessels comprised of stainless steel and/or glass. Numerous hardware approaches enabling interrogation and analysis of the contents of such vessels by, for example, optical, electronic, and electrochemical techniques have been described in the art. Dissolved oxygen may be measured by, for example, electrochemical probes with oxygen-permeable membranes, as well as fluorescent sensor techniques. Measurement of pH is possible by electrochemical techniques as well as fluorescent methods. Probes for measurement of optical characteristics of materials in rigid vessels by transmission, reflection, and attenuated total reflection (ATR) are also known in the art. Such probes are often of tubular form and primarily metal construction, protruding through a head plate or side wall of a vessel and into the fluid under process. Probes and sensors of this general description are commonly designed for robustness and longevity—tolerating use, cleaning, and often sterilization for many process cycles. Such multiple-use probes and sensors typically have form factors that are not accommodating to interfacing with single-use bioreactors, particularly flexible bioreactors and those with small working volumes. Flexible bioreactors, also known as bag bioreactors, lack rigidity—surfaces commonly distort during operation, making attachment and positioning of typical multiple-use probes difficult and unstable. Bioreactors with small working volumes simply do not have the surface area or volume to support many of the sensors and probes that are common in the art. Moreover, such prior art sensors and probes do not commonly fit within the model of single-use technology as they are not disposable and must be in contact with the process fluid, thereby requiring the cleaning, sterilization, and aseptic insertion steps that single-use technology seeks to avoid.
Regular cleaning and maintenance of multiple-use vessels is required to maintain process integrity, and sterile conditions are often necessary, demanding yet more laborious and/or costly cleaning and sterilization procedures. The maintenance, cleaning, and disinfection of multiple-use process vessels coupled with the high initial cost of the equipment has led to accelerating adoption of single-use, disposable vessels in multiple industries. These single-use vessels are most commonly constructed of polymers and are often purchased pre-sterilized such that the user may immediately put them to use. As such, sensors that will come into contact with the fluid are commonly integrated into the vessel before sterilization and sterilized with the vessel. Any sensors or connections to the vessel that are not integrated and sterilized with the vessel may be externally sterilized and installed via aseptic ports. While use of sensors or probes that are not installed into the vessel prior to sterilization of the vessel is feasible, it is typically undesirable due to the additional labor required of the end user as well as the increased probability of contamination. Such single-use vessels offer several additional benefits over conventional multiple-use bioreactors: ease of use; reduced setup labor for end users; significantly reduced cleanup time; and lower equipment costs. Single-use disposable bioreactors are available in a variety of sizes and form factors—working volumes range from sub-milliliter to thousands of liters.
A key aspect in bioprocessing is being able to transition processes from small-scale experiments in the research lab to a large-scale production environment. The research and effort to transition from small-scale experiments to production is known as scale-up, and this process is commonly challenging and time consuming. Scale-up often comprises three major phases—the research phase where initial studies are performed and processes are selected and verified; the pilot plant phase where processes are further studied, refined, and verified in higher volume processes; and the production phase where large-scale manufacturing is performed. The conditions present in small-volume research bioreactors may be markedly different from those present in the larger bioreactors in the pilot plant and on the production floor. Indeed, processes can vary considerably even between different bioreactors in the research lab. In order to execute the scale-up process in the most efficient manner possible, it is desirable to have the ability to optimize a plurality of process parameters and constituent concentrations, and often to be able to control such parameters and constituent concentrations. Ideally such monitoring and control capabilities will be uniform throughout the various stages of scale-up. Bioreactors having working volumes of microliters to few milliliters are commonly known as micro-bioreactors, and are often configured such that multiple micro-bioreactors are used to perform experiments in parallel. Such multiplexed experiments with cell culture or fermentation processes enable evaluation of process conditions, cell lines, or other variables in an efficient manner. So-called miniature-bioreactors commonly have working volumes of tens to few hundreds of milliliters, and may offer another step in the scale-up process. Similarly to micro-bioreactors, mini-bioreactors are often configured in groups for parallel experimentation, though with a working volume that better represents more standard process conditions. While reliable monitoring of constituent concentrations of fluids in bioprocesses such as nutrient analyte concentrations remains challenging even in large-volume bioreactors, the challenge is amplified with micro- and mini-bioreactors given the space constraints and form factors. Sensor technologies capable of providing such fluid constituent concentration information, and ideally control of such concentrations, in bioreactors used across the product development arc from research lab to production plant are desired in the biotechnology and pharmaceutical industries.
Sensors for measurement of a variety of parameters within single-use vessels have been demonstrated. For example, analysis of physical and chemical conditions such as pH and dissolved oxygen (DO) is possible by means of sensors comprising fluorescent dots within the bioreactor fluid. Single-use and disposable temperature and pressure sensors have been demonstrated. Optical interfaces for vessels of polymeric construction, which may be single-use and/or flexible vessels, are also known in the art, though to a far lesser extent than similar interfaces for multiple-use vessels. Interfaces for transmission, reflection, and ATR optical measurements have been disclosed; however these interfaces and ports are generally not optimized for near-infrared spectroscopic applications. Numerous polymers are available that are at least partially transparent to visible and short-wave infrared (SWIR), though these polymers are often substantially opaque or exhibit significant absorption structure at wavelengths longer than 1.5 μm.
Bioreactors commonly require frequent monitoring and strict control in order to ensure optimal environmental and nutritional conditions for fermentation, cell cultures, or similar processes contained therein. While sensors are available to continuously measure parameters such as DO and pH as is hardware and software to control these parameters, sensors and systems to monitor nutrients and chemical constituents in an automated fashion and control the levels thereof have historically been largely absent in the art. This is the case for both multiple- and single-use bioreactors, however sensor solutions to interface with single-use bioreactors have been particularly lacking.
Measurement of chemical constituents by spectroscopic methods, particularly infrared spectroscopic methods, presents a robust means to monitor said chemical constituents and control levels thereof within bioreactors and process vessels in general. In order to optically interface with polymeric vessels and their contents, integrated and robust optical interface solutions are desired. These solutions may be substantially transparent in the wavelength range of interest, thereby enabling high measurement stability and optical throughput. The requirement of material transparency is particularly challenging for infrared spectroscopy, principally near- and mid-infrared spectroscopy, where optical absorption by many commonly used polymers is unacceptably high when polymer thicknesses are within the satisfactory range to maintain mechanical integrity. When in an optical spectroscopic configuration, embodiments of optical sensors where the path or sample length through the vessel contents is selectable and/or controlled may be desirable for some applications. Embodiments where any optical elements that are to come in contact with the vessel contents are fused to the vessel and sterilized with the vessel are often preferable to solutions where optical monitoring components are inserted aseptically subsequent to sterilization.
BRIEF SUMMARYAs used herein, the terms “optical” and “light” refer to electromagnetic radiation having vacuum wavelengths between 300-20,000 nm.
As used herein, “near infrared”, “near-infrared”, and “NIR” mean the region of the electromagnetic spectrum generally spanning wavenumbers between 3300 cm−1 and 14,000 cm−1 (corresponding to wavelengths of approximately 0.7 μm to 3.0 μm).
As used herein, “interrogation” and “sampling” mean illuminating a sample with optical radiation and collecting at least a portion of the radiation having interacted with said sample for optical analysis.
As used herein, “working volume” refers to the typical volume of fluid contained within a vessel or container during a process and is most commonly less than the total volume of fluid that the vessel could retain.
As used herein, “miniature,” and “mini,” when used in reference to bioprocessing vessels means bioprocessing vessels having working volumes less than or equal to 0.25 liters.
As used herein, “constituent” means a chemical analyte, protein, DNA, component in a fluid, cell, or solid suspended in a fluid.
The present invention relates to miniature-bioprocessing vessels comprising features for optical interrogation of fluids contained within such bioprocessing vessels. Embodiments of receiver assemblies for receiving, housing, and positioning embodiments of such bioprocessing vessels are also provided. Embodiments of such receivers may also provide optical elements, sensors, and means for optical communication with optical instruments, and may be configured to receive a plurality of bioprocessing vessels. An optical instrument may be used in conjunction with embodiments of the present invention to determine and/or control quantities of substances in fluids contained within bioprocessing vessels. The invention pertains to optical transmission and transflection measurements in general and particularly to near-infrared spectroscopic analytical techniques.
A plurality of embodiments of bioprocessing vessels comprising features for optical interrogation is described herein. Embodiments of bioprocessing vessels provided by the present invention typically comprise at least one rigid polymer sidewall and may be comprised entirely of rigid polymer materials. In such embodiments, at least a portion of the polymeric vessel may be substantially transparent to the wavelengths of electromagnetic radiation being utilized either due to inherent lack of absorption or to use of a suitably thin section of polymer. In one embodiment of the present invention, an optical sampling region is provided whereby features extending outward from the primary volume of a bioprocessing vessel at least partially define the optical sampling region by providing a defined length of optical path through a fluid contained within the bioprocessing vessel. In another embodiment, an optical sampling region is provided whereby features extending into the primary volume of a bioprocessing vessel at least partially define the optical sampling region.
Embodiments are also described whereby bioprocessing vessels comprise integral optical probes extending into the vessel. In some embodiments, optical waveguides and/or optical elements within an optical probe communicate light into the fluid within a bioprocessing vessel where it may interact with the fluid, and a portion of the light having interacted with the fluid may be communicated by additional optical waveguides and/or elements to a sensor or optical instrument. In one embodiment, integral probes are provided where the input and output optical communication is provided on a single surface integrated with the probe. In another embodiment, input and output optical communication are provided on different sides of the optical probe coupled to different sides of a vessel. In yet another embodiment, only input optical waveguides and/or elements are provided, and light is sensed by a sensor in a receiver for the bioprocessing vessel.
The detailed description and drawings provided herein will offer additional scope to certain implementations of the present invention. It should be understood that the described implementations are provided as examples only. Those skilled in the art will recognize that numerous variations and modifications of the described implementations are within the scope of the invention.
An embodiment of a disposable bioprocessing vessel comprising features to provide an optical sampling region is shown in
The polymer materials that comprise the first 110 and second 120 surfaces in the optical sampling region 130 will preferably be materials being sufficiently transparent to the wavelength range of electromagnetic radiation used for optical interrogation. In the near-infrared wavelength range of the electromagnetic radiation spectrum, perfluorinated polymers such as fluorinated ethylene propylene are preferable due to their low optical absorption, chemical compatibility, and classification as USP Class VI compliant materials. Alternatively, if polymers exhibiting substantial absorption in the wavelength range of interest are to be used, at least portions of the first 110 and second 120 surfaces in the optical sampling region 130 may be manufactured to be sufficiently thin to provide sufficient optical throughput in the wavelength range of interest. For example, polycarbonate exhibits strong absorption features in the near-infrared wavelength range, however the transmission of polycarbonate is acceptable if the polycarbonate is sufficiently thin, and preferably less than 0.25 mm thick. Due to the sterility requirements common in bioprocessing applications, polymers chosen for manufacturing of the bioprocessing vessel 100 and optical sampling region 130 will preferably be amenable to sterilization by one or more techniques. Sterilization by irradiating with gamma or beta radiation is a common technique for disposable polymer components in bioprocessing applications. Both sterilant gas such as ethylene oxide or heat sterilization by autoclave are also sterilization options, and embodiments will preferably withstand sterilization by at least one sterilization technique and remain FDA and/or USP Class VI compliant after sterilization.
The sectional view in
In an embodiment similar to the bioprocessing vessel 100 with features that extend outward sideways from the primary volume of the vessel, an embodiment of a bioprocessing vessel 180 with features extending outward through the bottom of the vessel are also provided. First 110 and second 120 surfaces are provided and form an optical sampling region 130. Said bioprocessing vessel 180 shown in
Embodiments comprising disposable bioprocessing vessels with polymer regions for optical wavelength reference operations are provided by the present invention. Polymers for optical wavelength referencing may be the same polymer as the primary polymer comprising the bioprocessing vessel, or may be a different polymer having more desirable properties for wavelength reference operations. The disposable bioprocessing vessel 180 embodiment shown in
Embodiments of the present invention comprising composite polymer laminates are also provided. A disposable bioprocessing vessel or portion thereof may comprise a plurality of polymer layers adjacent to one another as shown in
The embodiment shown in
In another embodiment, features that extend inward into the disposable bioprocessing vessel are provided for optical interrogation of the fluid within the vessel. An embodiment shown in
Due to the fact that many polymers exhibit strong absorption features in certain wavelength ranges of the electromagnetic spectrum, it may be advantageous to provide a second polymer serving as an optical window in the optical sampling region of a disposable bioprocessing vessel. For example in the near-infrared wavelength range of the electromagnetic spectrum (comprising wavenumbers between 3300 cm−1 and 14,000 cm−1), strong absorption features may arise from C—H, C—O, O—H, and N—H chemical bonds. For this reason it may be preferable to use polymers lacking such chemical bonds in the optical sampling regions of disposable bioprocessing vessels designed for optical interrogation by such wavelengths. Perfluorinated polymers such as Teflon® polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), Teflon® fluorinated ethylene propylene (FEP), Teflon® amorphous fluoroplastics (AF), and Teflon® perfluoroalkoxy copolymer (PFA) lack the listed chemical bonds and thus may be preferable for polymer materials within the optical path. Alternatively, other polymer materials may be used if sufficiently thin to provide adequate optical transmission in the desired wavelength range. An embodiment is provided that comprises a second polymer being more optically transparent in the near-infrared wavelength range than the primary polymer used in the manufacture of disposable bioprocessing vessels. Such an embodiment is shown in
In yet another embodiment of the present invention, the optical path length may be formed by compression of the first 110 and/or second surfaces 120. The embodiment shown in
Embodiments of disposable bioprocessing vessels comprising integral optical probes extending into the fluid within the bioprocessing vessels are also provided by the present invention. Provision of optical probes enables alternative optical interfacing strategies to optical instrumentation and permits sampling the contents of bioprocessing vessels at locations more central to the vessel rather than at the periphery. One embodiment of a disposable vessel 340 comprising an integral optical probe 350 is shown in the isometric view in
The embodiment shown in
Additional embodiments of disposable bioprocessing vessels having integral optical probes are shown in
The embodiment shown in the sectional view in
Embodiments of receivers for disposable bioprocessing vessels are also provided by the present invention. Receivers may accommodate a single bioprocessing vessel, but are commonly configured to receive a plurality of bioprocessing vessels to perform multiple bioprocessing experiments simultaneously. Receivers may perform a plurality of functions such as measurement and/or control of temperature, agitation, aeration, pH, dissolved oxygen, cell density, cell viability, and chemical constituent concentrations. One embodiment of a receiver is shown in the isometric view in
The view in
The sectional view in
Methods are also provided by the present invention for determining quantities of substances within fluids contained within disposable bioprocessing vessels. Near-infrared electromagnetic radiation may be used to optically interrogate fluids, and the changes sensed in the collected near-infrared radiation after interaction with a fluid may be used to determine quantities of substances within fluids. Bioprocessing vessels located in a receiver assembly may first be selected for optical interrogation. Selection of a vessel may be performed for example mechanically as by translating an optical interface located on a mechanical translator, or optically as by activation of an optical sensor or switch. Near-infrared electromagnetic radiation is then communicated to a disposable bioprocessing vessel. Communication of near-infrared radiation may be provided by optical waveguides such as optical fibers, free-space optical elements, or a combination thereof. Optical communication elements may be provided in the receiver base assembly, on an optical interface, or both. For example, near-infrared electromagnetic radiation from an optical instrument may be communicated to a bioprocessing vessel via optical waveguides, and radiation having interacted with the fluid within a bioprocessing vessel may be sensed by an adjacent optical sensor. Radiation having interacted with the fluid within a bioprocessing vessel may also be communicated to an optical instrument for analysis. Radiation resulting from optical transmission or transflection measurements through the fluid in the bioprocessing vessel may be used by an optical instrument to determine one or more quantities of substances in a fluid.
Optical spectroscopy with near-infrared electromagnetic radiation offers a plurality of advantages for determining quantities of substances in fluids. Optical absorption features in the 3300 cm-1 to 14,000 cm-1 wavenumber range are often present for substances having C—H, O—H, C—O, N—H, S—H, and P—H chemical bonds, offering the possibility to determine quantities of substances containing such chemical bonds using near-infrared spectroscopy. While water is sufficiently strongly absorbing in several wavelength ranges throughout the infrared electromagnetic spectrum to limit the effectiveness of spectroscopic techniques to determine quantities of substances, the 3300 cm-1 to 5600 cm-1 wavenumber range provides a water transmission window centered at approximately 4600 cm-1. In this wavenumber range the water absorption is sufficiently low to allow adequate optical throughput through fluid samples with a sufficiently short optical path length to determine quantities of substances by spectroscopic techniques. In order to provide sufficient optical throughput through a fluid and also provide a satisfactory optical path length for interaction of electromagnetic radiation with the fluid, optical path lengths through fluids ranging from 0.5 mm to 2.0 mm are preferable for embodiments of the present invention. Measurements with near-infrared spectroscopic techniques may be used to determine quantities of substances in fluids such as alcohols, sugars, lipids, organic acids, peptides, and steroidal molecules as such substances often comprise optical absorption features at near-infrared wavelengths due to their chemical bonds. In addition to measurements of optical absorption by transmission or transflection measurement approaches to determine quantities of substances by their absorption spectra, near-infrared spectroscopic techniques may be used to determine parameters such as cell density, cell viability, or turbidity. Due to the reduction in optical scattering with increasing wavelength, optical path lengths between 0.5 mm and 2.0 mm may be used even when conducting high cell density bioprocesses such as Pichia pastoris fermentations. Use of wavenumbers higher than 5600 cm-1 (shorter wavelength than 1.8 μm) often requires short path lengths or operation with low cell density applications due to the increased optical scattering encountered and resulting optical attenuation.
Embodiments of the present invention including disposable bioprocessing vessels and receivers as well as associated methods provide for a plurality of bioprocessing applications such as a storage stage, a growth stage, a product formation stage, a purification stage, and a product formulation stage. For example, a growth stage may include cell culture, fermentation, or other bioprocesses whereby cell growth and/or product formation is desired. Embodiments of the present invention may be provided for processes such as batch processes as well as continuous processes such as perfusion processes. Downstream processes such as product purification may also utilize embodiments of the present invention for determination of constituents in fluids.
Embodiments of the present invention disposable bioprocessing vessels may also comprise polymer regions to provide an optical wavelength reference. The merits of providing polymer materials for wavelength reference operations have been described in U.S. patent application Ser. No. 14/631,917, the teachings of which are incorporated by this reference. Absorption features of polymers may be used advantageously as optical wavelength references, wherein said absorption features are used to provide a comparison of a measured optical spectrum of the polymer with a known optical spectrum of the polymer to determine the wavelength accuracy of an instrument. Such wavelength reference methods may provide enhanced stability of optical systems and measurements due to the establishment of a calibrated wavelength axis of a measurement. Instrumental drift due to for example drift in performance of instrument components or in environmental conditions may cause undesirable changes to an optical system whereby the wavelength axis of the measurement may deviate from an acceptable condition. Periodic verification and correction of the wavelength properties of an optical system by comparison with a known standard material is desirable to mitigate against such undesirable changes and thereby improve the stability of the optical system and accuracy of measurements made with the optical system. In embodiments of the present invention, a second beam of near-infrared electromagnetic radiation may be provided to optically interrogate a polymer region on a disposable bioprocessing vessel comprising a polymer suitable as an optical wavelength reference. Said polymer region will desirably provide no fluid sample within the second optical beam path such that the optical absorption experienced by the beam is only that of the polymer wavelength reference material. Said polymer used as a wavelength reference material will desirably have multiple optical absorption features within the wavelength range of the optical measurement in order to provide multiple features with which to make a comparison against a known optical spectrum of the polymer. In the near-infrared region of the electromagnetic spectrum, polymer materials such as nylon, polycarbonate, Kapton®, polymethylpentene (TPX), and polyether ether ketone (PEEK) may be provided as wavelength reference materials.
The present invention has been described with reference to the foregoing specific implementations. These implementations are intended to be exemplary only, and not limiting to the full scope of the present invention. Many variations and modifications are possible in view of the above teachings. The invention is limited only as set forth in the appended claims. All references cited herein are hereby incorporated by reference to the extent not inconsistent with the disclosure herein. Unless explicitly stated otherwise, flows depicted herein do not require the particular order shown, or sequential order, to achieve desirable results. In addition, other steps may be provided, or steps may be eliminated, from the described flows, and other components may be added to, or removed from, the described systems. Accordingly, other implementations are within the scope of the following claims. Any disclosure of a range is intended to include a disclosure of all ranges within that range and all individual values within that range.
Claims
1. A disposable bioprocessing vessel for containing a fluid sample, the vessel comprising:
- at least one rigid wall;
- an optical sampling region integral to the rigid wall and comprising a first and second surface to create an optical path between the first and second surfaces within the bioprocessing vessel, said first and second surfaces comprise a polymer at least partially transparent to near-infrared electromagnetic radiation and wherein the first and second surfaces are sufficiently thin to allow near-infrared electromagnetic radiation to pass therethrough, interact with the fluid sample, and be detected outside of the bioprocessing vessel to provide a transmission or transflection measurement of the fluid sample.
2. The disposable bioprocessing vessel of claim 1, wherein said polymer comprises at least one of polycarbonate or fluorinated ethylene propylene (FEP).
3. The disposable bioprocessing vessel of claim 2, wherein at least portions of the first and second surfaces are less than 0.25 mm thick.
4. The disposable bioprocessing vessel of claim 1, wherein said polymer comprises a composite polymer laminate comprising a first layer and a second layer wherein the second layer comprises a different polymer material than the first layer.
5. The disposable bioprocessing vessel of claim 1, wherein a length of the optical path defined by said first and second surfaces is between 0.5 mm and 2.0 mm inclusively.
6. The disposable bioprocessing vessel of claim 1, wherein said disposable bioprocessing vessel is suitable for sterilization by one or more of gamma irradiation, beta irradiation, ethylene oxide, or autoclave.
7. The disposable bioprocessing vessel of claim 1, wherein said second surface further comprises a reflector, wherein said reflector reflects at least a portion of said near-infrared electromagnetic radiation in the direction of the first surface where it may be sensed by a sensor, thereby providing an optical transflection measurement.
8. The disposable bioprocessing vessel of claim 1, wherein said polymer is at least partially transparent to near-infrared electromagnetic radiation transmitted through a fluid sample comprising wavenumbers between 3300 cm−1 and 5600 cm−1.
9. The disposable bioprocessing vessel of claim 1, wherein said disposable bioprocessing vessel has a working volume less than or equal to 0.25 liters.
10. The disposable bioprocessing vessel of claim 1, wherein said first and second surfaces extend outward from a primary volume of said bioprocessing vessel and define said optical path.
11. The disposable bioprocessing vessel of claim 1, wherein said first and second surfaces comprise one or more features extending inward into a primary volume of said bioprocessing vessel and defining said optical path therebetween.
12. The disposable bioprocessing vessel of claim 1, wherein said disposable bioprocessing vessel is configured for a process selected from the group consisting of a storage stage, a growth stage, a product formation stage, a purification stage, and a product formulation stage.
13. The disposable bioprocessing vessel of claim 1, wherein said first and second surfaces comprise regions with step-variable distances therebetween, thereby providing a plurality of optical paths of different optical path lengths.
14. The disposable bioprocessing vessel of claim 1, wherein said first and second surfaces comprise a second polymer, wherein the second polymer is more optically transparent than said polymer to near-infrared electromagnetic radiation, wherein at least a portion of said second polymer is within said optical path.
15. The disposable bioprocessing vessel of claim 14, wherein said second polymer comprises fluorinated ethylene propylene (FEP).
16. The disposable bioprocessing vessel of claim 1, wherein said vessel further comprises a region comprising a second polymer and at least a portion of said region does not surround a fluid sample within the disposable bioprocessing vessel, wherein said second polymer provides optical absorption features to enable an optical wavelength reference.
17. The disposable bioprocessing vessel of claim 1, wherein at least portions of said first and second surfaces are at least partially compressible, and wherein a length of an optical path through the fluid sample is defined by compression of said first and second surfaces.
18. A disposable bioprocessing vessel with features for optically sampling a fluid within said bioprocessing vessel, said bioprocessing vessel comprising:
- a top, a bottom, and at least one rigid sidewall, wherein the top, bottom, and rigid sidewall define an interior;
- an optical probe integral with at least one of the top, bottom, or rigid sidewall and protruding into the interior of said disposable bioprocessing vessel, said integral optical probe comprising at least one optical waveguide;
- wherein a portion of said integral optical probe is within the interior of said disposable bioprocessing vessel and provides optical communication between a fluid sample within said disposable bioprocessing vessel and an optical instrument whereby a near-infrared transmission or transflection measurement is provided.
19. The disposable bioprocessing vessel of claim 18, wherein the probe further comprises two optical elements positioned to provide an optical path length therebetween and within the interior of the bioprocessing vessel, whereby an optical transmission or transflection measurement through the fluid sample contained within the interior of said disposable bioprocessing vessel is provided.
20. The disposable bioprocessing vessel of claim 18, wherein said integral optical probe intersects two surfaces defining the interior of said disposable bioprocessing vessel, whereby near-infrared electromagnetic radiation is communicated through one of said surfaces, interacts with a fluid sample within said disposable bioprocessing vessel, and at least a portion of near-infrared electromagnetic radiation having interacted with said fluid sample is communicated through the other of said surfaces thereby providing an optical transmission measurement.
21. The disposable bioprocessing vessel of claim 18, wherein the length of optical path through said fluid is between 0.5 mm and 2.0 mm inclusively.
22. The disposable bioprocessing vessel of claim 18, wherein said disposable bioprocessing vessel has a working volume less than or equal to 0.25 liters.
23. A receiver assembly for receiving one or more disposable bioprocessing vessels and optically interrogating said one or more disposable bioprocessing vessels with near-infrared electromagnetic radiation, said receiver assembly comprising:
- a base assembly comprising one or more stations each configured to receive a disposable bioprocessing vessel comprising components for near-infrared optical interrogation, each of said one or more stations comprising features for alignment of said disposable bioprocessing vessels within said stations such that said bioprocessing vessels may be installed in only one orientation; one or more optical assemblies for optical communication of near-infrared electromagnetic radiation between said disposable bioprocessing vessels positioned within said stations and an optical instrument;
- wherein said optical assemblies for optical communication comprise one or both of an optical interface not integrated within said base assembly to provide optical communication with said disposable bioprocessing vessels or at least one optical assembly integrated within said base assembly.
24. The receiver assembly of claim 23, further comprising a mechanical translator configured to provide mechanical translation between said base assembly and said optical interface.
25. The receiver assembly of claim 23, wherein said receiver assembly is configured to receive a plurality of disposable bioprocessing vessels.
26. The receiver assembly of claim 23, wherein said stations are configured to receive disposable bioprocessing vessels, and wherein the disposable bioprocessing vessels comprise working volumes less than or equal to 0.25 liters.
27. The receiver assembly of claim 23, wherein said optical interface comprises one or more optical waveguides to communicate near-infrared electromagnetic radiation between an optical instrument and the disposable bioprocessing vessel.
28. The receiver assembly of claim 23, wherein said receiver assembly further comprises one or more optical sensors.
29. A method of determining the quantities of one or more substances in a fluid sample contained within a disposable bioprocessing vessel that is located in a receiver assembly, said method comprising the steps of:
- selecting a disposable bioprocessing vessel;
- communicating near-infrared electromagnetic radiation from an optical instrument to said disposable bioprocessing vessel;
- collecting near-infrared electromagnetic radiation having interacted with a fluid content of said disposable bioprocessing vessel and communicating said electromagnetic radiation to said optical instrument for analysis;
- determining the one or more quantities of substances in the fluid sample in said disposable bioprocessing vessel by utilizing the optical instrument to perform an optical transmission or transflection measurement.
30. The method of claim 29, wherein said optical instrument is configured to measure one or more of alcohols, sugars, lipids, organic acids, peptides, steroidal molecules, or proteins.
31. The method of claim 29, wherein said optical instrument is configured to measure one or more of cell density, cell viability, or turbidity.
32. The method of claim 29, wherein the step of determining the one or more quantities of substances is performed in a plurality of bioprocessing vessels.
33. The method of claim 29, wherein said method further comprises the step of communicating a second beam of near-infrared electromagnetic radiation through a portion of said disposable bioprocessing vessel and not interacting with a fluid sample, wherein the optical absorption features of said polymer provide an optical wavelength reference.
Type: Application
Filed: May 12, 2015
Publication Date: Nov 19, 2015
Inventors: Edwin John Koerperick (North Liberty, IA), Jonathon Todd Olesberg (Iowa City, IA), Christine Esther Evans (North Liberty, IA), Mark Allen Arnold (Iowa City, IA), Gary Wray Small (Coralville, IA)
Application Number: 14/709,685