Multipurpose sensor holder

Abstract

A probe holder for a bioreactor or other container or vessel that serves as a base platform or stand to hold a sensor or probe, such as a Raman probe, in an open position that is sterilized as part of an assembly that includes a sensor attached to a housing or container with a sterile connector. The holder helps a user to place the sensor or probe at least partially within or in fluid communication with the interior of the bioreactor or vessel and to hold and / or lock the sensor or probe in place during use.

Description

Technical Field

[0001] This application claims the priority of U.S. Provisional Application No. 63 / 335,963, filed on April 28, 2022, the disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to the measurement of fluid properties. More specifically, embodiments of the present disclosure relate to holders and housings for probes and / or sensors for measuring fluids within bioreactors, biocontainers, or other containers.

Background Art

[0003] Cell culture has been used for many years in the research and production of life sciences and biopharmaceuticals. Cell culture systems rely on a controlled environment for the maintenance, growth, expansion, and testing of cells. Despite often taking strict measures to avoid occurrences such as contamination by fungal or bacterial contamination, such occurrences still occur, often disrupting weeks of research and affecting operations for days or weeks. At the very least, the results of cell culture assays can be distorted by unexpected changes in cell physiology due to inconsistencies in the underlying cell culture. Researchers need to visually observe subtle changes in cell morphology, growth patterns, and growth rates that may indicate problems with a particular culture and carefully monitor and evaluate the health of the cells.

[0004] Researchers culturing mammalian cells often realize that maintaining cell culture is a very time-consuming task. It is necessary to visually evaluate the health of the cells by determining their morphology under a microscope, change the medium (feed), recover the cells (confluence), deal with contaminants, monitor metabolites and cell interactions, and carefully address other issues.

[0005] Unfortunately, modern laboratory environments present numerous obstacles to adequately monitoring cultured cells. For example, manually inspecting cell cultures 24 hours a day (e.g., every 2-4 hours) is impractical and often prohibitively costly. Furthermore, 24 / 7 manual monitoring of cell cultures often places a significant physical and mental burden on researchers, reducing their overall quality of life and increasing the likelihood of observational errors due to excessive fatigue. Moreover, fully automated cell culture monitoring systems are extremely cumbersome, complex, and require substantial investment.

[0006] Furthermore, simple visual inspection of cells provides only subjective assessments and leaves no permanent visual records or archives. This can lead to missing signs of problems with cells or cell cultures, severely impacting the quality of data generated in cell-based assays. The ability to supply healthy, living cell cultures is becoming increasingly important in today's highly competitive, multinational biology and biopharmaceutical industry.

[0007] Various sensors may be used in bioreactors, biocontainers, mixers, and other containers (such as disposable bags). These sensors may require or benefit from measuring various parameters within the bioreactor mixer or container (such as dissolved oxygen content, pH, CO2 content, glucose content, turbidity, and living cell density). Measuring the physical properties of a fluid in situ may result in small sample sizes and passage through individual low-flow regions, potentially not representing larger populations and leading to further discrepancies. Bioprocess systems typically include conduits, which are part of a closed system, through which fluids flow, and sampling through such conduits presents similar sampling problems.

[0008] In bioprocesses, such as those involving monoclonal antibodies, capsids, cell lines, and inline virus inactivation processes, measurements are performed from within tanks, for example, statically, or within fluid streams, such as liters per minute flowing through conduits. Furthermore, in some cases, measurements can be performed on samples taken from the finished product or after the completion of specific sub-operations. Sampling can be another vector for introducing undesirable contaminants into the process. All of the above represents challenges that processors attempting to measure the properties of biological fluids must overcome.

[0009] In recent years, the trend in bioprocessing has been skewed towards providing continuous processing, or enhancement processing, where biological fluids from one process are introduced into another, creating further challenges in sampling, measurement, and process monitoring. Process control is particularly difficult in the case of enhancement processing.

[0010] Process control under the demanding conditions of continuous processes requires at least the development of new sensors, or new methods for integrating existing probes and sensors, ensuring reliable and accurate data collection while simultaneously addressing new requirements, namely rapid response times for inline flow continuous processes. Such measurements typically require large probes. Response time is a function of the kinematics of chemical / biological processes and is usually slower than that of mechanical processes. This is why measurements such as conductivity and pH are more complex than, for example, sensing fluid pressure.

[0011] Recent technologies are attempting to optimize and improve the accuracy, reliability, and stability of long-term process testing using existing probes and sensors to measure pH, viable cell density (VCD), conductivity, turbidity, dissolved oxygen, and temperature. The placement of sensors within the process is also a crucial factor. [Overview of the Initiative] [Problems that the invention aims to solve]

[0012] The probe holder, which functions as a platform for holding the sensor in an open position for sterilization by autoclaving, gamma radiation, or ethylene oxide (ETO), acts as part of an assembly that includes the sensor mounted in a housing with a connector such as a sterile connector, and serves as a holder for semi-permanent mounting in a bioreactor, biocontainer, or container, assisting the user in making sterile connections and helping the user position and hold the sensor in place within the bioreactor, biocontainer, or container during sensor use, representing an advance in this technology.

[0013] To fulfill this advantage, it is desirable to provide a holder that performs one or more functions. [Means for solving the problem]

[0014] The problems of the prior art are solved by embodiments disclosed herein, including bioreactors or other containers or sensor or probe holders for containers. In some embodiments, probe holders are disclosed for positioning and holding a probe for engagement with a container, wherein the probe has a longitudinal axis and is longitudinally extendable between a compressed position and an extended position, and the holder includes a first movable member and a second movable member, the first and second movable members being movable relative to each other, and configured to support the probe in the extended position and to engage with the probe in the compressed position. In some embodiments, the holder functions as a base platform or stand for holding a sensor or probe in an open position that is sterilized by an autoclave, gamma, or ETO, etc., as part of an assembly including a sensor mounted on a housing or container with a sterile connector. In some embodiments, the holder functions as a holder for positioning and semi-permanently mounting a sensor or probe in a bioreactor, mixer, or container, making it easier for the user to make sterile connections. In some embodiments, the holder helps the user position the sensor or probe at least partially inside the bioreactor or container, or position it to be in fluid communication with the inside of the bioreactor or container, to hold and / or lock the sensor or probe in place during use. In some embodiments, when properly positioned by the holder, a portion of the sensor or probe makes physical contact with the contents of the bioreactor, mixer, or container, allowing the sensor or probe to measure or analyze one or more parameters of the contents in an efficient, reliable, and repeatable manner. In some embodiments, the holder permanently or semi-permanently (e.g., removable) fixes the sensor or probe to the bioreactor, container, or vessel. In some embodiments, the probe is a Raman probe.

[0015] In certain embodiments, the probe holder is designed to perform in-line and in-situ measurements. Embodiments described herein include a holder that supports and holds a sensor or probe in place when the entire assembly is autoclaved or otherwise sterilized. The holder allows the user to position the assembly in place before aligning and engaging the connector (e.g., a sterile connector). The holder holds the sensor or probe fixed in place while processing and / or measuring a sample in a container such as a bioreactor. The holder may be shipped assembled with bellows and a sterile connector, and the user attaches the selected sensor to the bellows. If bellows are present, they are expandable and foldable and protect the sensor or probe from damage by enclosing it. After the sensor or probe is attached to the holder, the assembly can be sterilized. After sterilization, the user aligns the holder assembly with the bioreactor / biocontainer / container. The user then connects the sterile connector and optionally removes a sterile barrier tab, for example. After opening the sterile connector, the fluid can be introduced into the bioreactor / biocontainer / container, and its parameters can be measured with a sensor or probe.

[0016] In some embodiments, the first and second movable members are linearly movable in the direction of the longitudinal axis.

[0017] In some embodiments, the first and second movable members are movable so as to be rotatable about a pivot axis perpendicular to the longitudinal axis.

[0018] In some embodiments, the probe holder includes an expandable and foldable bellows having a passage configured to accommodate at least a portion of the probe.

[0019] In some embodiments, the first movable member protects the expandable and foldable bellows when the expandable and foldable bellows are in a folded state.

[0020] In some embodiments, the holder further includes a sterile or sterile connector.

[0021] In some embodiments, the first movable member slides within a slot or groove of the second movable member.

[0022] In some embodiments, a probe holder is disclosed for positioning and holding a probe for engaging with a container, the probe having a longitudinal axis and being longitudinally extendable between a compressed position and an extended position, and the holder includes a slotted base, a movable member, and a support member, the movable member being movable within the slotted base relative to the support member. In some embodiments, the movable member includes a movable block that can be locked to the base. In some embodiments, the movable member is U-shaped. In some embodiments, the probe holder includes a clamp assembly having a U-shaped recess and a locking bar that can be positioned across the U-shaped recess. In some embodiments, the clamp assembly has a first free end and a second free end defining a U-shaped recess between them, and the locking bar is rotatable on the first free end. In some embodiments, the slotted base has two opposing, spaced-apart elongated side walls defining a channel between them.

[0023] The embodiments disclosed herein can take the form of various components and arrangements of components, as well as various process operations and arrangements of process operations. The drawings are for illustrative purposes only and should not be construed as limiting. This disclosure includes the following drawings. [Brief explanation of the drawing]

[0024] [Figure 1A] Figure 1A is a perspective view of the holder shown in a first position according to the first embodiment. [Figure 1B]Figure 1B is a perspective view of the holder shown in the second position according to the first embodiment. [Figure 1C] Figure 1C is a side view of the holder shown in the first position according to the first embodiment. [Figure 1D] Figure 1D is a side view of the holder shown in the second position according to the first embodiment. [Figure 1E] Figure 1E is a front view of the holder shown in the first position according to the first embodiment. [Figure 1F] Figure 1F is a front view of the holder shown in the second position according to the first embodiment. [Figure 1G] Figure 1G is a rear view of the holder shown in the first position according to the first embodiment. [Figure 1H] Figure 1H is a rear view of the holder shown in the second position according to the first embodiment. [Figure 1I] Figure 1I is a top view of the holder shown in the first position according to the first embodiment. [Figure 1J] Figure 1J is a bottom view of the holder shown in the first position according to the first embodiment. [Figure 2A] Figure 2A is a perspective view of the holder shown in the first position according to the first embodiment, including a general-purpose coupling device. [Figure 2B] Figure 2B is a perspective view of the holder shown in the second position according to the first embodiment, including a general-purpose coupling device. [Figure 3A] Figure 3A is a top view of a container arranged such that the holder of FIG. 1 is coupled to its port and another holder of FIG. 1 is coupled to another port, according to the first embodiment. [Figure 3B] Figure 3B is a first perspective view of the container of FIG. 3A. [Figure 3C] Figure 3C is a second perspective view of the container of FIG. 3A. [Figure 4A] Figure 4A is a perspective view of the holder shown in the first position according to the second embodiment. [Figure 4B]Figure 4B is a perspective view of the holder shown in a second position according to the second embodiment. [Figure 4C] Figure 4C is a side view of the holder shown in the first position according to the second embodiment. [Figure 4D] Figure 4D is a side view of the holder shown in the second position according to the second embodiment. [Figure 4E] Figure 4E is a front view of the holder shown in the first position according to the second embodiment. [Figure 4F] Figure 4F is a front view of the holder shown in the second position according to the second embodiment. [Figure 4G] Figure 4G is a rear view of the holder shown in the first position according to the second embodiment. [Figure 4H] Figure 4H is a rear view of the holder shown in the second position according to the second embodiment. [Figure 4I] Figure 4I is a side view of the holder shown in an intermediate position according to the second embodiment. [Figure 5A] Figure 5A is a perspective view of the holder shown in the first position according to the second embodiment, and includes a general-purpose coupling device. [Figure 5B] Figure 5B is a perspective view of the holder shown in a second position according to the second embodiment, and includes a general-purpose coupling device. [Figure 6A] Figure 6A is a perspective view of the holder shown in the first position according to the third embodiment. [Figure 6B] Figure 6B is a perspective view of the holder shown in the second position according to the third embodiment. [Figure 6C] Figure 6C is a side view of the holder shown in the first position according to the third embodiment. [Figure 6D] Figure 6D is a side view of the holder shown in the second position according to the third embodiment. [Figure 6E] Figure 6E is a front view of the holder shown in the first position according to the third embodiment. [Figure 6F]Figure 6F is a front view of the holder shown in the second position according to the third embodiment. [Figure 6G] Figure 6G is a rear view of the holder shown in the first position according to the third embodiment. [Figure 6H] Figure 6H is a rear view of the holder shown in the second position according to the third embodiment. [Figure 6I] Figure 6I is a bottom view of the holder shown in the second position according to the third embodiment. [Figure 6J] Figure 6J is a top view of the holder shown in the second position according to the third embodiment. [Figure 7] Figure 7 is a perspective view showing a third embodiment in which the holder of Figure 6B is connected to its port, and another holder of Figure 6B is connected to another port. [Figure 8A] Figure 8A is a perspective view of the holder shown in the first position according to the fourth embodiment. [Figure 8B] Figure 8B is a perspective view of the holder shown in the second position according to the fourth embodiment. [Figure 8C] Figure 8C is a side view of the holder shown in the first position according to the fourth embodiment. [Figure 8D] Figure 8D is a side view of the holder shown in the second position according to the fourth embodiment. [Figure 8E] Figure 8E is a front view of the holder shown in the first position according to the fourth embodiment. [Figure 8F] Figure 8F is a front view of the holder shown in the second position according to the fourth embodiment. [Figure 8G] Figure 8G is a rear view of the holder shown in the first position according to the fourth embodiment. [Figure 8H] Figure 8H is a rear view of the holder shown in the second position according to the fourth embodiment. [Figure 8I] Figure 8I is a top view of the holder shown in the second position according to the fourth embodiment. [Figure 9]Figure 9 is a perspective view showing a configuration according to the fourth embodiment, where the holder in Figure 8B is connected to its port, and another holder in Figure 8A is connected to another port. [Figure 10A] Figure 10A is a perspective view of the holder and sensor shown in the first position according to the fifth embodiment. [Figure 10B] Figure 10B is a top view of the holder and sensor shown in Figure 10A. [Figure 10C] Figure 10C is a side view of the holder and sensor shown in Figure 10A. [Figure 10D] Figure 10D is a bottom view of the holder and sensor shown in Figure 10A. [Figure 10E] Figure 10E is a front view of the holder and sensor shown in Figure 10A. [Figure 10F] Figure 10F is a rear view of the holder and sensor shown in Figure 10A. [Figure 11A] Figure 11A is a perspective view of the holder shown in Figure 10A without the sensor. [Figure 11B] Figure 11B is a top view of the holder shown in Figure 10A without the sensor. [Figure 11C] Figure 11C is a side view of the holder shown in Figure 10A without the sensor. [Figure 11D] Figure 11D is a bottom view of the holder shown in Figure 10A without the sensor. [Figure 11E] Figure 11E is a front view of the holder shown in Figure 10A without the sensor. [Figure 11F] Figure 11F is a rear view of the holder shown in Figure 10A without the sensor. [Figure 12A] Figure 12A is a perspective view of the holder and sensor shown in the second position according to the fifth embodiment. [Figure 12B] Figure 12B is a top view of the holder and sensor shown in Figure 12A. [Figure 12C] Figure 12C is a side view of the holder and sensor shown in Figure 12A. [Figure 12D] Figure 12D is a bottom view of the holder and sensor shown in Figure 12A. [Figure 12E] Figure 12E is a front view of the holder and sensor shown in Figure 12A. [Figure 12F] Figure 12F is a rear view of the holder and sensor shown in Figure 12A. [Figure 12G] Figure 12G is another perspective view of the holder and sensor shown in the second position according to the fifth embodiment. [Figure 12H] Figure 12H is another perspective view of the holder and sensor shown in the first position according to the fifth embodiment. [Figure 13A] Figure 13A is a perspective view of the holder and sensor shown in the first position according to the sixth embodiment. [Figure 13B] Figure 13B is a top view of the holder and sensor shown in Figure 13A. [Figure 13C] Figure 13C is a side view of the holder and sensor shown in Figure 13A. [Figure 13D] Figure 13D is a bottom view of the holder and sensor shown in Figure 13A. [Figure 13E] Figure 13E is a front view of the holder and sensor shown in Figure 13A. [Figure 13F] Figure 13F is a rear view of the holder and sensor shown in Figure 13A. [Figure 14A] Figure 14A is a perspective view of the holder shown in Figure 13A without the sensor. [Figure 14B] Figure 14B is a top view of the holder shown in Figure 13A without the sensor. [Figure 14C] Figure 14C is a side view of the holder shown in Figure 13A without the sensor. [Figure 14D] Figure 14D is a bottom view of the holder shown in Figure 13A without the sensor. [Figure 14E] Figure 14E is a front view of the holder shown in Figure 13A without the sensor. [Figure 14F] Figure 14F is a rear view of the holder shown in Figure 13A without the sensor. [Figure 15A]Figure 15A is a perspective view of the holder and sensor shown in the second position according to the sixth embodiment. [Figure 15B] Figure 15B is a top view of the holder and sensor shown in Figure 15A. [Figure 15C] Figure 15C is a side view of the holder and sensor shown in Figure 15A. [Figure 15D] Figure 15D is a bottom view of the holder and sensor shown in Figure 15A. [Figure 15E] Figure 15E is a front view of the holder and sensor shown in Figure 15A. [Figure 15F] Figure 15F is a rear view of the holder and sensor shown in Figure 15A. [Figure 16A] Figure 16A is a perspective view of the holder and sensor shown in the first position according to the seventh embodiment. [Figure 16B] Figure 16B is a top view of the holder and sensor shown in Figure 16A. [Figure 16C] Figure 16C is a side view of the holder and sensor shown in Figure 16A. [Figure 16D] Figure 16D is a bottom view of the holder and sensor shown in Figure 16A. [Figure 16E] Figure 16E is a front view of the holder and sensor shown in Figure 16A. [Figure 16F] Figure 16F is a rear view of the holder and sensor shown in Figure 16A. [Figure 17A] Figure 17A is a perspective view of the holder shown in Figure 16A without the sensor. [Figure 17B] Figure 17B is a top view of the holder shown in Figure 16A without the sensor. [Figure 17C] Figure 17C is a side view of the holder shown in Figure 16A without the sensor. [Figure 17D] Figure 17D is a bottom view of the holder shown in Figure 16A without the sensor. [Figure 17E] Figure 17E is a front view of the holder shown in Figure 16A without the sensor. [Figure 17F]Figure 17F is a rear view of the holder shown in Figure 16A without the sensor. [Figure 18A] Figure 18A is a perspective view of the holder and sensor shown in the second position according to the sixth embodiment. [Figure 18B] Figure 18B is a top view of the holder and sensor shown in Figure 18A. [Figure 18C] Figure 18C is a side view of the holder and sensor shown in Figure 18A. [Figure 18D] Figure 18D is a bottom view of the holder and sensor shown in Figure 18A. [Figure 18E] Figure 18E is a front view of the holder and sensor shown in Figure 18A. [Figure 18F] Figure 18F is a rear view of the holder and sensor shown in Figure 18A. [Modes for carrying out the invention]

[0025] For a more complete understanding of the components, processes, and apparatus disclosed herein, please refer to the accompanying drawings. The drawings are merely schematic representations for convenience and ease of demonstrating the disclosure and are therefore not intended to show the relative sizes or dimensions of the devices or their components, and / or to define or limit the scope of the exemplary embodiments.

[0026] In the following description, certain terms are used for clarity, but these terms are intended to refer only to specific structures of embodiments selected for illustration in the drawings and are not intended to define or limit the scope of the disclosure. In the drawings and the following description, similar numerical designations should be understood to refer to components of similar function.

[0027] The singular forms "a," "an," and "the" can refer to multiple objects unless the context clearly indicates otherwise.

[0028] As used herein, various devices and components may be described as “including” other components. The terms and variations thereof, such as “including,” “equipped,” “possess,” “may,” and “contain,” as used herein, are intended as unrestricted transitional phrases, terms, or words that do not preclude the possibility of additional components.

[0029] All ranges disclosed herein include the specified endpoints and can be combined independently (for example, the range “2 inches to 10 inches” includes the endpoints, 2 inches, 10 inches, and all intermediate values).

[0030] The approximate expressions used herein can be applied to modify quantitative expressions that may change without altering the underlying function. Therefore, values ​​modified by terms such as “approximately” or “substantially” may, in some cases, not be limited to the specified exact value. The modifier “approximately” should be considered to reveal a range defined by the absolute values ​​of two endpoints. For example, the expression “approximately 2 to approximately 4” also reveals the range “2 to 4”.

[0031] It should be noted that many of the terms used here are relative. For example, the terms "upper" and "lower" refer to relative positions; that is, the upper component is located at a higher elevation than the lower component, and should not be interpreted as requiring a specific orientation or position of the structure. As yet another example, the terms "internal," "external," "inward-facing," and "outward-facing" are center-referenced and should not be interpreted as requiring a specific orientation or position of the structure.

[0032] The terms "top" and "bottom" are relative to an absolute standard, that is, the Earth's surface. In other words, the top is always at a higher elevation relative to the Earth's surface than the bottom is.

[0033] The terms "horizontal" and "vertical" are used to indicate direction relative to an absolute standard, i.e., the height of the ground. However, these terms should not be interpreted as requiring structures to be perfectly parallel or perfectly perpendicular to one another.

[0034] In this specification, the terms “sensor” and “probe” are used interchangeably and refer to any measuring device or other device suitable for the application.

[0035] Referring here to Figures 1A through 1J, a first embodiment of the holder 10 is shown. Figures 1A, 1C, 1E, 1G, 1I, and 1J show the holder 10 supporting the sensor 100 just before the sensor is inserted into a container or container. In this position, the sensor 100 is supported and engaged by the holder 10. Figures 1B, 1D, 1F, and 1H show the holder 10 supporting the sensor 100 for sterilization such as autoclaving, where the sensor 100 is shown in an extended position and is not engaged by the holder 10 (e.g., the code 19 of the sensor 100 is not inserted into the radial groove 21), and the connector 200 (e.g., a sterile or aseptic connector) is not in a connected position. In some embodiments, the holder 10 comprises an expandable and foldable bellows 250 having an internal passage configured to receive a portion of the probe 100. In some embodiments, the foldable bellows 250 is part of an assembly having a connector 200 at one end and a probe adapter at the other end. This assembly can be wired to a support block as part of the connector end holder assembly and supported at the opposite probe end.

[0036] In the embodiments shown in Figures 1A and 1B, the holder 10 includes an L-shaped slotted member 12 having elongated support legs 13 (which may include openings 16 as a design detail to provide clearance for connectors) and slotted legs 14. The slotted legs 14 are located at one end of the support legs 13, extend perpendicularly to the support legs 13, and are spaced apart from the free end 13a on the opposite side of the support legs 13. The slots 15 of the slotted legs 14 optionally divide the slotted legs 13 longitudinally (vertically, as shown in Figures 1E and 1G). A probe support block 17 is positioned on the slotted legs 13 to assist in supporting the probe 100. The holder 10 in Figures 1A and 1B also includes a U-shaped member 20 having a base 20A and legs 20B and 20C extending perpendicularly at first and second spacings, respectively. Leg 20B may include a groove or U-shaped region 22 at its free end, shaped and positioned to receive and support the area of ​​the sensor 100, as shown in Figures 1A and 1G. For example, a curved groove. Leg 20C may include a radial groove 21, shaped and positioned to receive and support the area of ​​the probe 100, as shown in Figure 1B. Leg 20B also includes one or more projections 166 (two are shown in Figures 1A and 1C) that are received in the slot 15 of the slot leg 14, engage with the slot 15, and move within the slot 15. Thus, the slot 15 is configured to receive the projections 166, etc., for sliding engagement. The length of the slot 15 determines how far the slot leg 14 can be raised or lowered relative to leg 20B. Once the slot leg 14 is raised or lowered to the desired position, the projections 166, which are fasteners such as screws, can be tightened to fix the slot leg 14 in that position. Therefore, the legs 20B can be raised and fixed in place to engage and support the sensor 100. This allows the groove 22 to support the area of ​​the sensor 100, and the radial grooves 21 to receive a portion of the sensor 100 as shown in Figure 1A.

[0037] The sensor 100 can be connected to a port on the container 50 via a conduit 55 or the like using a suitable coupling device 200, such as an AseptiQuik® G connector commercially available from Calder Products. Other coupling devices may be used, as shown by the general-purpose coupling device 200' shown in Figures 2A (compression position sensor) and 2B (expansion position sensor 100), which are appropriately housed by the holder 10. Connection to the port on the container 50 may be made via a conduit 55 or the like (Figures 3A, 3B, 3C) that is in fluid communication with the inside of the container. Figures 3A, 3B, and 3C show a first sensor and holder assembly attached to a first conduit 55, which is in fluid communication with the internal volume of a vessel 50 via a coupling 200, such as an AseptiQuik® G connector, commercially available from Calder Products (disclosed in U.S. Patents 7,631,660 and 10,871,250, which are incorporated herein by reference), and a second sensor and holder assembly to be attached to a second conduit 55, which is in fluid communication with the internal volume of a vessel 50 via a coupling 200, such as an AseptiQuik® G connector. Other suitable connectors may also be used.

[0038] In certain embodiments, in the support positions shown in Figures 1B, 1D, 1F, and 1H, the holder 10 serves to support the probe 100 during sterilization, such as autoclaving. In this embodiment, the probe 100 is inserted into the bellows 250 and rests on the block 17 and leg 20C, with leg 20B positioned so as not to obstruct the expansion of the bellows 250 (e.g., on the underside). To deploy the probe 100, the holder 10 is activated to move the support leg 13 downward relative to the base 20A (or move the base 20A upward relative to the support leg 13), sliding the projection 166 within the slot 15 until it reaches the deployed position shown in Figures 1A, 1C, 1E, and 1G. In this position, the probe 100 is held in the arched recess 22 and groove 21, as shown in the figure, and is also supported by the block 17, and the bellows 250 is compressed as shown in the figure. Next, the assemblies can be connected by arranging them to connect to a bioreactor 50 or other container, as illustrated in Figures 3A, 3B, and 3C.

[0039] Figures 4A to 4H show a second embodiment of the holder 10' for the probe or sensor 100. Figure 4A shows the holder 10' supporting the probe 100 with the bellows 250 compressed, just before the probe is inserted into a container such as a bioreactor. In this position, the probe 100 is supported and engaged by the holder 10'. As in other embodiments, the folding bellows 250 is part of an assembly that includes a sterile connector at one end and a probe adapter at the other end. This assembly may be wired to a support block as part of the holder assembly at the connector end and supported at the opposite probe end. Figure 4B shows the holder 10' supporting the probe 100 in a flat orientation for sterilization, such as autoclaving. The probe 100 (and bellows 250) are shown in the extended position and are not engaged by the holder 10'. The legs 160b of the probe support block 17 and arm 160 function as probe supports as described below.

[0040] In this embodiment, the holder 10' includes first and second arms 130 and 160, respectively, which are pivot-connected to each other around a pin 150, etc., that defines a pivot axis. In the embodiments shown in Figures 4A and 4B, the second arm 160 is L-shaped and has an elongated main body 160a, which terminates with a leg 160b extending substantially perpendicularly. The leg 160b has a curved free end 160c, as is most commonly seen in Figures 4E and 4G, and is configured to support the probe 100 when in the position shown in Figure 4B. In the position shown in Figure 4A, the leg 160b can function as a leg or stand to support the probe 100.

[0041] To move the holder 10' from the probe support position in Figure 4B to the container probe engagement position in Figure 4A, the second arm 160 is rotated, for example, 180 degrees or approximately 180 degrees relative to the first arm 130 around the pin 150 (Figure 4I), and the leg 160b is rotated from the upward position shown in Figure 4B to the downward position below the first arm 130 as shown in Figure 4A. Next, the bellows 250 is compressed. In the position shown in Figure 4A, the leg 160b can be supported on the base material.

[0042] In some embodiments, the second arm 160 includes one or more legs 165 (two shown) extending in the opposite direction to a leg 160b that extends orthogonally, as is most commonly seen in Figures 4C, 4D, 4F, and 4G. When the holder 10' is in the position shown in Figure 4B, the one or more legs 165 serve to support the holder (and probe 100) on the substrate in order to engage the probe 100 with a container such as a bioreactor.

[0043] The sensor 100 can be connected to a port on the container 50 via a conduit 55 or the like using a suitable coupling device 200 such as AseptiQuik® G. Other coupling devices can also be used, as shown in the common coupling device 200' shown in Figures 5A (compression position sensor) and 5B (expansion position sensor).

[0044] Figure 6A shows a third embodiment of the sensor holder 10”. In the support positions shown in Figures 6B, 6D, 6F, 6H, 6I, and 6J, the holder 10”. serves to support the probe 100 during sterilization, such as autoclaving. In this position, the bellows 250 is extended and exposed, as best shown in Figures 6B and 6D. As in the other embodiments, the foldable bellows 250 is part of an assembly that includes a sterile connector at one end and a probe adapter at the other end. This assembly is wired to a support block as part of the holder assembly at the connector end and supported at the opposite probe end. The holder 10" comprises a body 610 and a sleeve 620. The body 610 and the sleeve 620 are slidable relative to each other by linear movement or the like between a first position shown in Figure 6B and a second position shown in Figure 6A. In some embodiments, the sleeve 620 comprises a curved profile 605, a bore 604, and a base 621 wider than the body 610 (Figure 6I), so that the body can move linearly relative to the arm 610 and move in and out of the sleeve 620. For example, the body 610 may have an elongated groove or slot 615 on the opposite side of the body, which is positioned and dimensioned to receive a corresponding tongue-shaped portion, rib, or projection 625 on the opposite side of the sleeve 620 (e.g., a tongue-shaped portion and groove structure). The rib 625 is slidable within its respective slot 615. Alternatively, the body 610 may have ribs and the sleeve 620 may have slots. The body 610 is provided with a through hole or bore 611 configured to receive a portion of the probe 100, as shown in the figure.

[0045] To deploy the probe 100, once the probe 100 is positioned in the holder 10”, the holder 10” is operated by sliding the body 610 against the sleeve 620 (for example, in the direction of arrow 603), so that the sleeve 610 accepts the free end of the body 610 and covers or surrounds and protects the compressed bellows 250, as shown in Figures 6A and 6C. The probe 100 can be connected to a port on the container 50 via a conduit 55 or the like using a suitable coupling device 200 (for example, an AseptiQuik® G connector commercially available from Calder Products). Other coupling devices can also be used, as shown in the general-purpose coupling device 200' in Figure 7.

[0046] Figure 8A shows a fourth embodiment of the sensor holder 10'''. In the support positions shown in Figures 8B, 8D, 8F, and 8H, the holder 10''' serves to support the probe 100 during sterilization, such as autoclaving. In this position, the bellows 250 is extended, as best shown in Figures 8B and 8D. As in the other embodiments, the foldable bellows 250 is part of an assembly that includes a sterile connector at one end and a probe adapter at the other end. This assembly may be wired to a support block as part of the holder assembly at the connector end and supported at the opposite probe end. The holder 10'' comprises a body 810 and an arm 820. The body 810 is generally L-shaped, with an arm 811 extending perpendicularly from one end, the arm 811 having a through hole 812 for receiving the sensor 100. The side edges 813a, 813b of the body 810 (Figure 8I) are C-shaped (Figure 8E), each defining a side groove for sliding engagement of the arm 820. Thus, the body 810 and the arm 820 are slidable relative to each other between a first position shown in Figure 8B and a second position shown in Figure 8A. In certain embodiments, the arm 820 moves linearly within the side groove of the body 810.

[0047] To deploy the probe 100, once the probe 100 is positioned in the holder 10''', the holder 10''' is activated by sliding the arm 820 relative to the body 810, as shown in Figures 8A and 8C, to compress the holder 10''' (and the bellows 250). The probe 100 can be connected to a port on the container 50 via a conduit 55 or the like using a suitable coupling device 200 (for example, an AseptiQuik® G connector commercially available from Calder Products). Other coupling devices can also be used, as shown in the general-purpose coupling device 200' in Figure 9.

[0048] In some embodiments, the holder is shipped with the bellows and sterile connector assembled, and the user screws in the selected sensor. After assembling the sensor into the holder, the assembly can be sterilized in an autoclave or the like. After sterilization, the user can assemble the holder assembly into the bioreactor / container 50 via the alignment cleat, and the user's hands are free to connect the sterile connector and pull the sterile barrier tab associated with the sterile connector. After the sterile connector is opened, the clamp can be removed from the tube and the sensor 100 can be pushed into the fluid in the container 50.

[0049] Figures 10–12 (for example, Figures 10A, 10B, 10C, 10D, 10E, 10F, 11A, 11B, 11C, 11D, 11E, 11F, 12A, 12B, 12C, 12D, 12E, 12F, 12G, and 12H) show a fifth embodiment of the sensor holder 1000. This sensor holder 1000 is suitable for use in MAST (Modular Automated Sampling Technology), for example, in sterile bioreactor sampling. As shown in Figures 10A and 12H, the holder 1000 comprises a base 1201 and an elongated member 1200 having channels 1203 defined by elongated side walls 1202A, 1202B opposite to the base, and the base having slots 1205. The movable block 1210 is located within a channel and includes a component (not shown) such as a peg, which is positioned in a slot and can be engaged by a locking knob 1211, allowing the base to be fixed in a desired position within the channel by acting on the locking knob 1211. In certain embodiments, the peg and the locking knob 1211 are screw-engaged, and relative rotation of the locking knob and the peg or the other component either fixes the block 1210 in a predetermined position within the holder's channel or unlocks the block. In certain embodiments, the block 1210 may include two spaced-apart fixing pins 1212A, 1212B extending upward from the block (arranged and configured to receive corresponding openings 1213A, 1213B (Figure 12A) within the automatic sampler body 1300 when the automatic sampler body 1300 is thus positioned and moves with the block). In certain embodiments, the holder 1000 also includes a support member 1220 shaped to receive and support the area of ​​the sensor as shown in the figure, and having a U-shaped or arched groove or notch 1220' at its positioned free end.

[0050] In some embodiments, the holder 1000 comprises an expandable and foldable bellows 2500 having an internal passage configured to receive a portion of the probe 100. In some embodiments, the foldable bellows 2500 is part of an assembly that includes a connector at one end and a probe adapter at the other end. This assembly may be wired to a support block as part of the holder assembly at the connector end and supported at the opposite probe end.

[0051] In certain embodiments, the holder 1000 supports the probe 100 during sterilization, such as autoclaving, in the support position shown in Figures 12A-12G (Figure 12A shows the deployed position with the autosampler body 1300 detached from pins 1212A and 1212B). In this embodiment, the probe 100 is inserted into the bellows 2500, and the assembly rests on the block 1210 and support member 1220. To deploy the probe 100, the holder 1000 is activated to move the block 1210 linearly within the slot 1205 of the channel 1203 to the deployed position shown in Figures 10A-10F and 12H. In this position, the probe 100 is held in the arc-shaped recess 1220' as shown in the figure, and is also supported by the block 1210, and the bellows 2500 is compressed as shown in the figure. The probe can be locked in this position by tightening the lock knob 1211. Next, the assembly can be joined by placing it in a bioreactor or other container for such joining.

[0052] Figures 13–15 (for example, Figures 13A, 13B, 13C, 13D, 13E, 13F, 14A, 14B, 14C, 14D, 14E, 14F, 15A, 15B, 15C, 15D, 15E, 15F) show a sixth embodiment of the sensor holder 2000, particularly suitable for pH / DO / VCD / pCO2 sensors. This embodiment is similar to the fifth embodiment in Figures 10–12, except that a movable U-shaped holder 2210 is present instead of the movable block 1210. In certain embodiments, the U-shaped holder 2210 has a U-shaped or arched groove or notch 2210' at its free end, having a shape similar to the groove or notch 1220', as is most commonly seen in Figures 14E and 14F, and is shaped and positioned to receive and support the area of ​​the sensor, as shown, for example, in Figure 15A. Similar to the fifth embodiment, the holder 2000 comprises an elongated member 1200 including a base 1201 and a channel 1203 defined by opposing elongated side walls 1202A, 1202B, the base comprising a slot 1205.

[0053] In certain embodiments, the holder 2000 supports the probe 100 during sterilization, such as during autoclaving, in the support positions shown in Figures 15A-15F. In this embodiment, the probe 100 is inserted through the bellows 2500, and the assembly rests on the U-shaped holder 2210 and the support member 1220. To deploy the probe 100, the holder 2000 is activated to move the block U-shaped holder 2210 linearly within the slot 1205 of the channel 1203 until it reaches the deployed position shown in Figure 13A. In this position, the probe 100 is held within the arc-shaped recesses 1220' and 2210' as shown in the figure, and the bellows 2500 is compressed as shown in the figure. The probe can be locked in this position by tightening the lock knob 1211. Thus, the block U-shaped holder 2210 can slide back and forth within the slot 1205 in the direction of arrow 2215 in Figure 14A. The assembly can then be coupled to a bioreactor or other container by arranging it for such coupling, as in the previous embodiments.

[0054] Figures 16–18 (for example, Figures 16A, 16B, 16C, 16D, 16E, 16F, 17A, 17B, 17C, 17D, 17E, 17F, 18A, 18B, 18C, 18D, 18E, 18F) show a seventh embodiment of a sensor holder 3000 particularly suited for Raman spectroscopy, such as a Raman ProCellics® analyzer or sensor used as a tool for inline and real-time process analysis in bioprocesses. This embodiment is similar to the sixth embodiment in Figures 13–15, but with the addition of a clamp assembly 3100 associated with a linearly movable member 3200. In certain embodiments, the U-shaped holder 2210 has a U-shaped or arched groove or notch 2210' at its free end, having a shape similar to that of the groove or notch 1220', as is most commonly seen in Figures 17E and 17F, and is shaped and positioned to receive and support the area of ​​the sensor, for example, as shown in Figure 18A. In certain embodiments, in the support position shown in Figures 18A-18F, the holder 3000 plays a role in supporting the probe 100 during sterilization, such as during autoclaving. In this embodiment, the probe 100 is inserted through the bellows 2500, and the assembly rests on the U-shaped holder 2210 and the support member 1220. It is also held in place by a clamp assembly 3100. This clamp assembly 3100 is also generally U-shaped in the illustrated embodiment and includes a lock bar 3110 that crosses the U-shaped opening when in the illustrated locked position. In certain embodiments, the lock bar 3100 is rotatable on the free end 3101 of the U-shaped clamp assembly 3100, insertable into an open slot at the other free end 3102 of the clamp assembly 3100, and can be locked in place by a lock knob 3105. In certain embodiments, the vertical position of the clamp assembly 3100 can be changed by sliding the clamp assembly vertically within the slot 3300 and locking it in the desired position using the lock knob 3301. To deploy the probe 100, the holder 3000 is activated to move the block U-shaped holder 2210 linearly within the channel 1203 to the deployed position shown in Figure 16A.In this position, the probe 100 is held by the clamp assembly 3100 in the arc-shaped recesses 1220' and 2210' as shown in the figure, and the bellows 2500 is compressed as shown in the figure. The probe can be locked in this position by tightening the lock knob 1211. The assembly can then be coupled to a bioreactor or other container by placing it for such coupling.

[0055] The sensor 100 can be connected to a port on the container 50 via a conduit 55 or the like using a suitable coupling device 200, such as an AseptiQuik® G connector, which is commercially available from Calder Products, Inc., as in the embodiments described above.

Claims

1. A probe holder for positioning and holding a probe for engaging with a container, wherein the probe has a longitudinal axis and is longitudinally extendable between a compressed position and an extended position, and the holder includes a first movable member and a second movable member, the first and second movable members being movable relative to each other and configured to support the probe in the extended position and to engage with the probe in the compressed position.

2. The probe holder according to claim 1, wherein the first and second movable members are linearly movable in the direction of the longitudinal axis.

3. The probe holder according to claim 1, wherein the first and second movable members are movable so as to be rotatable about a pivot axis perpendicular to the longitudinal axis.

4. The probe holder according to claim 1, further comprising an expandable and foldable bellows having a passage configured to receive the probe.

5. The probe holder according to claim 4, wherein the first movable member protects the expandable and foldable bellows when the expandable and foldable bellows are in a folded state.

6. The probe holder according to claim 1, further comprising a sterile connector.

7. The probe holder according to claim 1, wherein the first movable member slides within a slot or groove of the second movable member.

8. The probe holder according to claim 1, wherein the first and second movable members are supported on a base.

9. The probe holder according to claim 8, further comprising elongated side walls, which are positioned opposite and spaced apart, and which define a channel together with the base.

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