Multi-use sensor holder

Abstract

A probe holder for a bioreactor or other container or vessel functions as a base platform or support to hold a sensor or probe (e.g., a Raman probe) in its open position for sterilization as part of an assembly comprising the sensor, such as a Raman probe, in its open position. The sensor is attached to a housing or container with a clean connector. The holder assists a user in positioning the sensor or probe at least partially within or in fluid communication with the interior of a bioreactor or vessel, and holds and / or locks it in place during use of the sensor or probe.

Description

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

[0002] This disclosure relates to the measurement of fluid properties. More particularly, embodiments of this disclosure relate to holders and housings for probes and / or sensors for measuring fluids within bioreactors, biocontainers, or other vessels. BACKGROUND ART

[0003] Cell cultures have been used for many years in life science and biopharmaceutical research and production. Cell culture systems rely on a controlled environment for cell maintenance, growth, expansion, and testing. Despite often taking strict measures to avoid outbreaks such as contamination (e.g., fungal or bacterial contamination), such outbreaks still occur, often with the effect of damaging weeks of research and halting operations for days or weeks. At the very least, due to inconsistencies in basic cell culture, cell physiology undergoes unexpected changes, thus distorting the results of cell culture experiments. Researchers must vigilantly monitor and evaluate cell health by visually observing subtle changes in cell morphology, growth patterns, and growth rates, which may indicate problems with a particular culture.

[0004] Researchers culturing mammalian cells often find that the maintenance of cell cultures is a very time-consuming task. Care must be taken to address actions and other issues such as visually assessing the health of cells by determining cell morphology under a microscope, changing the culture medium (feeding), resuscitating cells (confluency), dealing with contamination, monitoring metabolites, or cell interactions.

[0005] Unfortunately, in a modern laboratory environment, there are many obstacles to the proper monitoring of cultured cells. For example, performing continuous (e.g., every 2 - 4 hours) manual inspections of cell cultures may be impractical and cost-prohibitive. In addition, continuously manually monitoring cell cultures generally takes a physical and mental toll on researchers, leading to a decline in overall quality of life and increasing the likelihood of observation errors due to excessive fatigue. Moreover, fully automated cell culture monitoring systems are overly cumbersome and complex and require a large capital investment.

[0006] In addition, a simple visual inspection of cells only provides a subjective assessment without a permanent visual record or archive. Signs of problems with cells and cell cultures may be missed, resulting in a serious detrimental impact on the quality of data generated from cell-based experiments. In today's competitive multinational biologic and biopharmaceutical industries, the ability to supply healthy live cell cultures is an increasingly serious issue.

[0007] A variety of sensors can be used with bioreactors, biocontainers, mixers, and other vessels (such as disposable bags, etc.), which may require or benefit from the measurement of various parameters inside the bioreactor mixer or vessel, such as dissolved oxygen content, pH, CO 2 content, glucose content, turbidity, viable cell density, etc. Considering the small sample size passing through discrete, low-flow regions, in-situ measurement of the physical properties of fluids may introduce other differences, which may not be representative of a larger volume. A bioprocessing system may include conduits, which are typically part of a closed system through which fluid flows, and similar sampling problems also occur when sampling through such conduits.

[0008] In some bioprocessing, such as monoclonal antibodies, capsids, cell lines, inline virus inactivation treatment, etc., measurements are made inside the tank (e.g., static measurements) or in the fluid flow through the conduit (e.g., several liters per minute). In addition, in some cases, measurements can also be performed on samples extracted after the finished product or a specific sub-operation is completed. Sampling can be another medium for introducing unwanted contaminants into the process. All of the above represent problems that need to be overcome for processors attempting to measure the properties of biological fluids.

[0009] More recently, the trend in bioprocessing has been towards providing continuous processing, i.e., intensified processing, where the biological fluid from one process is introduced into a separate process, which poses further challenges for sampling, measurement, and process monitoring. Process control is particularly challenging for intensified processing.

[0010] Process control in the harsh conditions of continuous processing requires at least the development of new sensors or the integration of existing probes and sensors in new ways, where reliable and accurate data collection is ensured while meeting updated requirements, i.e., the fast response time of inline flow continuous processing. Such measurements typically require large probes. The response time is a function of the kinetics of chemical / biological processes, which are generally slower than mechanical processes. This explains the complexity of measuring, for example, conductivity or pH compared to sensing the pressure of a fluid.

[0011] Recent technologies have attempted to use existing probes and sensors to measure pH, viable cell density (VCD), conductivity, turbidity, dissolved oxygen, and temperature to optimize and improve their accuracy, reliability, and stability in long-term processing trials. The placement of sensors in the process is also an important factor.

[0012] A probe holder represents an advancement in the art. The probe holder operates as a platform to hold a sensor in an open position for sterilization (e.g., via autoclave, gamma rays, or ethylene oxide (ETO)) as part of an assembly that includes a sensor attached to a housing having a connector (e.g., a clean connector); the probe holder operates as a holder to semi-permanently attach to a bioreactor, biocontainer, or vessel, which aids the user in making a sterile connection and which aids the user in placing and holding the sensor in a proper position within the bioreactor, biocontainer, or vessel during use of the sensor.

[0013] It would be desirable to provide such a holder having one or more functions to help meet this benefit. SUMMARY OF THE INVENTION

[0014] Problems of the prior art have been solved by the embodiments disclosed herein, which include a sensor or probe holder for a bioreactor or other container or vessel. In some embodiments, a probe holder for positioning and holding a probe for engagement with a container is disclosed, the probe having a longitudinal axis and being capable of extending between a compressed position and an extended position in a longitudinal direction, the holder including a first displaceable member and a second displaceable member, the first and second displaceable members being displaceable relative to each other and configured to support the probe in the extended position and engage the probe in the compressed position. In some embodiments, the holder functions as a base platform or bracket to hold a sensor or probe in an open position for sterilization (e.g., via autoclave, gamma rays, or ETO) as part of an assembly that includes the sensor attached to a housing or container with a clean connector. In some embodiments, the holder serves as a holder to position and semi-permanently attach a sensor or probe to a bioreactor, mixer, or vessel, thereby aiding the user in making a sterile connection more easily. In some embodiments, the holder aids the user in positioning the sensor or probe at least partially within a bioreactor or vessel or in fluid communication with the interior of a bioreactor or vessel and in holding and / or locking it in place during use of the sensor or probe. In some embodiments, when properly positioned by the holder, a portion of the sensor or probe physically contacts the contents of the bioreactor, mixer, or vessel, enabling 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 (i.e., removably) fixes the sensor or probe to a bioreactor, container, or vessel. In some embodiments, the probe is a Raman probe.

[0015] In some embodiments, the probe holder is designed to perform in-situ and in-embedded measurements. The embodiments described herein include a holder that supports and holds a sensor or probe in place during autoclaving or other sterilization of the entire assembly. The holder allows the user to position the assembly in place before aligning and engaging a connector (e.g., a sterile connector). During processing and / or measuring a sample in a container such as a bioreactor, the holder locks and holds the sensor or probe in place. The holder can be shipped assembled with a bellows and a sterile connector, where the user matches a selected sensor thereto. The bellows (if any) can be expandable and collapsible and protects the sensor from damage, etc. by surrounding the sensor or probe. After assembling the sensor or probe to the holder, the assembly can be sterilized. After sterilization, the user coordinates the holder assembly with the bioreactor / biological container / vessel. Then, the user can connect the sterile connector and, for example, optionally remove a sterile septum. After opening the sterile connector, fluid can be introduced into the bioreactor / biological container / vessel and its parameters can be measured with the sensor or probe.

[0016] In some embodiments, the first and second displaceable members are capable of linear displacement in the direction of the longitudinal axis.

[0017] In some embodiments, the first and second displaceable members are capable of pivotal displacement about a pivot axis orthogonal to the longitudinal axis.

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

[0019] In some embodiments, the first displaceable member protects the expandable and collapsible bellows when the expandable and collapsible bellows is in a collapsed state.

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

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

[0022] In some embodiments, disclosed is a probe holder for positioning and holding a probe for engagement with a container, the probe having a longitudinal axis and being capable of extending in a longitudinal direction between a compressed position and an extended position, the holder including a base with a slot, a displaceable member, and a support member, the displaceable member being capable of displacing relative to the support member in the base with the slot. In some embodiments, the displaceable member includes a movable block that can be locked in the base. In some embodiments, the displaceable member is U-shaped. In some embodiments, the probe holder includes a clamp assembly having a U-shaped recess and a locking rod that can be positioned to pass through the U-shaped recess. In some embodiments, the clamp assembly has a first free end and a second free end that define the U-shaped recess therebetween, and the locking rod can pivot on the first free end. In some embodiments, the base with the slot has two relatively spaced elongated side walls that define a channel therebetween. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The embodiments disclosed herein may take the form of various components and arrangements of components and various processing operations and arrangements of processing operations. The drawings are for illustrative purposes only of the preferred embodiments and should not be construed as limiting. This disclosure includes the following drawings.

[0024] Figure 1A is a perspective view of the holder shown in a first position according to a first embodiment;

[0025] Figure 1B is a perspective view of the holder shown in a second position according to a first embodiment;

[0026] Figure 1C is a side view of the holder shown in a first position according to a first embodiment;

[0027] Figure 1D is a side view of the holder shown in a second position according to a first embodiment;

[0028] Figure 1E is a front view of the holder shown in a first position according to a first embodiment;

[0029] Figure 1F is a front view of the holder shown in a second position according to a first embodiment;

[0030] Figure 1G is a rear view of the holder shown in a first position according to a first embodiment;

[0031] Figure 1HIs a rear view of the retainer shown in the second position according to the first embodiment;

[0032] Figure 1I Is a top view of the retainer shown in the first position according to the first embodiment;

[0033] Figure 1J Is a bottom view of the retainer shown in the first position according to the first embodiment;

[0034] Figure 2A Is a perspective view of the retainer shown in the first position according to the first embodiment, including a universal coupling device;

[0035] Figure 2B Is a perspective view of the retainer shown in the second position according to the first embodiment, including a universal coupling device;

[0036] Figure 3A Is a top view of the container, showing the retainer of FIG. 1 according to the first embodiment coupled to its port, and another retainer of FIG. 1 positioned to be coupled to its other port;

[0037] Figure 3B Is Figure 3A The first perspective view of the container;

[0038] Figure 3C Is Figure 3A The second perspective view of the container;

[0039] Figure 4A Is a perspective view of the retainer shown in the first position according to the second embodiment;

[0040] Figure 4B Is a perspective view of the retainer shown in the second position according to the second embodiment;

[0041] Figure 4C Is a side view of the retainer shown in the first position according to the second embodiment;

[0042] Figure 4D Is a side view of the retainer shown in the second position according to the second embodiment;

[0043] Figure 4E Is a front view of the retainer shown in the first position according to the second embodiment;

[0044] Figure 4F Is a front view of the retainer shown in the second position according to the second embodiment;

[0045] Figure 4GRear view of the retainer shown in the first position according to the second embodiment;

[0046] Figure 4H Rear view of the retainer shown in the second position according to the second embodiment;

[0047] Figure 4I Side view of the retainer shown in the intermediate position according to the second embodiment;

[0048] Figure 5A Perspective view of the retainer shown in the first position according to the second embodiment, including a universal coupling device;

[0049] Figure 5B Perspective view of the retainer shown in the second position according to the second embodiment, including a universal coupling device;

[0050] Figure 6A Perspective view of the retainer shown in the first position according to the third embodiment;

[0051] Figure 6B Perspective view of the retainer shown in the second position according to the third embodiment;

[0052] Figure 6C Side view of the retainer shown in the first position according to the third embodiment;

[0053] Figure 6D Side view of the retainer shown in the second position according to the third embodiment;

[0054] Figure 6E Front view of the retainer shown in the first position according to the third embodiment;

[0055] Figure 6F Front view of the retainer shown in the second position according to the third embodiment;

[0056] Figure 6G Rear view of the retainer shown in the first position according to the third embodiment;

[0057] Figure 6H Rear view of the retainer shown in the second position according to the third embodiment;

[0058] Figure 6I Bottom view of the retainer shown in the second position according to the third embodiment;

[0059] Figure 6J Top view of the retainer shown in the second position according to the third embodiment;

[0060] Figure 7 is a perspective view showing, according to the third embodiment, Figure 6B a retainer of which is coupled to its port, and another Figure 6B retainer of which is positioned to be coupled to its other port;

[0061] Figure 8A is a perspective view of a retainer shown in a first position according to the fourth embodiment;

[0062] Figure 8B is a perspective view of a retainer shown in a second position according to the fourth embodiment;

[0063] Figure 8C is a side view of a retainer shown in a first position according to the fourth embodiment;

[0064] Figure 8D is a side view of a retainer shown in a second position according to the fourth embodiment;

[0065] Figure 8E is a front view of a retainer shown in a first position according to the fourth embodiment;

[0066] Figure 8F is a front view of a retainer shown in a second position according to the fourth embodiment;

[0067] Figure 8G is a rear view of a retainer shown in a first position according to the fourth embodiment;

[0068] Figure 8H is a rear view of a retainer shown in a second position according to the fourth embodiment;

[0069] Figure 8I is a top view of a retainer shown in a second position according to the fourth embodiment;

[0070] Figure 9 is a perspective view showing, according to the fourth embodiment, Figure 8B a retainer of which is coupled to its port, and another Figure 8A retainer of which is positioned to be coupled to its other port;

[0071] Figure 10A is a perspective view of a retainer and a sensor shown in a first position according to the fifth embodiment;

[0072] Figure 10B is Figure 10A a top view of a retainer and a sensor;

[0073] Figure 10C isFigure 10A Side view of the retainer and the sensor;

[0074] Figure 10D is Figure 10A Bottom view of the retainer and the sensor;

[0075] Figure 10E is Figure 10A Front view of the retainer and the sensor;

[0076] Figure 10F is Figure 10A Rear view of the retainer and the sensor;

[0077] Figure 11A is Figure 10A Perspective view of the retainer shown without the sensor;

[0078] Figure 11B is Figure 10A Top view of the retainer shown without the sensor;

[0079] Figure 11C is Figure 10A Side view of the retainer shown without the sensor;

[0080] Figure 11D is Figure 10A Bottom view of the retainer shown without the sensor;

[0081] Figure 11E is Figure 10A Front view of the retainer shown without the sensor;

[0082] Figure 11F is Figure 10A Rear view of the retainer shown without the sensor;

[0083] Figure 12A Perspective view of the retainer and the sensor shown in the second position according to the fifth embodiment;

[0084] Figure 12B is Figure 12A Top view of the retainer and the sensor;

[0085] Figure 12C is Figure 12A Side view of the retainer and the sensor;

[0086] Figure 12D is Figure 12A Bottom view of the retainer and the sensor;

[0087] Figure 12E is Figure 12AFront view of the retainer and sensor;

[0088] Figure 12F is Figure 12A Rear view of the retainer and sensor;

[0089] Figure 12G Another perspective view of the retainer and sensor shown in the second position according to the fifth embodiment;

[0090] Figure 12H Another perspective view of the retainer and sensor shown in the first position according to the fifth embodiment;

[0091] Figure 13A Perspective view of the retainer and sensor shown in the first position according to the sixth embodiment;

[0092] Figure 13B is Figure 13A Top view of the retainer and sensor;

[0093] Figure 13C is Figure 13A Side view of the retainer and sensor;

[0094] Figure 13D is Figure 13A Bottom view of the retainer and sensor;

[0095] Figure 13E is Figure 13A Front view of the retainer and sensor;

[0096] Figure 13F is Figure 13A Rear view of the retainer and sensor;

[0097] Figure 14A is Figure 13A Perspective view of the retainer shown without the sensor;

[0098] Figure 14B is Figure 13A Top view of the retainer shown without the sensor;

[0099] Figure 14C is Figure 13A Side view of the retainer shown without the sensor;

[0100] Figure 14D is Figure 13A Bottom view of the retainer shown without the sensor;

[0101] Figure 14E is Figure 13AFront view of the retainer, shown without the sensor;

[0102] Figure 14F is Figure 13A Rear view of the retainer, shown without the sensor;

[0103] Figure 15A Perspective view of the retainer and sensor shown in the second position according to the sixth embodiment;

[0104] Figure 15B is Figure 15A Top view of the retainer and sensor;

[0105] Figure 15C is Figure 15A Side view of the retainer and sensor;

[0106] Figure 15D is Figure 15A Bottom view of the retainer and sensor;

[0107] Figure 15E is Figure 15A Front view of the retainer and sensor;

[0108] Figure 15F is Figure 15A Rear view of the retainer and sensor;

[0109] Figure 16A Perspective view of the retainer and sensor shown in the first position according to the seventh embodiment;

[0110] Figure 16B is Figure 16A Top view of the retainer and sensor;

[0111] Figure 16C is Figure 16A Side view of the retainer and sensor;

[0112] Figure 16D is Figure 16A Bottom view of the retainer and sensor;

[0113] Figure 16E is Figure 16A Front view of the retainer and sensor;

[0114] Figure 16F is Figure 16A Rear view of the retainer and sensor;

[0115] Figure 17A is Figure 16A Perspective view of the retainer, shown without the sensor;

[0116] Figure 17B is Figure 16A a top view of the retainer of

[0117] Figure 17C is Figure 16A a side view of the retainer of

[0118] Figure 17D is Figure 16A a bottom view of the retainer of

[0119] Figure 17E is Figure 16A a front view of the retainer of

[0120] Figure 17F is Figure 16A a rear view of the retainer of

[0121] Figure 18A is a perspective view of the retainer and sensor shown in the second position according to the sixth embodiment;

[0122] Figure 18B is Figure 18A a top view of the retainer and sensor of

[0123] Figure 18C is Figure 18A a side view of the retainer and sensor of

[0124] Figure 18D is Figure 18A a bottom view of the retainer and sensor of

[0125] Figure 18E is Figure 18A a front view of the retainer and sensor of

[0126] Figure 18F is Figure 18A a rear view of the retainer and sensor of DETAILED DESCRIPTION

[0127] A more complete understanding of the components, processes, and devices disclosed herein can be obtained by reference to the accompanying drawings. The drawings are merely schematic representations for convenience and ease of demonstrating the present disclosure and are therefore not intended to indicate the relative sizes and dimensions of the device or its components, and / or to define or limit the scope of the exemplary embodiments.

[0128] Although specific terms are used in the following description for clarity, these terms refer only to the specific structures of the selected embodiments for illustration in the drawings and are not intended to limit or restrict the scope of the present disclosure. In the following drawings and the following description, it should be understood that the same numerical designations refer to components having the same functions.

[0129] The singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0130] As used in the specification, various devices and components may be described as "including" other components. The terms "including", "comprising", "having", "has", "can", "containing", and their variants as used herein are intended as open transitional phrases, terms, or words that do not exclude the possibility of using other components.

[0131] All ranges disclosed herein include the stated endpoints and can be combined independently (e.g., a range of "from 2 inches to 10 inches" includes the endpoints 2 inches and 10 inches and all intermediate values).

[0132] As used herein, approximating language may be used to modify any quantitative representation that may vary without resulting in a change in the basic function associated with it. Accordingly, in some cases, a value modified by one or more terms (such as "about" and "substantially") may not be limited to the specified exact value. The modifier "about" should also be considered to disclose the range defined by the absolute values of the two endpoints. For example, the expression "from about 2 to about 4" also discloses the range "from 2 to 4".

[0133] It should be noted that many of the terms used herein are relative terms. For example, the terms "upper" and "lower" are relative to each other in position, i.e., the upper component is positioned at a higher height than the lower component, and should not be construed as requiring a specific orientation or position of the structure. For another example, the terms "inner", "outer", "inward", and "outward" are relative to the center and should not be construed as requiring a specific orientation or position of the structure.

[0134] The terms "top" and "bottom" are relative to an absolute reference (i.e., the earth's surface). In other words, facing the earth's surface, the top position is always positioned at a higher height than the bottom position.

[0135] The terms "horizontal" and "vertical" are used to indicate directions relative to an absolute reference (i.e., the ground level). However, these terms should not be construed as requiring the structures to be absolutely parallel or perpendicular to each other.

[0136] The terms "sensor" and "probe" are used interchangeably herein and refer to any measuring or other device suitable for the present application.

[0137] Now, looking at Figures 1A to 1J , a first embodiment of the retainer 10 is shown. Figure 1A , 1C , 1E, 1G, 1I, and 1J depict the retainer 10 supporting the sensor 100 just before the sensor 100 is to be inserted into a container or vessel. In this position, the sensor 100 is supported and engaged by the retainer 10. Figure 1B , 1D , 1F, and 1H show the retainer 10 supporting the sensor 100, for example, for sterilization (e.g., autoclaving), where the sensor 100 is shown in an extended position and not engaged by the retainer 10 (e.g., the wire 19 of the sensor 100 is not inserted into the radial groove 21), and the connector 200 (e.g., a sterile or clean connector) is not in a connected position. In some embodiments, the retainer 10 includes a deployable and collapsible bellows 250 having an internal passageway configured to receive a portion of the probe 100. In some embodiments, the collapsible bellows 250 is part of an assembly that includes a connector 200 at one end and a probe adapter at the other end. This assembly can be wired at the connector end to a support block that is part of the retainer assembly and supported at the opposite probe end.

[0138] In Figure 1A and 1B the embodiment shown, the retainer 10 includes an L-shaped slotted member 12 having an elongate support leg 13 (which may include an aperture 16 as a design detail to allow clearance for a connector) and a slotted leg 14. The slotted leg 14 extends orthogonally at one end of the support leg 13 and is spaced from the opposite free end 13a of the support leg 13. The slot 15 in the slotted leg 14 optionally bisects the slotted leg 13 in the longitudinal direction (vertically, as Figure 1E and 1G depicted). A probe support block 17 is located on the slotted leg 13 to assist in supporting the probe 100. Figure 1A and 1B The retainer 10 also includes a U-shaped member 20 having a base 20A and respective first and second spaced-apart orthogonally extending legs 20B and 20C. Leg 20B may include a groove or U-shaped region 22 at its free end, which is shaped and positioned to receive and support a region of the sensor 100 as shown in Figure 1A and 1G , e.g., an arcuate groove. Leg 20C may include a radial groove 21, which is shaped and positioned to receive and support as shown in Figure 1BA region of the probe 100 as shown. Leg 20B also includes one or more prongs 166 ( Figure 1A and 1C two are shown in), which are received by, engaged with, and move within the slot 15 of the slotted leg 14. Thus, the slot 15 is configured to receive one or more prongs 166, etc. for sliding engagement. The length of the slot 15 determines the degree to which the slotted leg 14 can be raised or lowered relative to leg 20B. When raising or lowering the slotted leg 14 to its desired position, one or more prongs 166, which can be fasteners (such as screws), can be tightened to fix the slotted leg 14 in that position. Accordingly, to engage and support the sensor 100, leg 20B can be raised and fixed in place, whereby the recess 22 supports a region of the sensor 100, and the radial recess 21 receives a portion of the sensor 100, as Figure 1A shown in.

[0139] The sensor 100 can be connected to a port of the container 50 via a conduit 55, etc. using a suitable coupling device 200 (such as a G connector commercially available from Colder Products Company). Other coupling devices can also be used, such as illustrated by the universal coupling device 200' in Figure 2A (sensor in the compressed position) and Figure 2B (sensor 100 in the extended position), which is suitably received by the retainer 10. The connection to the container 50 port can be made via a conduit 55, etc. ( Figure 3A 、 3B 、3C) that is in fluid communication with the interior of the container. Figure 3A 、 3B 、3C show a first sensor and retainer assembly and a second sensor and retainer assembly. The first sensor and retainer assembly is attached via a coupler 200 to a first conduit 55 that is in fluid communication with the interior volume of the container 50. The coupler 200 is, for example, a G connector, such as disclosed in U.S. Patent Nos. 7,631,660 and 10,871,250, the disclosures of which are incorporated herein by reference. The second sensor and retainer assembly is to be attached via a coupler 200 to a second conduit 55 that is in fluid communication with the interior volume of the container 50. The coupler 200 is, for example, a G connector. Other suitable connectors can also be used.

[0140] In certain embodiments, in Figure 1B 、 1D, in its support positions shown in 1F and 1H, the retainer 10 serves to support the probe 100 during sterilization (e.g., autoclaving). In this embodiment, the probe 100 is inserted through the bellows 250 and rests against the block 17 and the leg 20C, and the leg 20B is positioned so as not to obstruct the bellows 250 (e.g., beneath it), such that its deployment is not interfered with. To deploy the probe 100, the retainer 10 is actuated such that as the cam head 166 slides in the slot 15, the support leg 13 moves downward relative to the base 20A (or the base 20A moves upward relative to the support leg 13) until reaching Figure 1A , 1C , the deployment positions of 1E and 1G. In this position, the probe 100 is held in the arcuate recess 22 and the groove 21 as shown, and is also supported by the block 17, and the bellows 250 is in a compressed state as shown. Then, the assembly can be coupled to the bioreactor 50 or other container by positioning the assembly to facilitate coupling as exemplified in Figure 3A , 3B and 3C.

[0141] Figures 4A to 4H illustrates a second embodiment of the retainer 10' for the probe or sensor 100. Figure 4A depicts the retainer 10' supporting the probe 100 with the bellows 250 in a compressed state just prior to the probe being inserted into a container or vessel such as a bioreactor. In this position, the probe 100 is supported and engaged by the retainer 10'. As in other embodiments, the collapsible bellows 250 is part of an assembly that includes a clean connector at one end and a probe adapter at the other end. This assembly can be wired at the connector end to a support block that is part of the retainer assembly and is supported at the opposite probe end. Figure 4B shows the retainer 10' supporting the probe 100 in a horizontal orientation, e.g., for sterilization (e.g., autoclaving), where the probe 100 (and the bellows 250) is shown in an extended position and not engaged by the retainer 10'. As described below, the probe support block 17 and the leg 160b of the arm 160 serve as probe supports.

[0142] In this embodiment, the retainer 10' includes respective first and second arms 130, 160 that are pivotally connected together about a pin 150 etc. that defines a pivot axis. In Figure 4A and 4B the illustrated embodiment, the second arm 160 is L-shaped, having an elongate main portion 160a that terminates in a leg 160b that extends generally orthogonally. The leg 160b has a Figure 4E and 4GThe arcuate free end 160c, which is most visible, is configured to support the probe 100 when in the Figure 4B position. In the Figure 4A position, the leg 160b acts as a foot or support and can support the probe 100.

[0143] To actuated the retainer 10' from its Figure 4B probe support position to its Figure 4A container probe engagement position, the second arm 160 pivots about the pin 150 relative to the first arm 130 ( Figure 4I ), e.g., 180° or about 180°, causing the leg 160b to pivot from the Figure 4B upward position shown in to the Figure 4A downward position shown below the first arm 130. Then, the bellows 250 is compressed. In the Figure 4A position, the leg 160b can be supported on the substrate.

[0144] In some embodiments, the second arm 160 includes one or more feet 165 (two are shown), which extend in a direction opposite to the orthogonally extending leg 160b, as best visible in Figure 4C , 4D , 4F, and 4G. When the retainer 10' is in the Figure 4B position shown, the one or more feet 165 serve to support the retainer (and the probe 100) on the substrate for engagement of the probe 100 with a container, such as a bioreactor.

[0145] The sensor 100 can be connected to a port of the container 50 via a conduit 55, etc., using a suitable coupling device 200 (e.g., G). Other coupling devices can also be used, as illustrated by the universal coupling device 200” shown in Figure 5A (sensor in the compressed position) and Figure 5B (sensor 100 in the extended position).

[0146] Figure 6A A third embodiment of the sensor retainer 10” is illustrated. In its Figure 6B , 6D , 6F, 6H, 6I, and 6J support positions shown, the retainer 10” serves to support the probe 100 during sterilization (e.g., autoclaving). In this position, the bellows 250 is extended and exposed, as shown in Figure 6B and 6DBest visible in. As in other embodiments, the collapsible bellows 250 is part of an assembly that includes a clean connector at one end and a probe adapter at the other end. This assembly can be wired at the connector end to a support block that is part of a holder assembly and supported at the opposite probe end. The holder 10" includes a body 610 and a sleeve 620. The body 610 and the sleeve 620 are capable of sliding relative to each other between a first position shown in Figure 6B and a second position shown in Figure 6A , for example, by sliding relative to each other by linear displacement. In some embodiments, the sleeve 620 has a curved profile 605, holes 604, and a base 621 ( Figure 6I ) that is wider than the body 610, thereby allowing the body to linearly displace relative to the arm 610 and thus slide into and out of the sleeve 620. For example, the body 610 may include elongated grooves or slots 615 on opposite sides of the body, positioned and sized to receive corresponding tongues, ribs, or protrusions 625 (such as a tongue-and-groove structure) on opposite sides of the sleeve 620. The ribs 625 can slide in the respective slots 615. Alternatively, the body 610 can have ribs and the sleeve 620 can have slots. The body 610 has a through hole or opening 611 that is configured to receive a portion of the probe 100, as shown.

[0147] To deploy the probe 100, once the probe 100 is in the holder 10", the holder 10" is actuated by sliding the body 610 relative to the sleeve 620 (e.g., in the direction of arrow 603), such that as shown in Figure 6A and 6C , the sleeve 610 receives the free end of the body 610, thereby covering or enclosing and protecting the now compressed bellows 250. The probe 100 can be connected to a port of the container 50 via a conduit 55 or the like using a suitable coupling device 200 (such as a G connector commercially available from Colder Products Company). Other coupling devices can also be used, as illustrated by the universal coupling device 200' shown in Figure 7 .

[0148] Figure 8A A fourth embodiment of the sensor holder 10" 'is shown. In its support positions shown in Figure 8B , 8D , 8F, and 8H, the holder 10" 'acts to support the probe 100 during sterilization (e.g., during autoclaving). In this position, the bellows 250 is extended, as shown in Figure 8B and 8DBest visible in. As in other embodiments, the collapsible bellows 250 is part of an assembly that includes a clean connector at one end and a probe adapter at the other end. This assembly can be wired to a support block that is part of a holder assembly at the connector end and supported at the opposite probe end. The holder 10”' includes a body 810 and an arm 820. The body 810 is generally L-shaped, having an arm 811 that extends orthogonally at one end, and the arm 811 includes a through hole 812 for receiving the sensor 100. The sides 813a, 813b( Figure 8I ) are C-shaped( Figure 8E ), and each of the sides defines a respective side groove for slidably engaging the arm 820. Thus, the body 810 and the arm 820 are capable of sliding relative to each other between the first position shown in Figure 8B and the second position shown in Figure 8A . In some embodiments, the arm 820 linearly displaces in the side grooves of the body 810.

[0149] To deploy the probe 100, once the probe 100 is located in the holder 10”', the holder 10”' is actuated by sliding the arm 820 relative to the body 810, thereby compressing the holder 10”' (and the bellows 250), as shown in Figure 8A and 8C . The probe 100 can be connected to a port of the container 50 via a conduit 55 or the like using a suitable coupling device 200 (e.g., a G connector commercially available from Colder Products Company). Other coupling devices can also be used, as illustrated by the universal coupling device 200' shown in . Figure 9 In some embodiments, the holder is shipped assembled with the bellows and the sterile connector, and the user inserts the sensor of their choice. After assembling the sensor to the holder, the assembly can be sterilized, for example, by autoclaving. After sterilization, the user can assemble the holder assembly to the bioreactor / vessel 50 via an alignment splint, thereby freeing the user's hands to connect the sterile connector and pull away the sterile isolation sheet associated with the sterile connector. After the sterile connector is opened, the clamp can be loosened from the tube, and the sensor 100 can be pushed into the fluid in the vessel 50.

[0150] Figures 10 - 12 (e.g.,

[0151] , Figure 10A , 10B, 10C, 10D, 10E, 10F, 11A, 11B, 11C, 11D, 11E, 11F, 12A, 12B, 12C, 12D, 12E, 12F, 12G, and 12H) illustrate a fifth embodiment of the sensor holder 1000. This sensor holder 1000 is suitable for use in MAST (Modular Automated Sampling Technology), such as for sampling in a clean bioreactor. As Figure 10A and 12H shown, the holder 1000 includes an elongate member 1200 that includes a channel 1203 defined by a base 1201 and opposing elongate sidewalls 1202A, 1202B. The base includes a slot 1205. A movable block 1210 is located within the channel and includes a member such as a peg (not shown) that is positioned within the slot and can be engaged by a locking knob 1211 that can be actuated to lock the base in place at a desired position within the channel. In some embodiments, the peg, etc. and the locking knob 1211 can be threadedly engaged such that relative rotation of the locking knob and the peg, etc. locks the block 1210 in place within the channel of the holder or unlocks the block. In some embodiments, the block 1210 can include two spaced-apart fixed pins 1212A, 1212B that extend upwardly from the block and are positioned and configured to receive corresponding respective apertures 1213A, 1213B in the autosampler body 1300 ( Figure 12A ). When the autosampler body 1300 is so positioned, and moves with the block. In some embodiments, the holder 1000 further includes a support member 1220 that has a U-shaped or arcuate groove or notch 1220' at its free end, the shape and position of which are configured to receive and support an area of the sensor, as shown.

[0152] In some embodiments, the holder 1000 includes a deployable and collapsible bellows 2500 that has an internal passageway configured to receive a portion of the probe 100. In some embodiments, the collapsible bellows 2500 is part of an assembly that includes a connector at one end and a probe adapter on the other end. This assembly can be wired to a support block that is part of the holder assembly at the connector end and is supported at the opposite probe end.

[0153] In certain embodiments, in Figures 12A - 12G its supported position as shown, the holder 1000 serves to support the probe 100 during sterilization (such as during autoclaving) ( Figure 12Ashows the deployment position of the autosampler body 1300 disengaged from pins 1212A, 1212B. In this embodiment, the probe 100 is inserted through the bellows 2500, and the assembly is located on the block 1210 and the support member 1220. To deploy the probe 100, the retainer 1000 is actuated such that the block 1210 linearly displaces in the slot 1205 of the channel 1203 until reaching Figures 10A - 10F and the deployment positions of 12H. In this position, the probe 100 is held in the arcuate recess 1220' as shown and is also supported by the block 1210, and the bellows 2500 is in a compressed state as shown. The probe can be locked in this position by tightening the locking knob 1211. Then, the assembly can be coupled to a bioreactor or other container by positioning the assembly to facilitate such coupling.

[0154] Figures 13 - 15 (e.g., Figure 13A , 13B , 13C, 13D, 13E, 13F, 14A, 14B, 14C, 14D, 14E, 14F, 15A, 15B, 15C, 15D, 15E, and 15F) illustrate a sixth embodiment of a sensor retainer 2000 that is particularly suitable for pH / DO / VCD / pCO 2 sensors. This embodiment is similar to the fifth embodiment of Figures 10 - 12, except that the movable U-shaped retainer 2210 replaces the movable block 1210. In some embodiments, the U-shaped retainer 2210 has a U-shaped or arcuate groove or notch 2210' at its free end, which has a shape similar to the groove or notch 1220', as Figure 14E and 14F are best visible, and its shape and position are set to receive and support an area of the sensor, such as as Figure 15A shown. Similar to the fifth embodiment, the retainer 2000 includes an elongate member 1200, which includes a channel 1203 defined by a base 1201 and opposing elongate sidewalls 1202A, 1202B, and the base includes a slot 1205.

[0155] In some embodiments, in Figures 15A - 15F its support position as shown, the retainer 3000 serves to support the probe 100 during sterilization (e.g., during autoclaving). In this embodiment, the probe 100 is inserted through the bellows 2500, and the assembly is located on the U-shaped retainer 2210 and the support member 1220. To deploy the probe 100, the retainer 2000 is actuated such that the block U-shaped retainer 2210 linearly displaces in the slot 1205 of the channel 1203 until reaching Figure 13ADeployment location. At this location, the probe 100 is held in the arcuate recesses 1220' and 2210' as shown, and the bellows 2500 is in a compressed state as shown. The probe can be locked in this position by tightening the locking knob 1211. Thus, the block U-shaped retainer 2210 can slide back and forth in the slot 1205 in the Figure 14A direction of arrow 2215. Then, the assembly can be coupled to a bioreactor or other container by positioning the assembly to facilitate such coupling, as in the previous embodiments.

[0156] Figures 16 - 18 (e.g., Figure 16A , 16B , 16C, 16D, 16E, 16F, 17A, 17B, 17C, 17D, 17E, 17F, 18A, 18B, 18C, 18D, 18E, and 18F) illustrate a seventh embodiment of a sensor retainer 3000 that is particularly suitable for Raman spectroscopy (e.g., a sensor or Raman ProCellics TM analyzer) used as an in-line and real-time process analysis tool in bioprocessing. This embodiment is similar to the sixth embodiment of Figures 13 - 15, but adds a clamp assembly 3100 associated with the linearly displaceable member 3200. In some embodiments, the U-shaped retainer 2210 has a U-shaped or arcuate groove or notch 2210' at its free end, which has a shape similar to the groove or notch 1220', as Figure 17E and 17F best visible in, and its shape and position are set to receive and support an area of the sensor, such as as Figure 18A shown in. In some embodiments, in Figures 18A - 18FIn its shown support positions, the retainer 3000 serves to support the probe 100 during sterilization (e.g., autoclaving). In this embodiment, the probe 100 is inserted through the bellows 2500, and the assembly is located on the U-shaped retainer 2210 and the support member 1220. It is also held in place by the clamp assembly 3100 which, in the illustrated embodiment, is also generally U-shaped and includes a locking lever 3110 that, when in the shown locked position, passes through the U-shaped opening. In some embodiments, the locking lever 3100 is pivotable on the free end 3101 of the U-shaped clamp assembly 3100 and can be inserted into an opening slot in the other free end 3102 of the clamp assembly 3100 and locked in place by a locking knob 3105. In some embodiments, the vertical position of the clamp assembly 3100 can be modified by sliding it vertically in the slot 3300 and locking it in the desired position with a locking knob 3301. To deploy the probe 100, the retainer 3000 is actuated such that the block U-shaped retainer 2210 linearly shifts in the channel 1203 until it reaches Figure 16A the deployment position. In this position, the probe 100 is held in the arcuate recesses 1220' and 2210' as shown and is held by the clamp assembly 3100, and the bellows 2500 is in a compressed state as shown. The probe can be locked in this position by tightening the locking knob 1211. The assembly can then be coupled to a bioreactor or other vessel by positioning the assembly to facilitate such a coupling.

[0157] The sensor 100 can be connected to a port of the vessel 50 via a conduit 55 etc. using a suitable coupling device 200 (e.g., a G connector commercially available from Colder Products Company) ​

Claims

1. A probe holder for positioning and holding a probe for engagement with a container, the probe having a longitudinal axis and being capable of extending in a longitudinal direction between a compressed position and an extended position, the holder including a first displaceable member and a second displaceable member, the first and second displaceable members being displaceable relative to one another and being configured to support the probe in the extended position and engage the probe in the compressed position.

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

3. The probe holder according to claim 1, wherein, the first and second displaceable members are pivotally displaceable about a pivot axis orthogonal to the longitudinal axis.

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

5. The probe holder according to claim 4, wherein, the first displaceable member protects the expandable and collapsible bellows when the expandable and collapsible bellows is in a collapsed state.

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

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

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

9. The probe holder according to claim 8, further comprising relatively spaced elongated sidewalls that define a channel with the base.

10. A probe holder for positioning and holding a probe for engagement with a container, the probe having a longitudinal axis and being capable of extending in a longitudinal direction between a compressed position and an extended position, the holder including a base with a slot, a displaceable member, and a support member, the displaceable member being displaceable relative to the support member in the base with the slot.

11. The probe holder according to claim 10, wherein, the displaceable member includes a movable block that can be locked in the base.

12. The probe holder according to claim 10, wherein, the displaceable member is U-shaped.

13. The probe holder according to claim 10, further comprising a clamp assembly having a U-shaped recess and a locking rod that can be positioned to pass through the U-shaped recess.

14. The probe holder according to claim 13, wherein, the clamp assembly has a first free end and a second free end that define the U-shaped recess therebetween, and wherein the locking rod can pivot on the first free end.

15. The probe holder according to claim 10, wherein, the base with the slot has two relatively spaced elongated sidewalls that define a channel therebetween.

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