Apparatus and method for facilitating use of sensor in conjunction with vessel

Abstract

An apparatus for facilitating use of a sensor in conjunction with a vessel includes a body having an upper portion and a lower portion, the body extending across substantially an entire width of the vessel, the body configured for selective placement on a surface of a biological treatment device, the body includes a sensor recess formed in an upper portion of the body, the sensor recess configured to receive a sensor such that the sensor is at least partially embedded within the body. In use, the body is located between the surface of the biological treatment device and the vessel, the body allowing liquid in the vessel to stay near the sensor to facilitate use of the sensor at low vessel fill levels.

Description

Technical Field

[0001] Embodiments of the present invention generally relate to cell processing, and more specifically to apparatus and methods for facilitating the use of sensors (e.g., live cell density (VCD) sensors) in conjunction with vessels. Background Technology

[0002] Cell processing devices such as bioreactors, mixers, and fermenters are commonly used to perform biochemical and / or biological processes, and / or manipulate liquids and other products of such processes. These devices typically comprise flexible or collapsible disposable bags / vessels supported by an external rigid structure. The vessels are filled with the desired fluid for processing. The fluid within the vessel may require mixing or agitation to prevent particulate matter from settling at the bottom, which can be achieved, for example, by using a shaking platform to which the disposable vessel is attached.

[0003] Fluids typically introduced into the vessel include liquids such as cell culture media, serum, saline solutions, buffer solutions, and water, as well as gases such as air, oxygen, carbon dioxide, nitrogen, or mixtures thereof. Fluids are added to establish and maintain suitable growth and / or reaction conditions for the production of products from cellular material within the vessel.

[0004] As will be recognized, analysis of the cellular material (e.g., cells) within the vessel is important for ensuring conditions are optimal for growth and for growth to occur. In particular, analysis of the cellular material during processing is desirable to allow for real-time or near-real-time process control. In some cases, the analysis is performed via one or more sensors that are welded to / formed in the walls or surface of the vessel, or selectively attached to the walls or surface of the vessel.

[0005] For example, it is often desirable to assess live cell density (VCD), which provides a measurement of the total number of live cells within cellular material (e.g., cell culture) in a dish. This can be achieved via a VCD sensor that measures the dielectric constant of the cells. Such a sensor may include a sensor patch that can be formed in or attached to the bottom surface of the dish, and a transducer connected to the sensor patch during operation.

[0006] In use, the VCD sensor measures the dielectric constant of cells within the fluid above the sensor, meaning the sensor patch must be substantially submerged in the fluid. However, using such sensors in conjunction with a shaking platform device / bioreactor can be problematic when the fluid volume in the vessel is relatively low. When connected to the transducer, the sensor patch rises off the shaking platform, forming an island-like structure inside the vessel. In lower volumes, the VCD sensor may rise above the fluid level in the vessel, especially when the shaking platform is tilted or angled away from the sensor patch and fluid has accumulated at opposite ends of the vessel. As will be appreciated, this can lead to data loss / inaccurate VCD measurements and / or excessive signal loss.

[0007] The increased VCD sensor capacity may also require undesirable or impractical high minimum container fill levels to compensate. This fill level might necessitate larger bags / vessels and / or shaking platforms / trays than those currently commercially available. Furthermore, biopharmaceuticals are of high value, so it is generally desirable to produce only what is needed and minimize waste.

[0008] Furthermore, known solutions for erroneous sensor measurements attributed to fluctuations in fluid levels involve sophisticated spectrum-based systems that synchronize sensor measurements with the mixed motion of the bioreactor. Such systems involve specific hardware, such as sensors for measuring mixed motion variables of the bioreactor (e.g., angle, positional changes, instantaneous movement, etc.), and software for selectively triggering sensor measurements based on these variables and / or for selecting recorded values ​​from the sensors based on the measured motion.

[0009] To reduce equipment complexity and cost, improve efficiency, and for overall convenience, there is a need for devices and methods that allow existing shaking platform reactors (for a large existing customer base) to be used in conjunction with vessels equipped with VCDs without undesirably increasing the minimum vessel level, and without requiring complex hardware and / or measurement synchronization software. Summary of the Invention

[0010] Certain embodiments that are equivalent in scope to the originally presented subject matter are summarized below. These embodiments are not intended to limit the scope of the claimed subject matter, but are merely intended to provide a brief overview of possible embodiments. In fact, this disclosure may include a variety of forms that may be similar to or different from the embodiments described below.

[0011] According to an aspect of the invention, a device for facilitating the use of a sensor in conjunction with a vessel includes a body having an upper portion and a lower portion, the body extending across substantially the entire width of the vessel, the body being configured for selective placement on a surface of a bioprocessing device, the body including a sensor recess formed in the upper portion of the body, the sensor recess being configured to receive a sensor such that the sensor is at least partially embedded within the body. In use, the body is positioned between the surface of the bioprocessing device and the vessel, the body allowing liquid in the vessel to remain near the sensor to facilitate sensor use even at low vessel fill levels.

[0012] In one embodiment, the surface of the bioprocessing device may be a tray configured to be attached to a platform capable of oscillating about an axis to facilitate the bioprocessing procedure within the vessel.

[0013] In one embodiment, the sensor in the sensor recess may be a first part of a live cell density sensor configured to selectively engage with a second part of a live cell density sensor fixed to a vessel.

[0014] In this embodiment, the container is a single-use bioreactor bag.

[0015] In an embodiment, the upper portion of the body may include a first angular surface and a second angular surface, the first angular surface including a sensor recess; and in use, the body is located near a first end of the surface of the biological processing device, wherein the first angular surface faces the first end of the surface of the biological processing device, and the second angular surface faces the second end of the surface of the biological processing device opposite to the first end.

[0016] In an embodiment, the body may have a substantially triangular profile or cross-section, wherein the substantially obtuse angle is between the first angular surface and the second angular surface.

[0017] In one embodiment, the first angled surface may have an angle of approximately 15 degrees with the surface of the biological treatment device.

[0018] In one embodiment, the upper portion of the body may include an angled surface including a sensor recess; and in use, the body is located near a first end of the surface of the biological processing device, and the angled surface faces a second end of the surface of the biological processing device opposite to the first end.

[0019] In one embodiment, the body may have a substantially right-angled triangular profile or cross-section, wherein the longest side of the triangle is an angled surface with a sensor recess.

[0020] In one embodiment, the angled surface may be at an angle of approximately 15 degrees to the surface of the biological treatment device.

[0021] In one embodiment, the low vessel filling level may be less than approximately 50% of the total volume of the vessel.

[0022] In one embodiment, the lower portion of the body may include an attachment mechanism for securing the body to the surface of the biological treatment device.

[0023] In one embodiment, the sensor recess may be configured to allow a first portion of the sensor located within the sensor recess to rotate, such that it can be aligned with and engaged with a second portion of the sensor fixed to the vessel.

[0024] According to an aspect of the invention, a tray for receiving a bioprocessor dish and for attaching to a shaking platform of a bioprocessing device includes a first end and a second end opposite to the first end, and an angled portion adjacent to the first end of the tray having a sensor recess configured to receive a sensor such that the sensor is at least partially embedded within the angled portion; and when the platform is swung back and forth about an axis, the angled portion allows liquid in the dish to remain near the sensor, thereby facilitating the use of the sensor at low dish fill levels.

[0025] In one embodiment, the angled surface may be at an angle of approximately 15 degrees to the surface of the biological treatment device.

[0026] In one embodiment, the low vessel filling level may be less than approximately 50% of the total volume of the vessel.

[0027] In one embodiment, the sensor recess may be configured to allow a first portion of the sensor within the sensor recess to rotate, such that it can be aligned with and engage with a second portion of the sensor fixed to the vessel.

[0028] According to another aspect of the invention, a method for reducing the minimum vessel fill level to facilitate the use of a sensor includes: placing a body on the surface of a bioprocessing device, the body having an upper portion and a lower portion, the body extending across substantially the entire width of the vessel; connecting a first portion of a sensor located in a sensor recess formed in the upper portion of the body to a second portion of a sensor fixed to the vessel; and wherein the body is located between the surface of the bioprocessing device and the vessel, the body allowing liquid in the vessel to remain near the sensor to facilitate the use of the sensor at low vessel fill levels.

[0029] In one embodiment, the method may further include adding fluid to a vessel; and agitating the fluid in the vessel by shaking the surface of the biological treatment device about an axis to perform a biological treatment procedure.

[0030] In an embodiment, the sensor may be a live cell density sensor, and the method further includes using the live cell density sensor to measure the live cell density in the fluid.

[0031] Features described in the context of different aspects and embodiments of the invention may be used together and / or interchanged. Similarly, features described in the context of a single embodiment may also be provided individually or in any suitable sub-combination. Attached Figure Description

[0032] The invention will be better understood by referring to the following description of non-limiting embodiments, which are shown in the accompanying drawings: Figure 1 This is a perspective view suitable for use in conjunction with embodiments of the present invention in a shaking platform bioreactor system; Figure 2 yes Figure 1 The side view of the system depicts the platform and the attached tray at an angle, which will be generated by the system's rocking motion. Figure 3 This is an illustration of a bioreactor bag with a VCD sensor integrated into the bag. Figure 4 This is a diagram of a VCD sensor transducer. In use, this transducer is used in conjunction with... Figure 3 Sensor matching.

[0033] Figure 5 This is a simplified schematic diagram of a rocking platform bioreactor, depicting the matched VCD sensor and transducer and the resulting island effect.

[0034] Figure 6 According to embodiments of the present invention, this is for facilitating the combination of sensors with a container (e.g., Figure 3 and Figure 4 A perspective view of the equipment used (bioreactor bags and sensors).

[0035] Figure 7 It is placed on the tray of the shaking platform bioreactor. Figure 6 The view of the device.

[0036] Figure 8 yes Figure 7 A top view of the device.

[0037] Figure 9 yes Figure 6 The diagram shows a cross-section of the equipment and the rocking platform, depicting the platform in the first angled position.

[0038] Figure 10 yes Figure 9 The sectional view of the device depicts the platform in a second angular position opposite to the first position.

[0039] Figure 11According to another embodiment of the invention, it is used to facilitate the combination of a sensor with a container (e.g., Figure 3 and Figure 4 A perspective view of the equipment used (bioreactor bags and sensors).

[0040] Figure 12 It is placed on the tray of the shaking platform bioreactor. Figure 11 On the top of the device.

[0041] Figure 13 yes Figure 12 Additional view of the device.

[0042] Figures 14A to 14E This illustrates the use of quantification and application at various vessel filling levels. Figure 6 and Figure 11 A graph showing the test results of the percentage of VCD data loss associated with the device implementation.

[0043] Figure 15 It is an overview from Figures 14A to 14E The chart shown is a graph of the data obtained from the test.

[0044] Figure 16 This is a simplified schematic diagram of a shaking platform bioreactor and a device for facilitating the use of sensors combined with vessels, according to an alternative embodiment of the present invention. Detailed Implementation

[0045] The exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings, examples of which are shown in the drawings. Wherever possible, the same reference numerals used throughout the figures denote the same or similar parts.

[0046] As used in this article, the terms "flexible" or "foldable" refer to a structure or material that is flexible or can be bent without breaking, and may also refer to materials that are compressible or expandable. An example of a flexible structure is a bag formed from a polyethylene film.

[0047] As used herein, the term “vessel” means a flexible bag, flexible container, semi-rigid container, or rigid container, as appropriate. As used herein, the term “vessel” is intended to encompass bioreactor vessels with flexible walls or portions thereof, single-use flexible bags, and other containers or tubing commonly used for biological or biochemical processes, including cell culture / purification systems, fermentation systems, mixing systems, culture medium / buffer preparation systems, and filtration / purification systems.

[0048] As used in this article, the term "bag" refers to a flexible or semi-rigid container or vessel used, for example, for the contents of a bioreactor or mixer.

[0049] As used herein, “platform” refers to a shaking platform configured to receive and support vessels / bags during a bioprocessing procedure, i.e., the surface of a “shaking” bioreactor. This term includes, but is not limited to, bioreactor trays. Although specific shaking bioreactor systems are shown and described in association with, for example, trays attached to or mounted to a shaking platform, the invention is not limited to such systems.

[0050] The embodiments can be used in conjunction with a wide variety of biological and chemical processes. Some embodiments can be used in other industries where sensor analysis of fluids in environments with fluctuating fluid levels is desired. Similarly, embodiments of the invention can also be used in conjunction with sensors other than dielectric constant-based VCD sensors. For example, embodiments may be suitable for use in conjunction with capacitive or optical VCD sensors, or in conjunction with non-VCD sensors.

[0051] refer to Figure 1 The figure depicts an exemplary shaking platform or shaker bioreactor system 10 suitable for use in conjunction with embodiments of the present invention. As shown, system 10 includes a bioreactor 12 operatively connected to one or more peristaltic pumps 14. Bioreactor 12 is also operatively connected to a controller, such as a local or remote computer providing process / protocol monitoring, via a wired or wireless connection (not shown).

[0052] The bioreactor 12 includes a surface, such as a removable tray 20, configured to selectively receive and support vessels / bags 24 and move in a shaking manner / motion as described in more detail below. In an embodiment, the tray 20 may include a removable lid (not shown) having a hinged door that can be raised to access the tray 20, and any vessels 24 attached thereto.

[0053] Now for reference Figure 2 The bioreactor 12 includes a base 16 connected to a rocking platform 18, which in turn is connected to a tray 20. The base 16 houses a pivoting mechanism (e.g., a motor) that enables the rocking platform 18 to rock back and forth about an axis 22.

[0054] The tray 20 may include one or more heating elements, such as a heating plate 32, and may also include a temperature sensor to enable precise temperature control of the contents of the container / bag 24.

[0055] In use, the vessel / bag 24 is secured to the tray 20 via one or more attachment mechanisms 26, which in this embodiment are selectively lockable clips located at opposite ends of the tray 20. The rocking platform and the tray 20 can then pivot about axis 22 to produce a rocking motion to facilitate the biological treatment of the fluid 28 in the vessel 24.

[0056] During rocking, platform 18 forms an angle α with the horizontal plane at the end of its upward path, and the rear portion of rocking platform 18 moves back and forth from an angle of -α to +α. In embodiments, angle α can be changed by the user and is in the range of approximately 2° to 12°. However, as will be appreciated, embodiments of the invention are suitable for use in conjunction with reactor platforms that move at angles beyond this range.

[0057] Now for reference Figure 3 and Figure 4 In biological processing and other contexts, it is desirable to assess the density of living cells to evaluate, for example, cell growth. This can be achieved using a VCD sensor that measures the dielectric constant of cells. A VCD sensor is typically an assembly of several components, which may include a first part, such as a transducer 30, which is matched or connected to a second part (e.g., a sensor patch 40 fixed to a vessel 28).

[0058] In embodiments, the sensor patch 40 may be attached to the vessel 28 by welding (e.g., thermal welding) or otherwise formed in the flexible wall of the vessel 28. In a particular embodiment, the sensor patch 40 is welded to the bottom surface at one end of the vessel 28 such that the engagement portion 42 (e.g., a pin connector) faces downward, allowing the sensor patch 40 to selectively engage the transducer 30. As will be appreciated, the position of the sensor patch 40 may vary, and the embodiments are not limited to use with a sensor located in any particular vessel position.

[0059] However, as Figure 4 and Figure 5 As shown, the transducer 30 has a relatively high profile / height, causing it to extend upwards into the vessel 28 when placed on the tray 20 of the shaking platform bioreactor, raising the height of the sensor patch 40. This extension creates an island effect, where, during the shaking motion of the reactor, the sensor patch 40 may have almost no fluid 36 above it, or may be raised above the fluid level in the vessel 28. As will be appreciated, accurate VCD measurements cannot be obtained when there is insufficient fluid 36 above the sensor patch 40. The island effect is particularly pronounced at relatively low vessel filling levels and when the shaking platform is tilted away from the sensor patch 40.

[0060] Increasing the fill level of vessels to address the island effect is generally impractical, as the required minimum fill level would approach the maximum capacity of many existing vessels. For example, for a 2-liter vessel, the potentially suitable minimum fill level would increase from 100 ml to over 600 ml.

[0061] Place the transducer 30 directly on the tray 20. Figure 4This could also be undesirable, as movement of the unfixed transducer 30 during use can stress the area of ​​the vessel 28 surrounding the sensor patch 40. The height of the transducer 30 and sensor patch 40 can also alter the wavy motion within the fluid 36 generated by the shaking motion of the reactor. With the above considerations in mind, embodiments of the invention provide apparatus and methods for facilitating the use of a VCD and other sensors in conjunction with a vessel, particularly in cases of low vessel fill levels (e.g., fill levels less than approximately 50% of the total volume of the vessel).

[0062] Now for reference Figures 6 to 8 The image depicts a device 100 for facilitating the use of a sensor in conjunction with a container. The device generally includes a body 101 designed for selective placement on a surface of a bioprocessing apparatus. The body 101 includes an upper portion 102 and a lower portion 104, wherein the upper portion 102 faces upward toward the user, and the lower portion 104 faces downward and contacts a tray or other surface of the bioprocessing apparatus.

[0063] As shown in the figure, the upper portion 102 includes a first angled surface 106 and a second angled surface 108. The body 101 further includes end portions 112 at opposite ends of the body 101. In the depicted embodiment, the body 101 has a substantially hollow or open interior, and the lower portion 104 contacts the rocking platform bioreactor via the end portions 112. In other embodiments, the body 101 may be solid or semi-solid, and the entire lower side / lower portion 104 may contact the rocking platform.

[0064] In some embodiments, the lower portion 104 may include one or more surfaces, such as rubber feet, having a high coefficient of friction to prevent the body 101 from slipping / moving on the surface of the bioprocessing device when it is in motion. In other embodiments, the body 101 itself may be made of a material that resists slipping / moving. In still other embodiments, the weight of the vessel containing the fluid may be sufficient to prevent the device 100 from slipping / moving during use.

[0065] The first angled surface 106 includes a sensor recess 110. The sensor recess 110 is shaped to receive a transducer 30 of a VCD sensor. In the depicted embodiment, the sensor recess 110 has a substantially keyhole-shaped shape configured to approximate the shape of the transducer 30, and a depth approximates the height of the transducer 30, such that the transducer 30 can be at least partially embedded within the sensor recess 110. In an embodiment, the transducer 30 can be fully embedded within the sensor recess 110, such that when mated, the sensor patch 40 of the vessel 28 is substantially flush with the first angled surface 106.

[0066] Although the sensor recess 110 is depicted as having a keyhole shape, the shape and size of the sensor recess 110 may vary depending on the shape, size, and / or type of the sensor that the device 100 will use. In some embodiments, the first angled surface 106 may include multiple sensor recesses, or the sensor recess 110 may be configured to accommodate multiple sensors, such as multiple VCD sensors or sensors of different types.

[0067] In some embodiments, the sensor recess 110 may be configured / shaped to allow the transducer 30 to rotate slightly so that it can properly mate with the sensor patch 40 without the patch rotating and potentially stressing the vessel wall to which it is soldered / otherwise attached. In a particular embodiment, the tail portion 111 of the keyhole-shaped sensor recess 110 ( Figure 8 The transducer 30 can expand outward toward the recessed end to allow it to rotate + / - 5 degrees, so that the circular head portion of the transducer 30 can be properly aligned with the pin connection portion 42 of the sensor patch 40.

[0068] In other embodiments, the sensor recess 110 may also include electronics such as Bluetooth, power supply, and electronics for mapping / converting communication protocol data, eliminating the need for external / desktop modules to power, communicate with, and / or control the VCD sensor. As will be appreciated, the size and shape of the sensor recess 110 may vary depending on the size and shape of any such electronic components. In some embodiments, the body 101 may include one or more ports to allow for USB connectivity, etc.

[0069] refer to Figure 8 In embodiments where the body 101 is substantially hollow or open, the recess 110 may include one or more supports 114 that define the depth of the recess 110 and hold the sensor at that depth when it is received in the recess 110. As will be appreciated, in other embodiments, the recess 110 may be formed in / molded into a solid body, such that one or more supports 114 are not required.

[0070] like Figure 6 and Figure 10 As shown, embodiments of body 101 may also include an edge portion 107 configured to adjoin a surface of the tray 20 or a similar structure on the rocking platform, or other surfaces of the bioprocessing device. In embodiments, the edge portion 107 is angled or tilted to correspond to the angle of the forward-facing edge or lip of the tray 20 that holds the vessel 28 on the platform during use. As will be appreciated, the size and shape (and presence) of the edge portion 107 may vary, and embodiments are not limited in this respect.

[0071] Although the size of device 100 may vary, in embodiments, body 101 substantially extends across the entire width of the vessel to which device 100 will be used. The depth to which device 100 extends from front to back on the surface of the biological processing apparatus may also vary. However, for device 100, it may not be desirable to extend onto heating elements (e.g., heating plates) on the surface, thereby significantly inhibiting heat transfer from the heating elements into the fluid within the vessel. In some embodiments, device 100 may be at least partially constructed of a non-insulating or thermally conductive material to address this potential problem. In other embodiments, device 100 itself may include a heating element.

[0072] The overall height of the device 100 may also vary, but should be sufficient to allow the sensor to be embedded in the sensor recess formed therein in order to resolve the island effect mentioned above.

[0073] In a particular embodiment, the body 101 has a width of approximately 66.5 cm and a height of approximately 3.45 cm. The first angular surface 106 has a depth of approximately 7.4 cm (meaning the distance the body 101 extends (from front to back) on the surface of the bioprocessing device), and the second angular surface 108 has a depth of 5.1 cm. As mentioned, these dimensions can vary, and the invention is not limited in this respect.

[0074] In certain embodiments, device 100 may be made of a thermoplastic elastomer, such as high-density polyethylene (HDPE). While HDPE may be suitable due to its high strength-to-density ratio, other materials may be used without departing from the invention. In some embodiments, device 100 may be made of nylon, polyurethane, or acrylonitrile butadiene styrene. Device 100 may be vacuum cast, molded, or additively manufactured.

[0075] As will be recognized, other materials may also be used to manufacture device 100. Similarly, other manufacturing techniques may be employed without departing from the scope of the invention.

[0076] In one embodiment, device 100 may be an assembly of multiple panels, for example, these panels forming a first angular surface 106 and a second angular surface 108 and an end portion 112. The panels may be mechanically and / or chemically bonded together via adhesives. In other embodiments, device 100 may be monolithic and / or formed or molded from a single material.

[0077] Now for reference Figure 6 , Figure 9 and Figure 10The figure depicts the body 101, VCD sensors 30 and 40, tray 20, and vessel 28 in a sectional view. As shown, in the depicted embodiment, the device 100 has a substantially triangular profile (e.g., a side / end profile) or cross-section, characterized by an obtuse angle α between a first angular surface 106 and a second angular surface 108. The device 100 is substantially triangular because it has three main perimeter sides and / or corners. In this embodiment, angle α is approximately 130°. Additionally, the first angular surface 106 is at an angle b of approximately 15° with respect to the surface of the biological processing device (e.g., tray 20). As will be appreciated, the angles may vary without departing from the scope of the invention; however, angle b should be greater than the maximum platform tilt angle, which is 12° in this embodiment.

[0078] Embodiments of the present invention need not have a basic triangular outline or cross-section, and the body 101 may have alternative shapes, such as herringbone (without end portion 112), rectangle or quadrilateral, or arc / dome-shaped outline or cross-section or entirely other shapes.

[0079] As will be appreciated, body 101 has surfaces or edges that come into contact with the flexible vessel 28 during use, such as the point where the first angled surface 106 and the second angled surface 108 meet. In embodiments, these surfaces / edges may be shaped or otherwise designed to minimize stress loads on the flexible material of the vessel 28.

[0080] Refer again Figure 9 Device 100 and tray 20 are depicted in a first position, wherein dish 28 is tilted toward sensor patch 40 at a maximum angle of 12°. Dish 28 is depicted having fluid 36 at a fill level of approximately 10% (e.g., approximately 5% of the total dish volume). As shown, body 101 is positioned between the surface of the bioprocessing device (e.g., tray 20) and dish 28. A first angled surface 106 faces a first end of the bioprocessing device (not shown), such as the front. A second angled surface 108 faces a second end of the bioprocessing device opposite the first end, such as the back or rear.

[0081] As depicted, at the minimum 10% fill level, when the device 100 and tray 20 are in the first position and tilted toward the sensor patch 40 to its maximum angle of 12°, the sensor patch 40 is immersed in the fluid 36 in the vessel 28. In this first position, the angle between the sensor patch 40 / first angled surface 106 and the fluid fill level is approximately 27°, and the angle b with respect to the tray 20 is approximately 15°.

[0082] In fact, as Figure 10As shown, even in the second position where the vessel is tilted 12° away from the sensor patch 40, fluid still accumulates on the sensor patch 40, enabling VCD measurements. In the second position, the device 100 produces a tidal pool-like effect. In this position, the fill level of the fluid 36 is at an angle of approximately 3° between the sensor patch 40 and the first angled surface 106.

[0083] Now for reference Figures 11 to 13 An alternative embodiment of the device 200 of the present invention is depicted. In this embodiment, the body 201 has an upper portion 202, a lower portion 204, and an end portion 212. The upper portion 202 has an angled surface 209 including a sensor recess 210. As shown, the sensor recess 210 includes a keyhole-shaped portion 213, the size and shape of which are configured to receive a transducer 30 (or other sensor / sensor component) such that it is at least partially embedded therein, and a portion 215 configured to receive electronics.

[0084] The device 200 can be made of various materials and can have different shapes, sizes and angles as discussed in conjunction with the embodiments mentioned above.

[0085] However, in this embodiment, the angled surface 209 faces away from the first end of the surface of the bioprocessing device (e.g., tray 20) on which the device 200 is placed. The body 201 has a substantially right-angled triangular profile (e.g., side or end profile) or cross-section, wherein the longest side is the angled surface 209 with the sensor recess 210. In this embodiment, the angled surface 209 is at an angle of approximately 15° to the surface of the bioprocessing device (e.g., tray 20) on which the angled surface is placed. The device may also have an angled edge portion or surface, for example, the shortest side of the substantially triangular device 200 (e.g., tray 20). Figure 11 This edge can be angled to correspond to the angle of the front lip or edge of the tray 20 or other surfaces of the biological treatment device.

[0086] As shown in the figure, the device 200 is essentially wedge-shaped and does not create a tidal pool-like effect around the sensor patch 40. However, the device mitigates the island effect described herein by allowing the liquid in the vessel to remain near the VCD sensor.

[0087] In some embodiments, the angled surfaces 106, 209 may be integrally integrated into the surface of the bioprocessing device. For example, tray 20 may include angled portions, such as angled surfaces 106, 209 having sensor recesses. In one embodiment, the angled portions are adjacent to a first end (e.g., the front) of the tray and face a second end (e.g., the rear or back) of the tray to allow liquid in the vessel to remain near the sensor being shaken by the platform. In other embodiments, the angled surfaces may face the first end / front of the tray.

[0088] In some other embodiments, such as Figure 16 In the embodiment shown, tray 320 may not include the angled surface as described herein, but rather tray 320 itself may include a sensor recess / hole 310 located approximately at the midpoint of tray 320 on the upper portion 322 of tray 320. Hole 310 is relatively deep and will allow sensor patch 40 and transducer 30 to be almost always immersed in liquid 28 during shaking motion, even at low fill levels.

[0089] In such embodiments, tray 320 will be selectively placed on the shaking platform of the reactor. Thus, tray 320 will function as the device body as described herein, and the shaking platform will serve as the surface of the biological treatment apparatus on which the body is selectively placed.

[0090] In such embodiments, the size and shape of the aperture 310 will be configured to accommodate and embed the associated sensor, such as a VCD sensor or other sensors.

[0091] Embodiments of the invention also envision a method for reducing the minimum container filling level to facilitate the use of sensors. This method includes an initial step of placing the bodies 101, 201 of devices 100, 200 on the surface of a biological processing device (such as tray 20), the bodies 101, 201 having upper portions 102, 202 and lower portions 104, 204, the bodies 101, 201 extending across substantially the entire width of the container 28.

[0092] Once placed on the tray, the method involves connecting a first portion of the sensor (e.g., a VCD transducer 30 located in sensor recesses 110, 210 formed in the upper portions 102, 202 of the body) to a second portion of the sensor (e.g., a sensor patch 40) fixed to the vessel 28. The bodies 101, 201 are located between the surface of the biological processing device (tray 20) and the vessel 28, allowing liquid in the vessel 28 to remain near the sensor for use at low vessel fill levels.

[0093] In an embodiment, the method may further include adding fluid to a vessel and agitating the fluid in the vessel by shaking the surface of the bioprocessing device (e.g., tray 20) about an axis to perform a bioprocessing procedure.

[0094] In one embodiment, the sensor is a live cell density sensor, and the method further includes using the live cell density sensor to measure the live cell density within the fluid 28.

[0095] In some embodiments, multiple devices may be used in a single bioreactor.

[0096] Now go to Figures 14A to 14E and Figure 15 VCD tests were performed using a dielectric constant-based VCD sensor to evaluate the effectiveness of embodiments of the device of the present invention. Specifically, yeast experiments were conducted using a shaking platform bioreactor at vessel filling levels of 10% (75 g yeast), 20% (150 g yeast), 40% (200 g yeast), 60% (300 g yeast), and 100% (300 g yeast). For each filling level, tests were performed with the bioreactor tray empty, with the “tidal pool” device 100 described herein, and with the “wedge” device 200, respectively. Dielectric constant and conductivity were measured. The tests yielded (and are presented graphically) raw data without any data filtering.

[0097] like Figures 14A to 14E As shown, at each fill level, the results from devices 100 and 200 (data attributed to these devices are labeled 120 and 220, respectively) are superior to those obtained without the devices. In particular, for device 100, there is no interruption in data 120 during reactor agitation, representing essentially continuous VCD measurements with almost no data loss.

[0098] Figure 15 will come from Figures 14A to 14E The data is summarized in a table. As shown in the figure, "Instrument II" (which represents device 100) has no data loss. Instrument I (which represents device 200) has some data loss, but far less than in the VCD test without the device in use.

[0099] As used herein, elements or steps referred to in the singular and prefixed with the words "an" or "a" should be understood to not exclude a plurality of the said elements or steps unless such exclusion is explicitly stated. Furthermore, the reference to "an embodiment" of the invention is not intended to exclude the existence of additional embodiments also incorporating the said features. Moreover, unless explicitly stated to the contrary, embodiments that "comprise," "include," or "have" one or more elements having a particular attribute may include additional such elements that do not have that attribute.

[0100] While the dimensions and types of materials described herein are intended to define the parameters of the invention, they are by no means limiting and are exemplary embodiments. Many other embodiments will become apparent to those skilled in the art upon reviewing the above description.

[0101] Therefore, the scope of this invention should be determined with reference to the full scope of the appended claims together with their equivalents. In the appended claims, the terms "comprising" and "wherein" are used as their common English equivalents to the terms "including" and "wherein".

[0102] Furthermore, in the following claims, terms such as “first,” “second,” “upper,” “lower,” “bottom,” “top,” etc., are used merely as markers and are not intended to impose numerical or positional requirements on their objects. Additionally, the limitations of the following claims are not written in the form of device plus function, and are not intended to be interpreted in this way, unless and until such a claim explicitly uses the phrase “device, which is used for” followed by a statement of function without further structure.

[0103] This written description uses examples to disclose several embodiments of the invention, including the best mode, and also enables those skilled in the art to implement embodiments of the invention, including making and using any apparatus or system, and performing any incorporated methods. The scope of the invention is defined by the claims and may include other examples that may occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that are not different from the written language of the claims, or if they include equivalent structural elements that are not substantially different from the written language of the claims.

Claims

1. A device for facilitating the use of a sensor in conjunction with a vessel, comprising: A body having an upper portion and a lower portion, the body extending across substantially the entire width of the vessel, the body being configured for selective placement on the surface of a biological processing device, the body comprising: A sensor recess is formed in the upper portion of the body, the sensor recess being configured to receive a sensor such that the sensor is at least partially embedded in the body; In use, the body is located between the surface of the biological treatment device and the vessel, and the body allows the liquid in the vessel to remain near the sensor so that the sensor can be used when the vessel is at a low fill level.

2. The device according to claim 1, wherein, The surface of the biological treatment device is a tray, which is configured to be attached to a platform of the biological treatment device that can be oscillated about an axis to facilitate the biological treatment process within the vessel.

3. The device according to claim 1, wherein, The sensor in the sensor recess is the first part of the live cell density sensor, which is configured to selectively engage with the second part of the live cell density sensor fixed to the vessel.

4. The device according to claim 1, wherein, The container is a single-use bioreactor bag.

5. The device according to claim 1, wherein, The upper part of the body includes a first angular surface and a second angular surface, wherein the first angular surface includes the sensor recess; In use, the body is located near the first end of the surface of the biological treatment device, wherein the first angled surface faces the first end of the surface of the biological treatment device, and the second angled surface faces the second end of the surface of the biological treatment device opposite to the first end.

6. The device according to claim 5, wherein, The body has a substantially triangular profile or cross-section, wherein a substantially obtuse angle lies between the first angular surface and the second angular surface.

7. The device according to claim 5, wherein, The first angled surface is at an angle of approximately 15 degrees to the surface of the biological treatment device.

8. The device according to claim 1, wherein, The upper portion of the body includes an angled surface, and the angled surface includes a sensor recess; In use, the body is located near the first end of the surface of the biological treatment device, and the angled surface faces the second end of the surface of the biological treatment device opposite to the first end.

9. The device according to claim 8, wherein, The body has a substantially right-angled triangular outline or cross-section, wherein the longest side of the triangle is an angular surface with the sensor recess.

10. The device according to claim 8, wherein, The angled surface is at an angle of approximately 15 degrees to the surface of the biological treatment device.

11. The device according to claim 1, wherein, The low-fill level of the vessel is less than approximately 50% of the total volume of the vessel.

12. The device according to claim 1, wherein, The lower portion of the device includes an attachment mechanism for securing the body to the surface of the biological treatment device.

13. The device according to claim 1, wherein, The sensor recess is formed to allow a first portion of the sensor located within the sensor recess to rotate, such that it can be aligned with and engage with a second portion of the sensor fixed to the vessel.

14. A tray for receiving a bioprocessor dish and for attaching it to a shaking platform of a bioprocessing apparatus, the tray comprising: A first end and a second end opposite to the first end; as well as An angled portion adjacent to a first end of the tray, the angled portion having a sensor recess configured to receive a sensor such that the sensor is at least partially embedded within the angled portion; When the shaking platform oscillates back and forth about the axis, the angled portion allows liquid in the bioprocessor dish to remain near the sensor, facilitating the use of the sensor at low dish fill levels.

15. The pallet according to claim 14, wherein, The angled portion is at an angle of approximately 15 degrees to the surface of the biological treatment device.

16. The tray according to claim 14, wherein, The low-fill level of the vessel is less than approximately 50% of the total volume of the bioprocessor vessel.

17. The tray according to claim 14, wherein, The sensor recess is formed to allow a first portion of the sensor within the sensor recess to rotate, thereby aligning with and engaging a second portion of the sensor fixed to the bioprocessor dish.

18. A method for reducing the minimum fill level of a vessel to facilitate the use of a sensor, comprising: The body is placed on the surface of the biological processing device, the body having an upper portion and a lower portion, the body extending across substantially the entire width of the vessel; as well as The first part of the sensor located in the sensor recess formed in the upper part of the body is connected to the second part of the sensor fixed to the vessel; The body is located between the surface of the biological treatment device and the vessel, and the body allows the liquid in the vessel to remain near the sensor so that the sensor can be used when the vessel is at a low fill level.

19. The method of claim 18, further comprising: Add fluid to the vessel; as well as The biological treatment process is performed by agitating the fluid in the vessel by shaking the surface of the biological treatment device about its axis.

20. The method according to claim 19, wherein, The sensor is a live cell density sensor, and the method further includes using the live cell density sensor to measure the live cell density within the fluid.

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