Apparatus and method for thermal foam detection

Abstract

A foam identification system includes a thermal imaging camera and a controller connected to the thermal imaging camera. The thermal imaging camera images a surface of the liquid in the vessel exposed to the headspace of the vessel. The headspace is warmer or cooler than the liquid. The camera and the controller detect a change in temperature of the exposed surface of the liquid to identify foam on the exposed surface of the liquid.

Description

Technical Field

[0001] Embodiments of the present invention generally relate to bioprocessing apparatus, systems, and methods, and more particularly to thermal visualization and analysis of fluids in bioreactors to detect foam. Background Art

[0002] Bioreactors are often employed to perform biochemical and / or biological processes and / or manipulate liquids and other products of such processes. Such bioreactors typically include flexible or collapsible single-use disposable bags supported by an external rigid structure such as a stainless steel shell or frame. These bags are made of thin sheets of flexible plastic film and are positioned within a rigid shell and filled with the desired fluid for processing.

[0003] Growing biological materials such as mammalian cells, bacteria or yeast in a bioreactor often results in the generation of an undesirable foam layer that floats on top of the fluid in the bioreactor, such as in the headspace of a bioreactor bag. This foam layer is the result of several factors, including the addition of pressurized air to maintain the aerobic microorganisms, nutrients and growth factors present in the liquid growth medium, and waste products generated by the microorganisms. Over time, this foam layer can become unacceptably thick and, if not treated, can potentially clog the exhaust ports and filters of the bioreactor, prevent CO2 from escaping, and negatively affect the structural integrity of the bag. The foam also forms a barrier to liquid injected from above the fluid in the bioreactor and is problematic even at low fluid volume levels.

[0004] In order to reduce the foam layer to a reasonable thickness, chemical solutions such as anti-foam compounds are typically employed. With such compounds, several applications may be required during a single production run to ensure effectiveness. Conversely, too much anti-foam compound may be harmful to the biomaterial in the reactor. Mechanical solutions also exist, such as thermal probes and foam breakers, however, they are more effective in reducing the amount of existing foam rather than inhibiting foam formation.

[0005] In view of the above, accurate detection and monitoring of foam in bioreactor bags is important to determine when intervention is necessary. While foam detection solutions exist, they only detect foam levels in small areas or, in some cases, at a single point in the bioreactor bag, rather than evaluating the entirety of the exposed fluid surface in the bag. Furthermore, many such systems have been found to be generally effective only for detecting extreme foam events where the structure of the biomaterial or bag itself may have been compromised. Known solutions are also relatively large and expensive, and are not designed to ensure, for example, that a desired amount of anti-foam compound is applied in response to the actual foam level in the bag, and do not have the ability to quantify the amount of foam present.

[0006] In view of the foregoing, there is a need for an apparatus and system for observing fluid in a bioreactor bag that provides improved detection, monitoring, and mitigation of foam in the bag. Summary of the invention

[0007] The following summarizes certain embodiments that are comparable in scope to the original claimed subject matter. These embodiments are not intended to limit the scope of the claimed subject matter, but rather, these embodiments are intended only to provide a brief overview of possible embodiments. In fact, the present disclosure may encompass various forms that may be similar or different from the embodiments set forth below.

[0008] In an embodiment, a foam identification system includes a thermal imaging camera and a controller connected to the thermal imaging camera. The thermal imaging camera images the surface of the liquid in the vessel that is exposed to the head space of the vessel, the head space being warmer or cooler than the liquid. The camera and controller detect the temperature change of the exposed surface of the liquid to identify foam on the exposed surface of the liquid.

[0009] In another embodiment of the present invention, a method for identifying foam on the surface of liquid in a vessel includes: obtaining a temperature measurement of the liquid in the vessel; determining whether the head space of the vessel is warmer or cooler than the liquid; obtaining one or more temperature measurements of the surface of the liquid exposed to the head space of the vessel via a thermal imaging camera; detecting a temperature change of the exposed surface of the liquid; and identifying foam on the exposed surface based on the detected temperature change.

[0010] In yet another embodiment, a bioreactor system includes a frame, a thermal imaging camera, and a controller connected to the thermal imaging camera. The frame houses and supports the vessel. The thermal imaging camera is fixed to the frame and images the surface of the liquid exposed to the head space of the vessel. The head space is warmer or cooler than the liquid. The camera and controller detect the temperature change of the exposed surface of the liquid to identify foam on the exposed surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present invention will be better understood by reading the following description of non-limiting embodiments with reference to the accompanying drawings, in which:

[0012] Figure 1 is a front elevation view of a bioreactor system suitable for use with a foam identification system according to an embodiment of the present invention.

[0013] Figure 2 is a diagram of a foam identification system according to an embodiment of the present invention.

[0014] Figure 3 is a graph comparing the temperature within a bioreactor system over time.

[0015] Figure 4is a top view of a graph of foam levels within a bioreactor system as determined by a foam identification system in accordance with an embodiment of the present invention.

[0016] Figure 5 is a side cross-sectional view of a portion of a wall of a vessel configured for use with embodiments of the present invention.

[0017] Figure 6 is a side cross-sectional view of a viewing port of a vessel configured for use with embodiments of the present invention.

[0018] Figure 7 is an isometric view of an air curtain configured for use with embodiments of the present invention.

[0019] Figure 8 is a diagram of a foam identification system incorporating an air curtain according to an embodiment of the present invention.

[0020] Fig. 9 is a side view of a foam identification system according to an alternative embodiment of the present invention.

[0021] Fig.10 is a top view of a foam identification system according to an alternative embodiment of the present invention.

[0022] Fig.11 yes Fig.10 Side view of the foam identification system. DETAILED DESCRIPTION

[0023] Hereinafter, reference will be made in detail to exemplary embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference characters are used throughout the drawings to refer to the same or like parts.

[0024] As used herein, the terms "flexible" or "collapsible" refer to structures or materials that are pliable or capable of bending without breaking, and may also refer to compressible or expandable materials. An example of a flexible structure is a bag formed from a polyethylene film. The terms "rigid" and "semi-rigid" are used interchangeably herein to describe a "non-collapsible" structure, that is, a structure that does not fold, collapse, or otherwise deform to significantly reduce its elongated dimension under normal forces. Depending on the context, "semi-rigid" may also refer to a structure that is more flexible than a "rigid" element, such as a bendable tube or catheter, but is still a structure that does not collapse longitudinally under normal conditions and forces.

[0025] The term "vessel" as used herein means a flexible bag, a flexible container, a semi-rigid container, or a rigid container, as appropriate. The term "vessel" as used herein is intended to encompass bioreactor vessels having flexible or semi-rigid walls or portions of walls, single-use flexible bags, and other containers or conduits commonly used in biological or biochemical processes, including, for example, cell culture / purification systems, fermentation systems, mixing systems, media / buffer preparation systems, and filtration / purification systems.

[0026] As used herein, the term "bag" means a flexible or semi-rigid container or vessel that is used, for example, as a bioreactor or mixer for the contents therein. Although embodiments of the present invention are described for use with bioprocessing bags (including but not limited to bioreactor bags and mixer bags), embodiments may also be configured for use with other bags or vessels. Similarly, embodiments may be used to image, assess, and mitigate / treat other features or conditions in addition to the accumulation of foam in a bioreactor.

[0027] Furthermore, while the embodiments are described in conjunction with single-use stirred tank bioreactors and bioreactor systems, they are not limited thereto and may be used with a variety of vessels and associated equipment used in biological or biochemical processes. Additionally, the embodiments may be suitable for use in identifying foam in other non-biological / biochemical contexts. Certain embodiments may be useful in detecting other non-foam related conditions or events on a surface that may be identified via temperature differences or changes as described herein.

[0028] refer to Figure 1 , a bioreactor system 10 suitable for use with embodiments of the present invention is illustrated. The bioreactor system 10 includes a substantially rigid bioreactor housing 12 mounted atop a frame 14. The rigid housing 12 may be formed, for example, of stainless steel, polymers, composites, glass, or other metals, and may be cylindrical in shape, although other shapes may also be utilized without departing from the broader aspects of the present invention. As will be appreciated, the housing is configured to house and support vessels, such as a bioreactor bag 15. In certain embodiments, the housing 12 may be a substantially rectangular mixer housing.

[0029] As shown, a single-use flexible bioreactor bag 15 is disposed within the housing 12. As mentioned, the housing 12 can be of any size (or shape) as long as it is capable of supporting a vessel such as a single-use flexible bioprocess bag 15. For example, according to one embodiment, the housing 12 is capable of accepting and supporting a 10-2000 L flexible or collapsible bioprocess bag.

[0030] The bioreactor system 10 further includes a support structure 18 to which various equipment for biochemical and / or biological processes is attached. The support structure 18 can also be used to lift the bag 15 and hold the bag 15 in place within the housing 12. The support structure 18 is shown as having a plurality of leg portions 19, but other configurations may be employed.

[0031] Housing 12 includes an opening or aperture 20 where, among other things, a temperature probe 24 may be inserted into a thermowell or port in vessel 15 and then coupled, via, for example, a cable, to instrument tower 22. As will be appreciated, temperature probe 24 provides the temperature of the fluid in vessel 15.

[0032] Reference now Figure 2 , depicting a foam identification system 100 according to an embodiment of the present invention. As shown, the foam identification system 100 includes a thermal imaging camera 120 and a controller 130 operatively connected to the thermal imaging camera 120. In an embodiment, the thermal imaging camera 120 is fixed to the support structure 18 ( Figure 1 ). As described in more detail below, the thermal imaging camera 120 images the surface 142 of the liquid 144 in the vessel (e.g., bag) 15. In particular, the camera 120 images the surface 142 exposed to the head space 146 of the vessel 15. The head space 146 is the volume within the vessel 140 that is not occupied by the liquid 144 or the foam 148. The head space 146 includes a gas 147 (e.g., air) retained within the vessel 15, and the gas 147 is in contact with the exposed surface 142 of the liquid 144.

[0033] In the depicted embodiment, the vessel 15 includes an inlet 141 and an outlet 149 that allow a fluid (e.g., gas 147) to enter and exit the head space 146. The gas 147 within the head space 146 is warmer or cooler than the liquid 144 in the vessel 15. The temperature of the ambient air surrounding the vessel has a large effect on the temperature of the gas 147 within the head space 146. In an embodiment, even when the temperature of the gas 147 flowing into the head space 146 through the inlet 141 is not controlled, there is a sufficient temperature difference (e.g., 2-4°C) between the temperature of the liquid 144 and the temperature of the gas 147. Given the temperature difference between the temperature of the gas 147 and the temperature of the liquid 144, the camera 120 and the controller 130 can detect changes in the temperature of the exposed surface 142 to identify the presence and amount of foam 148 on the surface 142.

[0034] In an embodiment, thermal imaging camera 120 utilizes mid- to long-wavelength infrared imaging to collect temperature and radiation measurement data by directly reading heat without illumination. The mid- and long-wavelength infrared imaging discussed herein is not to be confused with short-wave or near-wavelength infrared imaging that requires illumination to generate an image. In some embodiments, thermal imaging camera 120 detects infrared light having a wavelength from about 7 μm to about 14 μm.

[0035] It is noteworthy that the thermal imaging camera 120 sees a wide field of view V rather than a point source, which is important due to the unpredictable nature of foam accumulation. In an embodiment, the field of view V is substantially the entirety of the exposed surface 142. In certain embodiments, the thermal camera 120 may utilize a wide angle lens and may include an auto focus function.

[0036] In an embodiment, the camera 120 and the controller 130 detect a change in temperature of the exposed surface 142 of the liquid 144 that indicates the formation or presence of foam 148 on the exposed surface 142. More specifically, the temperature of the exposed surface 142 of the liquid 144 will deviate (i.e., increase or decrease) from the temperature of the liquid 144 in the vessel 15 that is not exposed to the headspace, depending on whether the headspace is warmer or cooler than the liquid 144.

[0037] In certain embodiments, the thermal imaging camera 120 is radiometric. The thermal imaging camera 120 with an integrated radiometer can provide temperature data for each pixel of the image, thereby enabling the system 100 to tabulate and quantify (e.g., create a histogram, etc.) the foam by percent area, height, persistence, etc. The thermal imaging camera 120 allows the system 100 to obtain a thermal map without the need for an algorithm and to model the thermal map as height and / or over time.

[0038] The foam identification system 100 may also include a temperature control system that maintains the headspace 146 at a temperature that is warmer or cooler than the temperature of the liquid 144. The temperature control system may include a gas temperature controller 160 and at least one temperature monitor 162. In a specific embodiment, the temperature control system may utilize one or more temperature monitors 162, which may include a monitor 162 for gas flowing into the vessel 15 via the inlet 141, a monitor 162 for the temperature of the headspace 146, and / or a monitor for gas flowing out of the vessel outlet 149. As will be appreciated, various temperature monitors, such as temperature probe sensors, etc., may be utilized without departing from the scope of the present invention. In an embodiment, a temperature sensor 164 is used to monitor an area of ​​interest, i.e., the outer surface of the vessel 15, without contacting the environment inside the vessel. The gas temperature controller 160 and / or the temperature monitor 162 communicate with the controller 130 to provide the desired temperature.

[0039] The temperature monitor 162 detects the temperature of the gas flowing into the head space 146 through the inlet 141, the temperature of the gas flowing out of the head space 146 through the outlet 149, and / or the temperature of the gas 147 within the head space 146. In response to the measured temperatures, the temperature control system can adjust the head space temperature to maintain it at a set temperature or a certain degree (e.g., 5° C.) higher or lower than the temperature of the liquid 144 in the vessel 15. In an embodiment, the gas temperature controller 160 can be provided with a controlled temperature value of the liquid 144 in the vessel 15, can be provided with an ambient air value of the air outside the vessel 15, can be operably connected to a temperature probe 24 in a thermowell or port in the instrument tower 22 and / or the vessel 15, or can be operably connected to the temperature monitor 162 that detects the temperature of the gas flowing into the head space 146 through the inlet 141.

[0040] In other embodiments, the temperature of the liquid 144 in the vessel 15 can be approximated by measuring the temperature of the vessel wall through the exposed surface. More specifically, the temperature of the vessel wall through the exposed surface (if not blocked by foam) can be a suitable calibration substitute parameter for the controlled vessel temperature. That is, if the controlled vessel temperature is 37° C., for example, the thermal camera can be able to record the same temperature value by thermally imaging the vessel wall at or through the exposed surface. In this way, the system can be continuously calibrated without having to be provided with real-time temperature measurements of the liquid 144.

[0041] As will be appreciated, the gas temperature controller 160 may heat or cool the gas from the mass flow controller 180 before it is discharged into the head space 146 via the inlet 141. In an embodiment, the gas temperature controller 160 need not actively heat or cool the gas, but may simply comprise a coil that is close to the ambient air temperature. Such an embodiment may be effective where the difference between the temperature of the liquid 144 and the temperature of the ambient air outside of the vessel 15 is sufficient for foam detection. For example, an ambient air temperature of ~22°C may be sufficient.

[0042] In certain embodiments, the temperature control system and / or gas introduction may not be necessary and may be omitted entirely. Here, since the top of the vessel (e.g., bag) 15 containing the headspace 146 protrudes above and outside the rigid (e.g., stainless steel) vessel shell 12, the gas 147 in the headspace 146 will be sufficiently cooler than the liquid 144.

[0043] Alternative means of controlling the temperature of the gas 147 within the head space 146 (eg, heaters, lights, ambient air, etc.) do not depart from the invention disclosed herein.

[0044] Reference now Figure 2-4In an embodiment, the foam identification system 100 determines the presence and / or amount of foam for substantially all of the surface 142 of the liquid 144 exposed to the headspace 146. Typically, the headspace 146 will have a lower temperature than the temperature of the liquid in the vessel 15. The headspace 146 is exposed to ambient room air, which is at about 22°C, substantially cooler than the liquid temperature, which is typically set at about 37°C. The foam 148 on the exposed surface 146 will approach the temperature of the headspace 146 over time. The liquid on the exposed surface is less affected by the temperature of the headspace 146 and will remain relatively close to the controlled vessel temperature. As such, the presence and / or amount of foam can be identified based on temperature changes detected via thermal imaging, radiometric data, and / or the rate at which the exposed surface 142 changes temperature.

[0045] like Figure 3 , as the temperature of the gas 147 within the head space 146 decreases over time (represented by the lowest line on the graph), the foam temperature (middle line) approaches the head space temperature, as indicated by reference mark "A". As mentioned above, the liquid 144 (top line) is less affected by the temperature of the head space 146, as indicated by reference mark "B". The rate at which the surface temperature changes as the gas 147 within the head space 146 changes (as indicated by reference mark "C") is also an indicator of the formation and amount of foam on the surface 142. As will be appreciated, a relatively fast rate of temperature change indicates the formation of a relatively high amount / value of foam. Conversely, a slow rate of change indicates a relatively low amount / value of foam. A very slow rate of change may indicate normal cooling of the exposed surface 142 without the formation of foam.

[0046] By way of non-limiting example, Figure 4 The vessel 15 is shown set at a controlled vessel temperature of 37°C, having a headspace gas 147 having a lower temperature than the temperature of the liquid 144. In certain embodiments, it has been found that a temperature difference (positive or negative) of at least 0.5°C between the headspace gas 147 and the liquid 144 temperature is sufficient for foam identification, however a smaller temperature difference may also be sufficient. The exposed surface 142 is measured at 36°C, and the presence of low amount / value of foam is indicated by a measured surface temperature of 35°C, or 0.5 to 1.5 degrees lower than the exposed surface 142 temperature. High amount / value of foam is indicated by an exposed surface 142 temperature of 33°C, or 2-3 degrees lower than the liquid 144 temperature. In this example, the vessel wall temperature measured through the foam-free portion of the exposed surface 142 is found to be 37°C, the same as the controlled vessel temperature.

[0047] As will be appreciated, the specific temperature and / or magnitude of the temperature differential (higher or lower) indicative of foam may vary based on several factors including, but not limited to, the temperature of the headspace gas 147 and liquid 144 and the top purge gas flow temperature and rate.

[0048] As will be appreciated, embodiments of the present invention are useful in determining when chemical or mechanical defoaming should be performed, the amount of defoaming required for a given rate / amount of foam formation, and the efficacy of the defoaming treatment.

[0049] Reference now Figure 2 and Figure 6 In an embodiment, the foam identification system 100 includes a vessel 15 having a viewing port 50 that allows a thermal imaging camera 120 to image an exposed surface 142 of a liquid 144. In some embodiments, the viewing port 50 may be heated to reduce condensation, or may be equipped with an air curtain, as described in more detail below.

[0050] In an embodiment, the vessel 15 has a multilayer film construction including an innermost layer of a wetting material 200 (e.g., polyethylene) in contact with the liquid in the vessel. The observation port 50 may be formed on or bonded to the wetting material 200. In certain embodiments, the observation port 50 is made of low-density polyethylene (LDPE), which is a material that has been found to have excellent transmittance in the spectral range of interest (e.g., 7-14 μm). As will be appreciated, the thickness of the observation port 50 may vary depending on the material properties. Other materials with the desired transmittance may be utilized without departing from the scope of the present invention. In certain embodiments, polypropylene and polystyrene may be utilized.

[0051] In some embodiments, the viewing port 50 may be a single layer or multiple layers of the same material as the vessel 15 itself. In other words, the vessel 15 may not have a dedicated viewing port having a configuration that deviates from the configuration of the vessel 15. For example, a 15 to 20 mil thick LDPE sheet may provide suitable transmittance and structure for such an embodiment. In still other embodiments, the port 50 may be an internal wetted material 200 layer and may be formed by simply removing a layer located on top of the wetted material 200.

[0052] In certain embodiments, the viewing port 50 is circular and is significantly wider / larger in diameter than the lens of the thermal camera 120. Other viewing port 50 sizes and shapes may be employed without departing from the invention.

[0053] As mentioned, the camera 120 may be mounted on the support structure 18 so that the camera 120 is positioned above the vessel 15 and aimed vertically downward so that substantially all of the exposed surface 142 may be imaged. In this regard, the viewing port 50 may be located on an upper or top surface of the vessel 15. As will be appreciated, the viewing port 50 may be located in a variety of locations so long as substantially all of the exposed surface 142 may be imaged.

[0054] In one embodiment, the foam identification system 100 includes an air curtain 52, such as Figure 7 and Figure 8 . The air curtain 52 reduces vessel condensation to facilitate thermal imaging of the exposed surface 142. In an embodiment, the air curtain 52 is located within the vessel (e.g., bag) 15 and is aimed at the observation port 50, or other optically clear observation area of ​​the vessel 15. The air curtain 52 may be removable or fixedly attached to the wall of the vessel 15, and may utilize a gas (e.g., air, O2, or N2) in an existing top purge gas flow from a mass flow controller 180. As will be appreciated, in embodiments in which the air curtain 52 utilizes an existing gas flow, no additional hardware is required, only the air curtain 52 need be added to the vessel 15. In addition, the existing top purge gas flow provides a gas supply with a very low dew point below -40°C, which is ideal for preventing condensation. In addition, the use of the air curtain 52 may make the use of a heater unnecessary.

[0055] Specifically refer to Figure 7 , the exemplary air curtain 52 includes a nozzle or outlet portion 53 (through which the gas / air flow is directed) and a threaded base portion 55. The threaded base portion 55 can be directly attached to the mass flow controller 180 ( Figure 8 ) or otherwise connected to its fluid.

[0056] In use, the air curtain 52 directs the gas / air flow F toward the viewing port 50 to clear condensate from the area. In certain embodiments, the air curtain 52 may be selectively positionable so that the gas flow F can be directed by an operator to maximize the removal of condensate. In addition, the speed of the gas / air flow F may vary depending on the moisture content of the air in the head space, the temperature of the air in the head space, or other variables. In this regard, the air curtain 52 may be paired with a sensor or meter to measure moisture content, etc.

[0057] As will be appreciated, the air curtain 52 may be used to clear condensation from portions of the vessel / bag for purposes other than thermal imaging, such as for various external optical measurements.

[0058] In certain other embodiments, an air knife may be employed, however additional pressurized air and flow control may be required in such a configuration.

[0059] Reference now Figure 9-11 , alternative arrangements of thermal cameras may be employed. In one embodiment, thermal camera 120 may be positioned so that it images the side of the headspace of vessel 15. Such an arrangement may be suitable for vessels (e.g., bags) made entirely of material that is substantially transparent in the thermal spectrum, or vessels with side viewing ports.

[0060] In another embodiment, the system may include multiple thermal cameras 120 spaced around the perimeter of the vessel 15 and aimed at the headspace. In certain embodiments, one or more thermal cameras may be built into the rigid bioreactor housing 12. In still other embodiments, the thermal camera may be integral to the vessel / bag itself. In embodiments with multiple cameras or cameras built into the vessel / bag, lower resolution thermal imaging cameras may be used to reduce costs.

[0061] In use, the system 100 identifies the presence and / or amount of foam 148 on the surface 142 of the liquid 144 exposed to the headspace 146 in a variety of ways. In one embodiment, the system 100 detects the rate of temperature change on the exposed surface 142. In another embodiment, the thermal camera 120 and the controller 130 identify areas of foam 148 by comparing the temperature of the exposed surface 142 to the temperature of the liquid 144 to assess whether the exposed surface 142 is warmer or cooler than the liquid 144 by a predetermined amount, which is indicative of foam.

[0062] In yet another embodiment, the thermal camera 120 and controller 130 identify areas of the exposed surface 142 as foam 148 by comparing the temperature of the exposed surface 142 to the temperature of the headspace 146 to assess whether the exposed surface 142 is within a predetermined temperature range of the headspace temperature indicative of foam.

[0063] A method for identifying foam 148 on a surface of liquid 144 in a vessel 15 is provided. The method includes: obtaining a temperature measurement of the liquid 144 in the vessel 15; determining whether a headspace 146 of the vessel 15 is warmer or cooler than the liquid 144; obtaining one or more temperature measurements of a surface 142 of the liquid 144 exposed to the headspace 146 of the vessel 15 via a thermal imaging camera 120; detecting a change in temperature of the exposed surface 142 of the liquid 144; and identifying foam 148 on the exposed surface 142 based on the detected temperature change.

[0064] In one embodiment, the step of identifying foam 148 on exposed surface 142 includes comparing the temperature of exposed surface 142 of liquid 144 to the temperature of liquid 144 to assess whether exposed surface 142 is a predetermined amount warmer or cooler than liquid 144, which is indicative of foam. In another embodiment, the step of identifying foam 148 on exposed surface 142 includes comparing the temperature of exposed surface 142 to the temperature of headspace 146 to assess whether exposed surface 142 is within a predetermined temperature range of the headspace temperature indicative of foam.

[0065] In yet another embodiment, the step of identifying the foam 148 on the exposed surface 142 includes: obtaining a plurality of temperature measurements of the exposed surface 142 of the liquid 144; determining a rate of temperature change on the exposed surface 142 based on the plurality of temperature measurements of the exposed surface 142; and identifying the presence and / or amount of foam 148 on the surface of the liquid 144 by comparing the rate of temperature change to a predetermined value indicative of foam.

[0066] In one embodiment, the step of identifying foam 148 incorporates the step of maintaining the temperature of the headspace 146 warmer or cooler than the liquid 144. In one embodiment, the method of identifying foam 148 also includes mitigating the detected foam 148 on the exposed surface 142 of the liquid 144, for example, by applying an anti-foam agent to the vessel 15.

[0067] In an embodiment, the method of identifying foam 148 further includes removing condensation from the viewing port 50 of the vessel 15 via a condensation prevention system (eg, air curtain 52 , etc.) to facilitate identifying foam 148 by the thermal imaging camera 120 .

[0068] In some embodiments, the foam identification system 100 provides anti-foam injection feedback by analyzing foam levels during and after use of mechanical or gaseous solutions in addition to chemical anti-foam agents.The thermal imaging camera 120 provides data quantifying the input of anti-foam agents and / or the response of the foam 148 to the anti-foam agents.

[0069] As used herein, an element or step that is narrated in the singular and begins with the word "one" or "a kind of" should be understood as not excluding a plurality of said elements or steps, unless such exclusion is explicitly stated. In addition, reference to "one embodiment" of the present invention is not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the described features. In addition, unless explicitly stated to the contrary, an embodiment that "comprises", "includes" or "has" an element or multiple elements with a particular characteristic may include additional such elements that do not have that characteristic.

[0070] This written description uses examples to disclose several embodiments of the invention (including the best mode), and also to enable one of ordinary skill in the art to practice the embodiments of the invention (including making and using any devices or systems and performing any incorporated methods). The patentable scope of the invention is defined by the claims, and may include other examples that occur to one of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if such other examples include equivalent structural elements that are not substantially different from the literal language of the claims.

Claims

1. A foam identification system, comprising: a thermal imaging camera configured to image surfaces of liquid and foam in a vessel, the surfaces being exposed to a headspace of the vessel, the headspace being warmer or cooler than the liquid and the foam; a controller operatively connected to the thermal imaging camera; and Wherein the camera and the controller are configured to detect a change in temperature of the exposed surface to identify foam on the exposed surface.

2. The foam identification system according to claim 1, further comprising: A temperature control system is configured to maintain the headspace at a temperature warmer or cooler than the liquid.

3. The foam identification system according to claim 2, wherein: The temperature control system comprises: A gas temperature controller and at least one temperature monitor to detect the temperature of at least one of gas flowing into the head space, gas flowing out of the head space, and gas surrounding the vessel.

4. The foam identification system according to claim 1, further comprising: A temperature monitor is configured to measure a temperature of the head space.

5. The foam identification system according to claim 1, wherein: The thermal imaging camera provides data quantifying the input of anti-foam agent and / or the response of the foam to the anti-foam agent.

6. The foam identification system according to claim 1, wherein: The thermal imaging camera detects infrared light having a wavelength from about 7 μm to about 14 μm.

7. The foam identification system according to claim 1, wherein: The thermal imaging camera is radiometric.

8. The foam identification system according to claim 1, further comprising: A vessel having a viewing port configured to allow the thermal imaging camera to image the exposed surface of the liquid.

9. The foam identification system according to claim 8, wherein: The viewing port is heated to reduce condensation.

10. The foam identification system according to claim 1, further comprising: An air curtain is configured to reduce vessel condensation to facilitate thermal imaging of the exposed surface.

11. The foam identification system according to claim 1, further comprising: A housing is configured to house and support the vessel, the housing having a support structure to which the thermal imaging camera is mounted.

12. The foam identification system according to claim 11, wherein: The camera is mounted on the support structure such that the camera is positioned above the vessel and is aimed vertically downward so that substantially all of the exposed surface can be imaged.

13. The foam identification system according to claim 1, wherein: The vessel is a collapsible bioreactor bag.

14. The foam identification system according to claim 1, wherein: The system is configured to identify the presence and / or amount of foam on the surface of the liquid exposed to the headspace by detecting a rate of temperature change on the exposed surface.

15. The foam identification system according to claim 1, wherein: The camera and the controller identify areas of the exposed surface by comparing a temperature of the exposed surface to a temperature of the liquid to assess whether the exposed surface is warmer or cooler than the liquid by a predetermined amount, the predetermined amount indicative of foam.

16. The foam identification system according to claim 1, wherein: The camera and the controller identify areas of the exposed surface as foam by comparing a temperature of the exposed surface to a temperature of the headspace to assess whether the exposed surface is within a predetermined temperature range of the headspace temperature indicative of foam.

17. The foam identification system according to claim 1, wherein: The head space is cooler than the liquid in the vessel.

18. A method for identifying foam on the surface of a liquid in a vessel, comprising the steps of: obtaining a temperature measurement of the liquid in the vessel; determining whether a headspace of the vessel is warmer or cooler than the liquid; obtaining, via a thermal imaging camera, at least one temperature measurement of surfaces of the liquid and foam exposed to the headspace of the vessel; Detect temperature changes on exposed surfaces; as well as Foam is identified on the exposed surface based on the detected temperature change.

19. The method according to claim 18, wherein: The step of identifying foam on the exposed surface comprises: The temperature of the exposed surface is compared to the temperature of the liquid to assess whether the exposed surface is warmer or cooler than the liquid by a predetermined amount, the predetermined amount being indicative of foam.

20. The method according to claim 18, wherein: The step of identifying foam on the exposed surface comprises: The temperature of the exposed surface is compared to the temperature of the headspace to assess whether the exposed surface is within a predetermined temperature range of the headspace temperature that is indicative of the foam.

21. The method according to claim 18, wherein: The step of identifying foam on the exposed surface comprises: obtaining a plurality of temperature measurements of the exposed surface; determining a rate of temperature change on the exposed surface based on the plurality of temperature measurements of the exposed surface; and The presence and / or amount of foam on the surface of the liquid is identified by comparing the rate of temperature change to a predetermined value indicative of foam.

22. The method of claim 18, further comprising providing data quantifying input of an anti-foam agent and / or a response of the foam to the anti-foam agent.

23. The method according to claim 18, further comprising the steps of: The temperature of the headspace is maintained either warmer or cooler than the liquid.

24. The method according to claim 18, wherein: The head space is cooler than the liquid.

25. The method according to claim 18, further comprising the steps of: Foam detected on the exposed surface of the liquid is mitigated.

26. The method of claim 18, wherein: The thermal imaging camera detects infrared light having a wavelength from about 7 μm to about 14 μm.

27. The method according to claim 18, wherein: The thermal imaging camera is radiometric.

28. The method of claim 18, wherein: The step of determining whether the headspace of the vessel is warmer or cooler than the liquid comprises: The temperature of the head space is obtained via a head space temperature sensor and compared to the temperature measurement of the liquid.

29. The method of claim 18, wherein: The step of determining whether the headspace of the vessel is warmer or cooler than the liquid comprises: The temperature of the portion of the vessel wall in the head space is obtained via the thermal imaging camera, and the vessel wall temperature is then compared to the temperature measurement of the liquid.

30. The method according to claim 18, further comprising the steps of: Condensate is removed from the vessel via a condensation prevention system to facilitate identification of foam by the thermal imaging camera.

31. A bioreactor system comprising: a housing configured to receive and support the vessel; a thermal imaging camera secured to the housing, the thermal imaging camera configured to image a surface of the liquid and foam, the surface being exposed to a headspace of the vessel, the headspace being warmer or cooler than the liquid; a controller operatively connected to the thermal imaging camera; and Wherein the camera and the controller are configured to detect a change in temperature of the exposed surface to identify foam on the exposed surface.

32. The bioreactor system of claim 31 , further comprising: A temperature control system is configured to maintain the headspace at a temperature warmer or cooler than the liquid.

33. The bioreactor system of claim 32, wherein: The temperature control system comprises: A gas temperature controller and at least one temperature monitor to detect the temperature of at least one of gas flowing into the head space, gas flowing out of the head space, and gas surrounding the vessel.

34. The bioreactor system of claim 31 , further comprising: A temperature monitor is configured to measure a temperature of the head space.

35. The foam identification system of claim 31, wherein: The thermal imaging camera provides data quantifying the input of anti-foam agent and / or the response of the foam to the anti-foam agent.

36. The bioreactor system of claim 31, wherein: The thermal imaging camera detects infrared light having a wavelength from about 7 μm to about 14 μm.

37. The bioreactor system of claim 31, wherein: The thermal imaging camera is radiometric.

38. The bioreactor system of claim 31, further comprising: A vessel having a viewing port configured to allow the thermal imaging camera to image the exposed surface.

39. The bioreactor system of claim 38, wherein: The viewing port is heated to reduce condensation.

40. The bioreactor system of claim 31, further comprising: An air curtain is configured to reduce vessel condensation to facilitate thermal imaging of the exposed surface.

41. The bioreactor system of claim 40, further comprising a vessel; and in, The air curtain is located within the vessel.

42. The bioreactor system of claim 31, wherein: The camera is mounted on the support structure such that the camera is positioned above the vessel and is aimed vertically downward so that substantially all of the exposed surface can be imaged.

43. The bioreactor system of claim 38, wherein: The vessel is a collapsible bioreactor bag.

44. The bioreactor system of claim 31, wherein: The system is configured to identify the presence and / or amount of foam on the surface of the liquid exposed to the headspace by detecting a rate of temperature change on the exposed surface.

45. The bioreactor system of claim 31, wherein: A camera and controller identify areas of the exposed surface by comparing the temperature of the exposed surface to the temperature of the liquid to assess whether the exposed surface is warmer or cooler than the liquid by a predetermined amount, the predetermined amount indicative of foam.

46. ​​The bioreactor system of claim 31, wherein: The camera and the controller identify areas of the exposed surface as foam by comparing a temperature of the exposed surface to a temperature of the headspace to assess whether the exposed surface is within a predetermined temperature range of the headspace temperature indicative of foam.

47. The bioreactor system of claim 31, wherein: The head space is cooler than the liquid in the vessel.

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