Patent Application
20210395668
The present disclosure relates generally to devices for producing biological organisms, and more particularly, the monitoring of growth of biological organisms in such devices.
Photobioreactors are reactors that utilize a light source to support the growth of phototrophic microorganisms in a controlled, artificial environment. Photobioreactors may be used to support photosynthetic growth of various different organisms using, e.g., carbon dioxide and light. Examples of organisms that have been grown using photobioreactors include algae (e.g., macroalgae and/or microalgae), plants, mosses, cyanobacteria, and purple bacteria.
A monitoring system for a bioreactor is disclosed. In one embodiment, a monitoring system includes a cuvette arranged to receive a fluid from a bioreactor, wherein the fluid includes a portion of a biomass. The system further includes a light source arranged to project light, at wavelengths absorbable by the biomass, into the cuvette. A sensor is arranged to detect portions of the light that are not absorbed by the biomass. The system further includes a controller coupled to receive an indication of an amount of light detected by the sensor. The indication of the amount of detected light is usable to determine an amount of biomass in the cuvette.
In one embodiment, the monitoring system may be used to determine an amount of biomass in the bioreactor. The controller may be coupled to a computer system, and may convey the indication (or information corresponding thereto) to the computer system. The computer system can then use this indication/information to determine an amount of biomass in the cuvette and thus extrapolate to determine the amount of biomass in the bioreactor. Over a number of samples, a rate of change of the amount of biomass in the bioreactor can also be determined.
In various embodiments, the light projected into the cuvette may be at wavelengths that are absorbable by the biomass. Thus, the sensor detects only the remaining portion of the light that is not absorbed by the biomass and thus passes through the cuvette. For example, the biomass may be one or more strains of algae, with light projected at wavelengths that are absorbed by those algae strains. The amount of light detected by the sensor may thus be less than the amount of light projected. Accordingly, the relationship between the amount of biomass in the cuvette and the amount of light detected by the sensor is an inverse relationship.
The following detailed description makes reference to the accompanying drawings, which are now briefly described.
Although the embodiments disclosed herein are susceptible to various modifications and alternative forms, specific embodiments are shown by way of example in the drawings and are described herein in detail. It should be understood, however, that drawings and detailed description thereto are not intended to limit the scope of the claims to the particular forms disclosed. On the contrary, this application is intended to cover all modifications, equivalents and alternatives falling within the spirit and scope of the disclosure of the present application as defined by the appended claims.
This disclosure includes references to “one embodiment,” “a particular embodiment,” “some embodiments,” “various embodiments,” or “an embodiment.” The appearances of the phrases “in one embodiment,” “in a particular embodiment,” “in some embodiments,” “in various embodiments,” or “in an embodiment” do not necessarily refer to the same embodiment. Particular features, structures, or characteristics may be combined in any suitable manner consistent with this disclosure.
Within this disclosure, different entities (which may variously be referred to as “units,” “mechanisms,” other components, etc.) may be described or claimed as “configured” to perform one or more tasks or operations. This formulation [entity] configured to [perform one or more tasks] is used herein to refer to structure (i.e., something physical), More specifically, this formulation is used to indicate that this structure is arranged to perform the one or more tasks during operation. A structure can be said to be “configured to” perform some task even if the structure is not currently being operated. A “controller configured to control a system” is intended to cover, for example, a controller that has circuitry that performs this function during operation, even if the controller in question is not currently being used (e.g., is not powered on). Thus, an entity described or recited as “configured to” perform some task refers to something physical, such as a device, circuit, memory storing program instructions executable to implement the task, etc. This phrase is not used herein to refer to something intangible.
Reciting in the appended claims that a structure is “configured to” perform one or more tasks is expressly intended not to invoke 35 U.S.C. § 112(f) for that claim element. Accordingly, none of the claims in this application as filed are intended to be interpreted as having means-plus-function elements. Should Applicant wish to invoke Section 112(f) during prosecution, it will recite claim elements using the “means for” [performing a function] construct.
As used herein, the term “based on” is used to describe one or more factors that affect a determination. This term does not foreclose the possibility that additional factors may affect the determination. That is, a determination may be solely based on specified factors or based on the specified factors as well as other, unspecified factors. Consider the phrase “determine A based on B.” This phrase specifies that B is a factor that is used to determine A or that affects the determination of A. This phrase does not foreclose that the determination of A may also be based on some other factor, such as C. This phrase is also intended to cover an embodiment in which A is determined based solely on B. As used herein, the phrase “based on” is synonymous with the phrase “based at least in part on.”
As used herein, the phrase “in response to” or “responsive to” describes one or more factors that trigger an effect. This phrase does not foreclose the possibility that additional factors may affect or otherwise trigger the effect. That is, an effect may be solely in response to those factors, or may be in response to the specified factors as well as other, unspecified factors. Consider the phrase “perform A in response to B.” This phrase specifies that B is a factor that triggers the performance of A. This phrase does not foreclose that performing A may also be in response to some other factor, such as C. This phrase is also intended to cover an embodiment in which A is performed solely in response to B.
As used herein, the terms “first,” “second,” etc. are used as labels for nouns that they precede, and do not imply any type of ordering (e.g., spatial, temporal, logical, etc.), unless stated otherwise.
When used in the claims, the term “or” is used as an inclusive or and not as an exclusive or. For example, the phrase “at least one of x, y, or z” means any one of x, y, and z, as well as any combination thereof.
In the following description, numerous specific details are set forth to provide a thorough understanding of the disclosed embodiments. One having ordinary skill in the art, however, should recognize that aspects of disclosed embodiments might be practiced without these specific details. In some instances, well-known circuits, structures, signals, computer program instruction, and techniques have not been shown in detail to avoid obscuring the disclosed embodiments.
The present disclosure is directed to a monitoring system for a bioreactor. A bioreactor is an apparatus in which chemical processes that include the activity of biological organisms are carried out. For example, bioreactors can be used in the production of algae for other uses, although the disclosure is not limited to this application or this type of biomass.
In the apparatus of the present disclosure, the amount of biomass in the bioreactor may be periodically determined using the monitoring system. In particular, a sample of a fluid (e.g., water) that includes the biomass is transferred to a cuvette in the monitoring system. The cuvette includes optically clear (transparent) surfaces through which light can be projected, e.g., in the performance of spectrophotometry. The light projected into the cuvette may be done so at wavelengths that are absorbable by the biomass. A sensor receives a portion of the projected light that is not absorbed by the biomass and generates a corresponding indication. This indication is usable to determine the amount of biomass in the cuvette, which in turn may be extrapolated to determine the amount of biomass in the bioreactor. Over a number of periodic samples, a rate of change of the amount of biomass can be determined.
The monitoring system of the present disclosure also contemplates a cleaning cycle. Subsequent to performing a sampling, various embodiments of the monitoring system cause the cuvette to be flushed with a cleaning fluid. Embodiments are also possible and contemplated in which the cuvette includes a revolver-type structure wherein only one portion of the structure is actively used in the cuvette at a given time. Inactive portions may undergo a more thorough cleaning between uses as the active portion.
The monitoring system 100 shown here includes a cuvette 102 which is arranged to receive fluid from the bioreactor 150, as well as receiving fluid from a cleaning fluid source 180. A first valve 111 is coupled between the bioreactor 150 and a conduit 131 of the cuvette 102. The valve 111, in this embodiment, is controllable via a relay 121, which can be used to open and close the valve 111 based on signals received thereby. When open, the valve 111 allows fluid containing a portion of the biomass to flow from the bioreactor 150 into the conduit 131 of the cuvette 102.
The cuvette 102 of the illustrated embodiment includes both conduit 131 and conduit 133 which are commonly coupled to a mixing chamber 132. As noted above, a conduit 131 is arranged to convey fluid from the bioreactor 150 into the mixing chamber 132. A second conduit 133 is arranged to convey cleaning fluid into the mixing chamber 132. Similar to the arrangement discussed above, a valve 113 is coupled between the cleaning fluid source 180 and the cuvette 102. The valve 113 may be opened and closed by the relay 123 in response to a signal received by the latter.
Various types of cleaning fluid may be used for cleaning operations. In one embodiment, water is used as the cleaning fluid, although other types of fluids (which may include water) can be used as desired. Furthermore, in some embodiments, the cleaning fluid source 180 may be arranged to apply pressure to the cleaning fluid when conveyed into the cuvette 102. This may be useful, for example, when the types of biomass received by the cuvette 102 have a tendency to build up on its inner surfaces.
Another valve 112 and relay 122 combination in the embodiment shown is arranged to cause draining of the cuvette 102. The relay 122 may be used to open the valve 112 when it is desirable to drain fluid from the cuvette 102. When it is desired that the cuvette 102 retain fluid, the valve 112 is closed. After a sample of biomass is taken, the valve 112 may be opened to drain the cuvette 102 while returning the fluid containing the biomass back to the bioreactor 150. During cleaning operations, the mixing chamber 132 may be flushed with cleaning fluid while the valve 112 coupled thereto may remain open. Although not shown here, additional valves and pipes may be present to allow draining of the cleaning fluid to another location not associated with the bioreactor 150.
Sampling of the biomass may be performed using a light source 141 and a sensor 142 arranged near the mixing chamber 132 of the cuvette 102. The light source 141 may be any suitable type of light source, such as one or more light emitting diodes (LEDs), lasers (which can be coherent for specific wavelengths), or any other suitable type of illuminator. In various embodiments, the light source 141 projects light at wavelengths that are absorbable by the biomass. In one embodiment, the biomass comprises one or more strains of algae that absorb light in the visible spectrum range of 380-750 nanometers (nm). Accordingly, the light source 141 used in such an embodiment is selected to project light primarily within the visible spectrum. More generally, the wavelengths projected by the light source 141 in various embodiments may be selected based on the type of biomass to be processed in the bioreactor 150, and may include all or part of the visible spectrum.
Additional embodiments having different types of light sources are possible and contemplated. For example, an RGB (Red-Green-Blue) LED using pulse width modulation (PWM) is contemplated as a light source for another embodiment. The wavelengths used may be, in various embodiments, any visible wavelength in the 380-750 nm range. Generally, any suitable type of light source for the given implementation may be selected and used to project light into the cuvette for the purpose of sampling the biomass.
The sensor 142 is arranged to receive at least some of the light projected by the light source 141. In one embodiment, the sensor 142 may be arranged on an opposite side (relative to the light source 141) of the mixing chamber 132 of the cuvette 102. In some embodiments, the sensor 142 may be selected to be particularly sensitive to the wavelengths projected by the light source 141, while rejecting other wavelengths.
In the example of
Based on the detected light, the sensor 142 generates an indication, which may include one or more signals that are indicative of both the intensity and distribution of the light. In various embodiments, there is an inverse relationship between the amount of light detected by the sensor 142 (in terms of both intensity and distribution) and the amount of biomass in the mixing chamber.
Operations of the monitoring system 100 in the embodiment shown is conducted by a controller 105. In the embodiment shown, the controller 105 is coupled to the relays 121, 122, and 123 associated with valves 111, 112, and 113, respectively. Controller 105 is also coupled to the light source 141, and the sensor 142. To cause a sample of the biomass to be conducted, the controller 105 may cause the relay 121 to open valve 111, while keeping valves 112 and 113 shut. The valve 111 may be held open for a specified amount of time and/or until the cuvette 102 has received a specified amount of fluid (containing biomass) from bioreactor 150. Upon the cuvette 102 having received the specified amount of fluid, controller 105 may change the state of signals conveyed to the relay 121 to cause the valve 111 to be shut.
After allowing some settling time following the transfer of fluid from the bioreactor 150 into the cuvette 102, controller 105 continues the sampling process by conveying a signal to light source 141. Responsive to this signal, light source 141 begins projecting light into the cuvette 102. If biomass is present in the portion of cuvette 102 in which the light is projected (e.g., mixing chamber 132 in this example), some of this light may be absorbed. As noted above, light source 141 is configured in various embodiments to project light at wavelengths that are absorbed by the expected type of biomass. The light that traverses the entire distance through cuvette 102 may be detected by sensor 142. The light detected by sensor 142 results in the generation of an indication that is usable to determine the amount of biomass currently in the cuvette 102. The indication in one embodiment comprises signals indicative of the intensity and distribution of light received by the sensor.
Monitoring system 100 also includes computer system 106. Controller 105 in the embodiment shown forwards the indication received from sensor 142 to computer system 106. Embodiments are possible and contemplated in which controller 105 performs some pre-processing on the indication prior to forwarding to computer system 106. Upon receiving the indication (pre-processed or not), computer system 106 determines the amount of biomass present in the cuvette 102 for the given sample. Computer system 106 may also extrapolate from the amount of biomass determined to be in cuvette 102 to calculate an amount of biomass present in bioreactor 150. Over a number of different samples, computer system 106 may determine a rate of change (e.g., rate of growth) of the amount of biomass in the bioreactor. For example, if the bioreactor 150 is used to generate algae, computer system 106 may determine the rate of growth of the algae, and this information can be used to determine a time to harvest.
Upon completing of a sample in the illustrated embodiment, the controller 105 conveys a signal to relay 122 in order to cause the opening of the valve 112. When valve 112 is opened, the cuvette 102 is drained of fluids contained therein. In this example, the fluid, including the biomass is transferred back to the bioreactor 150. Although not explicitly shown, a pump may be implemented between valve 112 and bioreactor 150 to facilitate the transfer of fluid.
A cleaning operation may be performed by monitoring system subsequent to conducting a sample. After the fluid containing the biomass has been transferred back into the bioreactor 150, controller 105 may initiate the cleaning operation by causing relay 123 to open valve 113. When open, valve 113 allows cleaning fluid to be transferred into conduit 133 of cuvette 102. In some embodiments, cleaning fluid source 180 may include a pump or other mechanism to cause the cleaning fluid to be provided at a pressure greater than ambient pressure. The cleaning fluid may be any suitable cleaning fluid, and may be as simple as water. The cleaning fluid may exit cuvette 102 through the bottom of mixing chamber 132 and through valve 112, which remains open during the cleaning operation. In some embodiments, the cleaning fluid (e.g., water) may be transferred to bioreactor 150 and can thus be used as a base for the growth of biomass therein. In other embodiments, additional valves not explicitly shown here may be present to drain the cleaning fluid away from the bioreactor. The cleaning operation may be terminated by controller 105 causing relay 123 close valve 113 and, subsequently (e.g., after the cuvette has been fully drained), causing relay 122 to close valve 112.
In various embodiments, the controller functions carried out by controller 105 may be performed using artificial intelligence (AI) based analysis. For example, machine learning can be used to account for cloudiness in performing samples, where the cloudiness results from biomass adhering to the inner surfaces of cuvette 102 even after cleaning. Various forms of AI-based analysis may also be used to, e.g., adjust the sampling periodicity or other functions related to the automation of the sampling process. The AI/machine learning functions may be carried out on computer system 106 in one embodiment. In another possible embodiment, controller 105 may include functionality capable of carrying out the various AI/machine learning functions. These functions may also be divided between controller 105 and computer system 106 in some embodiments.
The sequence discussed above is further illustrated in the table illustrated in
It is noted that the sequence numbers shown in
In sequence step 0 in the chart of
In sequence step 1, the mix flow valve is open while the algae flow and water flow valve remains closed. If any excess fluid is still present in cuvette 102 at this time, it may be drained in response to the opening of the mix flow valve. Sequence step 2 corresponds to the cleaning operation, and includes both the mix flow valves and water flow valves being open. It is noted that the cleaning operation may be performed both before and after a sampling operation in some embodiments.
A fill operation is illustrated as sequence step 3. During the fill operation, the algae flow valve is open, while the water flow and mix flow valves are closed. There may, in some embodiments, be a delay (e.g., 10 seconds, as shown here) between the time the valves are positioned as listed and the beginning of algae water flow into the cuvette 102. Once flow begins, algae water flows into cuvette 102 through conduit 131. The fill operation may continue for a specified time and/or until a specified amount of algae water has been transferred into the cuvette 102.
In sequence step 4, a sampling operation is performed. Upon filling the cuvette 102 to the specified amount, the algae flow valve is closed. After the fill operation is complete, there may be a waiting period (e.g., 5 seconds as shown here) to allow the settling of the fluid transferred. When enough time has elapsed for the fluid to settle, sampling may be performed. In this particular example, sampling includes activating a red LED, reading the sensor, and taking an average of the light value detected thereby. This average may be used to generate an indication that is forwarded to, e.g., controller 105 and computer system 106 for further processing to determine an amount of algae present in the cuvette during the given sample. It is noted, however, that the light source may be something other than an LED, and similarly, the sensor may operate in a different manner than in this particular example.
In sequence step 5, a cleaning operation (similar to that of sequence step 2) may be performed. In some embodiments, the cleaning operation may be skipped at this point. Generally speaking, a cleaning operation may be performed at any desired time in accordance with the specifications of the particular implementation of monitoring system 100. In the example shown, after completion of sequence step 5, and in accordance with sequence step 6, the monitoring system 100 may return to the normal phase.
Method 300 includes transferring a first fluid from a bioreactor to a mixing chamber of a cuvette, wherein the first fluid includes a portion of a biomass generated by the bioreactor (block 305). The method further includes projecting light, from a light source, into the cuvette, wherein the light is projected at wavelengths absorbable by the biomass (block 310). After projecting the light from the light source, the method includes detecting, using a sensor, portions of the light not absorbed by the biomass (block 315). After detecting portions of the light not absorbed by the biomass, the method continues with receiving, at a controller, an indication of an amount of the light detected by the sensor (block 320). Thereafter, the method includes determining, using a computer system coupled to the controller, an amount of biomass present in the bioreactor based on the indication (block 325).
In various embodiments, the method includes, repeating, over a number of periodic intervals, the transferring, the projecting, the detecting, the receiving and the determining. Based on these repeated samples, the method may also include calculating, using indications received over the number of periodic intervals a rate of growth of the biomass.
Performing a sample in various embodiments includes causing a first relay to open a first valve using the controller and receiving, in the cuvette, the first fluid from the bioreactor, in response to opening the first valve. Thereafter, the method includes causing the first relay to close the first valve subsequent to the cuvette receiving a specified amount of the first fluid.
Cleaning operations may also be performed at various times during operation of the monitoring system. Accordingly, the method further includes the controller causing a cleaning operation to be performed, wherein performing the cleaning operation comprises. Causing the cleaning operation includes the controller causing a second relay to open a second valve. In response to opening the second valve, the method includes draining the cuvette in response to opening the second valve and causing a third relay to open a third valve, using the controller. Thereafter, the method includes flushing the cuvette with a cleaning fluid received via the third valve. To complete the clearing operation, the flow of cleaning fluid may be cut off by closing the third valve after a specified amount of time, followed by closing the second valve subsequent to closing the third valve.
The monitored biomass may be virtually any type of biomass that can be part of a biochemical reaction occurring in a bioreactor. In one embodiment, the biomass may be one or more different strains of algae. In such an embodiment, projecting light at wavelengths absorbable by the biomass comprises projecting light at wavelengths from 380 nanometers to 750 nanometers, which is the visible spectrum.
Method 400 includes opening a biomass valve and transferring fluid containing a portion of the biomass therein into a cuvette (block 405). The biomass valve may correspond to, for example, valve 111 of monitoring system 100 shown in
Upon completing the transfer of the biomass-containing fluid, the fluid may be allowed to settle for a specified time. Once settle, the method continues with the projecting of light into the cuvette, the detecting of an amount of light passing through the cuvette, generating an indication of the amount of light detected, and providing the indication to a controller (block 415). The light may, in various embodiments, be projected at wavelengths that are absorbable by the particular type of biomass. The amount of light detected may thus have an inverse relationship with the amount of biomass in the cuvette. Thus, greater amounts of biomass present in the cuvette may correspond to lower amounts of light detected.
After the indication has been generated, Method 400 continues with the opening of a drain valve and the return of the biomass-containing fluid to the bioreactor (block 420). The drain valve may correspond to, e.g., valve 112 of the system illustrated in
Method 500 begins with the taking of a first sample of biomass to determine a first amount of biomass in a bioreactor (block 505). The sample may determine an amount of biomass in a cuvette. Subsequently, an extrapolation may be performed to determine an amount of biomass in the bioreactor based on the amount of biomass detected in the cuvette. At a specified time subsequent to that of the first biomass sample, a second sample is taken to determine a second amount of biomass in the bioreactor (block 510). A difference between the first and second amounts of biomass is then determined (block 515). Based on the elapsed time and difference in amount of biomass between the first and second sample, the rate of growth of the biomass is determined (block 520).
More generally, the methodology discussed herein contemplates determining a rate of change of the amount of biomass. The change in the biomass can include an increase or a decrease. The information obtained by this methodology can be used in various ways. For example, the information may be used to determine when it is time to harvest the biomass when the bioreactor is used in a production environment. In another example, the methodology discussed herein may be used to determine the efficacy of a process used to generate biomass in, e.g., a research environment.
Although the example above is applied to the mixing chamber portion of cuvette 102, the revolver structure may be utilized with, e.g., either one or both of the conduits 131 and 133. Embodiments are possible and contemplated in which all three portions of the cuvette shown in
Utilization of an embodiment of the revolver structure 600 may allow for more thorough cleaning of inactive portions thereof. For example, manual cleaning may be performed on portions of the revolver structure not currently in use and/or may allow for the use of stronger cleaning agents while alleviating the chances of contaminating the biomass/fluid in the bioreactor.
Numerous variations and modifications will become apparent to those skilled in the art once the above disclosure is fully appreciated. It is intended that the following claims be interpreted to embrace all such variations and modifications.
This Application claims priority to U.S. Provisional Patent Application 63/042,965, file Jun. 23, 2020, and which is hereby incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63042965 | Jun 2020 | US |
