Systems and methods for producing bioproducts
Inventors
Ray, Roderick J. • Carroll, Adam S. • Downey, Brandon J. • Graham, Lisa J.
Assignees
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Publication Number
US-12281297-B2
Publication Date
2025-04-22
Expiration Date
Abstract
The present disclosure is directed to systems and methods for sampling and/or controlling the productivity of a bioreactor. The system and methods can include a vessel capable of providing an environment suitable for containing whole broth that can produce the bioproduct, wherein the whole broth contains media and at least one undissolved species, an automated sampling system, a first analytical instrument, and a control system.
Core Innovation
The invention relates to systems and methods for making a bioproduct by using an automated sampling system to extract a sample from a vessel containing whole broth that can produce the bioproduct. The whole broth contains media and at least one undissolved species, selected from live cells, dead cells, cell fragments, solid substrates having cells adhered thereto, and mixtures thereof. The sample is delivered to an analytical instrument where at least one property of the whole broth in the sample is measured.
In response to the measured property, the system generates at least one first signal and then generates at least one output signal that controls at least one device configured to alter at least one property of the whole broth within the vessel. The device alters the at least one property within the vessel based on the generated output signal, thereby integrating aseptic automated sampling, analytics, and control in the process of making a bioproduct.
The automated sampling system is operably connected to the vessel and capable of extracting the sample from the vessel at predetermined intervals. The automated sampling system comprises a variable volume reservoir including a reservoir, a reservoir inlet, and a reservoir outlet different from the reservoir inlet, and extracting the sample comprises delivering the sample into the reservoir through the reservoir inlet and discharging the sample from the reservoir by reducing a volume of the reservoir so the sample exits through the reservoir outlet.
Claims Coverage
Independent claim clm-00001 covers a complete closed-loop method for making a bioproduct using automated extraction of whole broth, analytical measurement, signal generation, and control of devices to alter broth properties. The claim includes 4 inventive features relating to automated sampling with a variable volume reservoir and periodic sampling intervals, along with defining undissolved species categories.
Automated periodic aseptic sampling of whole broth containing undissolved species
Extracting a sample from a vessel containing whole broth that can produce the bioproduct, where the whole broth contains media and at least one undissolved species selected from live cells, dead cells, cell fragments, solid substrates having cells adhered thereto, and mixtures thereof, with the automated sampling system operably connected to the vessel and capable of extracting the sample from the vessel at predetermined intervals.
Analytical measurement of whole broth properties delivered from the sample
Delivering the sample to an analytical instrument and measuring at least one property of the whole broth in the sample with the analytical instrument, generating at least one first signal in response to the measured at least one property.
Signal-driven device control to alter broth properties within the vessel
Generating at least one output signal that controls at least one device configured to alter at least one property of the whole broth within the vessel, where the at least one output signal is generated in response to the at least one first signal, and altering the at least one property of the whole broth within the vessel by the at least one device.
Variable volume reservoir sampling architecture with inlet/outlet and movable member
Having the automated sampling system comprise a variable volume reservoir including a reservoir, a reservoir inlet, and a reservoir outlet different from the reservoir inlet, with extracting the sample comprising delivering the sample into the reservoir through the reservoir inlet and discharging the sample from the reservoir by reducing a volume of the reservoir to cause the sample to exit the reservoir through the reservoir outlet, where the variable volume reservoir comprises a movable member and a housing and the movable member moves between a first position drawing sample and a second smaller volume discharging sample.
The inventive concept is the combination of periodic automated sampling of whole broth containing undissolved species, measurement with an analytical instrument to generate signals, and using those signals to control in-vessel devices that alter broth properties, implemented with a variable volume reservoir sampling architecture using a movable member between drawing and discharging positions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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