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Publication Number
US-11999932-B2
Publication Date
2024-06-04
Expiration Date
Abstract
The present invention is related to the field of fluidic devices, and in particular, microfluidic cell culture systems. The present invention provides pumping, recirculation and sampling for a microfluidic device or devices. The present invention provides solutions to the control of microfluidics for both terrestrial and space applications, including the control over the movement of fluids in zero gravity or microgravity.
Core Innovation
The invention relates to a microfluidic cell-culture control platform and a method of moving liquid that uses a container with one or more liquid reservoirs in fluidic communication with one or more fluidic devices and with a first working fluid reservoir and a second working fluid reservoir. The container further comprises a portion of the second working fluid, and there is no mixing of the working fluid with the liquid. Pressure is imparted to the second working fluid by introducing the first working fluid such that liquid in the one or more reservoirs is displaced and flows into the one or more fluidic devices, thereby moving the liquid.
The platform provides microfluidic control using a sealed container and conduits-only fluid exchange so the working fluid does not contact or mix with the culture media. The assembly includes flexible cell culture media reservoirs and one or more flexible reagent reservoirs, together with a pump and a working fluid reservoir. Working-fluid pumping displaces culture media into one or more microfluidic devices to perfuse cells without displacing reagent, and then working-fluid pumping can displace reagent from at least one flexible reagent reservoir into the microfluidic devices for introduction of reagent.
For downstream handling, the platform includes a method of collecting samples from microfluidic devices without mixing of working fluid with cell culture media by pumping working fluid to displace culture media into the microfluidic devices and into a sampling conduit. Samples are collected from the sampling conduit. The platform also enables recirculating culture media through microfluidic devices without reversing the direction of fluid flow, by moving fluid from outlet ports into a recirculation pathway in a direction of inlet ports while preventing mixing of the working fluid with the cell culture media.
Claims Coverage
The partial claim set includes four independent claims. Across these independent claims, the main inventive theme is pumping a working fluid to displace and move cell-culture liquids through microfluidic devices while maintaining no mixing of the working fluid with the culture media, coupled with sealed, conduits-based fluid exchange and microfluidic-specific operations for perfusion, reagent introduction, sampling, and recirculation.
No-mixing pressure-driven liquid displacement using first and second working fluids
A method of moving liquid that provides an assembly with one or more liquid reservoirs contained within a container in fluidic communication with a first working fluid reservoir and a second working fluid reservoir; the container further comprises a portion of the second working fluid; there is no mixing of the working fluid with the liquid; introducing the first working fluid into the container under conditions that pressure is imparted on the second working fluid such that liquid in the one or more reservoirs is displaced and flows into one or more fluidic devices, thereby moving the liquid.
Reagent introduction to microfluidic devices via separate displacement of culture media and flexible reagent reservoirs
A method of introducing reagent into microfluidic devices that provides an assembly comprising one or more flexible cell culture media reservoirs and one or more flexible reagent reservoirs within a container, the container in fluidic communication with a pump and a working fluid reservoir, and that there is no contact or mixing of the working fluid with the cell culture media; pumping the working fluid into the container so culture media is displaced and flows into the microfluidic devices to perfuse cells while reagent is not displaced; and pumping the working fluid so reagent in at least one flexible reagent reservoir is displaced and flows into the microfluidic devices, thereby introducing reagent.
Sample collection from microfluidic devices using a working-fluid displacement into a sampling conduit
A method of collecting samples from microfluidic devices that provides an assembly with reservoirs containing cell culture media in fluidic communication with one or more microfluidic devices, and with a sampling conduit such that there is no mixing of the working fluid with the cell culture media; pumping the working fluid into the container so the culture media is displaced and flows into the microfluidic devices causing fluid to exit the microfluidic devices and enter the sampling conduit; and collecting samples from the sampling conduit.
Recirculating culture media without reversing fluid flow
A method of recirculating culture media through microfluidic devices without reversing the direction of fluid flow that provides an assembly with reservoirs in fluidic communication with one or more microfluidic devices and a recirculation pathway, wherein there is no mixing of the working fluid with the cell culture media; and pumping the working fluid into the container such that culture media flows into the one or more microfluidic devices in a direction so that fluid exits an outlet port and enters the recirculation pathway, moving in the direction of the inlet port.
Across the independent claims, the coverage centers on pumping a working fluid to displace culture media and move liquids through microfluidic devices while maintaining no mixing between the working fluid and the culture media, and then extending this displacement concept to perfuse cells with culture media, to introduce reagent via separately displaced flexible reagent reservoirs, to collect samples via a sampling conduit, and to recirculate culture media through a recirculation pathway without reversing flow direction.
Stated Advantages
Allows moving liquid by displacing and flowing liquid into one or more fluidic devices using pressure imparted on a working fluid.
Prevents mixing of working fluid with liquid during liquid displacement.
Provides reagent introduction into microfluidic devices without displacing reagent during culture-media perfusion.
Allows perfusion of cells while avoiding contact or mixing of the working fluid with the cell culture media.
Enables sample collection from a sampling conduit using a system where there is no mixing of the working fluid with the cell culture media.
Enables recirculating culture media through microfluidic devices without reversing the direction of fluid flow.
Documented Applications
Perfusing cells on a surface in one or more microfluidic devices by displacing culture media into the microfluidic devices using a working fluid.
Introducing reagent into microfluidic devices by displacing reagent from flexible reagent reservoirs into the microfluidic devices.
Collecting samples from microfluidic devices by directing fluid into a sampling conduit and collecting samples from the sampling conduit.
Recirculating culture media through microfluidic devices by moving culture media into devices and returning fluid via a recirculation pathway without reversing fluid flow direction.
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