Process technology for biological product manufacturing and downstream purification
Inventors
Criscione, Jason M. • Ersen, Ali • Linton, John R. • Datwani, Sammy S.
Assignees
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Publication Number
US-11396526-B2
Publication Date
2022-07-26
Expiration Date
Abstract
Provided herein are, inter alia, biological manufacturing and downstream purification processes.
Core Innovation
The invention provides a free-flow electrophoresis apparatus for separating a mixture into two or more fractions, at least one fraction containing a biological product. Continuous fluid flow is enabled between at least one inlet and at least one outlet, and separation is performed using a fluidic channel created between two parallel plates configured to create an electric field gradient orthogonal to the direction of fluid flow.
The apparatus includes electrode channels comprising an anodic electrode channel and a cathodic electrode channel, connected to the main separation channel by liquid contact through a wall gap positioned between the electrode channels and the main separation channel. The design further includes at least one electrode channel de-bubbler comprising at least one gas permeable and hydrophobic membrane or porous material configured to remove electrolysis bubbles near the point of generation by a vacuum system, to create a bubble-free main separation channel.
Operational stability and integration are addressed by at least one liquid circuit breaker configured to disconnect a liquid connected to voltage prior to interacting with at least one sensor or detector. The apparatus also includes an active cooling system and at least one collection vessel, and staged purification is described by connecting at least two free-flow electrophoresis apparatuses in series and operating in one or more electrophoresis modes including isoelectric focusing mode, zone electrophoresis mode, and isotachophoresis mode.
Claims Coverage
The claim coverage identifies one independent claim defining a free-flow electrophoresis apparatus architecture with five main inventive features: continuous flow separation with an orthogonal electric field gradient, coupled anodic/cathodic electrode channels through a wall gap, bubble-free operation using a de-bubbler with vacuum and hydrophobic gas-permeable or porous materials, a liquid circuit breaker before sensing/detection, and active cooling with a collection vessel.
Continuous fluid flow separation with orthogonal electric field gradient
A free-flow electrophoresis apparatus for separating a mixture into two or more fractions, at least one fraction containing a biological product, comprising at least one inlet and at least one outlet permitting continuous fluid flow, and at least one fluidic channel between two parallel plates configured to create an electric field gradient orthogonal to the direction of fluid flow.
Anodic and cathodic electrode channels coupled via a wall gap
Electrode channels comprising an anodic electrode channel and a cathodic electrode channel, connected to the main separation channel by liquid contact through a wall gap positioned between the electrode channels and the main separation channel.
Vacuum-assisted bubble-free electrode-channel de-bubbler
At least one electrode channel de-bubbler comprising at least one gas permeable and hydrophobic membrane or porous material configured to remove electrolysis bubbles near the point of generation by a vacuum system to create a bubble-free main separation channel.
Liquid circuit breaker to disconnect voltage-connected liquid before sensing
At least one liquid circuit breaker configured to disconnect a liquid connected to voltage prior to interacting with at least one sensor or detector.
Active cooling and collection vessel integration
An active cooling system and at least one collection vessel.
Across the independent claim, the inventive coverage centers on a continuous free-flow electrophoresis architecture that uses parallel-plate channels with an orthogonal electric field gradient, couples anodic and cathodic electrode channels to the main separation channel through a wall gap, and removes electrolysis bubbles using a gas permeable and hydrophobic membrane or porous material de-bubbler with vacuum. The claim set also covers a liquid circuit breaker before sensing/detection, together with active cooling and a collection vessel.
Stated Advantages
Continuous steady-state operation.
Reduced risk of bubble interference by creating a bubble-free main separation channel.
High-throughput purification.
Reduced footprint.
Reduced product loss.
Reduced membrane fouling/occlusion.
Documented Applications
Separating a mixture into two or more fractions, where at least one fraction contains a biological product, using free-flow electrophoresis.
Staged purification by connecting at least two free-flow electrophoresis apparatuses in series and operating in one or more electrophoresis modes including isoelectric focusing mode, zone electrophoresis mode, and isotachophoresis mode.
Continuous biological-product purification workflow that optionally couples dynamic filtration with magnetic affinity/charge-based modules and free-flow electrophoresis.
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