Portable Fluidic Platform For Rapid Cell-Free Production of Protein Biologics

• Main Authors: Pendleton, Erik D, Sasmor, Henri M, Dresios, John, Hicks, William L, Amendt, Eric M, Sullivan, Challise J, Griffey, Richard Holmes
• Format: Patent
• Language: English
• Published: 21.05.2020
• Subjects: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SEPARATION; SPIRITS; TRANSPORTING; VINEGAR; WINE

A portable fluidic platform for rapid and flexible end-to-end production of recombinant protein biologics includes a bioreactor system hosting stable and robust cell-free translation systems that is fluidically integrated with modular protein separation functionalities (e.g., size exclusion, ion exchange or affinity chromatography systems) for purification of the cell-free expressed product and which are configurable for process-specific isolation of different proteins, as well as for formulation. The bioreactor utilizes lysates from engineered eukaryotic (e.g., yeast) or prokaryotic (e.g., bacterial) strains that contain factors for protein folding and posttranslational modifications. Combination of various purification modules on the same fluidic platform allows flexibility of re-routing for purification of different proteins depending on specific target requirements. Protein synthesis and purification modules are integrated into self-contained disposable fluidic cartridge that eliminates cross-contamination between runs. The platform allows for flexible production of protein biologics within 24 hours (from DNA to purified product).