title: Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care.
abstract: Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care.
authors.affiliation: Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering &Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Pinera
authors.affiliation: Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Ningren
authors.initials: N
authors.lastname: Han
authors.affiliation: Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering &Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Cleto
authors.affiliation: Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering &Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Jicong
authors.identifier: 0000-0002-5253-3365
authors.initials: J
authors.lastname: Cao
authors.affiliation: Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering &Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Purcell
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Kartik A
authors.initials: KA
authors.lastname: Shah
authors.affiliation: Pharyx Inc., Woburn, Massachusetts 01801, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ram
authors.affiliation: Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering &Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02412, USA.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lu
mesh_terms: D001688:Biological Products; D019149:Bioreactors; D004958:Estradiol / Q000378:metabolism; D005818:Genetic Engineering; D010843:Pichia / Q000378:metabolism*; D019095:Point-of-Care Systems; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000627:therapeutic use; D058615:Synthetic Biology; D014170:Transformation, Genetic
chemical_list: D001688:Biological Products; D011994:Recombinant Proteins; D004958:Estradiol