Integrated biofabrication for electro-addressed in-film bioprocessing.
Many recent advances in bioprocessing have been enabled by developments in miniaturization and microfluidics. A continuing challenge, however, is integrating multiple unit operations that require distinct spatial boundaries, especially with included labile biological components. We have suggested "biofabrication" as a means for organizing cells and biomolecules in complex configurations while preserving function of individual components. Polysaccharide films of chitosan and alginate that are assembled on-chip by electrodeposition are "smart" configurable interfaces that mediate communication between the biological systems and microfabricated devices. Here, we demonstrate the scalable performance of a production address, where incubated cells secrete antibodies, and a capture address, where secreted antibody is retained with specificity and subsequently assayed. The antibody exchange from one electro-address to another exemplifies integrated in-film bioprocessing, facilitated by the integrated biofabrication techniques used. This in-film approach enables complex processes without need for microfluidics and valving. Finally, we have shown scalability by reducing electrode sizes to a 1 mm scale without compromising film biofabrication or bioprocessing performance. The in situ reversible deposition of viable cells, productivity characterization, and capture of secreted antibodies could find use in bioprocessing applications such as clonal selection, run-to-run monitoring, initial scale-up, and areas including drug screening and biopsy analysis.
Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Jessica L
JL
Terrell
Tanya
T
Gordonov
Yi
Y
Cheng
Hsuan-Chen
HC
Wu
Darryl
D
Sampey
Xiaolong
X
Luo
Chen-Yu
CY
Tsao
Reza
R
Ghodssi
Gary W
GW
Rubloff
Gregory F
GF
Payne
William E
WE
Bentley
D000464:Alginates / Q000737:chemistry*; D000906:Antibodies / Q000737:chemistry*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D055664:Electrochemical Techniques / Q000379:methods*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008839:Microelectrodes
D000464:Alginates; D000906:Antibodies; D006603:Hexuronic Acids; D007074:Immunoglobulin G; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D048271:Chitosan