A microfluidic array with cellular valving for single cell co-culture.
We present a highly parallel microfluidic approach for contacting single cell pairs. The approach combines a differential fluidic resistance trapping method with a novel cellular valving principle for homotypic and heterotypic single cell co-culturing. Differential fluidic resistance was used for sequential single cell arraying, with the adhesion and flattening of viable cells within the microstructured environment acting to produce valves in the open state. Reversal of the flow was used for the sequential single cell arraying of the second cell type. Plasma stencilling, along the linear path of least resistance, was required to confine the cells within the trap regions. Prime flow conditions with minimal shear stress were identified for highly efficient cell arraying (∼99%) and long term cell culture. Larger trap dimensions enabled the highest levels of cell pairing (∼70%). The single cell co-cultures were in close proximity for the formation of connexon structures and the study of contact modes of communication. The research further highlights the possibility of using the natural behaviour of cells as the working principle behind responsive microfluidic elements.
Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Otto-Hahn-Str. 6b, D-44227, Dortmund, Germany.
Jean-Philippe
JP
Frimat
Marco
M
Becker
Ya-Yu
YY
Chiang
Ulrich
U
Marggraf
Dirk
D
Janasek
Jan G
JG
Hengstler
Joachim
J
Franzke
Jonathan
J
West
D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D059010:Single-Cell Analysis / Q000295:instrumentation* / Q000379:methods; D046888:Tissue Array Analysis / Q000295:instrumentation* / Q000379:methods