Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays.
We present a soft lithographic method to fabricate multiphenotype cell arrays by capturing cells within an array of reversibly sealed microfluidic channels. The technique uses reversible sealing of elastomeric polydimethylsiloxane (PDMS) molds on surfaces to sequentially deliver various fluids or cells onto specific locations on a substrate. Microwells on the substrate were used to capture and immobilize cells within low shear stress regions inside channels. By using an array of channels it was possible to deposit multiple cell types, such as hepatocytes, fibroblasts, and embryonic stem cells, on the substrates. Upon formation of the cell arrays on the substrate, the PDMS mold could be removed, generating a multiphenotype array of cells. In addition, the orthogonal alignment and subsequent attachment of a secondary array of channels on the patterned substrates could be used to deliver fluids to the patterned cells. The ability to position many cell types on particular regions within a two dimensional substrate could potentially lead to improved high-throughput methods applicable to drug screening and tissue engineering.
Khademhosseini
Ali
A
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Yeh
Judy
J
Eng
George
G
Karp
Jeffrey
J
Kaji
Hirokazu
H
Borenstein
Jeffrey
J
Farokhzad
Omid C
OC
Langer
Robert
R
D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology*; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods; D018920:Coculture Techniques / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005434:Flow Cytometry / Q000295:instrumentation* / Q000379:methods; D017022:Flow Injection Analysis / Q000295:instrumentation / Q000379:methods; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D010641:Phenotype