Cell culture and cell assays using digital microfluidics

摘要

Devices and methods for implementing cell-based assays and long-term cell culture. The device and method are based on digital microfluidics (DMF) which is used to actuate nanoliter droplets of reagents and cells on a planar array of electrodes. DMF method is suitable for assaying and culturing both cells in suspension and cells grown on surface (adherent cells). This method is advantageous for cell culture and assays due to the automated manipulation of multiple reagents in addition to reduced reagent use and analysis time. No adverse effects of actuation by DMF were observed in assays for cell viability, proliferation, and biochemistry. These results suggest that DMF has great potential as a simple yet versatile analytical tool for implementing cell-based assays and cell culture on the microscale.

主权项

1. A digital microfluidic device for conducting cell assays and cell culture, comprising:
a first substrate; a first array of discrete electrodes formed on said first substrate; at least one first coating covering each discrete electrode, such that said discrete electrodes are electrically insulated from one another, and wherein an outer surface of said at least one first coating forms a first hydrophobic working surface; a second substrate; at least one second coating covering the second substrate, wherein an outer surface of the at least one second coating forms a second hydrophobic working surface; at least one reference electrode provided on said first substrate or said second substrate; wherein said second substrate is provided in a spaced relationship relative to said first substrate, thus defining a space between said first substrate and said second substrate capable of contacting a cell-containing liquid droplet between said first hydrophobic working surface and said second hydrophobic working surfaces; wherein said discrete electrodes and said reference electrode are connectable to an electrode controller, such that said discrete electrodes and said reference electrode may be activated to translate the cell-containing liquid droplet; and wherein one or both of said first hydrophobic working surface and said second second hydrophobic working surface includes at least one locally modified hydrophilic hydrophilic region, such that within said locally modified hydrophilic region, said one or both of said first hydrophobic working surface and said second hydrophobic working surface is configured for cell attachment and cell culture, and wherein said discrete electrodes and said reference electrode may be activated to selectively contact the cell-containing liquid droplet with said locally modified hydrophilic region for attachment of cells from the cell-containing liquid droplet to said locally modified hydrophilic region for subsequent cell culture.