Microfluidic encapsulation of cells in alginate capsules for high throughput screening

Abstract

Microdroplet systems can drastically reduce costs and increase throughput in high throughput screening (HTS) assays. While droplets are well suited for biomolecular screening, cell-based screens are more problematic because eukaryotes typically require attachment to solid supports to maintain viability and function. This paper describes an economical, off-the-shelf microfluidic system which encapsulates eukaryotic cells in gelatinous alginate capsules for the purpose of HTS. The flow-through system consists of i) a cross junction, which forms monodisperse droplets of alginate and cell suspension in an immiscible carrier fluid, followed by ii) a T junction which delivers BaCl(2) to crosslink and solidify each droplet. With an appropriate carrier fluid, the system is self-synchronized and can produce cell-alginate-BaCl(2) capsules with virtually 100% reliability. Droplet volumes and frequency are determined by flow rates and the diameter of the cross junction. The present implementation, which utilizes 1.5 mm Teflon tubing and plastic junctions, can generate 0.4-1.4 microL droplets at frequencies >10 droplets/sec. Cell viability is >80% at 4 hours post-encapsulation. With low recurring cost (<USD 2) and no need for automation robots, this can be an initial step towards economical cell-based HTS.