Droplet-Based Microfluidic Platforms for the Encapsulation and Screening of Mammalian Cells and Multicellular Organisms

Abstract

High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

An optimised detector for in-situ high-resolution NMR in microfluidic devices

“…In particular, they provide very tightly controlled and tailored environments for the culture of cells [1,2], tissues [3], and small organisms [4]. In principle, NMR spectroscopy would complement such systems very well, enabling non-destructive and non-invasive observation of metabolic processes over a period of time.…”

Encapsulation of single cells into monodisperse droplets by fluorescence-activated droplet formation on a microfluidic chip

“…In addition to compartmentalizing reactions, droplet-based microfluidics can also be used to encapsulate prokaryotic [14][15][16][17][18] and eukaryotic cells [19][20][21][22][23], and even the embryos of multicellular organisms [24,25], which opens up a new avenue for cell analysis. Recently, Brouzes et al [19] developed a droplet-based viability assay that permitted quantitative analysis of cell viability and growth within compartmentalized aqueous droplets.…”

“…By encapsulating human monocytic U937 cells, they screened a drug library for its cytotoxic effect against the U937 cells. Clausell-Tormos et al [24] reported a droplet-based microfluidic platform, in which human cells were compartmentalized and grown in aqueous droplets separated by carrier oil with biocompatible surfactants. Droplets containing cells could then be collected and incubated for several days.…”

Single cell kinase signaling assay using pinched flow coupled droplet microfluidics

“…The capillary electrophoresis system was automatized to analyze $3.5 cells/min. [4][5][6][7][8][9][10] Compared with these methods, the droplet based technology is attractive [11][12][13][14][15][16][17][18][19][20][21] because of its ultra high throughput cell encapsulations ($1000 droplets/s) [22][23][24] and accurate fluidic controls. Accordingly, a wide range of droplet base single cell polymerase chain reactions (PCR) were carried out in previous studies.…”