Each droplet represents an individual reaction vessel. (Image: Fabrice Gielen)
The days when scientists carried out experiments by mixing chemicals in large glass flasks are long gone. Nowadays, tests are performed in trays punctuated by a number of “microwell” holes that mean just a few microlitres (millionths of a litre) of each sample is needed. The difficulty with going much smaller is that it’s hard to move liquid around at this scale because really tiny drops tend to clump together or evaporate (Lab on a Chip, "Dynamics of microfluidic droplets").
Although the potential of encapsulating single cells was identified as early as the 1950s (Nature, "Antibody Production by Single Cells"), the droplet field has really picked up pace with the emergence of fabrication technologies borrowed from the semiconductor industry.
Droplets are an attractive proposition for tackling needle-in-a-haystack problems, such as isolating very rare cells with a unique mutation or molecular make-up. For example, cells from a tumour can sometimes break off and circulate through the bloodstream, potentially causing cancer elsewhere in the body (metastasis). Finding a way to detect these circulating tumour cells (CTCs) would essentially provide a blood test update on the state of a patient’s cancer. But they are very hard to find because they exist at concentrations as low as one per 10 ml of blood (Nature Reviews Cancer, "Challenges in circulating tumour cell research"). Using a microdroplet technique could allow doctors to quickly comb through the cells from a patient’s blood sample to find a CTC (Molecular Oncology, "Droplet Digital PCR of Circulating Tumor Cells From Colorectal Cancer Patients Can Predict KRAS Mutations Before Surgery").
Microdroplet techniques do have their limits. For example, small molecules can sometimes diffuse through the oil phase making droplets in effect leaky compartments. Yet there are still many potential advances to be made. For example, one can envision truly personalised medicine where many different drugs are rapidly tested against many different patient cells to find which one is best to prescribe. Microdroplets have had just a decade of use. Think of what they could achieve in the future.
Source: By Fabrice Gielen. Research Fellow in Microfluidics, University of Exeter