Summer 2018
Drug Discovery World
Microfluidics Driving Innovation and Streamlining Single Cell Analysis
By Dr Frank F. Craig
Summer 2018

Microfluidic platforms that harness picodroplet technology (picolitre volume aqueous droplets in stabilised oil emulsions) are unlocking the potential of single cell analysis to enable exciting new discoveries and advances with the potential to transform scientific research, drug development and precision medicine.

These systems compartmentalise single cells and trap their released molecules, enabling tens of millions of novel single cell tests to be performed on each biochip per day.

Our scientific understanding of cellular processes and signalling pathways has historically been informed by analyses of cellular populations, providing a global appreciation of molecular responses to external stimuli. However, this approach is inherently limited as it provides information only regarding the average response of the population and doesn’t account for heterogeneity (1). Bulk assays also mask the many complex multifunctional processes occurring at a single cellular level that allow fine tuning of specific biological responses, such as immunological pathways where the quality of an individual cell’s response may be more important than the overall level (1-3).

The introduction of single cell analysis technologies has opened up new possibilities for the study of rare variant cells, found in both naturally occurring and engineered populations (4). Examples of rare cells include circulating tumour cells (CTCs), antigen-specific lymphocytes within the immune system and haematopoietic stem cells (HSCs) (4). These rare variants, occurring at rates of one in a million or one in a billion, can reveal insights concerning cancer-causing mutations, novel approaches to treatment, drug resistance and discovery of new viable medicines (5). Single cell analysis has driven a rapid evolution in scientific understanding regarding cellular variability and differentiation between tissue types as well as variants within individual tissues.

These advances are providing a deeper appreciation of important variations in gene expression, cell cycle processes and responses to specific environmental factors (5). Projects such as the Human Cell Atlas Project are using single cell techniques to map and explore critical cellular differences within individuals and comparing these variations across populations (6). This work will highlight critical modifications associated with disease to aid the development of highly efficacious medicines with improved toxicity profiles (6).

In an industry that is becoming increasingly focused on precision medicines, the biopharmaceutical community has embraced the opportunity of single cell analysis in both naturally occurring and engineered cell lines. Molecules such as cytokines and antibodies represent novel and extremely commercially attractive therapeutic options for the management of cancers, inflammatory disorders and immunological diseases. Monoclonal antibodies are now the fastest growing therapeutic class (7,8).

Forecasts suggest that this market will be worth approximately $125 billion by 2020 (7,8). Unsurprisingly, many commercial developers are now seeking the most efficient and precise methods of monoclonal antibody identification and generation to meet the growing demand and advance this field of medicine (7,8). These types of treatment support a more targeted approach to disease management, but identification of those rare cells producing the highest quality and/or yield of a specific molecule may require analysis of millions or billions of cells...

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