potential to enhance the range of technologies in which microfluidics may be applied26. Splitting picodroplets may further increase the throughput of picodroplet production and increase assay sen- sitivity25. In addition to human cell analysis, picodroplet

microfluidic systems are demonstrating increasing value in the exploration of microbial resistance and biodiversity25. One of the issues associated with metagenomic analysis of microbial colonies is that virulent, fast-growing strains can out-grow slower growing cultures and this diversity is lost when examining samples using traditional whole genome amplification (WGA) techniques27. Picodroplet microfluidic systems separate the different micro- bial strains for analysis so that insights can be drawn from each strain independently27. The applications and possibilities for this tech-

Sphere Fluidics Cyto-Mine®

New horizons in microfluidics Genome editing and tissue engineering are emerg- ing areas that are also embracing microfluidic innovations21,23. Genetic reprogramming of cell lines, such as stem cells, has generated a number of excellent in vitro models for research concerning signalling pathways, cellular behaviour and human disease24. With traditional methodologies, this area of research faced similar challenges (in terms of throughput and specificity) to that of rare cell detection and isolation. Manual identification of targets among hundreds of thousands of cells was limited by excessive costs and resulted in scientists constraining analyses to lower numbers, making recognition of specific cell types extremely diffi- cult. Microfluidic techniques have been shown to improve efficiency of genetic editing and cellular reprogramming processes by as much as 50-fold24. The confined and easily regulated microenviron- ment also results in production of high quality and durable cell lines. Pioneering concepts that are taking microfluidic

technology to new levels include the development of picodroplet fusion that will provide insights concerning specific cell-cell interactions and pair- ing. This concept is being adapted for single cell genome editing studies25,26. Picodroplet fusion may also facilitate parallel detection procedures (eg mass spectrometry and functional assays), offering further efficiencies and allowing in-depth analysis of precious cellular/tissue samples. Picodroplet splitting or fission also has the


nology are expanding rapidly as it becomes adopt- ed more extensively across the academic research and commercial biopharmaceutical sectors. Stripping away much of the complexity associated with multi-process analysis and speeding up deliv- ery of results has opened up new opportunities to improve understanding of cellular biology and its application in medicine.

Productive partnerships A number of exciting collaborations are ongoing in this area. For example, we are currently working with researchers to develop a machine that imple- ments high quality, automated, single cell engineer- ing/genome editing using an integrated system with- in a disposable biochip. Tools such as this will free researchers from lengthy, manual procedures, allow- ing them to focus instead on experimental design and interpretation of results. This tool should also cut consumable costs by minimally 50-fold. Many government and commercial stakeholders

have seen the potential of single cell analysis tech- nology and forged partnerships that have nurtured and driven the development of microfluidic inno- vations. Much of this work has been supported by grants from national funding bodies, such as Innovate UK, as well as biopharmaceutical com- panies, fuelling the field with the rich and diverse range of expertise and experience that each part- ner brings. Partners have been able to shape the way in which

this technology has developed by sharing insights concerning the most useful applications for pico- droplet microfluidics in their area of work. This has led to the development of platforms that are tailored to the needs of the end user, with enhanced features and functionality that provide optimal results.

Drug Discovery World Summer 2018

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