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Abstract
Personalized medicine – healthcare based on individual genetic variation – has the potential to transform the way healthcare is delivered to patients. The promise of personalized medicine has been predicated on the predictive and diagnostic power of genomic and proteomic biomarkers. Biomarker screening may help improve health outcomes, for example, by identifying individuals’ susceptibility to diseases and predicting how patients will respond to drugs. Microfluidic droplet technology offers an exciting opportunity to revolutionize the accessibility of personalized medicine. A framework for the role of droplet microfluidics in biomarker detection can be based on two main themes. Emulsion-based microdroplet platforms can provide new ways to measure and detect biomolecules. In addition, microdroplet platforms facilitate high-throughput screening of biomarkers. Meanwhile, surface-based droplet platforms provide an opportunity to develop miniaturized diagnostic systems. These platforms may function as portable benchtop environments that dramatically shorten the transition of a benchtop assay into a point-of-care format.
Financial & competing interests disclosure
The authors are supported by NIH (U54CA151838, R01CA155305, R21CA173390) and NSF (1159771, 0967375).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
The ability to detect extremely rare populations of nucleic acids from a background of normal targets has the potential to transform clinical medicine, especially in heterogeneous diseases such as cancer. In light of this, droplet-based technologies enabling digitization of biochemical assays are highly desirable.
The ability to generate monodisperse droplets at extremely high-throughput facilitates experiments previously rendered impossible due to the practical constraint on the number of reactions that can be performed using traditional bench-top technologies.
Many droplet platforms have complicated workflows – after droplets are generated, they are incubated offline and detected in a second microfluidic device. Future work should focus on integrating droplet generation, incubation and detection on a single device for facile operation. Toward this end, we have demonstrated amplification-free detection of pathogenic cells on a single device.
Many microfluidic devices have demonstrated the capability of detection of biological contents at single-molecule resolution yet are limited to the analysis of a single sample under a homogeneous reagent condition. We have presented a way to overcome this limitation by integrating a capillary which functions as a cartridge for a library of samples and integrating valves on our microfluidic device for excellent control over droplet compositions.
Droplets boast extremely high-throughput and are amenable to automation. In the future, special efforts should be devoted to ease of use as well as cost to promote routine adoption of droplet technology in research and clinical settings. We are confident that droplet-based technologies will define a new era of molecular diagnostics.