Droplet microfluidics offers unmatched advantages for high throughput assays on single cells, viruses, and even molecules. Using pico-liter drops as individual reaction vessels, drop microfluics ensures high reaction efficiencies even with minimal input material, providing single molecule sensitivity. After performing massively parallelized assays, individual drops can be screened one-by-one and the drops containing the desired products can be selected using a microfluidic-sorter. Drops can also be used as templates for polymerization reactions of enclosed substances, generating highly monodisperse products with a defined structure. We are developing new microfluidic modules and platforms to enable new biological measurements and ultra-sensitive assays. We also seek to understand the fluid dynamics inside microfluidic channels to enable precise control of drops and cells.
Single Virus Genomics
Droplet microfluidics has shown potential for enabling the high-throughput screening of virus populations with single virus resolution. Our research aims to develop new techniques to enable viral genomics at the level of single virions. We aim to use these techniques to study viral evolution and infectivity. We also aim to study viral re-assortment. This process occurs when two different virions co-infect the same host cell. During replication and packaging, genome segments from different parent viruses are combined to form reassorted progeny viruses. Viral reassortment is responsible for multiple influenza pandemics, but is poorly understood. We will use droplet microfluidics to rapidly identify viral genomes of reassorted virions in a high-throughput manner. Our platforms will enable direct characterization of viral populations at the resolution of a single virus.
Circular RNA Diagnostics
Circular RNAs (circRNAs) constitute a largely unexplored class of biomolecules that is gaining traction as potential biomarkers for various diseases. Though classified mostly as non-coding RNAs, some have also been shown to code for proteins. However, their functions are generally not well understood. By studying circRNA concentrations as a function of disease stage, it may be possible to exploit them for early disease diagnosis as well as prognosis. To this end, we aim to develop a liquid biopsy platform to quantify circRNAs. This platform will employ a digital RT-PCR assay based on droplet microfluidics, where each drop serves as an individual bioreactor for the amplification of single-molecule targets. Millions of these drops can be generated and then counted via an optical detection scheme, allowing for high-throughput and precise quantification of circRNA molecules.
Microparticles have broad applications in diagnostics, pharmaceuticals, and biological research. Droplet microfluidic techniques are ideal for production of highly monodisperse, functional microparticles and microcapsules. Emulsion droplets are used to template microparticle formation, enabling precise control of the physical and chemical properties of the resulting particles. Leveraging our expertise in droplet-base particle synthesis, we developed hydrogel microspheres for rapid point-of-care diagnostics. We also use droplet methods to form drug delivery microcapsules with controlled release properties.
Multiphase microfluidic flow dynamics is complex and requires the consideration of inertial forces, viscous forces, surface tensions, as well as particle and channel dimensions/geometries. A paradigm-shift in this area was inertial microfluidics, which showed that despite the conventional wisdom of the time, inertia could play a non-negligible role in microfluidics and could be used for the focusing of particles. However, most studies have utilized solid particles, which differ from droplets, as the former does not factor in deformability, internal circulation, and viscosity ratios. We aim to study how the coupled physical characteristics of the multiphase droplet microfluidic system can affect the stability and the spatial self-ordering of droplets, both laterally and longitudinally. A better understanding of these hydrodynamic interactions will grant new insight into the fluid physics of multiphase flows involving many deformable particles, such as cells. This knowledge can also enable more integrated on-chip droplet processing by exploiting the spatial self-ordering of the droplets, thus eliminating the need for further manual handling of drops or the added complication of using active force components.