Developing droplet microfluidic technologies for single-cell and single-molecule assays

In the past decade, growing number of commercialized “lab on a chip” systems have been addressing needs in biology for patients and researchers. The ability to miniaturize conventional systems used in lab while increasing sensitivity in addition to newly developed platforms, have enabled new applications such as point-of-care diagnostics and single-cell sequencing. This dissertation focuses on new droplet microfluidic platforms developed for addressing the current challenges (controlling encapsulation beyond Poisson distribution, removing bulky and expensive pumps,…) in commercialization of single-cell and single-molecule assays. In chapter 1, current state of the art, recent commercialized products and their limitations are discussed.In chapter 2, new findings about particle interactions in single-phase microfluidics leading to “preferred interparticle spacings” and trajectory attractors in inertial microflow regimes are presented. Furthermore, these findings have been combined with new modifications made to conventional flow focusing droplet generators in order to avoid jetting regime in inertial regimes, thus allowing making use of preferred spacing between cells/particles in inertial flows for controlling number of cells/particles encapsulated in droplets (one cell/particle per drop). Our findings could be used for many applications such as drug discovery. The other application could be for droplet sequencing (drop-seq) where for example RNA of individual cells are sequenced and it is important that only one cell is present in each droplet to generate unbiased data. In chapter 3 and 4 of the dissertation, new patented technology for generation of droplets, replacing bulky and expensive pumps, with body force exerted on the ferrofluid by magnetic field acting on magnetic nanoparticles mixed with the fluid. Thus the cost and footprint of the device is reduced significantly, allowing for use in limited-resource settings (global health) for quantification of biomolecules by controlled magnetic dosing of nanoliter droplets