Decoupled Space and Time Gradients for Particle Enrichment, Sorting and Isolation

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The use of micro-nano particles, such as, solid particles, capsules and liquid emulsions have immense applications in multiple industries: from emulsions in cosmetics, paint and agriculture, metal nanoparticles for anti-bacterial and high-quality optical coatings, and micro-nano capsules for drug delivery and therapeutics. In all these applications particle size is crucial to ensure the desired functionality. For example, size of drug delivery capsules ensures timely targeted delivery of drugs to the appropriate location in the body, or size of an emulsion determines stability and shelf-life of a cosmetic product.During manufacturing of particles, particle sizes are controlled via downstream processes of enrichment and sorting. Such enrichment and sorting processes are also widely used in microfluidic healthcare diagnostic technologies for separation and isolation of biological cells for emerging applications in personalized cancer therapeutics and drug discovery. The precision, efficiency, yield and scalability of these particle processing techniques determines the eventual quality and cost of the product. A key challenge in developing scalable particle processing technologies is the flexibility to balance throughput and precision. The technology should also be label-free and employ low shear forces to avoid contamination and particle viability.This research project will address the above challenges in particle enrichment, sorting and isolation by investigating a new mechanism to manipulate particles using fluid flow field gradients. The mechanism relies on low frequency liquid oscillations in closed channels will be used to create spatial and temporal gradients in the flow field which will drive particles to specific locations in the channel. A key feature of this mechanism is that these spatial and temporal gradients will be de-coupled, which is fundamentally not possible in existing acoustic [Wiklund, Lab Chip, 12, 2018-2028 (2012)] or capillary wave-based [Agrawal, et al., Phys. Rev. App., 2, 064008 (2014)] mechanisms (due to coupled wavelength and frequency). This decoupling will allow an independent control of collection and destabilizing forces on particles providing an independent control of process efficiency and throughput. Low frequency oscillations are also less energy intensive which aids scalability of the mechanism.A combination of analytical and numerical modeling, and experiments will be used to investigate particle motion in these decoupled spatial and temporal gradient flow fields. The effect of channel designs, actuation parameters and particle properties (size, density and stiffness) on collection stability and collection speed will be characterized for different hard and soft particles, such as, solid micro-nano particles, liquid emulsions and biological cells. A key outcome of this research will be to explore the mechanism's scalability and utility to enrich particles like solids and droplet emulsions as a downstream process in particle production, and sort and isolate biological cells for a bio-medical analysis tool.The direct application of this research will be a novel low energy intensive method for bulk, size-based particle enrichment and sorting to be used as a downstream process in manufacturing of nanoparticles and emulsions for drug delivery and coatings. The supported applications of this research will be in developing a new class of microfluidic devices for sorting and isolating cells which will support bio-medical and clinical research in cell therapies, cancer treatment and personalized medicine. The project is supported by companies with an expertise in healthcare diagnostics and pharmaceutical manufacturing to explore the above applications.