Microfluidic Biological Processors: Towards Micro Biosystems on a Chip

The basic life components (genes, protein, cells) function at critical length scales; the aggregate of these multi-scale reactions enables precise and complex living operations,  such as the immune response, regulation and adaptation, repair and maintenance, and hierarchical self-assembly. Rapid advancements in microfluidic technology are beginning to enable large-scale, high-throughput processing of molecular and cellular operations. An ultimate vision would be to analyze, manipulate, and recapitulate complex physiological processes in chip-scale, microfluidic platforms. These platforms would enable rapid and accurate diagnosis of onset of diseases, monitoring of chronic and high-risk patients, and would even offer relatively healthy people the option to regulate their dietary and other daily life choices (e.g. exercise, stress, etc.).  The vast amount of information that will be acquired would match treatments with genomic makeup, and enable personalized medicine, point-of-care diagnostics, and targeted theranostics in wearable, distributable, and field-portable platforms. 

  One particular platform, droplet microfluidics, can break up the fluid sample into millions of picoliter-sized drops at 1000s/second rates.  As a result, a complex fluid can be "digitized" into large numbers of discretized volumes, while enabling accurate mixtures, rapid mixing, and confined constituents for high sensitivity and high SNR detection. Another focus of my lab is in the development of microfluidic platforms for sorting and processing of cells and cell-like lipid vesicles. This is motivated by the fact that cells host the most basic molecular functions of life and also form the basic unit of living creatures; the ability to detect, manipulate and sort at the cellular scale is critical to all aspects of life science and medicine. Cell-like lipid vesicles can mimic specific functions of the biological counterpart in vivo and provide an effective platform for integrating detection and targeted treatment.   I will introduce 3 categories of microfluidic platforms in my lab: (1) Droplet microfluidics for various biological applications. An example is a high-density 3D droplet array platform for DNA studies and genetic analyses. Here, we take advantage of droplet microfluidics to produce bioreactors at the cellular scale. These picoliter droplets confine sample and reagent for single molecular amplification for high dynamic range gene detection. Another example is the generation multi-layer functional lipid vesicles designed for in vivo targeted imaging and treatment. I will also present recent efforts in our lab to make droplet microfluidics more practical for various applications. These include ultra high-speed droplet generation, combinatorial droplet arrays, low-cost droplet generation platforms, and portable integration platforms. (2) Cell (and cell-like vesicle) sorting platforms for cell biology studies and sample preparation. Examples include passive sorting based on viscoelastic properties and active sorting based on dielectrophoresis and air-cavity acoustic transducer platforms. Applications include the enrichment of stem cells for cell transplantation and blood cell separations. (3) A microfluidic platform for in vitro growth of perfused 3D vascularized tissue. The immediate application of this platform would be in drug development and drug screening with long-term prospects for larger tissues for regenerative medicine.

Speaker: Abraham Lee, UC Irvine