(6hu) Microfluidic Processes to Engineer Hydrogel Particles and Their Applications in Biomedical Engineering

Combining my expertise in microfluidics and soft matter, my group’s research will focus on the hydrogel microparticle synthesis, characterization, and manipulation to improve their capabilities in diagnosis and bioengineering. The overall goal is to fine-tune the functionalities of microparticles and to spatially arrange them in a specific pattern to engineer new functional soft matters. I envision that my group will resolve the current limitation of diagnosis (i.e. sensitivity, assay time, dynamic range, multiplexity) and provide a complex in vitro platform which cannot be fabricated by conventional technologies. More specifically, two major research area is outlined below.

Functional hydrogel microparticle synthesis

Hydrogel provides the solution-like environment at a molecular level, enabling the molecular transport through the material and solution-based reaction inside it. On the other hand, it also has the solid-like mechanical properties, making it easy to handle. These characteristics make hydrogel appealing in a variety of biomedical fields, such as medicine, tissue engineering, and diagnosis. As the technology evolves, there is an increasing interest to make micron-sized hydrogels while finely tuning their structure and functionalities. For instance, cell-sized hydrogels enable to make a complex microenvironment with a high spatial resolution. In bioassay, the ability to encode more than a million code in a small sensing region provides high sensitivity and multiplexity. During my Ph.D. under Dr. Patrick S. Doyle at MIT, I worked on the microfluidic lithography technique, stop flow lithography, to synthesize functional hydrogel microparticles. Among various particle synthesis techniques, microfluidic lithography enables to synthesize the uniform hydrogel microparticle with high geometric and chemical anisotropies. During my doctoral research, I synthesized the microparticles with the following functionalities: multiplexed, highly sensitive microRNA detection; spatially selective cell-adhesiveness; and upconverting emission for anti-counterfeiting. In my group, we will advance the microfluidic lithography techniques. We will utilize our knowledge of polymer synthesis and chemical reaction to provide more diverse functionalities. In addition, for the rational design of microparticles, we will conduct the dimensionless analysis to understand the mechanism of the particle synthesis process and the factors governing the bioassays. Our lab’s effort will improve the capabilities of hydrogel microparticles in biomedical engineering.

Soft matter manipulation

Arranged particles can provide unlimited encoding capacities and fast decoding capabilities. Large scale particle arrays would reduce the significant amount of time and effort in the analysis. Furthermore, spatial positioning exponentially increases the encoding capacities and play an important role in both biomedical application and material science. During my doctoral research, I developed a platform, porous microwell array, which utilizes the hydrodynamic force to arrange the microparticles. This technology simultaneously fulfills the desired capabilities of particle manipulation: scalability, precision, specificity, and versatility. It arranges the large scale of particles at a precise location with high throughput. In addition, I conducted the scaling analysis to propose a dimensionless number for specific positioning of microparticles depending on their characteristics (i.e., size modulus, shape), and experimentally validated this scaling theory. The driving force, hydrodynamic force, acts on particles in the same manner regardless of their chemical compositions, fulfilling the versatility. Using this platform, I demonstrated the following applications: microenvironment fabrication for neutrophil chemotaxis, and upconverting particle arrays for anti-counterfeiting. Furthermore, I applied the same technology to arrange the following soft matters other than hydrogel microparticles: particle-in-droplet arrays for signal amplified miRNA detection; live microbe array for the study of antibiotic susceptibility and immune response. During my postdoctoral research with Dr. Daniel Irimia and Dr. Adam B. Raff at Harvard Medical School and Massachusetts General Hospital, using the same principle, I have worked on the following fields: human skin-on-a-chip for skin infection diagnosis; and neuro-spheroid arrays for the study of Alzheimer disease.

In my group, we will advance the particle manipulation technique to improve its capabilities. We will utilize other porous materials to apply the technology to smaller objects, such as Brownian colloids or nanoparticles. We will study the synergistic effect of hydrodynamic force and other driving forces to achieve higher specificity with more sorting standards. In addition, we will achieve the complete automation of device fabrication and particle manipulation process for commercialization. As demonstrated in the previous research, we will apply the same technology to various micron-sized objects, such as droplets, cells, crystals, and spheroids. I envision that our soft matter manipulation technology will pave the way to advance the current limitations in diagnosis and tissue engineering.

Teaching Interests:

I am interested to teach a wide range of core courses in Chemical Engineering. For undergraduate courses, I look forward to teaching the following courses: fluid mechanics, heat and mass transfer, thermodynamics, reaction engineering, and engineering mathematics. For graduate levels, I am prepared to teach transport phenomena and thermodynamics. Besides those core courses, I would like to also create new courses in the fields of microfluidics and colloid/interface science.

Selected publications:

Tentori, A.M., Nagarajan, M.B., Kim, J.J., Zhang, W.C., Slack, F.J. and Doyle, P.S. "Quantitative and multiplex microRNA assays from unprocessed cells in isolated nanoliter well arrays", Lab on a Chip, 18(16): 2410-2424, 2018.

Kim, J.J.*, Reátegui, E.*, Hopke, A., Jalali, F., Roushan, M., Doyle, P.S. and Irimia, D. "Large-scale Patterning of Living Colloids for Dynamic Studies of Neutrophil-Microbe Interactions", Lab on a Chip, 18(11): 1514-1520, 2018.

Chen, L.*, Kim, J.J.*, Doyle, P.S., " Microfluidic platform for selective microparticle parking and paired particle isolation in droplet arrays", Biomicrofluidics, 12(2): 024102, 2018. (This paper has been selected as an Editor’s Pick)

Kim, J.J.*, Chen, L.*, Doyle, P.S., "Microparticle Parking and Isolation for Highly Sensitive MicroRNA Detection", Lab on a Chip, 17(18): 3120-3128, 2017.

Kim, J.J.*, Bong, K.W.*, Reátegui, E., Irimia, D., and Doyle, P.S., "Porous Microwells for Geometry-Selective, Large-Scale Microparticle Arrays," Nature Materials, 16(1): 139-146, 2017. (This paper has been featured at MIT news: http://news.mit.edu/2016/better-way-to-assay-microparticle-arrays-0930)

Eral, H.B.*, Safai, E.R.*, Keshavarz, B.*, Kim, J.J., Lee, J., and Doyle, P.S., "Governing Principles of Alginate Microparticle Synthesis with Centrifugal Forces," Langmuir, 32(28): 7198-7209, 2016.

Bong, K.W.*, Kim, J.J.*, Cho, H., Lim, E., Doyle, P.S., Irimia, D., "Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin-Biotin Interactions," Langmuir, 31(48): 13165-13171, 2015.

Lee, J.*, Bisso, P.W.*, Srinivas, R.L., Kim, J.J., Swiston, A.J., and Doyle, P.S., "Universal Process-Inert Encoding Architecture for Polymer Microparticles", Nature Materials, 13(5): 524-529, 2014. (This paper has been featured at MIT news: http://news.mit.edu/2014/tiny-particles-could-help-verify-goods)

* denotes equal contribution.