(3gw) Biologically-Inspired Complex Fluids and Soft Matter

Human bodies are made up of soft cells and tissues suspended in an aqueous environment, with a growing consensus that in addition to molecular biology, mechanical cues play a vital role in governing the pathophysiology. The interplay between biological activities and mechanical properties relies on a fundamental understanding of how the deformation and transport of soft materials under flowing conditions occurs in a biological environment. Furthermore, harnessing the mechanics of nature represents an ongoing engineering effort to tackle a variety of problems in both biological and synthetic systems. To advance the development of this interdisciplinary area, experimental designs need to incorporate physiological flow conditions and geometries while classical mechanical models need to account for biological complexities. A synergistic investigation using both approaches is extremely valuable for exploring the multidimensional parameter space in a quantitative manner, thus enabling the next generation of precision-based engineering applications such as personalized medicine and diagnostics. This challenging research goal can be met using my unique skillset: theoretical fluid mechanics and numerical methods from my PhD training and experimental biology and engineering from my postdoc research. Based on my combined expertise in theory and experiments, my lab will apply the principles of complex fluids, soft matter and mass transport to understand biophysical mechanisms and develop biomimetic applications at the cellular level, tissue/suspension level and organ/system level. To fulfill these missions, I will develop theory-driven predictive models to describe the deformability of cellular entities, relate microscopic structures to tissue and suspension mechanics and evaluate the influence of fluid flows on organ functions. To validate the theoretical predictions, I will also improve in vitro experimental setups with appropriate time scales, length scales and flow strengths to mimic the physiological environment and simultaneously examine mechanical and biological activities. My lab will venture into a variety of novel biologically-inspired problems such as biomechanics of engineered cells, rheology of biocompatible hydrogels and solvents, and microfluidic processing of complex organs. Each research area represents emerging engineering applications lacking a fundamental physical understanding guiding the design parameters and therefore can benefit significantly from my proposed research.

Understanding Particle Migration, Margination and Adhesion in Cellular Suspensions, Department of Chemical Engineering, Stanford University (advised by Professor Eric S.G. Shaqfeh)

In my PhD thesis, I developed a theoretical model to predict the shear-induced cross-flow movements of red blood cells (migration) and platelets (margination) in microchannels and their influence on platelet adhesion for hemostasis and thrombosis. There exists abundant experimental evidence that the platelet-induced thrombus formation is strongly influenced by the blood flow conditions and the presence of red blood cells. While full scale computer simulations are powerful tools to study the motions of various blood cells under flow, they suffer from long computational time and high costs. In my theory, I applied microhydrodynamic principles of deformable and rigid particles in pressure-driven flow at zero inertia for red blood cells and platelets in microcirculation. Their cross-flow motions are thus governed by two fundamental physical mechanisms: shear-induced diffusion and deformability-induced lift. Platelet adhesion was introduced to the theory as a multi-scale kinetic model with the capability of performing both bottom-up and top-down investigations: predicting the overall effect of drugs based on changes in receptor-ligand binding kinetics and hypothesizing the molecular mechanism behind blood types based on observed differences in platelet adhesion dynamics. I also performed computer simulations and microfluidic experiments to validate my theoretical predictions. Overall this theory presents a pioneering approach to studying cellular suspensions in an efficient manner by drawing an analogy to classical microparticle suspensions. It opens up research opportunities to design in vitro experiments which can analyze and distinguish the motions of various cell types and microparticles based on mechanical properties and relate macroscopic cell adhesions to microscopic binding events under flow.

Tackling Biological Transport Barriers for Drug Delivery, Wyss Institute for Biologically-inspired Engineering, Harvard University (advised by Professor Samir Mitragotri)

My postdoctoral research consists of two major experimental projects which focus on designing novel transdermal and subcutaneous drug delivery systems based on a fundamental understanding of transport phenomena in biological environments. First, I am developing a microfluidic model to study the transport of subcutaneously-administered drugs from the injection site to systemic circulation in vitro. Despite being an attractive drug administration route due to high patient compliance, subcutaneous injection lacks reliable preclinical models to predict drug pharmacokinetics for clinical translation. I used microfluidic processing to construct multiple dense two-dimensional and three-dimensional tissue cultures mimicking various components of the subcutaneous environment and related the spatio-temporal transport measurement to drug pharmacokinetics. Utilizing transport theories and microhydrodynamic principles to optimize the processing conditions, my work enables standardized microfluidic assays with simple setups to achieve higher biological complexity than before. This method can be applied to constructing a variety of “organs-on-chips” mimicking biological transport barriers.

Secondly, I investigated the mechanism of ionic liquids and deep eutectic solvents enhancing the permeation of macromolecules across the skin. Using these biocompatible chemicals to tackle the skin transport barrier is a novel strategy to deliver biologics which are large molecules, but its development is hampered by a lack of knowledge on the interactions among drugs, enhancer-based solvents and the skin. I measured the skin permeability of macromolecules ex vivo and investigated structural changes in skin lipids and proteins using spectroscopic methods. I elucidated the enhancement mechanism based on ionic and hydrogen bonding interactions and predicted transdermal drug transport based on a porous media theory. These findings have advanced our fundamental understanding of ionic liquids for transdermal applications compared to conventional molecular liquids.

Select Publications:

1. Q.M.Qi and S.Mitragotri, “A Subcutaneous Tissue Chip for Assessing Biologics Transport”, in prep. (2020).
2. Q.M.Qi, M.Duffy, A.M.Curreri, J.P.R.Balkaran, E.L.Tanner and S.Mitragotri, “Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery", Advanced Functional Materials, in review (2020).
3. Q.M.Qi and S.Mitragotri, “Mechanism of transdermal delivery of macromolecules assisted by ionic liquids”, Journal of Controlled Release 311-312, 162-169 (2019).
4. Q.M.Qi, I.Oglesby, E.Dunne, J.Cowman, A.J.Ricco, D.Kenny and E.S.G.Shaqfeh, “In-vitro measurement and modeling of platelet adhesion on VWF-coated surfaces in channel flow", Biophysical Journal 116, 6 (2019).
5. Q.M.Qi and E.S.G.Shaqfeh, “Microstructure and rheology of cellular blood flow, platelet margination and adhesion”, Dynamics of Blood Cell Suspensions in Microflows, ISBN:9781138032057 (2019).
6. Q.M.Qi and E.S.G.Shaqfeh, “Time-dependent particle migration and margination in the pressure-driven channel flow of blood", Phys. Rev. Fluids 3, 034302 (2018).
7. Q.M.Qi and E.S.G.Shaqfeh, “Theory to predict particle migration and margination in the pressure-driven channel flow of blood", Phys. Rev. Fluids 2, 093102 (2017).

Teaching Interests:

With my undergraduate and graduate degrees in chemical engineering, I am qualified to teach core chemical engineering courses at any level. I also look forward to teaching electives in applied mathematics, complex fluids, numerical and simulation techniques, biomechanics, microfluidics and biomedical engineering. With my postdoc experience in an interdisciplinary institute, I am fully aware of the diverse academic backgrounds of students with undergraduate degrees outside chemical engineering. Therefore, I participated in various science communication workshops and I am confident to make my courses accessible and engaging to a diverse student body. In addition, I am a strong advocate of quantitative skills for all chemical engineering students. I plan to incorporate computational modules to my courses that will benefit students doing experimental research. I actively participated in student-sponsored seminar series at Stanford and Harvard. I am excited to organize guest lecture series inviting speakers from chemical engineering and other disciplines.

Service

Coming to the United States as an international student, I deeply value diversity in the scientific community and I am committed to recruiting talented individuals from all over the world through education and mentorship. Throughout my career, I have actively participated in various events supporting women in science. I have formally mentored two undergraduates and two PhD students who have minority backgrounds. I will strive to recognize diversity, equity and inclusion in my lab, and I hope to continue my pursuit in teaching, research and beyond.