1. Cerebral Microcirculation.  

Neurovascular coupling or cerebral functional hyperemia forms the basis for functional brain imaging. Defects in functional hyperemia are believed to contribute to synaptic loss and cognitive decline in multiple neurodegenerative diseases, including Alzheimer disease. To date, significant efforts have been made to identify the mechanisms driving functional hyperemia but the results are debating. Indeed, majority of studies in this field focus on neurovascular unit (i.e., vascular walls, glial cells, and neurons) and the roles of red blood cells (RBCs) are significantly overlooked. Our lab has conducted the first formalized study and unveiled a previously unrealized regulatory role of RBCs in capillary hyperemia in the brain. Our study provides a novel insight to neurovascular coupling in the brain and will have broad impact in functional brain imaging and diagnosis/management of brain disease.



Representative Publications

Wei, H., Kang, H., Rasheed, I-Y., Luo, N., Zhou, S., Wang, Y., Richardson, K., Palmer, A., Xu, C.,       Wan, J., Nedergaard, M. (2016) Erythrocytes are oxygen-sensing regulators of the cerebral microcirculation. Neuron, 91, 851-862.


Fan, R., Emery, T., Zhang, Y., Xia, Y., Sun, J., Wan, J. (2016) Effect of circulatory shear flow on the viability and proliferation of circulating colon cancer cells.  Sci. Rep. 6, 27073. 

    

    Fan, R., Emery, T., Zhang, Y., Xia, Y., Sun, J., Wan, J. (2016) In vitro microfluidic circulatory system for circulating cancer cells. Nature Protocol Exchange. doi:10.1038/protex.2016.037.


Cinar, E., Zhou S., DeCourcey, J., Wang, Y., Waugh, R.E., Wan, J. (2015) Piezo1 regulates mechanotransductive release of ATP from human red blood cells. Proc. Nat. Acad. Sci. USA, 112, 11783-11788.


Forsyth A. M., Wan, J., Owrutsky, P.D., Abkarian, M., and Stone, H. A. (2011) A multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release. Proc. Nat. Acad. Sci. USA, 108, 10986-10991.


Wan, J., Forsyth, A. M., and Stone, H. A. (2011) Red blood cell dynamics: from cell deformation to adenosine-5'-triphosphate release. Integr. Biol. 3, 972-981.  


Wan, J., Ristenpart, W. D., and Stone, H. A. (2008) Dynamics of shear-induced ATP release from red blood cells. Proc. Nat. Acad. Sci. USA. 105, 16432-16437.





We demonstrate a microfluidic approach to investigate the dynamics of shear-triggered release of ATP from human red blood cells.  (A) Schematic of the experimental apparatus (not to scale). A mixture of RBCs and luciferase/luciferin solution are pumped through a microfluidic constriction. (BRepresentative experimental measurements of the photon emission rate resulting from the reaction between luciferase/luciferin and ATP, measured versus position along the channel

2. Organ-on-a-Chip.

Organ-on-a-chip technology produces 3D mini-organs or tissues in microfluidics, mimicking complex structures and cellular interactions in vivo, and thus provides functional in vitro organ models to study fundamental mechanisms of disease development, drug toxicity screening and drug development. As an emerging concept and a rapid growth field in tissue engineering, organ-on-a-chip technology is expected to revolutionize cell biology in general and the current approaches in tissue engineering and cell culture in particular. My lab is developing microfluidics and 3D bio-printing approaches to construct 1) in vitro biomimetic functional brain-on-chip devices; 2) functional intestine and colon on-a-chip devices by regulating the growth of intestinal organoids in a 3D hydrogel matrix.

 

Representative Publications

Piou, M., Fan, R., Darling, E., Cormier, D., Sun, J., Wan. J. (2016) Bioprinting cell-laden Matrigel/agarose constructsJ. Biomater Appl., 0885328216669238


Fan, R., Naqvi, K., Patel, K.,  Sun, J., Wan, J. (2015) Microfluidic generation of oil-free cell-containing hydrogel particles. Biomicrofluidics. 9, 052602.


Fan, R., Sun, Y., Wan, J. (2015) Leaf-inspired artificial microvascular networks (LIAMN) for 3D cell culture. RSC Advances. 5, 90596-9060



 
We demonstrate a concept of leaf-inspired artificial microvascular networks (LIAMN) for 3D cell culture in hydrogel constructs. A framework of branching models was incorporated to construct LIAMN that enables a long-term cell culture and the formation of spheroid in 3D hydrogel. The presented approach is expected to pave a new way to realize vascularization in 3D cell culture and the development of functional artificial organs. We are also developing 3D printing technologies for tissue engineering.



3. 
Advanced Functional Materials.


The high surface-area-to-volume ratio, superior heat and mass transfer, controlled reagent mixing and improved reaction rates make microfluidics an attractive approach for multiphase processes, reactions, and material synthesis. My lab investigates the dynamics of emulsion droplets and bubbles in microfluidics and develops emulsion-based approaches to produce artificial red blood cells and functional microbubbles for drug and oxygen delivery and biomedical imaging. In addition, we identified, for the first time, the regulatory roles of flow in the anodic growth of TiO2 nanotubes and demonstrated that flow not only controls the diameter, length, and crystal orientations of TiO2 nanotubes but also regulates the spatial distribution of nanotubes inside microfluidic devices and orientation on silicon substrates. Our approach provides a promising strategy to integrate silicon with hierarchical TiO2 nanotube arrays that may find applications in nanoelectronics, silicon-based photonics, and photovoltaic solar cells. Most importantly, the demonstrated role of flow in anodic growth of TiO2 nanotubes may apply broadly to a many electrochemical reactions where the local mass transport plays a critical role in reaction kinetics and material synthesis.



 Representative Publications


Fan, R., Chen, X., Wang, Z., Custer, D., Wan, J. (2017) Flow-regulated growth of titanium dioxide (TiO2) nanotubes in microfluidics. Small, in press. (Featured as a frontispiece article).

 

Lu, T., Fan, R., Delgadillo, L., Wan, J. (2016) Stabilization of carbon dioxide (CO2) bubbles in micrometer-diameter aqueous droplets and the formation of hollow microparticles. Lab On Chip. 16, 1587-1592. (Featured as cover article).


Koppula, K. S., Veerapalli, K. R., Fan, R., Wan, J. (2016) Integrated microfluidic system with simultaneous emulsion generation and concentration. J Colloid Interface Sci. 466, 162-167.

 

Ge, H. Xu, H., Lu, T., Li, J., Chen, H., Wan, J. (2015) Microfluidic production of porous carbon spheres with tunable size and pores. J Colloid Interface Sci. 461, 168-172.


 Li, J., Wang, Y., Chen, H., Wan, J. (2014) Electrowetting on dielectrics for manipulating oil drops and gas bubbles in aqueous-shell compound drops. Lab on Chip. 14, 4334-4337.


Shim, S., Wan, J., Hilgenfeldt, S., Panchal, P., Stone, H. A. (2014) Dissolution without disappearing: multicomponent gas exchange for CO2 bubbles in a microfluidic channel. Lab on Chip. 14, 2428–2436. 


Chen, H., Li, J., Wan, J., Weitz, D. A., and Stone, H. A. (2013) Gas-core triple emulsions for ultrasound triggered release. Soft Matter. 9, 38-42. (Featured as back cover article).


Wan, J., Shi, L., Benson, B., Bruzek, M. J., Anthony, J. E., Sinko, P. J., Prudhomme, R. K., and Stone H. A. (2012) Microfluidic generation of droplets with a high-loading of nanoparticles. Langmuir. 28, 13143–13148.


Wan, J., (2012) Microfluidic-based synthesis of hydrogel particles for cell microencapsulation and cell-based drug delivery. Polymers, 4, 1084-1108. Invited Review.


 

We are developing microfluidic approaches to synthesis functional particles and nanomaterials for drug delivery, energy storage and photo catalytic CO2 reduction.