1. Cellular Biomechanics

We are interested in mechanistically how biological cells "know" and respond to externally applied mechanical forces. We are developing state-of-art experimental models and devices and exploring the mechanosensing dynamics of red blood cells, circulating cancer cells and primary erythroid cells. We expect the outcomes of our investigation will fundamentally advance our understanding of mechanobiology and enhance our ability to treat diseases with effective therapeutic strategies.



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. Microvascular and Tissue Engineering

Construction of a vascular architecture capable of distributing oxygen and nutrients within engineered tissue constructs is critically important for the development of functional living organs. In particular, controlled engineering of complex, hierarchical microvascular networks remains a challenging yet unaccomplished task. Although formations of microvascular architectures using methods such as direct writing, microfluidics, and electrical discharge have been demonstrated, effective approaches to produce functional three-dimensional (3D) complex microvascular networks are still missing. Lack of such a system is an important problem, because, without it, acquiring the ability to sustain 3D tissue culture constructs with a physiologically relevant size is highly unlikely, and consequently in vitro development of transplantable organ constructs will be extremely difficult.

We aim to develop novel technologies and materials to construct 3D microvascular networks and thus to engineer vascularized tissue constructs. Such results are expected to have an important positive impact, because in addition to provide novel and innovative technology for tissue engineering, the developed approaches are highly likely to provide functional microvascular grafts and transplantable tissues for clinical practice.

 


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. Complex fluids, emulsions, and functional materials

We aim to provide fundamental understandings of fluid behavior at small scales and particularly the roles of microfluidics in emulsions (droplets and bubbles), chemical reactions and material synthesis.  We are currently developing microfluidic approaches and/or 3D printing techniques to investigate 1) bio-inspired materials and technology for drug delivery and imaging, and 2) energy storage materials and solar fuels.   



 Representative Publications


 
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.