2014-2015

Optofluidic Lasers on Chip

A major challenge in tissue engineered organ transplantation is revascularization. How to fabricate a perfusable microvascular network in neotissues to support the tissue growth in vivo is crucial. We are working to tackle this problem by developing a two-step approach for synthesizing neotissues with perfusable microvasculature. First we use a microfluidic system to create a large-scale endothelialized microvessels that can be retrieved to form a free-standing microvascular network. Second, this microvascular network is used as a template to seed perivascular and tissue specific cells to grow neotissues. This modular approach is generic and versatile for the potential application to a range of functional tissues including liver, bone, and pancreatic tissues.

Computing with Microfluidics

Microfluidics has endeavored to bring the advantages of integrated circuits to chemical and biological processes. However, system integration still falls far short of microelectronics, as on-chip pumps and valves typically require off-chip electronic and pneumatic components in order to function, thus increasing cost, complexity, and size. Pneumatic microfluidic valves are similar in many ways to electronic transistors, suggesting the possibility of constructing mechanical computers out of microfluidic circuits. Following this strategy, we have built a variety of digital logic systems, including a programmable finite state machine. These logic circuits can control networks of pumps and valves for liquid handling, allowing multistep laboratory procedures to be encoded into autonomous microfluidic networks. These devices contain no electronics and are powered simply by a static pressure differential. We envision that this technology will be attractive for laboratory automation and point-of-care medical applications.

Probing multicellular communication in the context of the tumor ecosystem

The role of cell-cell communication in many aspects of cancer (initiation, progression, resistance) is becoming increasingly apparent. We have developed a number of simple tools to improve our ability to manipulate and probe the nature of these multicellular interactions both in isolation and in the context of the tumor microenvironment. These include 2D and 3D compartmentalized culture platforms to explore paracrine signaling and matrix interactions as well as lumen-based organotypic models to understand structure/function relationships. In addition, we have developed tools to enable multianalyte extraction from small precious samples from patients. We are applying these tools to understand how cell-cell communication influences various aspects of cancer development in the context of the tumor ecosystem. Examples include the transition from DCIS to IDC in breast cancer, metastasis to bone in prostate cancer, angiogenesis in kidney cancer, hormone response in breast cancer and resistance to therapy in multiple myeloma.

New Microanalytical Techniques for Studying Bacteria

Bacteria exhibit remarkable abilities to organize and adapt themselves in dynamic environments; however, relatively few quantitative techniques exist for studying bacterial behavior. Their small size (sub-micrometer dimensions) and motility (up to several body lengths per second) presents exceptional challenges for bacterial cell analysis. These unique characteristics must be addressed in order to investigate the chemical and physical micro-environments that bacterial cells respond to and create.In this talk, I will present several bioanalytical tools that my group is developing and optimizing specifically for microbiological applications. We utilize micro/nano-fluidic devices to manipulate and isolate bacterial cells. Once the cells are positioned in the devices, we use surface plasmon resonance imaging (SPRi) to study biofilm formation and removal, and microfabricated electrochemical sensors to detect the production of toxins. These systems are quite versatile as they can be used to study microbial species in complex environments, with applications ranging from biophysics to point-of-care diagnostics to industrial processes.