The understanding of our world starts from what can be seen and sensed.  The subject broadens toward big objects such as stars in outer-space and small objects such as quanta.  As human builds up reasonable knowledge of the surrounding world, the attraction has been directed into living beings.  In my personal view (apparently biased), on one hand biology today is at the exploring stage similar to that of physics before Newton’s principles: there is no succinct beauty as F=Ma yet in biology.  On the other hand biotechnology is at the booming stage similar to that of computer science in 1950s: it is inevitably going to change many aspects of our lives. 

One thing I noticed when I was at Temple University is that biologists, doctors, and engineers all have their own ways of thinking and expressing scientific issues.  Sometimes they are talking as if using different languages (apparently not the difference between English and Chinese).  I felt that the field of  bioengineering would build bridges among them.  Hence my motivation as a mechanical/electrical engineer jumping into the pool of bioengineering with the hope to contribute my one penny in understanding biology.

My study area is to apply microsystems in biochemistry.  The goal of Lab-on-a-Chip technology is to scale down the routine biochemical laboratory into a chip around the size of a coin, to scale up the process time orders faster while necessitate only drops of reagent solution.  I am particularly interested in studying biomolecular reactions in a bio-microelectromechanical system (bioMEMS).  Towards this goal, my research activities span from manufacturing and optimizing a bioMEMS device to manipulating biomolecules and detecting their behaviors in a microchannel.

For multi-step biochemical reactions in microfluidics, there is a need of better controlling the selection from multiple solution sources and pumping into microchannels.  For this purpose, I built a microfluidic control system as in Fig.1 (c).

Recently, I have fabricated microfluidic devices with dead-volume free world-to-chip packaging by adding an extra aligner plugs during the soft lithography molding process. This design minimizes parasitic reactions (non-specific binding at channel surfaces and/or reaction in aqueous volumes) in microfluidics for sequential bioreactions in bioMEMS (Fig.2(b)).

A cross-channel microfluidic device was also fabricated to minimize the non-specific binding of enzyme on microchannel wall surface and improve signal-to-background ratio of site-specific enzymatic reactions in microfluidics (Fig.2(c)).

Chitosan is an ideal interface material for biomolecular assembly due to its intrinsic pH dependant solubility. The amine groups on chitosan have pKa value of 6.3. When applying electric signal onto electrodes in chitosan solution, high pH region is formed at cathode surface due to hydrogen evolution, and Chitosan molecules deprotonated, immobilized at cathode surface (Fig.3).

Electrodeposited chitosan on spatially selective electrodes inside microfluidic channels is a perfect interface material to assemble proteins (e.g., enzymes) and DNAs in microchannels for bio-reaction process and subsequent test. An example of assembling green fluorescent protein (GFP) is shown in Fig.4.

Antibiotic resistance is an increasing public health problem and few new drugs for bacterial pathogenesis have been obtained without bypass this resistance.  Quorum sensing (QS) is a newly-discovered system mediated by extracellular chemical signals known as “autoinducers”.  As bacterial cells accumulate in number and density, secreted autoinducers accumulate in their immediate surroundings, and these autoinducers can coordinate population-scale changes in gene regulation when the number of cell reaches a “quorum” level.  The capability to intercept and rewire this communication network opens the door to antimicrobial drug discovery. 

My research goals are to (1) reconstruct and interrogate the autoinducer-2 (AI-2) synthesis pathway and (2) study QS and biofilm formation in bioMEMS, which belong to the Deutsch Foundation of Nano-Bio Initiative and the NSF EFRI program of "bacterial communication".

Surface Enhanced Raman Spectroscopy, or Surface Enhanced Raman Scattering, is a surface sensitive technique that results in the enhancement of Raman scattering by molecules adsorbed on rough metal surfaces. The enhancement factor of up to 10^14 allows the technique to be sensitive enough to detect single molecules. The integration of SERS into microsystems have recently been explored by many researchers.

In the last few months, I am actively involved in our research team (w/ Susan, Dean) of facilely fabricating SERS substrate in a microfluidic channel as an in situ sensing and quantification site. I am interested in (1) facile fabrication of metallic nanostructure, and (2) in situ SERS detection and quantification of bioreaction products in microfluidic channel.

Inspired by a presentation in microTAS 2007, I am seeking the synthesis of vertical chitosan membrane. Given the availability of chitosan for subsequent biofunctionalization, I forsee a lot of applications of our membrane in the processes in chemical engineering and metabolic engineering.

Despite the laminar flows in microfluidics, an steady flow interface is highly desired to fabricate well-controlled membrane. Our team (w/ Dean, Jeff) have built a pneumatic pumping system to generate pulse-free flows. We have demonstrated the formation of vertical chitosan membrane in microchannels. Exciting research is under active investigation.

I was once actively involved in the project of assessing the risk of nanoparticles to health and environment using cell-based bioMEMS, mainly focusing on cell transport, maintenance and sensing. With the develop of nanotechnology and application of nanoparticles in different areas, concern arises regarding the risk of various particles in the nano-scale size that can easily transport through cell membranes. The ideal of using cell-based bioMEMS to evaluate the risk of nanoparticles is every interesting. Recently my focus has been sort of distracted to other projects, but this is still one of my favorites.