Over the last half-decade I have helped develop MLSI in the laboratory of Prof. Quake at Stanford University. Prof. Quake's technology is based on using an elastomeric material called PDMS to fabricate devices containing several layers of microfluidic channels using a technique termed multilayer soft lithography (MSL). With MSL it is possible to create structures that form functional micro-valves. Extending on this simple concept I designed the first LSI device containing thousands of valves in an area the size of a postage stamp. These early devices showed that it is possible to fabricate functional devices with almost arbitrary complexity with relative ease. Over the last several years I have been applying MLSI to solve problems in Systems Biology centered around performing protein biochemistry with greater ease and larger scale than can be accomplished with classical bench-top approaches.
In particular I have been studying how basic-helix-loop-helix (bHLH) transcription factors (TFs) recognize and bind to DNA. I established the first comprehensive binding energy landscape of a TF using a novel method for detecting interactions between molecules. This method is based on the mechanical induced trapping of molecular interactions (MITOMI) via a movable membrane. Establishing the exact modus operandi for any transcription factor allows one to determine what genes it targets in vivo. This in turn allows one to not only establish transcriptional regulatory network topology but also the underlying parameters that drive the network, such as interaction strengths and dynamics of interacting nodes.
I am also interested in applying MITOMI to various other forms of molecular interactions important in a cellular environment such as protein-protein and protein-RNA interactions. Studying protein-small molecule interactions on the other hand will be useful in screening potential pharmaceuticals in high-throughput.
- Maerkl S.J. and S.R. Quake, ``Programming Microfluidic Devices with Molecular Information, # 60/762,344.
- Maerkl S.J. and S.R. Quake, ``Mechanically Induced Trapping of Molecular Interactions, # 60/762,300.
- Maerkl S.J., Thorsen T., Bao X., Quake, S.R. and Studer V., ``Microfluidic Large Scale Integration, # WO2004028955.