Ph.D. Texas A&M University, 2003
High Throughput Bioanalytical Chemistry and Biophysical Chemistry at the Single Molecular Level
Micro total analysis system (mTAS), a.k.a. lab-on-a-chip, integrates a variety of lab components on a chip as small as one inch square in area. In a typical lab-on-a-chip scheme, chemicals can be synthesized, purified and analyzed on a single chip. The technique is indispensable in the emerging fields such as genomics and proteomics, where huge sets of data are collected and analyzed. It is also very useful in the screening processes to identify promising drug leads or optimal conditions for crystallization. The low cost and high-throughput capability make this technique ideal for sensor development. Combining with laser tweezers or magnetic tweezers (see below), our lab is interested in the methodology development and bioanalytical application of this technique, for example in the fields of ultra sensitive sensors and screening methods.
Since the discovery of the laser tweezers in the 1980s, the application of this technique has been mostly limited to the physics where it originated. The lag of the application in chemistry can be attributed to the following reasons. First, tiny amount of the material contained inside a trapped object prevents the use of many traditional detection methods, such as UV-vis and IR. Second, to build a strong optical trap, objectives with short working distance are often used. This leaves little accessible space to incorporate other detection methods. Our lab uses unique capabilities of the laser tweezers, i.e., force detection in the range of picoNewtons and spatial measurement down to Angstroms, to follow the chemical interactions such as binding events between receptors and ligands.
Compared to laser tweezers (see above), magnetic tweezers have advantages of lower force range (fN-pN), less drift, and full compatibility with a typical lab-on-a-chip layout. Magnetic objects can be easily incorporated into microfluidic channels on a chip and manipulated by an external magnet. These objects can be used to control the fluidics at the micrometer scale, which is one of the most difficult tasks in the development of lab-on-a-chip techniques.
Using laser tweezers or magnetic tweezers on a chip, we are interested in the study of single biomacromolecules. Compared to ensemble bulk assays where average information is obtained, single molecular experiments produce stochastic signals that reveal sub-group properties in a population or energetic sub-trajectories in a transition process. In particular, we will study the mechanical properties of DNA and the activities of DNA-associated proteins in a high-throughput manner.
Our group is interdisciplinary and collaboration is expected with groups from material sciences and biosciences. Incoming members have ample opportunities to learn subjects through coworkers from other fields.
Scholarly, Creative & Professional Activities
- "The Tertiary DNA Structure in the Single-Stranded hTERT Promoter Fragment Unfolds and Refolds by Parallel Pathways via Cooperative or Sequential Events", Zhongbo Yu; Vanessa Gaerig; Yunxi Cui; HyunJin Kang; Vijay Gokhale; Yuan Zhao; Laurence Hurley*; Hanbin Mao*. Journal of the American Chemical Society, 2012, 134, 5157-5164.
- “Intramolecular folding in three tandem guanine repeats of human telomeric DNA", Deepak Koirala, Tomoko Mashimo, Yuta Sannohe, Zhongbo Yu, Hanbin Mao* and Hiroshi Sugiyama*, Chemical Communications, 2012, 48, 2006-2008.
- “A Single-Molecule Platform for Investigation of Interactions between G-quadruplexes and Small-Molecule Ligands”. Deepak Koirala, Soma Dhakal, Beth Ashbridge, Yuta Sannohe, Raphine Rodriguez, Hiroshi Sugiyama, Shankar Balasubramanian, Hanbin Mao*, Nature Chemistry, 2011, 3, 782-787.
- “Detection of Single Nucleotide Polymorphism Using Tension-Dependent Stochastic Behavior of a Single-Molecule Template”. Deepak Koirala, Zhongbo Yu, Soma Dhakal, Hanbin Mao*, Journal of the American Chemical Society, 2011, 133, 9988-91.
- “Coexistence of an ILPR i-motif and a partially folded structure with comparable mechanical stability revealed at the single molecular level”, Soma Dhakal, Joseph Schonhoft, Deepak Koirala, Zhongbo Yu, Soumitra Basu, Hanbin Mao*, Journal of the American Chemical Society, 2010, 132, 8991-8997.
- "Direct Experimental Evidence for Quadruplex-Quadruplex Interaction within the Human ILPR", Joseph Schonhoft, Rabindra Bajracharya, Soma Dhakal, Zhongbo Yu, Hanbin Mao*, Soumitra Basu*, Nucleic Acids Research, 2009, 37, 3310-3320.
- "ILPR G-quadruplexes Formed in Seconds Demonstrate High Mechanical Stabilities", Zhongbo Yu, Joseph D Schonhoft, Soma Dhakal, Rabindra Bajracharya, Ravi Hegde, Soumitra Basu*, and Hanbin Mao*, Journal of the American Chemical Society, 2009, 131,1876–1882.