High-Throughput Bioanalytical Chemistry and Biophysical Chemistry at the Single Molecular Level

Bioanalytical Chemistry

Lab-on-a-chip

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.

Laser Tweezers

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.

Magnetic Tweezers

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.

Biophysical Chemistry

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.

Selected Publications

1. Mao, H. & Luchette, P. An integrated laser-tweezers instrument for microanalysis of individual protein aggregates. Sensors and Actuators, B: Chemical B129, 764-771 2008.

2. Luchette, P., Abiy, N. & Mao, H. Microanalysis of clouding process at the single droplet level. Sensors and Actuators, B: Chemical B128, 154-160 2007.

3. “Temperature Control Methods in a Laser-tweezers System”, Hanbin Mao, J. Ricardo Arias-González, Steve Smith, Ignacio Tinoco Jr. & Carlos Bustamante, Biophysical Journal, 2005, 89, 1308-1316 .

4. “Measuring LCSTs by Novel Temperature Gradient Methods: Evidence for Intermolecular Interactions in Mixed Polymer Solutions”, Hanbin Mao, Chunmei Li, Yanjie Zhang, David Bergbreiter, Paul S Cremer, Journal of the American Chemical Society, 2003, 125, 2850-2851.

5. “A Versatile, Sensitive Microfluidic Assay for Bacterial Chemotaxis”, Hanbin Mao, Paul Cremer and Michael Manson, Proceedings of National Academy of Sciences of USA, 2003, 100, 5449-5454.

6. “A Microfluidic Device with a Linear Temperature Gradient for Parallel and Combinatorial Measurements”, Hanbin Mao, Tinglu Yang, Paul Cremer, Journal of the American Chemical Society, 2002, 124, 4432-4435.

7. “Design and Characterization of Immobilized Enzymes in Microfluidic Systems”, Hanbin Mao , Tinglu Yang, Paul Cremer, Analytical Chemistry, 2002, 74, 379-385.

Last Updated: 15 August 2008