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Mechano-analytical Chemistry: A New Interdisciplinary Field

By combining Analytical Chemistry and Single-molecule Biophysics, we created a new chemistry field: Mechano-Analytical Chemistry.  We have used the following techniques to develop this new field.

• 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 was 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 room 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. Most importantly, magnetic tweezers have high-throughput. 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- and magnetic-tweezers on a chip, we have been investigating fundamental properties of biomacromolecules including DNA and proteins.  In addition, we have pioneered ultrasensitive and high-throughput biosensing method called Single-Molecule Mechanochemical Sensing (or SMMS).  With many patents awarded, we have used SMMS to detect trace level of biomarkers for various diseases, as well as toxins such as mercury in the environment.

Our research is interdisciplinary.  We carry out many collaborative projects with groups from materials and biosciences. Incoming members have ample opportunities to learn subjects through coworkers from other fields.

Selected Publications

1. "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.

2. "Interaction of G-quadruplexes in the Full-length 3' Human Telomeric Overhang", Jibin Abraham Punnoose, Yunxi Cui, Deepak Koirala, Philip M. Yangyuoru, Chiran Ghimire, Prakash Shrestha, and Hanbin Mao. Journal of the American Chemical Society, 2014,136 (52), 18062-18069.