Arup Chakraborty Research Group

Developing the capability to identify molecules such as pathogens, cancer indicators, chemical weapons, or biohazards is a goal that is of paramount importance to many professions, including the health care industry and the military.  While many approaches to this endeavor have been explored, we have been considering a tactic that is motivated by some recent experiments [1,2,3].  In these experiments, a group of identical ‘probe’ molecules are end-attached to one surface of a micro-cantilever beam.  The attached probes interact repulsively with each other, which causes the cantilever to bend, or deflect (see Figure 1).  The deflection is measured optically.  A solution containing ‘target’ molecules, or molecules that can bind to the probe, is then introduced.  When binding takes place, the nature of the interactions on the cantilever surface is changed, and thus the deflection changes.

 Results from these experiments suggest that the identity, and sometimes the concentration, of the target molecule can be related to the change in deflection.  Thus, we envision a microfluidic array of cantilevers, each of which has a different probe immobilized on the active surface.  When a fluid sample enters the device, the deflection of each cantilever is monitored separately.  The identity and perhaps concentration of each target can then be determined based on the change in deflection of each cantilever.  A simple schematic of such a device is shown in Figure 2.

     Development of this system will involve designing, for each target of interest, a probe-target-cantilever system that yields observable and reproducible deflections.  This general problem requires a set of design rules or strategies applicable to all systems of interest.  Development of such rules requires that we understand, at a very fundamental level, the relationship between molecular binding and the characteristics of the target and probe molecules.  

We approach this general bioengineering problem by applying the techniques that have been developed in areas such as polymer physics, surfactant modeling, and the study of interfacial phenomena.  For example, we are currently studying a subset of the experiments which involve observing the change in deflection upon hybridization of DNA [2].   This involves attempting to predict deflections for cantilevers that have ssDNA or dsDNA immobilized on one surface, and thereby estimating the change in deflection upon hybridization.  We have currently applied a variety of approaches from polymer physics, such as scaling laws, self consistent field calculations, Monte Carlo simulations, and theories of nematic systems.  All of these efforts are supported by close synergy with experimental investigations. 

References 

1.  Fritz, J.; Baller, M. K.; Lang, H. P.; Rothuizen, H.; Vettiger, P.; Meyer, E.; Guntherodt, H.-J.; Gerber, Ch.; Gimzewski, J. K, Science, 288, 316 (2000). 

2.  Wu, G.; Ji, H.; Hansen, K. M.; Thundat, T.; Datar, R. H.; Cote, R. J., Hagan, M. F.; Chakraborty, A. K.; Majumdar, A., PNAS, 98, 1560 (2001).  

3.  Wu, G.; Datar, R. H.; Hansen, K. M.; Thudat, T.; Cote, R. J. Majumdar, A., Nat. Biotechnol., 19, 856 (2001)