Paper NS1+BI-WeA8
Microfabricated Cantilever Arrays for Drug Screening Based on DNA-Drug Intercalation

Wednesday, October 17, 2007, 4:00 pm, Room 615

The ability of a cantilever sensor to generate nanomechanical motion from biomolecular interactions can have wide applications in drug discovery. Microfabricated cantilever arrays offer high sensitivity multiplexed detection in real-time in liquid medium. DNA strands when selectively immobilized on one side of the cantilever surface exhibit surface stress variation during interaction with different chemicals. We have used microfabricated piezoresistive cantilever arrays to demonstrate surface stress variation due to immobilization of ssDNA, hybridization and drug interaction that could form the basis for multiplexed detection of chemicals and drugs intercalating with dsDNA. It is shown that immobilization of ssDNA results in a compressive stress while hybridization results in tensile stress. Intercalation between adjacent base pairs results in stiffening, lengthening and unwinding of the double helix, causing it to expand and lose native conformation. Intercalation of chemicals into immobilized dsDNA produces a characteristic oscillatory response pattern. We have investigated the surface stress pattern due to interaction of chemicals such as ethidium bromide and anti-tumor drugs with dsDNA immobilized on cantilever arrays. The dynamic signature pattern can provide new insight on the kinetics and nanomechanics of DNA-drug intercalation. We have used x-ray photoelectron spectroscopy to carry out elemental analysis in order to confirm the presence of the intercalating agent in the DNA. Microfabricated cantilever arrays find potential applications in drug screening, identification of various toxins, and biological sensing.