Microcantilever deflection induced to hybridization of monomolecular DNA films: lower immobilization densities lead to larger deflections?

Experimental results show that specifi c binding between a ligand and surface immobilized receptor such as hybridization of single-stranded DNA (ssDNA) immobilized on a microcantilever surface leads to cantilever defl ection. The binding induced defl ection may be used as a method for detection of biomolecules, such as pathogens and biohazards. Mechanical deformation induced because of hybridization of surface immobilized DNA strands is a commonly used system to demonstrate the effi cacy of microcantilever sensors; therefore, hybridization induced cantilever defl ection has been reported for range of parameters that chain distributions – ssDNA immobilization densities, hybridization effi ciencies, and ssDNA conformation [1–7]. However, it has been hard to draw general conclusions on the DNA hybridization induced defl ections because a large range of defl ections has been reported for similar density of hybridized DNA strands on the cantilever. To understand the mechanism underlying the cantilever defl ections, a theoretical model that incorporates the infl uence of ligand/receptor complex surface distribution, conformation, confi guration, and empirical interchain potential is developed to predict the binding induced defl ections. The cantilever bending induced because of hybridization of DNA strands is predicted for different receptor immobilization densities, hybridization effi ciencies, receptor confi guration, and spatial arrangements. Predicted defl ections are compared with experimental reports to validate the modeling assumptions and identify the infl uence of various components on mechanical deformation. Comparison of numerical predictions and experimental results suggest that initial immobilization density of receptors is a primary factor that determines the conformation and distribution of hybridized DNA strands and in turn, the cantilever defl ection associated with DNA hybridization. Contrary to our expectations, the cantilever defl ections are found to be larger for smaller receptor immobilization densities. For high immobilization densities, hybridization-induced mechanical deformation is determined primarily by immobilization density and hybridization effi ciency as the hybridized DNA strands are restricted to be in standing-up conformation, whereas at lower immobilization densities, different conformations and spatial arrangement of hybridized chains need to be considered in determining the cantilever defl ection. In addition, for similar immobilization densities, changing the immobilized receptor confi guration from one end-tethered to both end-tethered leads to larger cantilever defl ection on hybridization. Comparison of numerical predictions and experimental results highlights the importance of immobilized receptor confi gurations, immobilization density, and spatial disorder imposed during immobilization and hybridization on the hybridization induced cantilever bending.