以基板電壓作生醫感測晶片再生的物理機制及參數研究

Abstract

The literature showed that the immune type biosensors can be regenerated by applying a voltage of order of one volt across the combined macromolecules, but the underlying physics was not clarified. Such a method for regeneration via physical means is of particular interest for developing possible implantable biosensor where the conventional regeneration via chemical elution is unavailable. Thus the goal of this dissertation is to carry out a rigorous study for understanding the physics behind the regeneration, and a detailed parametric study which is helpful for designing effective re-generable biosensor using substrate electric potential. By incorporating an electric double layer force and a van der Waals force into a weight-ensemble Brownian dynamics simulation under a prescribed molecular interaction force between specific interacting macromolecules, we found that the dissociation rate constant for biotin-streptavidin increases exponentially with , and reaches more than 400 folds when equals one volt. The results are qualitatively similar using either the result from molecular dynamic simulation or the Lennard-Jones model for the prescribed interaction force between biotin and streptavidin. Examination of detailed forces shows that it is the electric double layer force that lowers the energy barrier mainly set by the molecular interaction force associated with the specific interacting molecules, so that the random thermal force has more chance to tear those associated macromolecules apart. With the enhanced dissociation rate constant obtained, a series of macroscopic diffusion simulation was performed with the aid of the commercial software, COSMOL. The result agrees fairly well with the previous experiment for the entire association-dissociation process. Also the calculations with the enhanced dissociation rate constants explain quantitatively the experimental finding that the regeneration using square-wave voltage is superior to that using saw-tooth voltage. This is because that the dissociation rate constant increases exponentially with the applied voltage, and the associated complex is exposed to larger applied voltage (and thus much larger dissociation rate constant) over a longer time duration for the square-wave voltage manipulation. Parametric studies were performed including effects of different applied signals, different surrounding temperature, and different linker lengths. It is found that the regeneration is enhanced as the applied voltage increases, as the temperature increases, and as the linker length decreases.