AC biasing for electrical detection of biomolecules

Abstract

In various medical and biological applications, the label-free (i.e., electrical) detection of charged biomolecules such as DNA/RNA and proteins offers a number of advantages over the well-established optical methods. Electrical nanobiosensors, in particular, have additional advantages in terms of speed of sensing, accuracy of detection, and the possibility of semiconductor device integration. However, degradation of the signal due to nonspecific binding with background molecules reduces the sensitivity and selectivity of the electrical biosensor and has prevented its successful application. In this dissertation, I propose to study the electrochemical reaction that takes place between the target and probe molecules to enhance the association rate constant and between the biomolecules and the surface of a carbon nanotube (CNT) to suppress the adsorption of nonspecific biomolecules in serum throughout the experiment and the numerical result of the simulation. For the enhancement of the association rate constant between the probe and the target molecules, the specific pulse train applied to the device consists of the carbon nanotube network channel formed on the concentric electrodes. In order to optimize the association efficiency, various input conditions are considered for DNA hybridization experiments (i.e., frequency, size of the gold nanoparticle, and the ionic strength of the electrolyte). Compared with the DC and non-biasing conditions, the pulse-biasing method offers better selectivity and sensitivity enhancement in a buffer solution to detect the dengue virus?specific DNA sequence, and a very low limit of detection can be achieved in serum. To suppress the adsorption of nonspecific binding of biomolecules in serum, the specific pulse train is applied to the device. There is no need for an additional CNT surface treatment (e.g., Tween-20, polyethylene glycol [PEG], or the like) and no additional washing step for the nonspecific binding of biomolecules in serum owing to the systematic factor change such as the concentration of hydrogen ion and dynamic motion of the biomolecules through the electric field. Each moment of signal change from positive bias to negative bias or from negative bias to positive bias could suppress the undesired binding event with nonspecific molecules. This experiment and simulation using the pulsed-bias scheme can be extended to general electrical biosensor platforms for detecting DNA and proteins and to determine the optimal conditions for maximizing the sensitivity and selectivity of the sensor by considering the electrical characteristics of biomolecules.