A cost-effective self-sensing biosensor for detection of biological species at ultralow concentrations

Abstract

Detection of ultrasmall masses and identification of biological molecules have been made possible as a result of advances in nanotechnology. Development of biosensing tools has significantly contributed to high-throughput diagnosis and analytical sensing exploiting high affinity of biomolecules. MicroCantilever (MC)-based detection has emerged as a promising biosensing tool for offering label-free and cost-effective sensing capabilities. One of the main criteria determining the success of each biosensor is the capability of the sensing platform to operate in aqueous media. Although being characterized with high sensitivity and simplicity, MCs do not provide an effective tool for measurement of marker proteins in liquid media due to large hydrodynamic damping and losses in the surrounding liquid. In this study, we describe two approaches to high sensitivity biomolecular detection using piezoelectric microcantilevers. (i) Immobilized Mass Detection in Air using electro-mechanical resonance: a unique self-sensing measurement technique is reported utilizing a self-sensing circuit consisting of a piezoelectric MC to address the mentioned limitation. The capability of the self-sensing measurement technique was first verified by detecting ultrasmall biological masses immobilized over the surface of MC by monitoring the shift in fundamental mechanical resonance frequency of the system in air and comparing it with optical-based measurement. This was further utilized for calibration of mass detection in liquid media. (ii) Immobilized Mass Detection in Liquid using the electrical self-sensing circuit's resonance: Once the capability to detect adsorbed mass was verified, the self-sensing platform was implemented to detect different concentrations of target molecule (glucose in this study) in liquid media by adopting the highly sensitive resonance frequency of the whole circuit instead of the mechanical response of MC. Molecular binding occurring over the surface of MC changes the capacitance of the total interface thus changing the resonance frequency of the circuit. The amount of shift in the measured circuit's resonance frequency provides qualitative and quantitative insight into the amount of target protein concentration. The reported diagnostic platform offers a simple, cost-effective, all-electronics method of detection where the need for any bulky, expensive optical based measurement is eliminated. Utilizing this technique, physiological concentration of glucose as low as 500 nM was measured in liquid media. This sensitivity is significantly higher than what has been previously reported using other mechanical resonance techniques.