Piezoelectric Mass-Sensing Devices as Biosensors—An Alternative to Optical Biosensors?

TLDR

Early quartz resonators used mass layers for frequency tuning, and Sauerbrey's 1959 finding that resonance shift is proportional to deposited mass laid the groundwork for piezoelectric mass‑sensing devices, which have since become key tools for studying biomolecular interactions and cell adhesion and may compete with other label‑free sensors such as SPR and interferometry. New oscillator circuits enabling thickness‑shear‑mode resonators to operate in fluids, combined with the sensitivity of piezoelectric transducers to mass, interfacial phenomena, viscoelasticity, surface charge, and roughness, allow label‑free detection of biomolecules and cells. These advances have been applied to monitor cell, liposome, and protein adhesion, revealing morphological changes in response to drugs and biopolymer water content without labor‑intensive techniques.

Abstract

In the early days of electronic communication-as a result of the limited number of quartz resonators available-frequency adjustment was accomplished by a pencil mark depositing a foreign mass layer on the crystal. In 1959, Sauerbrey showed that the shift in resonance frequency of thickness-shear-mode resonators is proportional to the deposited mass. This was the starting point for the development of a new generation of piezoelectric mass-sensitive devices. However, it was the development of new powerful oscillator circuits that were capable of operating thickness shear mode resonators in fluids that enabled this technique to be introduced into bioanalytic applications. In the last decade adsorption of biomolecules on functionalized surfaces turned in to one of the paramount applications of piezoelectric transducers. These applications include the study of the interaction of DNA and RNA with complementary strands, specific recognition of protein ligands by immobilized receptors, the detection of virus capsids, bacteria, mammalian cells, and last but not least the development of complete immunosensors. Piezoelectric transducers allow a label-free detection of molecules; they are more than mere mass sensors since the sensor response is also influenced by interfacial phenomena, viscoelastic properties of the adhered biomaterial, surface charges of adsorbed molecules, and surface roughness. These new insights have recently been used to investigate the adhesion of cells, liposomes, and proteins onto surfaces, thus allowing the determination of the morphological changes of cells as a response to pharmacological substances and changes in the water content of biopolymers without employing labor-intense techniques. However, the future will show whether the quartz-crystal microbalance will assert itself against established label-free sensor devices such as surface plasmon resonance spectroscopy and interferometry.