Acoustic biosensors

Abstract

Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors.

Keywords: acoustic biosensors; bulk acoustic waves; microelectromechanical system (MEMS); piezoelectricity; quartz crystal microbalance; surface acoustic waves.

Figure 1.. Graphic depicting in general terms the processes for the generation of surface and bulk acoustic waves

Figure 2.. (A) Schematic depiction of antibody immobilization (Phase 1) on to the surface of a quartz sensor followed by the introduction of the target analyte (Phase 2). (B) Depiction of frequency against dissipation plots may be observed in QCM-D experiments

In Phase 1, frequency decreases due to loading of the antibody on to the surface, while increased dissipation is recorded, due to the viscoelastic nature of the antibody. After a period, loosely bound antibody is removed, resulting in a slight increase in frequency as mass is lost or as coupled water is lost. In the second phase, the target analyte is introduced, resulting in a frequency decrease and dissipation increase as it binds to the antibody immobilized during Phase 1. PDB accession codes in (A): 1IGT [10] for the antibody and 3HFM [11] for the analyte.

Figure 3.. (A) Optical micrograph of a coupled silicon MEMS resonator platform where the spatial separation between the sensor and transducer resonators is utilized to achieve electrical isolation and fluidic interfacing to sensing layer [45]; (B) image of the above device co-integrated with a microfluidic interface.