Recent advances of surface acoustic wave-based sensors for noninvasive cell analysis

Surface acoustic wave (SAW)-based sensors have become a widely used method for monitoring cells and cell mechanics. SAW as a noninvasive sensing technique have not only proven to be versatile, fast, and cost-efficient [1], but also allow for in-depth analysis of detected materials and their mechanical properties [2]. At the beginning of the 21st century, proteins were immobilized rapidly, reproducibly, and with high specificity on a SAW sensor [3]. Since cell membranes contain a large variety and number of proteins, it is challenging to transfer the high specificity of protein detection to cell detection. Nevertheless, these early studies paved the way for more detailed investigations on membrane proteins and their surface interactions: in 2008, Saitakis et al. used Love waves to identify the number of HLA-A2 molecules on LG2 and K562 cells on the sensor surface [4]. As one of the earliest studies employing SAW to detect viscous properties of biomaterials, Laenge et al. defined the measurable viscosity range of different protein solutions [5]. Since then, SAWs were also used to measure elasticity changes and localize diseased regions in whole-chicken breast tissue [6]. The SAW sensor technique has been proven to detect the adhesion process of fibroblasts [7], bacteria [8], and viruses such as bacteriophages [9], Coxsackie virus, and Sin Nombre virus B4 (SNV) [10]. To keep track of the rapid advances in SAW biosensing techniques and the widening field of applications, some reviews have been published: in 2012, Saitakis et al. discussed advances in acoustic biosensors for cell applications, and concluded that the technique should become more user-friendly and automized and that the damping effects of coatings could be a limitation [2]. The choice of smart coating materials, difficulties such as attenuating effects in liquids, and the maintenance of cell culture conditions on sensors were also highlighted in the 2019 SAW roadmap article [11]. As a promising future direction, an integration of actuator and sensor devices on one platform to simultaneously assemble and characterize biomaterials was proposed 11, 12. Reviews usually provide a wide overview of acoustic biosensing 2, 13, so that the application of SAW sensors specifically to the field of cell biology has not been the main focus so far. To fill this gap, we here provide a compact review with special focus on SAW-based detection of cells and cellular properties. As a basis for understanding the sensing technique, we will first give an overview of the working principle and most frequently used SAW types. Then, we review the advances of SAW sensing over the past years, with emphasis on developments from 2019 to 2022, dividing the field of application into the three main categories: 1) cell adhesion and growth, 2) viscoelastic properties, and 3) bacteria and virus detection.

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