Novel Acoustic Wave Microsystems for Biophysical Studies of Cells

Single cell analysis is an important topic for understanding of diseases. In this understanding, biomechanics approach serves as an important tool as it relates and connects the mechanical properties of biological cells with diseases such as cancer. In this context, analysis methods based on ultrasonics are promising owing to their non-invasive nature and ease of use. However, there is a lack of miniature systems that provide accurate ultrasonic measurements on single cancer cells for diagnostic purposes.;The platform presented in this study exploits high frequency acoustic interaction and uses direct coupling of Rayleigh type SAWs with various samples placed inside microcavities to analyze their structural properties. The samples used are aqueous glycerin solutions and polystyrene microbeads for demonstrating proper system operation, and lead up to biological cells. The microcavity is instrumental in trapping a predetermined volume of sample inside and facilitating the interaction of the surface waves with the sample in question via a resonance condition. Ultimately, the resultant SAW reaching the output transducer incurs a phase delay due to its interaction with the sample in the microcavity. The system operates in a different manner compared to similar systems as a result of multiple wave reflections in the small volume and coupling back to the piezoelectric substrate.;The proposed microsystem was first analyzed using finite element methods. Liquid and solid media were modeled by considering frequency dependent characteristics. Similarly, mechanical behavior of cells with respect to different conditions is considered, and biological cells are modeled accordingly. Prototype devices were fabricated on quartz and lithium niobate in a cleanroom environment. Process steps were optimized separately for devices with microcavities. Precise fabrication, alignment, and bonding of PDMS microchannels were carried out. Soft microprobes were fabricated out of SU-8, a biocompatible polymer, for dispensing cells into microcavities. A high frequency PCB including a matching circuit was designed for the SAW devices. 3D printed housing was also prepared for demonstrating the integration capability.;Experimental results were collected first for analysis of high glycerin content in deionized water. Furthermore, polystyrene microbeads were counted with the system, and their sizes were differentiated experimentally to demonstrate the operation with solid media. Ultimately, biological cells were sensed and characterized. After tumor cells in media were transported to and trapped in microcavities, the proposed platform used SAW interaction between the substrate and the cells to extract their mechanical stiffness based on the ultrasound velocity. Measurements showed that output phase information is an indicator of the stiffness modulus of the trapped cells. Small populations of various types of cells such as MCF7, MDA-MB-231, SKBR3, and JJ012 were characterized and characteristic moduli were estimated for each cell population.;In conclusion, the results indicate that high frequency stiffness modulus is a possible biomarker for aggressiveness of the tumor and that microcavity coupled SAW devices are a good candidate for non-invasive interrogation and high frequency biophysical studies of single cells. The proposed system is a successfully miniaturized ultrasonic biosensor and can be integrated with microchannels to obtain higher throughput upon refinement of the design as evidenced by the initial results with microfluidics. Improvement in performance and signal strength is also shown to be possible through matching circuits as demonstrated.