At the laboratory scale, chemical lysis is the most commonly used method for cell disruption due to its high efficiency, low cost, and compatibility with analytical techniques like PCR and electrophoresis. However, chemical lysis has drawbacks related to the use of reagents, such as the need for downstream chemical removal or long processing times. Therefore, new cell lysis methods that minimize chemical use and equipment complexity are being investigated. Among these, acoustic-based lysis, particularly using Surface Acoustic Wave (SAW) technology, shows promise. SAW generates high-shear regions in the fluid that can damage the cell membrane, but this technology presents significant limitations, such as difficulty in generating strong enough shear forces for effectively disrupting cell membranes, low volume capacity, and poor compatibility with lab workflows. The goal of this thesis is to advance the application of SAW-based cell lysis by optimizing the control and manipulation of acoustic streaming in open microfluidic systems. The objectives are to enhance the acoustic-induced shear stress through the design and optimization of interdigital transducer (IDT) configurations, to maximize the exposure of cells to acoustic-induced shear stress lysis efficiency by optimizing droplet size, to extend the application of these optimized SAW techniques to larger volumes and to investigate the role of shear stress magnitude and exposure duration in the cell lysis performance. In this work, the use of high-frequency SAW-devices for cell lysis is studied. Short attenuation lengths associated with high-frequency SAW (>100 MHz), lead to shorter recirculation lengths, enhancing acoustic streaming velocity and shear forces. We demonstrate that by using a 120 MHz SAW-device, acoustic-induced shear stress is sufficient for achieving efficient cell disruption. Chemical-free cell disruption due to acoustic streaming induced shear stress is achieved in 20 μL droplets with an efficiency of 50-60% for a total process time of 4 minutes. Further, we demonstrate the possibility of enhancing cell lysis efficiency by reducing the droplet size, which increases cell exposure to high shear stress. A challenge of SAW actuation in small droplets is the droplet displacement and nebulization when the size of the droplet becomes comparable to the SAW width. These effects are counteracted by reducing the aperture of the IDT, which concentrates the acoustic energy in a narrower region of the droplet, enabling cell lysis in small droplets. By reducing the droplet size to 5 μL and using a micro-sized IDT, cell lysis efficiency increases up to 80%. The total lysis time is reduced to 60 seconds. These results can be explained by an enhancement of cell exposure to shear stress. These observations suggest an accumulative damage of the cell membrane exposed to repetitive, short-term shear. A deeper analysis of these observations reveals that there is a shear stress threshold of 0.26 Pa over which if it is exceeded, cells lysis occurs. Above this threshold value, the extracted DNA gets proportional to the shear stress. A relation between cell lysis and the accumulative damage on the cells is suggested. Last, the limitations in volume capacity and compatibility with lab workflows of SAW-based cell lysis methods are addressed with the development of a mobile IDT. This device allows more precise and effective transmission of acoustic energy throughout the sample, enhancing acoustic streaming in larger volumes. Cell lysis with an efficiency of 90-100% is achieved in 50 μL droplets in 75 seconds. In addition, this device enables direct transmission of the acoustic energy into samples contained in assay tubes or microwells, avoiding wave damping in the container walls. This method brings an alternative to in-droplet SAW-based lysis, improving SAW-based compatibility with lab workflows. Cell lysis is also enabled in assay tubes containing 100 μL of sample, with an efficiency of 90-100% in 45 seconds. Compared to chemical lysis, this method presents equal compatibility with lab workflows and offers comparable efficiencies, while reducing the process time by 15 times and avoiding the use of reagents. In summary, this work advances the application of Surface Acoustic Wave (SAW) technology for cell lysis by optimizing acoustic streaming and addressing key limitations associated with its use. The scientific impact of these findings lies in their potential for wide-ranging applications in cell biology, diagnostics, and molecular biology, particularly in settings where reagent-free, rapid, and scalable cell lysis is critical. Additionally, the results provide a strong foundation for future research into the development of more efficient and versatile SAW-based lysis systems that can be integrated into lab workflows.