Generation, dynamics and control of microbubbles in microdevices

The impact of microfluidic technologies in the field of life sciences has noticeably increased during the last decade, due to the need of developing innovative microfluidic platforms for biomedical applications. The present experimental work focuses on the development of microfluidic systems aimed at the investigation of the generation, dynamics and control of bubbles inmicrochannels. The dissertation, after an introduction on manufacturing techniques, is divided in three parts devoted to the explanation and discussion of the main topics addressed during the research activities. The rst part concerns on the break-up phenomenon of microbubbles in a T-junction microfluidic structure which is particularly relevant in several applications involving microbubble generation technology. The bubble curvature and velocity eld during break-up are investigated using a smart microfluidic device that allows a double orthogonal view. Such device was designed, developed, and manufactured to offers the possibility to reconstruct a three-dimensional velocity eld. Combining microPIV (Particle Image Velocimetry) and the double view, two planar velocity elds are obtained showing all three components of the velocity in their intersection line. Furthermore, the reconstruction of the three-dimensional velocity field is possible by spanning the two planes along the transversal axes of the microchannel. The proposed chip could be used as microfluidic platform for T-junction break-up studies or as a benchmark for more sophisticated techniques to reconstruct 3D velocity eld or 3D tracking. The system combined with dedicated optical elements and placed on the stage of a traditional inverted microscope simultaneously yields a double orthogonal view without the need of two synchronized cameras or more complex and expensive systems. In the second part of the thesis, an experimental study of ultrasonic Bessel beam generation is presented. Microbubbles combined with ultrasounds are widely exploited to image biological tissues due to their strong echogenicity. The bubble dynamics is modied by the interactions with the ultrasound field inducing secondary mechanical effects on tissues. Different ways to focus ultrasounds on the target zone can be adopted. In order to be compatible with biological applications, ultrasound must be able to reach deep tissues without exceeding the maximum threshold of energy that induce damage. In this context, alternative systems to the traditional Gaussian focused beam, like Bessel beam here proposed, can potentially target biomedical applications more effciently. Here, a preliminary innovative large-scale annular structure was realized to demonstrate the scattering resistance and self-healing of an ultrasonic Bessel beam. An array of synchronous emitters is radially arranged. The emitters are tilted in order to generate a symmetric cone eld which builds a constructive interference with the shape of a first order Bessel function. The generated beam, as in the case of light, is able to resist the scattering of tissues and to go in depth without focusing all the energy in a single point. The main outcome of this part has been to demonstrate that the ultrasound Bessel-function emission pattern leads to scattering resistance and self-healing capability, as expected. It is important to notice that the same ultrasound eld generated in large scale could be transferred to smaller wavelengths, compatible with biological applications. The last part of the thesis deals with the study of microbubbles generation and control in microchannels and their possible application in drug delivery. Microbubbles generated with microfluidic structures are widely used in biomedical applications due to the high generation rate and size control, which depends on the flow rates of the liquid and gaseous phases. In particular, an endothelial barrier in a microchannel (blood-vessel-on-chip) has been realized and the blood vessel permeability enhancement in presence of ultrasounds-mediated microbubbles was studied. The main goal of this part is the development of a microbubbles generator to be integrated to the blood-vessel-on-chip. The generator is characterized by the flow-focusing geometry and exploits a small orice where gas and liquid converge and form microbubbles. As the reduced size facilitates gas diffusion in liquid, microbubbles are coated with biocompatible layer by adding lipids in the liquid phase resulting in bubbles of constant size over time. The microbubbles formed at the orice are then directed towards the endothelium and excited by a traditional ultrasound set-up. After sending cycles of sinusoidal bursts, the acoustic response is detected and evaluated through the analysis of sub- and ultra-harmonic generated by the microbubbles dynamics. The flow-focusing generator was adopted to investigate the microbubbles generation and the dynamics when the bubbles production rate and size increase. In such conditions, the channel following the orice is completely lled with bubbles that arrange in a ordered structure due to attractive forces, a process widely exploited in the engineering of biomaterials. The dissertation ends with a brief analysis of these bubbles structures, in particular aimed at the comprehension of the center of mass vibration and liquid phase viscosity effects.