In 2015 over half of the total deaths worldwide were due to the top ten causes of mortality, as stated by the World Health Organization. Heart disease, cancer, and diabetes are particularly prominent, especially in developing countries. In the last decades a significant amount of effort has been made by the scientific community in order to address these pathologies, from both the screening and the treatment points of view. To date, early-detection seems to be one of the most effective strategies in reducing the mortality. By diagnosing one of these pathologies at very early stages, the survival rate can be significantly enhanced. For example, the 5-year survival rate of women with breast cancer is ⇡72% for stage III (before metastasis), ⇡93% for stage II and close to 100% for stage I and 0 (American Cancer Society data). Automated, cheap, and portable devices that can help in diagnosing these illnesses would be a breakthrough for life-science applications, particularly for point-of-care (PoC) purposes. These devices are the so-called lab-on-chips (LoCs). LoCs are chips with a small surface (mm2–cm2) that embed many operations that are usually performed by trained personnel in a centralized laboratory facility. These operations include centrifugation, reagent mixing, heating, particle separation, cell counting, analyte detection, amongst many others. By making use of innovative plastic materials, piezoelectric substrates and cleanroom facilities for fabrication, it is possible to realize these novel devices that can potentially fulfill all the requirements for early-detection and PoC. In this PhD thesis, I present my research on this topic. During my studies, I exploited two promising technologies for LoCs, namely surface acoustic wave (SAW) and surface plasmon resonance (SPR), through which I explored novel configurations for microfluidics and biosensing on nanostructured devices. I started studying the effects of SAWs on liquid droplets, with particular attention to the heating and mixing and how these phenomena could be exploited for treating biological samples. I investigated how SAWs affect cell cultures and how they can improve cell-proliferation by generating fluid motion inside standard Petri dishes. Then, I demonstrated a microfluidic SPR biosensor enhanced by the presence of SAW-induced fluid mixing. By means of the SAW-generated fluid recirculation, this device can detect analytes in a significantly reduced time. Next, I demonstrated two different SAW-based biosensors, a cantilever with a SAW-based readout and a SAW-resonator. The performance of both of them were suitable for biomedical assays. In particular, the SAW-resonator is promising in the light of cancer biomarker detection, as it is almost ten times more sensitive than similar commercially available sensing units. Finally, I moved towards the development of a full-SAW microfluidic platform for biosensing, combining SAW-microfluidics and SAWbiosensing. I further improved the SAW-resonator chip design by integrating multiplexing and microfluidic channels for liquid sample handling. I also developed custom-made software for fast and reliable data acquisition and post-processing. The experiments presented here are performed with artificial fluids: biotin-avidin was chosen for the biorecognition model, as it is well known to mimic the biomolecular processes of biomarkers detection. In final chapters I show and discuss experiments in the presence of biological noise (i.e., non-specific binding molecules) and evaluate the biosensor performance with samples more similar to body fluids. The studies I carried out are promising in the light of development of versatile, portable, and sensitive SAW-based LoC for early-detection of pathologies, and show enhanced performance in both detection of biomolecules and reduced detection times with respect to traditional methods.
Surface-acoustic-wave based biosensors and microfluidic devices for Life-science applications / Agostini, Matteo. - (2018 Jul 13).
|Titolo:||Surface-acoustic-wave based biosensors and microfluidic devices for Life-science applications|
|Supervisore interno:||Ratto, Gian Michele|
|Data di pubblicazione:||2018-07-13|
|Settore Scientifico Disciplinare:||FIS/07 FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA)|
|Parole chiave (inglese):||biomedical devices|
microfluidic SPR biosensor
surface acoustic wave (SAW)
surface plasmon resonance (SPR)
|Editore:||Scuola Normale Superiore|
|Appare nelle tipologie:||9.1 Tesi di Dottorato|