Integrated optical platform for biosensor applications

Biosensors are essential tools for the daily life of everybody, used in various environments from clinical exams for patients up to control of water quality in distribution sites. There are several technologies available for implementing biosensors, but research in this field is always looking for new solutions, aiming for higher sensitivity, faster responses, wide dynamics range, solution suitable for low cost implementations, etc. The three years of Ph.D. have been mostly dedicated to the research on integrated optics circuits for biosensing application. The field of biosensors is a wide multidisciplinary field regarding different competences to successfully arrive to a prototype. The research has mainly concentrated on the implementation of an innovative, robust, and reliable integrated optical device for the detection of several analytes. The reported activities have been connected within a EU project, a Regional project, a collaboration with companies, and an internal project. Both label-free and label-based approaches have been explored. With label-free assay, the biotransducer has to convert the biological event without the support of any other kind of additional elements or processes. An optical device based on integrated microring resonators, whose resonance wavelength is affected by the presence of analytes over the waveguide has been conceived, realized, and tested. The platform showed important results, for example by detecting Ovalbumin protein (a Ricin A toxin simulant) down to a concentration of 400 pM. Detection of DNA was also achieved, focusing in particular on the functionalization of the microring resonator with a novel method based on Micro-Contact Printing. We decided to move to label-based approach, and in particular to exploit a combination of optical and magnetic approaches, in collaboration with Nanomagnetism for Biology and Spintronics Group (NaBiS) of prof. R. Bertacco. In our research, we combined the use of magnetic beads as labels with our optical device, exploiting the invasive impact that these beads have on the optical mode. The first results showed an enhancement of the detection limit of almost three orders of magnitude when magnetic beads were used. Following this path, we designed a novel platform that increases the interaction of optical detection and magnetic properties. By the use of an electromagnet, we were able to actually move the beads. The oscillation of the beads induces a variation of the evanescent optical field and hence a fluctuation of the optical phase. If a biological molecule links the beads to the optical device, the oscillation applied to the beads is transformed into a stretch of the molecule itself and can be detected from the output optical power. This Opto-magnetic platform has some advantages, the main one is the possibility of an on-off detection, since the signal is revealed just in presence of molecules,magnetic beads, and magnetic field. We tested this platform by using DNA strand to link the optical waveguide to the beads. The results show that the platform works correctly, as the signals matched with the expected values, in particular the stretch constant of the DNA matched with the observed displacement of the beads. A patent was filled to cover this innovative concept. The second path was to improve the resolution in the detection of resonance wavelength shift. In the first experiments, detection of wavelength shifts was perform by spanning a tunable laser source over a certain wavelength range. With this method, achieving a resolution under 10 pm is very critical. To overcome these limitations, we developed an electronic-photonic platform together with STMicroelectronics (STm). The main concept is the locking of a tunable laser to a microring resonator through an electronic feedback loop. In particular, we designed an add-drop microring resonator, whose powers at the output ports are balanced by the tuning of a laser wavelength. In this scheme, biological events will induce a shift of the microring resonance that is tracked by the electrical signal that drive the laser. The platform required a lay activity in collaboration with STm in order to be designed and tested. As results, we were able to distinguish step changes in the wavelength shift down to tens of femtometers, with a bandwidth of 1 kHz. In conclusion, with this Ph.D. work, we developed optical platforms for biosensing. The obtained results are beyond the state-of-the-art concerning optical biosensors. The close relationship with other research groups and industries have been essential for this path, allowing to generate innovative ideas and concepts. The experimental side of the Ph.D. has been wide and essential, in particular in the Photonic Device Laboratory and in Polifab. The future steps will focus on the integration of the two platforms in a single solution, capable of joining the main features of the both.

I biosensori sono strumenti essenziali nella vita quotidiana, basti pensare al loro uso negli ospedali o nei processi di controllo qualità di cibi e bevande. Esistono molteplici tecnologie che permettono di ottenere dei biosensori, ma negli ultimi anni la ricerca si è focalizzata su quelle soluzioni che puntano ad avere un’alta sensibilità, assieme a un responso veloce ad un costo accessibile. Questi tre anni di dottorato sono stati dedicati alla ricerca di come l’ottica integrata possa rispondere alle necessità del settore dei biosensori. Poiché questo settore richieda un approccio multidisciplinare per ottenere un prototipo funzionante, in questo lavoro di ricerca ci si è soffermati sulla parte tecnologica del biosensore, ottenendo comunque risultati sperimentali completi di corrispettivi biologici. La tesi si divide in tre capitoli principali, oltre alla introduzione sui biosensori e l’ottica integrata. All’inizio si affrontano i biosensori ottici “label-free”, cioè quelli che riescono a determinare la quantità di un certa sostanza senza l’aggiunta di altri elementi o molecole. Da questi primi risultati si sono aperte due strade, corrispondenti ai due capitoli. Il primo percorso utilizza la stessa piattaforma ma aggiungendo delle nano-sfere magnetiche, che da un lato permettono l’aumento della sensibilità del sensore, dall’altro implementano un meccanismo nuovo per la rivelazione della sostanza cercata, unendo all’approccio ottico quello magnetico. La seconda strada, invece, segue un miglioramento della piattaforma ottica, allo scopo di ottenere una migliore risoluzione nelle misure, e quindi una migliore sensibilità del biosensore. In conclusione, con questo lavoro di tesi si presentano i migliori risultati ottenuti in questi tre anni di lavoro. La ricerca ha portato diversi riconoscimenti, tra cui una domanda di brevetto, diverse pubblicazioni e attività di ricerca con aziende esterne, finanziate da progetti regionali ed europei.