Multiscale fabrication of functional materials for life sciences

Regenerative medicine claims for a better understanding of the cause-effect relation between cell behaviour and environment signals. The latter encompasses topographical, chemical and mechanical stimuli, electromagnetic fields, gradients of chemo-attractants and haptotaxis. In this perspective, a spatial control of the structures composing the environment is required. In this thesis I describe a novel approach for the multiscale patterning of biocompatible functional materials in order to provide systems able to accurately control cell adhesion and proliferation. The behaviour of different neural cell lines in response to several stimuli, specifically chemical, topographical and electrical gradients is presented. For each of the three kind of signals, I chose properly tailored materials and fabrication and characterization techniques. After a brief introduction on the state of art of nanotechnology, nanofabrication techniques and regenerative medicine in Chapter 1 and a detailed description of the main fabrication and characterization techniques employed in this work in Chapter 2, in Chapter 3 an easy route to obtain accurate control over cell proliferation close to 100% is described (chemical control). In Chapter 4 (topographical control) it is shown how the multiscale patterning of a well-established biocompatible material as titanium dioxide provides a versatile and robust method to study the effect of local topography on cell adhesion and growth. The third signal, viz. electric field, is investigated in Chapter 5 (electrical control), where the very early stages of neural cell adhesion are studied in the presence of modest steady electric fields. In Chapter 6 (appendix) a new patterning technique, called Lithographically Controlled Etching (LCE), is proposed. It is shown how LCE can provide at the same time the micro/nanostructuring and functionalization of a surface with nanosized objects, thus being suitable for applications both in regenerative medicine in biosensing.

Hybrid portable systems for bio-nanosensors

The promising development in the routine nanofabrication and the increasing knowledge of the working principles of new classes of highly sensitive, label-free and possibly cost-effective bio-nanosensors for the detection of molecules in liquid environment, has rapidly increased the possibility to develop portable sensor devices that could have a great impact on many application fields, such as health-care, environment and food production, thanks to the intrinsic ability of these biosensors to detect, monitor and study events at the nanoscale. Moreover, there is a growing demand for low-cost, compact readout structures able to perform accurate preliminary tests on biosensors and/or to perform routine tests with respect to experimental conditions avoiding skilled personnel and bulky laboratory instruments. This thesis focuses on analysing, designing and testing novel implementation of bio-nanosensors in layered hybrid systems where microfluidic devices and microelectronic systems are fused in compact printed circuit board (PCB) technology. In particular the manuscript presents hybrid systems in two validating cases using nanopore and nanowire technology, demonstrating new features not covered by state of the art technologies and based on the use of two custom integrated circuits (ICs). As far as the nanopores interface system is concerned, an automatic setup has been developed for the concurrent formation of bilayer lipid membranes combined with a custom parallel readout electronic system creating a complete portable platform for nanopores or ion channels studies. On the other hand, referring to the nanowire readout hybrid interface, two systems enabling to perform parallel, real-time, complex impedance measurements based on lock-in technique, as well as impedance spectroscopy measurements have been developed. This feature enable to experimentally investigate the possibility to enrich informations on the bio-nanosensors concurrently acquiring impedance magnitude and phase thus investigating capacitive contributions of bioanalytical interactions on biosensor surface.

Nano-fabrication of complex functional structures using non- conventional lithography

In Chapter 1 I will present a brief introduction on the state of art of nanotechnologies, nanofabrication techniques and unconventional lithography as a technique to fabricate the novel electronic device as resistive switch so-called memristor is shown. In Chapter 2 a detailed description of the main fabrication and characterization techniques employed in this work is reported. Chapter 3 parallel local oxidation lithography (pLOx) describes as a main technique to obtain accurate patterning process. All the effective parameters has been studied and the optimized condition observed to highly reproducible with excellent patterned nanostructures. The effect of negative bias, calls local reduction (LR) studied. Moreover, the use of AC bias shows faster patterning process respect to DC bias. In Chapter 4 (metal/ e-SiO2/ Si nanojunction) it is shown how the electrochemical oxide nanostructures by using pLOx can be used in the fabrication of novel devices call memristor. We demonstrate a new concept, based on conventional materials, where the lifetime problem is resolved by introducing a “regeneration” step, which restores the nano-memristor to its pristine condition by applying an appropriate voltage cycle. In Chapter 5 (Graphene/ e-SiO2/ Si), Graphene as a building block material is used as an electrode to selectively oxidize the silicon substrate by pLOx set up for the fabrication of novel resistive switch device. In Chapter 6 (surface architecture) I will show another application of pLOx in biotechnology is shown. So the surface functionalization combine with nano-patterning by pLOx used to design a new surface to accurately bind biomolecules with the possibility of studying those properties and more application in nano-bio device fabrication. So, in order to obtain biochips, electronic and optical/photonics devices Nano patterning of DNA used as scaffolds to fabricate small functional nano-components.