Advanced CMOS Interfaces for Bio-Nanosensors

The improvement of devices provided by Nanotechnology has put forward new classes of sensors, called bio-nanosensors, which are very promising for the detection of biochemical molecules in a large variety of applications. Their use in lab-on-a-chip could gives rise to new opportunities in many fields, from health-care and bio-warfare to environmental and high-throughput screening for pharmaceutical industry. Bio-nanosensors have great advantages in terms of cost, performance, and parallelization. Indeed, they require very low quantities of reagents and improve the overall signal-to-noise-ratio due to increase of binding signal variations vs. area and reduction of stray capacitances. Additionally, they give rise to new challenges, such as the need to design high-performance low-noise integrated electronic interfaces. This thesis is related to the design of high-performance advanced CMOS interfaces for electrochemical bio-nanosensors. The main focus of the thesis is: 1) critical analysis of noise in sensing interfaces, 2) devising new techniques for noise reduction in discrete-time approaches, 3) developing new architectures for low-noise, low-power sensing interfaces. The manuscript reports a multi-project activity focusing on low-noise design and presents two developed integrated circuits (ICs) as examples of advanced CMOS interfaces for bio-nanosensors. The first project concerns low-noise current-sensing interface for DC and transient measurements of electrophysiological signals. The focus of this research activity is on the noise optimization of the electronic interface. A new noise reduction technique has been developed so as to realize an integrated CMOS interfaces with performance comparable with state-of-the-art instrumentations. The second project intends to realize a stand-alone, high-accuracy electrochemical impedance spectroscopy interface. The system is tailored for conductivity-temperature-depth sensors in environmental applications, as well as for bio-nanosensors. It is based on a band-pass delta-sigma technique and combines low-noise performance with low-power requirements.

Cancer and aging: a multidisciplinary medicinal chemistry approach on relevant biological targets such as proteasome, sirtuins and interleukin 6

It is well known that ageing and cancer have common origins due to internal and environmental stress and share some common hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury. Moreover, ageing is involved in a number of events responsible for carcinogenesis and cancer development at the molecular, cellular, and tissue levels. Ageing could represent a “blockbuster” market because the target patient group includes potentially every person; at the same time, oncology has become the largest therapeutic area in the pharmaceutical industry in terms of the number of projects, clinical trials and research and development (R&D) spending, but cancer remains one of the leading causes of mortality worldwide. The overall aim of the work presented in this thesis was the rational design of new compounds able to modulate activity of relevant targets involved in cancer and aging-related pathologies, namely proteasome and immunoproteasome, sirtuins and interleukin 6. These three targets play different roles in human cells, but the modulation of its activity using small molecules could have beneficial effects on one or more aging-related diseases and cancer. We identified new moderately active and selective non-peptidic compounds able to inhibit the activity of both standard and immunoproteasome, as well as novel and selective scaffolds that would bind and inhibit SIRT6 selectively and can be used to sensitize tumor cells to commonly used anticancer agents such gemcitabine and olaparib. Moreover, our virtual screening approach led us also to the discovery of new putative modulators of SIRT3 with interesting in-vitro and cellular activity. Although the selectivity and potency of the identified chemical scaffolds are susceptible to be further improved, these compounds can be considered as highly promising leads for the development of future therapeutics.

The role of the West African Monsoon in the tropical to mid-latitudes climate

The interaction between atmosphere–land–ocean–biosphere systems plays a prominent role on the atmospheric dynamics and on the convective rainfall distribution over the West Africa monsoon area during the boreal summer. In particular, the initialization of convective systems in the Sub – Sahelian region has been directly linked to soil moisture heterogeneities identified as the major triggering, development and propagation of convective systems. The present study aims at investigating African monsoon large scale convective dynamics and rainfall diurnal cycle through an exploration of the hypothesis behind the mechanisms of a monsoon phenomenon as an emergence of a collective dynamics of many propagating convective systems. Such hypothesis is based on the existence of an internal self – regulation mechanism among the various components. To achieve these results a multiple analysis was performed based on remote sensed rainfall dataset, and global and regional modelling data for a period of 5 seasons: 2004 - 2008. Satellite rainfall data and convective occurrence variability were studied for assessing typical spatio – temporal signatures and characteristics with an emphasis to the diurnal cycle footprint. A global model and regional model simulation datasets, specifically developed for this analysis and based on Regional Atmospheric Modelling System – RAMS, have been analysed. Results from numerical model datasets highlight the evidence of a synchronization between the destabilization of the convective boundary layer and rainfall occurrence due to the solar radiation forcing through the latent heat release. This supports the conclusion that the studied interacting systems are associated with a process of mutual adjustment of rhythms. Furthermore, this rainfall internal coherence was studied in relation to the West African Heat Low pressure system, which has a prominent role in the large scale summer variability over the Mediterranean area since it is acting as one of dynamic link between sub tropical and midlatitudes variability.