Nanoscale Sensors for Ultrasensitive Label-free Detection of Cancer Biomarkers and Monitoring of Therapeutic Compounds

Prostate cancer is a life-threatening malignant disease, one the most common cancer types in men and leading cause of death among men because of cancer. Considering the state of the art for the diagnosis of prostate cancer a man overall has to suffer uncomfortable and invasive medical tests, usually in the environment of a hospital or medical clinic, long waiting times for the results of the medical assessment, and, nonetheless still risking the possibility to obtain an uncertain medical outcome. In this case the results of the diagnosis tests do not clearly and certainly indicate the actual existence or absence of cancer. Therefore, the medical test should be repeated and/or further inconvenient tests should be performed increasing the time and financial costs, as well as, the emotional stress for the patient. Meanwhile, reliable, low-cost, and accessible therapeutic compound monitoring systems for individualized healthcare, and especially for treatment of malignant diseases, such as prostate cancer and AIDS are a very important aspect in medical practice. This requirements are even more highlighted for drugs demonstrating very narrow therapeutic window, that is also depicted at low concentrations. Moreover, point-of-care biosensors for therapeutic compounds monitoring bring the treatment to the patient0s bedside, minimizing the interfering factors in medical treatments, providing a flexible and robust cut-of-technology for the monitoring of treatment, with higher efficacy and lower side effects for patients. The realization of novel ultrasensitive nano-bio-sensors for the direct and label-free detection of chemical and biological species, that present high reliability, robustness and the advantage of a quick data acquisition is therefore, the main objective of the thesis. The work presented in this thesis aims to achieve optimum sensing output in both diagnostics and therapeutics fields, for detecting a malignant disease at early stages, and for efficient screening of therapeutic drugs used in chemotherapy, allowing the possibility for continuous monitoring. Silicon nanowires with their unique properties such as the high surface-to-volume ratio and the size comparable to biomolecules, and combined with the specificity of immune-sensing techniques, are natural candidates for the fabrication of nanosensors. Moreover, memristive properties, exhibited by nanofabricated devices coupled with biological processes, introduce innovating solutions to the biosensing filed. In addition, graphene-based nanostructures, only recently suggested in literature, are hereby demonstrated as novel structures in electrochemistry for effective drug monitoring. Finally, complete biosensing platforms are suggested through the design and realization of a printed circuit electronic board for automatized sensing readout, along with the fabrication of a microfluidic circuit for straightforward bio-functionalization and bio-detection procedures. These aspects pave the way for the actual development of point-of-care devices, a significant aspect for treatment in hospitals and bench to bedside applications. New possibilities for multi-panel detection are also presented by the selective functionalization of individual nanodevices on a singe chip. This new aspect shows high potential for Lab-on-a Chip applications and multiplex detection of different biomarkers on the same chip, or for both biomarkers and therapeutic compounds paving the way for theranostics.


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