## 1 Introduction  
A biosensor is an analytical device constituted by a biological recognition element, generally defined as a probe immobilized on a transduction system, which converts a molecular interaction into a useful signal. There are several types of biosensors based on different sensing recognition mechanisms such as amperometric, electrochemical, optical, and thermometric. In an optical biosensor, the interaction between the biomolecular probe, bound on its surface, and the target analyte is transduced in a change of an optical signal (e.g., phase, intensity, color, and fluorescence) [1; 2; 3]. In the last few decades, the market of optical biosensors has grown very rapidly due to their high sensitivity, specificity, real-time response, and the possibility of performing remote sensing in flammable environments. The semiconductors currently used in the microelectronic industry, such as silicon and its related materials (silicon oxide, silicon nitrides, and porous silicon), have been extensively exploited in biosensor fabrication, and hundreds of papers and reviews can be found in recent literature [4; 5; 6; 7; 8]. On the other hand, nanostructured metal oxides showed great potential for the detection of biomolecules, owing to several characteristics such as the controllable size/shape, large specific surface area, biocompatibility, catalytic and optical properties, and chemical stability [9]. Among them, nanostructured zinc oxide (nZnO) is considered an interesting transducer material due to its multifunctional characteristics. The nZnO is an n-type semiconductor with a wide direct band gap of 3.37 eV, and a large excitonic binding energy of 60 meV, thus allowing an efficient excitonic emission even at room temperature [10; 11]. Under UV laser irradiation, nZnO is able to emit intense photoluminescence (PL) of which the spectrum is characterized by a peak at 380 nm, due to free exciton recombination and a broad visible band related to the surface and lattice defects [12]. Different methods for fabrication of nZnO-based devices are available, such as Vapor-Liquid-Solid growth (VLS), Metal Organic Chemical Vapor Deposition (MOCVD), and High-Pressure Pulsed Laser Deposition (HP-PLD) [13; 14]. Recently, hydrothermal synthesis was proposed as an advantageous alternative approach because it requires mild experimental conditions, simple equipment, low-cost reagents, and it can be indifferently used on several surfaces [15]. One of the key issues in the developing of biosensors is the functionalization strategy used to correctly immobilize the bioprobes on the material surfaces. From this point of view, the nZnO allows covalent binding of the biomolecules on its surface by using a soft chemical strategy, preserving the specific functionalities of the biological compounds and controlling their orientation. The use of the ZnO nanowires obtained by the hydrothermal method as a photoluminescence biosensor was demonstrated [14]. In this work, nanostructured fluorine (F)-doped ZnO (nZnO-F) was directly grown on a crystalline silicon substrate via hydrothermal synthesis, and chemically modified in order to fabricate a technological platform for biosensing purposes [15]. F\({}^{-}\) ions, usually used as a doping precursor, played a significant role in the morphological, electrical and optical properties of nanostructured ZnO [16]. Extensive studies reported in Reference [15], demonstrated that F atoms mainly occupy oxygen vacancies present in the material, without producing any substantial change of plasma frequency but only the enhancement of scattering rate due to an increase of grain boundary density. A proper functionalization procedure was developed to covalently immobilize the Protein A (PrA), used as a model molecule on the semiconductor surface. The functionalized nZnO-F was characterized by the Fourier Transform Infrared Spectroscopy, water contact angle, and fluorescence microscopy.