Optrode-Assisted Multiparametric Near-Infrared Spectroscopy for the Analysis of Liquids.

We demonstrate a sensing scheme for liquid analytes that integrates multiple optical fiber sensors in a near-infrared spectrometer. With a simple optofluidic method, a broadband radiation is encoded in a time-domain interferogram and distributed to different sensing units that interrogate the sample simultaneously; the spectral readout of each unit is extracted from its output signal by a Fourier transform routine. The proposed method allows performing a multiparametric analysis of liquid samples in a compact setup where the radiation source, measurement units, and spectral readout are all integrated in a robust telecom optical fiber. An experimental validation is provided by combining a plasmonic nanostructured fiber probe and a transmission cuvette in the setup and demonstrating the simultaneous measurement of the absorption spectrum and the refractive index of water-methanol solutions.

Innovative Photonic Sensors for Safety and Security, Part II: Aerospace and Submarine Applications.

The employability of photonics technology in the modern era's highly demanding and sophisticated domain of aerospace and submarines has been an appealing challenge for the scientific communities. In this paper, we review our main results achieved so far on the use of optical fiber sensors for safety and security in innovative aerospace and submarine applications. In particular, recent results of in-field applications of optical fiber sensors in aircraft monitoring, from a weight and balance analysis to vehicle Structural Health Monitoring (SHM) and Landing Gear (LG) monitoring, are presented and discussed. Moreover, underwater fiber-optic hydrophones are presented from the design to marine application.

Innovative Photonic Sensors for Safety and Security, Part I: Fundamentals, Infrastructural and Ground Transportations.

Our group, involving researchers from different universities in Campania, Italy, has been working for the last twenty years in the field of photonic sensors for safety and security in healthcare, industrial and environment applications. This is the first in a series of three companion papers. In this paper, we introduce the main concepts of the technologies employed for the realization of our photonic sensors. Then, we review our main results concerning the innovative applications for infrastructural and transportation monitoring.

Innovative Photonic Sensors for Safety and Security, Part III: Environment, Agriculture and Soil Monitoring.

In order to complete this set of three companion papers, in this last, we focus our attention on environmental monitoring by taking advantage of photonic technologies. After reporting on some configurations useful for high precision agriculture, we explore the problems connected with soil water content measurement and landslide early warning. Then, we concentrate on a new generation of seismic sensors useful in both terrestrial and under water contests. Finally, we discuss a number of optical fiber sensors for use in radiation environments.

Advanced Lab-on-Fiber Optrodes Assisted by Oriented Antibody Immobilization Strategy.

Lab-on-fiber (LoF) optrodes offer several advantages over conventional techniques for point-of-care platforms aimed at real-time and label-free detection of clinically relevant biomarkers. Moreover, the easy integration of LoF platforms in medical needles, catheters, and nano endoscopes offer unique potentials for in vivo biopsies and tumor microenvironment assessment. The main barrier to translating the vision close to reality is the need to further lower the final limit of detection of developed optrodes. For immune-biosensing purposes, the assay sensitivity significantly relies on the capability to correctly immobilize the capture antibody in terms of uniform coverage and correct orientation of the bioreceptor, especially when very low detection limits are requested as in the case of cancer diagnostics. Here, we investigated the possibility to improve the immobilization strategies through the use of hinge carbohydrates by involving homemade antibodies that demonstrated a significantly improved recognition of the antigen with ultra-low detection limits. In order to create an effective pipeline for the improvement of biofunctionalization protocols to be used in connection with LoF platforms, we first optimized the protocol using a microfluidic surface plasmon resonance (mSPR) device and then transferred the optimized strategy onto LoF platforms selected for the final validation. Here, we selected two different LoF platforms: a biolayer interferometry (BLI)-based device (commercially available) and a homemade advanced LoF biosensor based on optical fiber meta-tips (OFMTs). As a clinically relevant scenario, here we focused our attention on a promising serological biomarker, Cripto-1, for its ability to promote tumorigenesis in breast and liver cancer. Currently, Cripto-1 detection relies on laborious and time-consuming immunoassays. The reported results demonstrated that the proposed approach based on oriented antibody immobilization was able to significantly improve Cripto-1 detection with a 10-fold enhancement versus the random approach. More interestingly, by using the oriented antibody immobilization strategy, the OFMTs-based platform was able to reveal Cripto-1 at a concentration of 0.05 nM, exhibiting detection capabilities much higher (by a factor of 250) than those provided by the commercial LoF platform based on BLI and similar to the ones shown by the commercial and well-established bench-top mSPR Biacore 8K system. Therefore, our work opened new avenues into the development of high-sensitivity LoF biosensors for the detection of clinically relevant biomarkers in the sub-ng/mL range.

Design and Optimization of All-Dielectric Fluorescence Enhancing Metasurfaces: Towards Advanced Metasurface-Assisted Optrodes.

The need for miniaturized biological sensors which can be easily integrated into medical needles and catheters for in vivo liquid biopsies with ever-increasing performances has stimulated the interest of researchers in lab-on-fiber (LOF) technology. LOF devices arise from the integration of functional materials at the nanoscale on the tip of optical fibers, thus endowing a simple optical fiber with advanced functionalities and enabling the realization of high-performance LOF biological sensors. Consequently, in 2017, we demonstrated the first optical fiber meta-tip (OFMT), consisting of the integration of plasmonic metasurfaces (MSs) on the optical fiber end-face which represented a major breakthrough along the LOF technology roadmap. Successively, we demonstrated that label-free biological sensors based on the plasmonic OFMT are able to largely overwhelm the performance of a standard plasmonic LOF sensor, in view of the extraordinary light manipulation capabilities of plasmonic array exploiting phase gradients. To further improve the overall sensitivity, a labelled sensing strategy is here suggested. To this end, we envision the possibility to realize a novel class of labelled LOF optrodes based on OFMT, where an all-dielectric MS, designed to enhance the fluorescence emission by a labelled target molecule, is integrated on the end-face of a multimode fiber (MMF). We present a numerical environment to compute the fluorescence enhancement factor collected by the MMF, when on its tip a Silicon MS is laid, consisting of an array of cylindrical nanoantennas, or of dimers or trimers of cylindrical nanoantennas. According to the numerical results, a suitable design of the dielectric MS allows for a fluorescence enhancement up to three orders of magnitudes. Moreover, a feasibility study is carried out to verify the possibility to fabricate the designed MSs on the termination of multimode optical fibers using electron beam lithography followed by reactive ion etching. Finally, we analyze a real application scenario in the field of biosensing and evaluate the degradation in the fluorescence enhancement performances, taking into account the experimental conditions. The present work, thus, provides the main guidelines for the design and development of advanced LOF devices based on the fluorescence enhancement for labelled biosensing applications.

Improving the width of lossy mode resonances in a reflection configuration D-shaped fiber by nanocoating laser ablation.

The full width at half maximum (FWHM) of lossy mode resonances (LMRs) in the optical spectrum depends on the homogeneity of the thin film deposited. In this Letter, a method for improving the FWHM is applied for an LMR generated by a D-shaped optical fiber in reflection configuration. For this purpose, three samples with different attenuation were deposited with DC sputtering thin films of SnO2-x, and a further controlled immersion of the samples in water was performed. A laser-cleaner method was used to improve the FWHM characteristics of one of the samples from 106 to 53 nm. This improvement can be applied to thin-film-based sensors where there is a problem with the inhomogeneity of the coating thickness. Moreover, with this technique, it was proved that a coated length of just 3-4 mm permits the generation of an LMR, with implications for the miniaturization of the final device.

Analysis of uncoated LPGs written in B-Ge doped fiber under proton irradiation for sensing applications at CERN.

In this contribution, a complete dissertation concerning the behavior of a Long Period Grating (LPG) inscribed in a B-Ge co-doped optical fiber by means of an excimer laser and exposed to proton irradiation during a recent extensive campaign performed at the European Organization for Nuclear Research (CERN) with a fluence of 4.4·1015 p∙cm-2 is provided. The experimental results have been thus combined for the first time to the best of our knowledge with numerical simulations in order to estimate the variations of the major parameters affecting the grating response during the ultra-high dose proton exposure. From the correlation between experimental and numerical analysis, the irradiation exposure was found to induce a maximal variation of the core effective refractive index of ~1.61·10-4, responsible of a resonance wavelength red shift of ~44 nm in correspondence of the highest absorbed radiation dose of 1.16 MGy. At the same time, a relevant decrease close to ~0.93·10-4 in the refractive index modulation pertaining to the grating was estimated, leading to a reduction of the resonant dip visibility of ~12 dB. The effect of the proton beam on the spectral response of the LPG device and on the optical fiber parameters was assessed during the relaxation phases, showing a partial recovery only of the wavelength shift without any relevant change in the dip visibility revealing thus a partial recovery only in the refractive index of the core while the reduction of the refractive index modulation observed during the irradiation remained unchanged.

A novel method for EBT3 Gafchromic films read-out at high dose levels.

In this work, we report on a novel approach for measuring the dose absorbed by the EBT3 Gafchromic™ films exposed to 1 MeV electron beam and 250 kV X-rays in the range 0.5-100 Gy. Although EBT3 is specifically designed to obtain best performance for applications where the maximum dose is less than 10 Gy, there are certain clinical applications requiring dose ranges well above this value. In order to cover wider dose ranges, further models characterized by a thinner sensitive layer and/or different chemical composition have been released. Another method exploiting the three-channel flatbed scanner to delay the saturation point of EBT3 has been also reported. The technique proposed here, aimed at extending the sensitivity of the EBT3 film to high doses up to 100 Gy while ensuring a low dose uncertainty, is based on a broadband analysis of the absorption spectrum of the film in response to irradiation. By combining a wavelength-based approach with the monitoring of two characteristic peaks of the EBT3 absorption spectrum, we demonstrated the capability of measuring the dose in the range 0.5-100 Gy with an experimental uncertainty below 4% for doses lower than 5.52 Gy and below 2% for higher dose levels. Finally, through a dynamic fitting procedure integrating the two aforesaid approaches, a total uncertainty lower than 4%, including both the experimental and fitting errors, was achieved in the whole range 0.5-100 Gy. These results are promising in view of a potential application of this technique in the field of clinical dosimetry at high dose levels.

Real-time dosimetry with radiochromic films.

Radiochromic film dosimetry has been widely employed in most of the applications of radiation physics for over twenty years. This is due to a number of appealing features of radiochromic films, such as reliability, accuracy, ease of use and cost. However, current radiochromic film reading techniques, based on the use of commercial densitometers and scanners, provide values of dose only after the exposure of the films to radiation. In this work, an innovative methodology for the real-time reading of radiochromic films is proposed for some specific applications. The new methodology is based on opto-electronic instrumentation that makes use of an optical fiber probe for the determination of optical changes of the films induced by radiation and allows measurements of dose with high degree of precision and accuracy. Furthermore, it has been demonstrated that the dynamic range of some kinds of films, such as the EBT3 Gafchromic films (intensively used in medical physics), can be extended by more than one order of magnitude. Owing to the numerous advantages with respect to the commonly used reading techniques, a National Patent was filed in January 2018.

A novel Lab-on-Fiber Radiation Dosimeter for Ultra-high Dose Monitoring.

In this work, we report on the first demonstration of Lab on Fiber (LOF) dosimeter for ionizing radiation monitoring at ultra-high doses. The new dosimeter consists in a metallo-dielectric resonator at sub-wavelength scale supporting localized surface plasmon resonances realized on the optical fiber (OF) tip. The resonating structure involves two gold gratings separated by a templated dielectric layer of poly(methyl methacrylate) (PMMA). Two LOF prototypes have been manufactured and exposed at the IRRAD Proton Facility at CERN in Geneva to 23 GeV protons for a total fluence of 0.67 × 1016 protons/cm2, corresponding to an absorbed dose of 1.8 MGy. Experimental data demonstrated the "radiation resistance" feature of the LOF devices and a clear dependence of the reflected spectrum versus the total dose, expressed by a cumulative blue-shift of ~1.4 nm of the resonance combined with a slight increase of 0.16 dBm in the reflected spectrum. The numerical analysis carried out to correlate the experimental results with the dimensional and physical properties of the resonator, expected to be tightly connected to the absorbed dose, suggests that the main phenomenon induced by exposure to proton beam and able to explain the measured spectral behavior is the reduction of the PMMA thickness, which is also consistent with past literature in the field. Preliminary results demonstrated the potentiality of the proposed platform as dosimeter at MGy dose levels for high energy physics experiments.

Label-free fiber optic optrode for the detection of class C ß-lactamases expressed by drug resistant bacteria.

This paper reports the experimental assessment of an automated optical assay based on label free optical fiber optrodes for the fast detection of class C ß-lactamases (AmpC BLs), actually considered as one of the most important sources of resistance to ß-lactams antibiotics expressed by resistant bacteria. Reflection-type long period fiber gratings (RT-LPG) have been used as highly sensitive label free optrodes, while a higher affine boronic acid-based ligand was here selected to enhance the overall assay performances compared to those obtained in our first demonstration. In order to prove the feasibility analysis towards a fully automated optical assay, an engineered system was developed to simultaneously manipulate and interrogate multiple fiber optic optrodes in the different phases of the assay. The automated system tested in AmpC solutions at increasing concentrations demonstrated a limit of detection (LOD) of 6 nM, three times better when compared with the results obtained in our previous work. Moreover, the real effectiveness of the proposed optical assay has been also confirmed in complex matrices as the case of lysates of Escherichia coli overexpressing AmpC.

Long period fiber grating nano-optrode for cancer biomarker detection.

We report an innovative fiber optic nano-optrode based on Long Period Gratings (LPGs) working in reflection mode for the detection of human Thyroglobulin (TG), a protein marker of differentiated thyroid cancer. The reflection-type LPG (RT-LPG) biosensor, coated with a single layer of atactic polystyrene (aPS) onto which a specific, high affinity anti-Tg antibody was adsorbed, allowed the label-free detection of Tg in the needle washouts of fine-needle aspiration biopsies, at concentrations useful for pre- and post-operative assessment of the biomarker levels. Analyte recognition and capture were confirmed with a parallel on fiber ELISA-like assay using, in pilot tests, the biotinylated protein and HRP-labeled streptavidin for its detection. Dose-dependent experiments showed that the detection is linearly dependent on concentration within the range between 0 and 4 ng/mL, while antibody saturation occurs for higher protein levels. The system is characterized by a very high sensitivity and specificity allowing the ex-vivo detection of sub ng/ml concentrations of human Tg from needle washouts of fine-needle aspiration biopsies of thyroid nodule from different patients.

Lab-on-fiber technology: a new vision for chemical and biological sensing.

The integration of microfluidics and photonic biosensors has allowed achievement of several laboratory functions in a single chip, leading to the development of photonic lab-on-a-chip technology. Although a lot of progress has been made to implement such sensors in small and easy-to-use systems, many applications such as point-of-care diagnostics and in vivo biosensing still require a sensor probe able to perform measurements at precise locations that are often hard to reach. The intrinsic property of optical fibers to conduct light to a remote location makes them an ideal platform to meet this demand. The motivation to combine the good performance of photonic biosensors on chips with the unique advantages of optical fibers has thus led to the development of the so-called lab-on-fiber technology. This emerging technology envisages the integration of functionalized materials on micro- and nano-scales (i.e. the labs) with optical fibers to realize miniaturized and advanced all-in-fiber probes, especially useful for (but not limited to) label-free chemical and biological applications. This review presents a broad overview of lab-on-fiber biosensors, with particular reference to lab-on-tip platforms, where the labs are integrated on the optical fiber facet. Light-matter interaction on the fiber tip is achieved through the integration of thin layers of nanoparticles or nanostructures supporting resonant modes, both plasmonic and photonic, highly sensitive to local modifications of the surrounding environment. According to the physical principle that is exploited, different configurations - such as localized plasmon resonance probes, surface enhanced Raman scattering probes and photonic probes - are classified, while various applications are presented in context throughout. For each device, the surface chemistry and the related functionalization protocols are reviewed. Moreover, the implementation strategies and fabrication processes, either based on bottom-up or top-down approaches, are discussed. In conclusion we highlight some of the further development opportunities, including lab-in-a-needle technology, which could have a direct and disruptive impact in localized cancer treatment applications.