Splitter-Based Sensors Realized via POFs Coupled by a Micro-Trench Filled with a Molecularly Imprinted Polymer.

An optical-chemical sensor based on two modified plastic optical fibers (POFs) and a molecularly imprinted polymer (MIP) is realized and tested for the detection of 2-furaldehyde (2-FAL). The 2-FAL measurement is a scientific topic of great interest in different application fields, such as human health and life status monitoring in power transformers. The proposed sensor is realized by using two POFs as segmented waveguides (SW) coupled through a micro-trench milled between the fibers and then filled with a specific MIP for the 2-FAL detection. The experimental results show that the developed intensity-based sensor system is highly selective and sensitive to 2-FAL detection in aqueous solutions, with a limit of detection of about 0.04 mg L-1. The proposed sensing approach is simple and low-cost, and it shows performance comparable to that of plasmonic MIP-based sensors present in the literature for 2-FAL detection.

A Novel Approach to Realize Plasmonic Sensors via Multimode Optical Waveguides: A Review.

In recent decades, the Surface Plasmon Resonance (SPR) phenomenon has been utilized as an underlying technique in a broad range of application fields. Herein, a new measuring strategy which harnesses the SPR technique in a way that is different from the classical methodology was explored by taking advantage of the characteristics of multimode waveguides, such as plastic optical fibers (POFs) or hetero-core fibers. The sensor systems based on this innovative sensing approach were designed, fabricated, and investigated to assess their ability to measure various physical features, such as magnetic field, temperature, force, and volume, and to realize chemical sensors. In more detail, a sensitive patch of fiber was used in series with a multimodal waveguide where the SPR took place, to alter the mode profile of the light at the input of the waveguide itself. In fact, when the changes of the physical feature of interest acted on the sensitive patch, a variation of the incident angles of the light launched in the multimodal waveguide occurred, and, as a consequence, a shift in resonance wavelength took place. The proposed approach permitted the separation of the measurand interaction zone and the SPR zone. This meant that the SPR zone could be realized only with a buffer layer and a metallic film, thus optimizing the total thickness of the layers for the best sensitivity, regardless of the measurand type. The proposed review aims to summarize the capabilities of this innovative sensing approach to realize several types of sensors for different application fields, showing the high performances obtained by exploiting a simple production process and an easy experimental setup.

Analysis of Plasmonic Sensors Performance Realized by Exploiting Different UV-Cured Optical Adhesives Combined with Plastic Optical Fibers.

Polymer-based surface plasmon resonance (SPR) sensors can be used to realize simple, small-size, disposable, and low-cost biosensors for application in several fields, e.g., healthcare. The performance of SPR sensors based on optical waveguides can be changed by tuning several parameters, such as the dimensions and the shape of the waveguides, the refractive index of the core, and the metal nanofilms used to excite the SPR phenomenon. In this work, in order to develop, experimentally test, and compare several polymer-based plasmonic sensors, realized by using waveguides with different core refractive indices, optical adhesives and 3D printed blocks with a trench inside have been used. In particular, the sensors are realized by filling the blocks' trenches (with two plastic optical fibers located at the end of these) with different UV-cured optical adhesives and then covering them with the same bilayer to excite the SPR phenomenon. The developed SPR sensors have been characterized by numerical and experimental results. Finally, in order to propose photonic solutions for healthcare, a comparative analysis has been reported to choose the best sensor configuration useful for developing low-cost biosensors.

Polymer Doping as a Novel Approach to Improve the Performance of Plasmonic Plastic Optical Fibers Sensors.

In this work, Fe2O3 was investigated as a doping agent for poly(methyl methacrylate) (PMMA) in order to enhance the plasmonic effect in sensors based on D-shaped plastic optical fibers (POFs). The doping procedure consists of immerging a premanufactured POF sensor chip in an iron (III) solution, avoiding repolymerization and its related disadvantages. After treatment, a sputtering process was used to deposit a gold nanofilm on the doped PMMA in order to obtain the surface plasmon resonance (SPR). More specifically, the doping procedure increases the refractive index of the POF's PMMA in contact with the gold nanofilm, improving the SPR phenomena. The doping of the PMMA was characterized by different analyses in order to determine the effectiveness of the doping procedure. Moreover, experimental results obtained by exploiting different water-glycerin solutions have been used to test the different SPR responses. The achieved bulk sensitivities confirmed the improvement of the plasmonic phenomenon with respect to a similar sensor configuration based on a not-doped PMMA SPR-POF chip. Finally, doped and non-doped SPR-POF platforms were functionalized with a molecularly imprinted polymer (MIP), specific for the bovine serum albumin (BSA) detection, to obtain dose-response curves. These experimental results confirmed an increase in binding sensitivity for the doped PMMA sensor. Therefore, a lower limit of detection (LOD), equal to 0.04 µM, has been obtained in the case of the doped PMMA sensor when compared to the one calculated for the not-doped sensor configuration equal to about 0.09 µM.

Exploiting Plasmonic Phenomena in Polymer Optical Fibers to Realize a Force Sensor.

In this work, a novel sensing approach to realize a force optical fiber sensor is designed, developed, and experimentally tested. The proposed sensing methodology exploits the effects of deformation due to an applied force on a patch of plastic optical fiber (POF) connected at the input of a surface plasmon resonance (SPR) sensor realized in a D-shaped POF. Therefore, the proposed force sensor system consists of an SPR D-shaped POF sensor, connected to a spectrometer, within input of a POF patch, connected to a light source used for interacting with the applied force. When the applied force on the patch changes, the mode profile of the light in the multimode POF patch and the SPR-POF sensor change too, so the SPR spectra shift. The obtained experimental results demonstrate that the proposed sensor has a resolution of the force sensor equal to about 22 mN and an excellent linear response in the range from 0 N to 0.5 N.

Non-Specific Responsive Nanogels and Plasmonics to Design MathMaterial Sensing Interfaces: The Case of a Solvent Sensor.

The combination of non-specific deformable nanogels and plasmonic optical probes provides an innovative solution for specific sensing using a generalistic recognition layer. Soft polyacrylamide nanogels that lack specific selectivity but are characterized by responsive behavior, i.e., shrinking and swelling dependent on the surrounding environment, were grafted to a gold plasmonic D-shaped plastic optical fiber (POF) probe. The nanogel-POF cyclically challenged with water or alcoholic solutions optically reported the reversible solvent-to-phase transitions of the nanomaterial, embodying a primary optical switch. Additionally, the non-specific nanogel-POF interface exhibited more degrees of freedom through which specific sensing was enabled. The real-time monitoring of the refractive index variations due to the time-related volume-to-phase transition effects of the nanogels enabled us to determine the environment's characteristics and broadly classify solvents. Hence the nanogel-POF interface was a descriptor of mathematical functions for substance identification and classification processes. These results epitomize the concept of responsive non-specific nanomaterials to perform a multiparametric description of the environment, offering a specific set of features for the processing stage and particularly suitable for machine and deep learning. Thus, soft MathMaterial interfaces provide the ground to devise devices suitable for the next generation of smart intelligent sensing processes.

Detection of 2-Furaldehyde in Milk by MIP-Based POF Chips Combined with an SPR-POF Sensor.

An innovative optical-chemical sensor has been used to detect the 2-furaldehyde (2-FAL) in milk. The proposed sensing approach exploits the refractive index changing in a microstructured chip based on a plastic optical fiber (POF) with orthogonal micro-holes containing a specific molecularly imprinted polymer (MIP). This POF-MIP chemical chip modifies the surface plasmon resonance (SPR) phenomena excited in another sensor chip realized in POFs (SPR-POF) and connected in series. The proposed sensor configuration exploits MIP receptors avoiding any modification of the gold film of the SPR platform. This work reports the performance, particularly the high sensitivity and low detection limit, in complex matrices such as buffalo milk fortified with 2-FAL and in different commercial kinds of cow milk thermally treated for pasteurization. The measurements were carried out in about ten minutes by dropping the solution under-test on the planar D-shaped POF surface of the chemical chip. In contrast, on the gold surface of the SPR-POF platform, a water drop is always placed to excite the SPR phenomenon, which is modulated by the chemical chip via MIP-2-FAL binding. Furthermore, the experimental results demonstrated the pros and cons of the proposed sensor system. Thanks to the high sensitivity of the sensor system, the detection of 2-FAL in the diluted milk sample (1:50) was achieved. The dilution is required to reduce the interferent effect of the complex matrix.

The Role of Tapered Light-Diffusing Fibers in Plasmonic Sensor Configurations.

In this work, we experimentally analyzed the effect of tapering in light-diffusing optical fibers (LDFs) when employed as surface plasmon resonance (SPR)-based sensors. Although tapering is commonly adopted to enhance the performance of plasmonic optical fiber sensors, we have demonstrated that in the case of plasmonic sensors based on LDFs, the tapering produces a significant worsening of the bulk sensitivity (roughly 60% in the worst case), against a slight decrease in the full width at half maximum (FWHM) of the SPR spectra. Furthermore, we have demonstrated that these aspects become more pronounced when the taper ratio increases. Secondly, we have established that a possible alternative exists in using the tapered LDF as a modal filter after the sensible region. In such a case, we have determined that a good trade-off between the loss in sensitivity and the FWHM decrease could be reached.

Proof of Concept for a Quick and Highly Sensitive On-Site Detection of SARS-CoV-2 by Plasmonic Optical Fibers and Molecularly Imprinted Polymers.

The rapid spread of the Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen has generated a huge international public health emergency. Currently the reference diagnostic technique for virus determination is Reverse Transcription Polymerase Chain Reaction (RT-PCR) real time analysis that requires specialized equipment, reagents and facilities and typically 3-4 h to perform. Thus, the realization of simple, low-cost, small-size, rapid and point-of-care diagnostics tests has become a global priority. In response to the current need for quick, highly sensitive and on-site detection of the SARS-CoV-2 virus in several aqueous solutions, a specific molecularly imprinted polymer (MIP) receptor has been designed, realized, and combined with an optical sensor. More specifically, the proof of concept of a SARS-CoV-2 sensor has been demonstrated by exploiting a plasmonic plastic optical fiber sensor coupled with a novel kind of synthetic MIP nano-layer, especially designed for the specific recognition of Subunit 1 of the SARS-CoV-2 Spike protein. First, we have tested the effectiveness of the developed MIP receptor to bind the Subunit 1 of the SARS-CoV-2 spike protein, then the results of preliminary tests on SARS-CoV-2 virions, performed on samples of nasopharyngeal (NP) swabs in universal transport medium (UTM) and physiological solution (0.9% NaCl), were compared with those obtained with RT-PCR. According to these preliminary results, the sensitivity of the proposed optical-chemical sensor proved to be higher than the RT-PCR one. Furthermore, a relatively fast response time (about 10 min) to the virus was obtained without the use of additional reagents.

An Eco-Friendly Disposable Plasmonic Sensor Based on Bacterial Cellulose and Gold.

In several application fields, plasmonic sensor platforms combined with bio-receptors are intensively used to obtain biosensors. Most of these commercial devices are based on a disposable chip. Usually a gold chip, functionalized with a specific bio-receptor, inside a costly sensor system, is used. In this work, we propose a low-cost and small-size sensor system, used for monitoring a disposable plasmonic chip, based on an innovative optical waveguide made of bacterial cellulose (BC). In particular, we have sputtered gold on the green slab waveguide that is able to excite localized surface plasmon resonance (LSPR). Experimental results are presented on the capabilities of using the BC-based composite as an eco-friendly plasmonic sensor platform, which could be exploited for realizing disposable biosensors. The sensor has been used with optical fibers and simple equipment. More specifically, the fibers connect the green disposable LSPR sensor with a light source and with a spectrometer. The novel plasmonic sensing approach has been tested using two different optical waveguide configurations of BC, with and without ions inside BC.

A Molecularly Imprinted Polymer on a Plasmonic Plastic Optical Fiber to Detect Perfluorinated Compounds in Water.

A novel Molecularly Imprinted Polymer (MIP) able to bind perfluorinated compounds, combined with a surface plasmon resonance (SPR) optical fiber platform, is presented. The new MIP receptor has been deposited on a D-shaped plastic optical fiber (POF) covered with a photoresist buffer layer and a thin gold film. The experimental results have shown that the developed SPR-POF-MIP sensor makes it possible to selectively detect the above compounds. In this work, we present the results obtained with perfluorooctanoate (PFOA) compound, and they hold true when obtained with a perfluorinated alkylated substances (PFAs) mixture sample. The sensor's response is the same for PFOA, perfluorooctanesulfonate (PFOS) or PFA contaminants in the C4⁻C11 range. We have also tested a sensor based on a non-imprinted polymer (NIP) on the same SPR in a D-shaped POF platform. The limit of detection (LOD) of the developed chemical sensor was 0.13 ppb. It is similar to the one obtained by the configuration based on a specific antibody for PFOA/PFOS exploiting the same SPR-POF platform, already reported in literature. The advantage of an MIP receptor is that it presents a better stability out of the native environment, very good reproducibility, low cost and, furthermore, it can be directly deposited on the gold layer, without modifying the metal surface by functionalizing procedures.

Toward Nano- and Microplastic Sensors: Identification of Nano- and Microplastic Particles via Artificial Intelligence Combined with a Plasmonic Probe Functionalized with an Estrogen Receptor.

Nano- and microplastic particles are a global and emerging environmental issue that might pose potential threats to human health. The present work exploits artificial intelligence (AI) to identify nano- and microplastics in water by monitoring the interaction of the sample with a sensitive surface. An estrogen receptor (ER) grafted onto a gold surface, realized on a nonexpensive and easy-to-produce plastic optical fiber (POF) platform in order to excite a surface plasmon resonance (SPR) phenomenon, has been developed in order to carry out a "smart" sensitive interface (ER-SPR-POF interface). The ER-SPR-POF interface offers output data useful for exploiting a machine learning-based approach to achieve nano- and microplastic particle sensors. This work developed a proof-of-concept sensor through a training phase carried out by different particles, in terms of materials and size. The experimental results have demonstrated that the proposed "smart" ER-SPR-POF interface combined with AI can be used to identify the kind of particles in terms of the materials (polystyrene; poly(methyl methacrylate)) and size (20 µm; 100 nm) with an accuracy of 90.3%.

POF-based biosensors for cortisol detection in seawater as a tool for aquaculture systems.

A surface plasmon resonance (SPR) phenomenon implemented via D-shaped polymer optical fiber (POF) is exploited to realize cortisol biosensors. In this work, two immonosensors are designed and developed for the qualitative as well as quantitative measurement of cortisol in artificial and real samples. The performances of the POF-based biosensors in cortisol recognition are achieved using different functionalization protocols to make the same antibody receptor layer over the SPR surface via cysteamine and lipoic acid, achieving a limit of detection (LOD) of 0.8 pg/mL and 0.2 pg/mL, respectively. More specifically, the use of cysteamine or lipoic acid changes the distance between the receptor layer and the SPR surface, improving the sensitivity at low concentrations of about one order of magnitude in the configuration based on lipoic acid. The LODs of both cortisol biosensors are achieved well competitively with other sensor systems but without the need for amplification or sample treatments. In order to obtain the selectivity tests, cholesterol and testosterone were used as interfering substances. Moreover, tests in simulated seawater were performed for the same cortisol concentration range achieved in buffer solution to assess the immunosensor response to the complex matrix. Finally, the developed cortisol biosensor was used in a real seawater sample to estimate the cortisol concentration value. The gold standard method has confirmed the estimated cortisol concentration value in real seawater samples. Liquid-liquid extraction was implemented to maximize the response of cortisol in liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis.

Plasmonic immunosensors based on spoon-shaped waveguides for fast and on-site ultra-low detection of ochratoxin A in coffee samples.

The high toxicity and occurrence of ochratoxin A (OTA) in grains and foods has been a growing concern due to the impacts on health and the economy in many countries. In this sense, simplified devices with high sensitivity and specificity for local monitoring are enthusiastically pursued. In this work, we report for the first time the detection of ochratoxin A in coffee samples using a spoon-shaped waveguide immunosensor. The biosensor was built with the surface of the spoon-shaped waveguide covered by a 60 nm layer of gold to enable the SPR phenomenon. The measurements indicated a linear relationship between the change in the SPR phenomenon values and the OTA concentration in the range from 0.2 ppt to 5 ppt. When analyzed in coffee samples, the biosensor was highly selective and did not suffer matrix interference. The developed biosensor represents a promising analytical device for coffee quality analyses, as it is portable, simple, and suitable for onsite detection of target analytes.

Plasmon resonance biosensor for interleukin-1ß point-of-care determination: A tool for early periodontitis diagnosis.

Among pro-inflammatory cytokines, Interleukin-1ß is crucially involved in several inflammatory-based diseases and even cancer. Increased Interleukin-1ß levels in oral fluids have been proposed as an early marker of periodontitis, a broadly diffused chronic inflammatory condition of periodontal-supporting tissues, leading eventually to tooth loss. We describe the development of a portable surface-plasmon-resonance-based optical fiber probe suitably coated with an anti-Interleukin-1ß antibody monolayer. A pico-nanomolar linear range of determination was obtained in both buffer solution and saliva with a rapid (3 min) incubation and high selectivity in presence of interferents. Higher Interleukin-1ß concentration in the saliva of a periodontitis patient compared to a healthy control was determined. These measurements were validated by an automated ELISA system. Our results sustain the potential applicability of the proposed SPR-POF as diagnostic point-of-care device for real-time monitoring of salivary Interleukin-1ß, that can support early detection of oral inflammatory-based pathologies and rapid and timely therapeutic decisions.

3D-printed biosensors in biomedical applications exploiting plasmonic phenomena and antibody self-assembled monolayers.

In this work, a 3D-printed plasmonic chip based on a silver-gold bilayer was developed in order to enhance the optical response of the surface plasmon resonance (SPR) probe. More specifically, numerical and experimental results were obtained on the 3D-printed SPR platform based on a silver-gold bilayer. Then, the optimized probe's gold plasmonic interface was functionalized with a specific antibody directed against the p27Kip1 protein (p27), an important cell cycle regulator. The 3D-printed plasmonic biosensor was tested for p27 detection with good selectivity and a detection limit of 55 pM. The biosensor system demonstrated performance similar to commercially available ELISA (enzyme-linked immunoassay) kits, with several advantages, such as a wide detection range and a modular and simple-based architecture. The proposed biosensing technology offers flexible deployment options that are useful in disposable, low-cost, small-size, and simple-to-use biochips, envisaging future applications in experimental and biomedical research.

Estradiol Detection for Aquaculture Exploiting Plasmonic Spoon-Shaped Biosensors.

In this work, a surface plasmon resonance (SPR) biosensor based on a spoon-shaped waveguide combined with an estrogen receptor (ERα) was developed and characterized for the detection and the quantification of estradiol in real water samples. The fabrication process for realizing the SPR platform required a single step consisting of metal deposition on the surface of a polystyrene spoon-shaped waveguide featuring a built-in measuring cell. The biosensor was achieved by functionalizing the bowl sensitive surface with a specific estrogen receptor (ERα) that was able to bind the estradiol. In a first phase, the biosensor tests were performed in a phosphate buffer solution obtaining a limit of detection (LOD) equal to 0.1 pM. Then, in order to evaluate the biosensor's response in different real matrices related to aquaculture, its performances were examined in seawater and freshwater. The experimental results support the possibility of using the ERα-based biosensor for the screening of estradiol in both matrices.

Immuno-SPR biosensor for the detection of Brucella abortus.

A proof of principle biosensor for the Brucella abortus recognition onsite is presented. The system is based on a plasmonic optical fiber probe functionalized with an oriented antibody layer immobilized on a short polyethyleneglycol (PEG) interface through carbodiimide chemistry and protein G as an intermediate layer. The biosensor is inserted in a holder built in 3D printing technology, obtaining a custom holder useful for housing the sample to be measured and the equipment. The removable sensor chip is a low-cost Surface Plasmon Resonance (SPR) platform based on D-shaped plastic optical fibers (POFs), built-in in 3D printed connectors, used here for the first time to detect bacteria via a bio-receptor layer specific for its membrane protein. The performances of the biosensor in Brucella abortus recognition are tested by using two different SPR-POF probes combined with the same bio-receptor layer. The best sensor configuration has presented a sensitivity at low concentrations of one order of magnitude greater than the other. A limit of detection (LoD) of 2.8 bacteria/mL is achieved well competitive with other systems but without the need for amplification or special sample treatments. Specificity has been tested using Salmonella bacteria, and reproducibility, regenerability and stability are moreover evaluated. These experimental results pave the way for building an efficient and specific biosensor system for Brucella abortus detection onsite and in a few minutes. Moreover, the proposed POF-based SPR biosensor device, with respect to the already available technologies, could be a Point-of-care-test (POCT), simple to use, small-size and portable, low-cost, don't necessary of a microfluidic system, and can be connected to the Internet (IoT).

Towards a point-of-care test to cover atto-femto and pico-nano molar concentration ranges in interleukin 6 detection exploiting PMMA-based plasmonic biosensor chips.

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required. In this work, two IL-6 biosensors are obtained by exploiting the combination of the same antibody self-assembled monolayer with two different plasmonic probes. This approach has demonstrated, via experimental results, that two different IL-6 concentration ranges can be explored. More specifically, IL-6 in an atto-femto molar range can be detected via polymer-based nanoplasmonic chips. On the other hand, a pico-nano molar range is obtained by a surface plasmon resonance platform in plastic optical fibers. As a proof of concept, the detection of IL-6 at the femto molar range has been obtained in Saliva and Serum. The results show that the proposed sensing approach could be useful in developing Point-of-Care devices based on a general setup with the capability to exploit both the plasmonic biosensor chips to monitor the IL-6 in the concentration range of interest, to provide an important support for the diagnosis and monitoring of oral and systemic diseases.

Sensing Approaches Exploiting Molecularly Imprinted Nanoparticles and Lossy Mode Resonance in Polymer Optical Fibers.

In this work, two different lossy mode resonance (LMR) platforms based on plastic optical fibers (POFs) are developed and tested in a biochemical sensing scenario. The LMR platforms are based on the combination of two metal oxides (MOs), i.e., zirconium oxide (ZrO2) and titanium oxide (TiO2), and deposited on the exposed core of D-shaped POF chips. More specifically, two experimental sensor configurations were obtained by swapping the mutual position of the Mos films over to the core of the D-shaped POF probe. The POF-LMR sensors were first characterized as refractometers, proving the bulk sensitivities. Then, both the POF-LMR platforms were functionalized using molecularly imprinted nanoparticles (nanoMIPs) specific for human transferrin (HTR) in order to carry out binding tests. The achieved results report a bulk sensitivity equal to about 148 nm/RIU in the best sensor configuration, namely the POF-TiO2-ZrO2. In contrast, both optical configurations combined with nanoMIPs showed an ultra-low detection limit (fM), demonstrating excellent efficiency of the used receptor (nanoMIPs) and paving the way to disposable POF-LMR biochemical sensors that are easy-to-use, low-cost, and highly sensitive.