Label-Free Detection of African Swine Fever and Classical Swine Fever in the Point-of-Care Setting Using Photonic Integrated Circuits Integrated in a Microfluidic Device.

Swine viral diseases have the capacity to cause significant losses and affect the sector's sustainability, a situation further exacerbated by the lack of antiviral drugs and the limited availability of effective vaccines. In this context, a novel point-of-care (POC) diagnostic device incorporating photonic integrated circuits (PICs), microfluidics and information, and communication technology into a single platform was developed for the field diagnosis of African swine fever (ASF) and classical swine fever (CSF). The device targets viral particles and has been validated using oral fluid and serum samples. Sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device, and PCR was the reference method employed. Its sensitivities were 80.97% and 79%, specificities were 88.46% and 79.07%, and DOR values were 32.25 and 14.21 for ASF and CSF, respectively. The proposed POC device and PIC sensors can be employed for the pen-side detection of ASF and CSF, thus introducing novel technological advancements in the field of animal diagnostics. The need for proper validation studies of POC devices is highlighted to optimize animal biosecurity.

Synthesis and Raman Detection of 5-Amino-2-mercaptobenzimidazole Self-Assembled Monolayers in Nanoparticle-on-a-Mirror Plasmonic Cavity Driven by Dielectric Waveguides.

Functionalization of metallic surfaces by molecular monolayers is a key process in fields such as nanophotonics or biotechnology. To strongly enhance light-matter interaction in such monolayers, nanoparticle-on-a-mirror (NPoM) cavities can be formed by placing metal nanoparticles on such chemically functionalized metallic monolayers. In this work, we present a novel functionalization process of gold surfaces using 5-amino-2-mercaptobenzimidazole (5-A-2MBI) molecules, which can be used for upconversion from THz to visible frequencies. The synthesized surfaces and NPoM cavities are characterized by Raman spectroscopy, atomic force microscopy (AFM), and advancing-receding contact angle measurements. Moreover, we show that NPoM cavities can be efficiently integrated on a silicon-based photonic chip performing pump injection and Raman-signal extraction via silicon nitride waveguides. Our results open the way for the use of 5-A-2MBI monolayers in different applications, showing that NPoM cavities can be effectively integrated with photonic waveguides, enabling on-chip enhanced Raman spectroscopy or detection of infrared and THz radiation.

Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project.

This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.

Light Guidance Aided by the Toroidal Dipole and the Magnetic Quadrupole in Silicon Slotted-Disk Chains.

Far-field scattering of high-index nanoparticles can be hugely reduced via interference of multipolar moments giving rise to the so-called anapole states. It has been suggested that this reduced scattering can contribute to efficient transmission along periodic chains of such nanoparticles. In this work, we analyze via numerical simulation and experiments the transmission of light along chains of regular and slotted silicon disks in the frequency region over the light cone. We do not observe transmission at wavelengths corresponding to the excitation of the first electric anapole for regular disks. However, large transmission along straight and curved chains is observed for slotted disks due to the simultaneous excitation of the toroidal dipole and magnetic quadrupole modes in the disks. Photonic band calculations unveil that such large transmission can be ascribed to leaky resonances, though bound states in the continuum do not appear in the structures under analysis. Experiments at telecom wavelengths using silicon disk chains confirm the numerical results for straight and bent chains. Our results provide new insights into the role of radiationless states in light guidance along nanoparticle chains and offer new avenues to utilize Mie resonances of simple nanophotonic structures for on-chip dielectric photonics.

Accurate Transfer of Individual Nanoparticles onto Single Photonic Nanostructures.

Controlled integration of metallic nanoparticles (NPs) onto photonic nanostructures enables the realization of complex devices for extreme light confinement and enhanced light-matter interaction. For instance, such NPs could be massively integrated on metal plates to build nanoparticle-on-mirror (NPoM) nanocavities or photonic integrated waveguides (WGs) to build WG-driven nanoantennas. However, metallic NPs are usually deposited via drop-casting, which prevents their accurate positioning. Here, we present a methodology for precise transfer and positioning of individual NPs onto different photonic nanostructures. Our method is based on soft lithography printing that employs elastomeric stamp-assisted transfer of individual NPs onto a single nanostructure. It can also parallel imprint many individual NPs with high throughput and accuracy in a single step. Raman spectroscopy confirms enhanced light-matter interactions in the resulting NPoM-based nanophotonic devices. Our method mixes top-down and bottom-up nanofabrication techniques and shows the potential of building complex photonic nanodevices for multiple applications ranging from enhanced sensing and spectroscopy to signal processing.

Room-Temperature Silicon Platform for GHz-Frequency Nanoelectro-Opto-Mechanical Systems.

Nanoelectro-opto-mechanical systems enable the synergistic coexistence of electrical, mechanical, and optical signals on a chip to realize new functions. Most of the technology platforms proposed for the fabrication of these systems so far are not fully compatible with the mainstream CMOS technology, thus, hindering the mass-scale utilization. We have developed a CMOS technology platform for nanoelectro-opto-mechanical systems that includes piezoelectric interdigitated transducers for electronic driving of mechanical signals and nanocrystalline silicon nanobeams for an enhanced optomechanical interaction. Room-temperature operation of devices at 2 GHz and with peak sensitivity down to 2.6 cavity phonons is demonstrated. Our proof-of-principle technology platform can be integrated and interfaced with silicon photonics, electronics, and MEMS devices and may enable multiple functions for coherent signal processing in the classical and quantum domains.

Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits.

Swine viral diseases challenge the sector's sustainability by affecting productivity and the health and welfare of the animals. The lack of antiviral drugs and/or effective vaccines renders early and reliable diagnosis the basis of viral disease management, underlining the importance of point-of-care (POC) diagnostics. A novel POC diagnostic device utilizing photonic integrated circuits (PICs), microfluidics, and information and communication technologies for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A (SIV) was validated using spiked and clinical oral fluid samples. Metrics including sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device. For PRRSV, the device achieved a sensitivity of 83.5%, specificity of 77.8%, and DOR values of 17.66, whereas the values for SIV were 81.8%, 82.2%, and 20.81, respectively. The POC device and PICs can be used for the detection of PRRSV and SIV in the field, paving the way for the introduction of novel technologies in the field of animal POC diagnostics to further optimize livestock biosecurity.

Photonic Label-Free Biosensors for Fast and Multiplex Detection of Swine Viral Diseases.

In this paper we present the development of photonic integrated circuit (PIC) biosensors for the label-free detection of six emerging and endemic swine viruses, namely: African Swine Fever Virus (ASFV), Classical Swine Fever Virus (CSFV), Porcine Reproductive and Respiratory Syndrome Virus (PPRSV), Porcine Parvovirus (PPV), Porcine Circovirus 2 (PCV2), and Swine Influenza Virus A (SIV). The optical biosensors are based on evanescent wave technology and, in particular, on Resonant Rings (RRs) fabricated in silicon nitride. The novel biosensors were packaged in an integrated sensing cartridge that included a microfluidic channel for buffer/sample delivery and an optical fiber array for the optical operation of the PICs. Antibodies were used as molecular recognition elements (MREs) and were selected based on western blotting and ELISA experiments to ensure the high sensitivity and specificity of the novel sensors. MREs were immobilized on RR surfaces to capture viral antigens. Antibody-antigen interactions were transduced via the RRs to a measurable resonant shift. Cell culture supernatants for all of the targeted viruses were used to validate the biosensors. Resonant shift responses were dose-dependent. The results were obtained within the framework of the SWINOSTICS project, contributing to cover the need of the novel diagnostic tools to tackle swine viral diseases.

Performance improvement of a silicon nitride ring resonator biosensor operated in the TM mode at 1310†nm.

Silicon-based ring resonators have been demonstrated to be a key element to build lab-on-chip devices due to their ability to perform as label-free photonic sensors. In this work, we demonstrate photonic biosensing using silicon nitride ring resonators operated in the TM mode around 1310 nm wavelengths. Our results show that operating the devices using the TM mode results in an increased sensitivity in comparison with the typically used TE mode, while working at 1310 nm wavelengths compared to 1550 nm contributes to an increased quality factor. As a result, a reduction in the intrinsic limit of detection is achieved, indicating the suitability of TM modes in the 1310 nm regime for biosensing using integrated photonics.

Integration of Microfluidics, Photonic Integrated Circuits and Data Acquisition and Analysis Methods in a Single Platform for the Detection of Swine Viral Diseases.

Viral diseases challenge the health and welfare of pigs and undermine the sustainability of swine farms. Their efficient control requires early and reliable diagnosis, highlighting the importance of Point of Care (POC) diagnostics in veterinary practice. The objective of this study was to validate a novel POC system that utilizes Photonic Integrated Circuits (PICs) and microfluidics to detect swine viral pathogens using oral fluids and Porcine Parvovirus (PPV) and Porcine Circovirus 2 (PCV-2) as proofs of concept. The sensitivity and specificity of the device were calculated for both viruses, and Receiver Operating Characteristic (ROC) curves were drawn. PPV had an Area Under Curve (AUC) value of 0.820 (95% CI: 0.760 to 0.880, p < 0.0001), and its optimal efficiency threshold of detection shifts was equal to 4.5 pm (68.6% sensitivity, 77.1% specificity and Limit of Detection (LOD) value 106 viral copies/mL). PCV-2 had an AUC value of 0.742 (95% CI: 0.670 to 0.815, p < 0.0001) and an optimal efficiency threshold of shifts equal to 6.5 pm (69.5% sensitivity, 70.3% specificity and LOD 3.3 × 105 copies/mL). In this work, it was proven that PICs can be exploited for the detection of swine viral diseases. The novel device can be directly deployed on farms as a POC diagnostics tool.

Radiationless anapole states in on-chip photonics.

High-index nanoparticles are known to support radiationless states called anapoles, where dipolar and toroidal moments interfere to inhibit scattering to the far field. In order to exploit the striking properties arising from these interference conditions in photonic integrated circuits, the particles must be driven in-plane via integrated waveguides. Here, we address the excitation of electric anapole states in silicon disks when excited on-chip at telecom wavelengths. In contrast to normal illumination, we find that the anapole condition-identified by a strong reduction of the scattering-does not overlap with the near-field energy maximum, an observation attributed to retardation effects. We experimentally verify the two distinct spectral regions in individual disks illuminated in-plane from closely placed waveguide terminations via far-field and near-field measurements. Our finding has important consequences concerning the use of anapole states and interference effects of other Mie-type resonances in high-index nanoparticles for building complex photonic integrated circuitry.

Slow light bimodal interferometry in one-dimensional photonic crystal waveguides.

Strongly influenced by the advances in the semiconductor industry, the miniaturization and integration of optical circuits into smaller devices has stimulated considerable research efforts in recent decades. Among other structures, integrated interferometers play a prominent role in the development of photonic devices for on-chip applications ranging from optical communication networks to point-of-care analysis instruments. However, it has been a long-standing challenge to design extremely short interferometer schemes, as long interaction lengths are typically required for a complete modulation transition. Several approaches, including novel materials or sophisticated configurations, have been proposed to overcome some of these size limitations but at the expense of increasing fabrication complexity and cost. Here, we demonstrate for the first time slow light bimodal interferometric behaviour in an integrated single-channel one-dimensional photonic crystal. The proposed structure supports two electromagnetic modes of the same polarization that exhibit a large group velocity difference. Specifically, an over 20-fold reduction in the higher-order-mode group velocity is experimentally shown on a straightforward all-dielectric bimodal structure, leading to a remarkable optical path reduction compared to other conventional interferometers. Moreover, we experimentally demonstrate the significant performance improvement provided by the proposed bimodal photonic crystal interferometer in the creation of an ultra-compact optical modulator and a highly sensitive photonic sensor.

Continuous Detection of Increasing Concentrations of Thrombin Employing a Label-Free Photonic Crystal Aptasensor.

Thrombin generation is a complex and finely regulated pathway that provokes dynamical changes of thrombin concentration in blood when a vascular injury occurs. In order to characterize the initiation phase of such process, when thrombin concentration is in the nmol/L range, a label-free optical aptasensor is proposed here. This aptasensor combines a 1D photonic crystal structure consisting of a silicon corrugated waveguide with thrombin binding aptamers on its surface as bioreceptors. As a result, this aptasensor has been demonstrated to specifically detect thrombin concentrations ranging from 270 pmol/L to 27 nmol/L with an estimated detection limit of 33.5 pmol/L and a response time of ~2 min. Furthermore, it has also been demonstrated that this aptasensor is able to continuously respond to consecutive increasing concentrations of thrombin and to detect binding events as they occur. All these features make this aptasensor a good candidate to continuously study how thrombin concentration progressively increases during the initiation phase of the coagulation cascade.

Ultra-low loss hybrid ITO/Si thermo-optic phase shifter with optimized power consumption.

Typically, materials with large optical losses such as metals are used as microheaters for silicon based thermo-optic phase shifters. Consequently, the heater must be placed far from the waveguide, which could come at the expense of the phase shifter performance. Reducing the gap between the waveguide and the heater allows reducing the power consumption or increasing the switching speed. In this work, we propose an ultra-low loss microheater for thermo-optic tuning by using a CMOS-compatible transparent conducting oxide such as indium tin oxide (ITO) with the aim of drastically reducing the gap. Using finite element method simulations, ITO and Ti based heaters are compared for different cladding configurations and TE and TM polarizations. Furthermore, the proposed ITO based microheaters have also been fabricated using the optimum gap and cladding configuration. Experimental results show power consumption to achieve a π phase shift of 10 mW and switching time of a few microseconds for a 50 µm long ITO heater. The obtained results demonstrate the potential of using ITO as an ultra-low loss microheater for high performance silicon thermo-optic tuning and open an alternative way for enabling the large-scale integration of phase shifters required in emerging integrated photonic applications.

Green and Sustainable Manufacture of Ultrapure Engineered Nanomaterials.

Nanomaterials with very specific features (purity, colloidal stability, composition, size, shape, location…) are commonly requested by cutting-edge technologic applications, and hence a sustainable process for the mass-production of tunable/engineered nanomaterials would be desirable. Despite this, tuning nano-scale features when scaling-up the production of nanoparticles/nanomaterials has been considered the main technological barrier for the development of nanotechnology. Aimed at overcoming these challenging frontier, a new gas-phase reactor design providing a shorter residence time, and thus a faster quenching of nanoclusters growth, is proposed for the green, sustainable, versatile, cost-effective, and scalable manufacture of ultrapure engineered nanomaterials (ranging from nanoclusters and nanoalloys to engineered nanostructures) with a tunable degree of agglomeration, composition, size, shape, and location. This method enables: (1) more homogeneous, non-agglomerated ultrapure Au-Ag nanoalloys under 10 nm; (2) 3-nm non-agglomerated ultrapure Au nanoclusters with lower gas flow rates; (3) shape-controlled Ag NPs; and (4) stable Au and Ag engineered nanostructures: nanodisks, nanocrosses, and 3D nanopillars. In conclusion, this new approach paves the way for the green and sustainable mass-production of ultrapure engineered nanomaterials.

Alignment tolerant, low voltage, 0.23†V.cm, push-pull silicon photonic switches based on a vertical pn junction.

In this paper, we present the design, fabrication and characterization of a carrier depletion silicon-photonic switch based on a highly doped vertical pn junction. The vertical nature of the pn junction enables the device to exhibit a modulation efficiency as high as 0.23 V.cm. Fast switching times of 60ps are achieved in a lumped configuration. Moreover, the process flow is highly tolerant to fabrication deviations allowing a seamless transfer to the 350 nm process node of a commercial complementary-metal-oxide semiconductor (CMOS) foundry. Overall, this work showcases the possibility of fabricating highly efficient carrier depletion-based silicon photonic switches using medium resolution lithography.

Design and Development of Photonic Biosensors for Swine Viral Diseases Detection.

In this paper we introduce a field diagnostic device based on the combination of advanced bio-sensing and photonics technologies, to tackle emerging and endemic viruses causing swine epidemics, and consequently significant economic damage in farms. The device is based on the use of microring resonators fabricated in silicon nitride with CMOS compatible techniques. In the paper, the designed and fabricated photonic integrated circuit (PIC) sensors are presented and characterized, showing an optimized performance in terms of optical losses (30 dB per ring) and extinction ration for ring resonances (15 dB). Furthermore, the results of an experiment for porcine circovirus 2 (PCV2) detection by using the developed biosensors are presented. Positive detection for different virus concentrations has been obtained. The device is currently under development in the framework of the EU Commission co-funded project SWINOSTICS.

A Diagnostic Device for In-Situ Detection of Swine Viral Diseases: The SWINOSTICS Project.

In this paper, we present the concept of a novel diagnostic device for on-site analyses, based on the use of advanced bio-sensing and photonics technologies to tackle emerging and endemic viruses causing swine epidemics and significant economic damage in farms. The device is currently under development in the framework of the EU Commission co-funded project. The overall concept behind the project is to develop a method for an early and fast on field detection of selected swine viruses by non-specialized personnel. The technology is able to detect pathogens in different types of biological samples, such as oral fluids, faeces, blood or nasal swabs. The device will allow for an immediate on-site threat assessment. In this work, we present the overall concept of the device, its architecture with the technical requirements, and all the used innovative technologies that contribute to the advancements of the current state of the art.

Detection of miRNA cancer biomarkers using light activated Molecular Beacons.

Early detection of cancer biomarkers can reduce cancer mortality rate. miRNAs are small non-coding RNAs whose expression changes upon the onset of various types of cancer. Biosensors that specifically detect such biomarkers can be engineered and integrated into point-of-care devices (POC) using label-free detection, high sensibility and compactness. In this paper, a new engineered Molecular Beacon (MB) construct used to detect miRNAs is presented. Such a construct is immobilized onto biosensor surfaces in a covalent and spatially oriented way using the photonic technology Light Assisted Molecular Immobilization (LAMI). The construct consists of a Cy3 labelled MB covalently attached to a light-switchable peptide. One MB construct contains a poly-A sequence in its loop region while the other contains a sequence complementary to the cancer biomarker miRNA-21. The constructs have been characterized by UV-Vis spectroscopy, mass spectrometry and HPLC. LAMI led to the successful immobilization of the engineered constructs onto thiol functionalized optically flat quartz slides and Silicon on Insulator (SOI) sensor surfaces. The immobilized Cy3 labelled MB construct has been imaged using confocal fluorescence microscopy (CFM). The bioavailability of the immobilized engineered MB biosensors was confirmed through specific hybridization with the Cy5 labelled complementary sequence and imaged by CFM and FRET. Hybridization kinetics have been monitored using steady state fluorescence spectroscopy. The label-free detection of miRNA-21 was also achieved by using integrated photonic sensing structures. The engineered light sensitive constructs can be immobilized onto thiol reactive surfaces and are currently being integrated in a POC device for the detection of cancer biomarkers.

High signal-to-noise ratio ultra-compact lab-on-a-chip microflow cytometer enabled by silicon optical antennas.

We experimentally demonstrate an all-silicon nanoantenna-based micro-optofluidic cytometer showing a combination of high signal-to-noise ratio (SNR) > 14 dB and ultra-compact size. Thanks to the ultra-high directivity of the antennas (>150), which enables a state-of-the-art sub-micron resolution, we are able to avoid the use of the bulky devices typically employed to collimate light on chip (such as lenses or fibers). The nm-scale antenna cross section allows a dramatic reduction of the optical system footprint, from the mm-scale of previous approaches to a few µm2, yielding a notable reduction in the fabrication costs. This scheme paves the way to ultra-compact lab-on-a-chip devices that may enable new applications with potential impact on all branches of biological and health science.