Multiplexed Near-Field Optical Trapping Exploiting Anapole States.

Optical tweezers have had a major impact on bioscience research by enabling the study of biological particles with high accuracy. The focus so far has been on trapping individual particles, ranging from the cellular to the molecular level. However, biology is intrinsically heterogeneous; therefore, access to variations within the same population and species is necessary for the rigorous understanding of a biological system. Optical tweezers have demonstrated the ability of trapping multiple targets in parallel; however, the multiplexing capability becomes a challenge when moving toward the nanoscale. Here, we experimentally demonstrate a resonant metasurface that is capable of trapping a high number of nanoparticles in parallel, thereby opening up the field to large-scale multiplexed optical trapping. The unit cell of the metasurface supports an anapole state that generates a strong field enhancement for low-power near-field trapping; importantly, the anapole state is also more angle-tolerant than comparable resonant modes, which allows its excitation with a focused light beam, necessary for generating the required power density and optical forces. We use the anapole state to demonstrate the trapping of 100's of 100 nm polystyrene beads over a 10 min period, as well as the multiplexed trapping of lipid vesicles with a moderate intensity of <250 µW/µm2. This demonstration will enable studies relating to the heterogeneity of biological systems, such as viruses, extracellular vesicles, and other bioparticles at the nanoscale.

A Novel Hybrid Platform for Live/Dead Bacteria Accurate Sorting by On-Chip DEP Device.

According to the World Health Organization (WHO) forecasts, Antimicrobial Resistance (AMR) will be the leading cause of death worldwide in the next decades. To prevent this phenomenon, rapid Antimicrobial Susceptibility Testing (AST) techniques are required to drive the selection of the most suitable antibiotic and its dosage. In this context, we propose an on-chip platform, based on a micromixer and a microfluidic channel, combined with a pattern of engineered electrodes to exploit the di-electrophoresis (DEP) effect. The role of the micromixer is to ensure the proper interaction of the antibiotic with the bacteria over a long time (≈1 h), and the DEP-based microfluidic channel enables the efficient sorting of live from dead bacteria. A sorting efficiency of more than 98%, with low power consumption (Vpp = 1 V) and time response of 5 s, within a chip footprint of ≈86 mm2, has been calculated, which makes the proposed system very attractive and innovative for efficient and rapid monitoring of the antimicrobial susceptibility at the single-bacterium level in next-generation medicine.

Tunable narrow band add-drop filter design based on apodized long period waveguide grating assisted co-directional coupler.

Tunable add/drop filter based optical interconnects are an integral part of data centers as well as optical communications. Although add/drop filters based on ring resonators and waveguide Bragg gratings are well developed, long period waveguide grating (LPWG) based add/drop filters have little been investigated so far. In this article, we propose an apodized LPWG assisted co-directional coupler for narrow band add/drop filtering by combining silicon (Si) waveguide with titanium dioxide (TiO2) waveguide geometry. The proposed structure has been analyzed by combining the finite element method (FEM) and transfer matrix method (TMM), showing a good side lobe suppression ratio (SLSR) equal to 25.7 dB and an insertion loss of 0.6 dB. Owing to the high group index difference of Si and TiO2 waveguides, a narrow band response of 1.4 nm has been achieved with 800µm long LPWG. The opposite thermo-optic coefficients of Si and TiO2 ensures a good thermal tunability of the central wavelength. Considering a thin metallic heater of titanium nitride (TiN) the thermal tuning efficiency is found to be 0.07 nm/mW. Further, two LPWGs have been cascaded to realize a tunable dual channel filter with a minimum channel spacing of 185 GHz and a channel crosstalk better than 20 dB, showing its potential application towards dense wavelength division multiplexing.

Highly Sensitive Refractive Index Sensor Based on Polymer Bragg Grating: A Case Study on Extracellular Vesicles Detection.

The measurement of small changes in the refractive index (RI) leads to a comprehensive analysis of different biochemical substances, paving the way to non-invasive and cost-effective medical diagnosis. In recent times, the liquid biopsy for cancer detection via extracellular vesicles (EV) in the bodily fluid is becoming very popular thanks to less invasiveness and stability. In this context, here we propose a highly sensitive RI sensor based on a compact high-index-coated polymer waveguide Bragg grating with a metal under cladding. Owing to the combined effect of a metal under cladding and a high-index coating, a significant enhancement in the RI sensitivity as well as the dynamic range has been observed. The proposed sensor has been analyzed by combining finite element method (FEM) and coupled-mode theory (CMT) approaches, demonstrating a sensitivity of 408-861 nm/RIU over a broad dynamic range of 1.32-1.44, and a strong evanescent field within a 150 nm proximity to the waveguide surface compliant with EV size. The aforementioned performance makes the proposed device suitable for performing real-time and on-chip diagnoses of cancer in the early stage.

Novel Micro-Nano Optoelectronic Biosensor for Label-Free Real-Time Biofilm Monitoring.

According to the World Health Organization forecasts, AntiMicrobial Resistance (AMR) is expected to become one of the leading causes of death worldwide in the following decades. The rising danger of AMR is caused by the overuse of antibiotics, which are becoming ineffective against many pathogens, particularly in the presence of bacterial biofilms. In this context, non-destructive label-free techniques for the real-time study of the biofilm generation and maturation, together with the analysis of the efficiency of antibiotics, are in high demand. Here, we propose the design of a novel optoelectronic device based on a dual array of interdigitated micro- and nanoelectrodes in parallel, aiming at monitoring the bacterial biofilm evolution by using optical and electrical measurements. The optical response given by the nanostructure, based on the Guided Mode Resonance effect with a Q-factor of about 400 and normalized resonance amplitude of about 0.8, allows high spatial resolution for the analysis of the interaction between planktonic bacteria distributed in small colonies and their role in the biofilm generation, calculating a resonance wavelength shift variation of 0.9 nm in the presence of bacteria on the surface, while the electrical response with both micro- and nanoelectrodes is necessary for the study of the metabolic state of the bacteria to reveal the efficacy of antibiotics for the destruction of the biofilm, measuring a current change of 330 nA when a 15 µm thick biofilm is destroyed with respect to the absence of biofilm.

Measured radiation effects on InGaAsP/InP ring resonators for space applications.

Photonic ring resonators can be considered building blocks of new concept satellite payloads for implementing several functions, such as filtering and sensing. In particular, the use of a high Q-factor ring resonator as sensing element into a Resonant Micro Optic Gyroscope (RMOG), provides a remarkable improvement of the performance with respect to the competitive technologies. To qualify a ring resonator for Space applications, the radiation effects on it in the Space must be carefully evaluated. Here, we investigate the effects of gamma radiation on a high Q InGaAsP/InP ring resonator, for the first time, to our knowledge. The ring resonator under study has a footprint of about 530 mm2 and it is based on a InGaAsP/InP rib waveguide, with a width of 2 µm and a thickness of 0.3 µm, formed on a 0.7 µm thick slab layer on an InP substrate 625 µm thick. For a total dose of about 320 krad Co60 gamma irradiation, a mean variation of about 13% and 4% was measured for Q and extinction ratio (ER), respectively, with respect to the values before irradiation (Q = 1.36 × 106, ER = 6.24 dB). Furthermore, the resonance peak red-shifts with a linear behaviour was observed increasing the total dose of the absorbed radiation, with a maximum resonance detuning of about 810 pm. These non-significant effects of a quite high gamma radiation dose confirm the potential of high-Q InP-based ring resonators into Space systems or subsystems.

Monitoring of individual bacteria using electro-photonic traps.

Antimicrobial resistance (AMR) describes the ability of bacteria to become immune to antimicrobial treatments. Current testing for AMR is based on culturing methods that are very slow because they assess the average response of billions of bacteria. In principle, if tests were available that could assess the response of individual bacteria, they could be much faster. Here, we propose an electro-photonic approach for the analysis and the monitoring of susceptibility at the single-bacterium level. Our method employs optical tweezers based on photonic crystal cavities for the trapping of individual bacteria. While the bacteria are trapped, antibiotics can be added to the medium and the corresponding changes in the optical properties and motility of the bacteria be monitored via changes of the resonance wavelength and transmission. Furthermore, the proposed assay is able to monitor the impedance of the medium surrounding the bacterium, which allows us to record changes in metabolic rate in response to the antibiotic challenge. For example, our simulations predict a variation in measurable electrical current of up to 40% between dead and live bacteria. The proposed platform is the first, to our knowledge, that allows the parallel study of both the optical and the electrical response of individual bacteria to antibiotic challenge. Our platform opens up new lines of enquiry for monitoring the response of bacteria and it could lead the way towards the dissemination of a new generation of antibiogram study, which is relevant for the development of a point-of-care AMR diagnostics.

Design of an ultra-compact graphene-based integrated microphotonic tunable delay line.

The design of a continuously tunable optical delay line based on a compact graphene-based silicon Bragg grating is reported. High performance, in terms of electro-optical switching time (tswitch < 8 ns), delay range (Δτ = 200 ps), and figure of merit FOM = Δτ/A = 1.54x105 ps/mm2, has been achieved with an ultra-compact device footprint (A ~1.3 x 10-3 mm2), so improving the state-of-the-art of integrated optical delay lines. A continuous and complete tunability of the delay time can be achieved with a very low delay loss ( = 0.03 dB/ps) and a weak power consumption ( = 0.05 mW/ps). A flat bandwidth B = 1.19 GHz has been calculated by exploiting the slow-light effect in the device. This performance makes the proposed optical delay line suitable for several applications in Microwave Photonics (MWP), such as beamsteering/beamforming, for which large delay range, flat and wide bandwidth and small volume are required.

Design of a New Ultracompact Resonant Plasmonic Multi-Analyte Label-Free Biosensing Platform.

In this paper, we report on the design of a bio-multisensing platform for the selective label-free detection of protein biomarkers, carried out through a 3D numerical algorithm. The platform includes a number of biosensors, each of them is based on a plasmonic nanocavity, consisting of a periodic metal structure to be deposited on a silicon oxide substrate. Light is strongly confined in a region with extremely small size (=1.57 µm²), to enhance the light-matter interaction. A surface sensitivity Ss = 1.8 nm/nm has been calculated together with a detection limit of 128 pg/mm². Such performance, together with the extremely small footprint, allow the integration of several devices on a single chip to realize extremely compact lab-on-chip microsystems. In addition, each sensing element of the platform has a good chemical stability that is guaranteed by the selection of gold for its fabrication.

Photonic and Plasmonic Nanotweezing of Nano- and Microscale Particles.

The ability to manipulate and sense biological molecules is important in many life science domains, such as single-molecule biophysics, the development of new drugs and cancer detection. Although the manipulation of biological matter at the nanoscale continues to be a challenge, several types of nanotweezers based on different technologies have recently been demonstrated to address this challenge. In particular, photonic and plasmonic nanotweezers are attracting a strong research effort especially because they are efficient and stable, they offer fast response time, and avoid any direct physical contact with the target object to be trapped, thus preventing its disruption or damage. In this paper, we critically review photonic and plasmonic resonant technologies for biomolecule trapping, manipulation, and sensing at the nanoscale, with a special emphasis on hybrid photonic/plasmonic nanodevices allowing a very strong light-matter interaction. The state-of-the-art of competing technologies, e.g., electronic, magnetic, acoustic and carbon nanotube-based nanotweezers, and a description of their applications are also included.

Graphene-based fine-tunable optical delay line for optical beamforming in phased-array antennas.

The design of an integrated graphene-based fine-tunable optical delay line on silicon nitride for optical beamforming in phased-array antennas is reported. A high value of the optical delay time (τg=920 ps) together with a compact footprint (4.15 mm2) and optical loss <27 dB make this device particularly suitable for highly efficient steering in active phased-array antennas. The delay line includes two graphene-based Mach-Zehnder interferometer switches and two vertically stacked microring resonators between which a graphene capacitor is placed. The tuning range is obtained by varying the value of the voltage applied to the graphene electrodes, which controls the optical path of the light propagation and therefore the delay time. The graphene provides a faster reconfigurable time and low values of energy dissipation. Such significant advantages, together with a negligible beam-squint effect, allow us to overcome the limitations of conventional RF beamformers. A highly efficient fine-tunable optical delay line for the beamsteering of 20 radiating elements up to ±20° in the azimuth direction of a tile in a phased-array antenna of an X-band synthetic aperture radar has been designed.

New ultrasensitive resonant photonic platform for label-free biosensing.

A multi-analyte biosensing platform with ultra-high resolution ( = 0.2 ng/mL),-which is appropriate for the detection in the human serum of a wide range of biomarkers, e.g. those allowing the lung cancer early diagnosis, has been designed. The platform is based on a new configuration of planar ring resonator. The very strong light-matter interaction enabled by the micro-cavity allows a record limit-of-detection of 0.06 pg/mm(2), five times better than the state-of-the-art. The device with footprint = 2,200 µm(2) for each ring, due to its features, has the potential to be integrated in lab-on-chip microsystems for large-scale screenings of people with high risk of developing cancer.

Low-loss passive waveguides in a generic InP foundry process via local diffusion of zinc.

Generic InP foundry processes allow monolithic integration of active and passive elements into a common p-n doped layerstack. The passive loss can be greatly reduced by restricting the p-dopant to active regions. We report on a localized Zn-diffusion process based on MOVPE, which allows to reduce waveguide loss from 2 dB/cm to below 0.4 dB/cm. We confirm this value by fabrication of a 73 mm long spiral ring resonator, with a record quality factor of 1.2 million and an extinction ratio of 9.7 dB.

High performance InP ring resonator for new generation monolithically integrated optical gyroscopes.

An InP ring resonator with an experimentally demonstrated quality factor (Q) of the order of 10(6) is reported for the first time. This Q value, typical for low loss technologies such as silica-on-silicon, is a record for the InP technology and improves the state-of-the-art of about one order of magnitude. The cavity has been designed aiming at the Q-factor maximization while keeping the resonance depth of about 8 dB. The device was fabricated using metal-organic vapour-phase-epitaxy, photolithography and reactive ion etching. It has been optically characterized and all its performance parameters have been estimated. InP waveguide loss low as 0.45 dB/cm has been measured, leading to a potential shot noise limited resolution of 10 °/h for a new angular velocity sensor.

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

BACKGROUND: Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. RESULTS: We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. CONCLUSION: We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated microfluidic platforms explicitly developed for the task of biochemical model identification will hopefully reduce the effects of the 'data rich--data poor' paradox in Systems Biology.

Efficient Chemical Sensing by Coupled Slot SOI Waveguides.

A guided-wave chemical sensor for the detection of environmental pollutants or biochemical substances has been designed. The sensor is based on an asymmetric directional coupler employing slot optical waveguides. The use of a nanometer guiding structure where optical mode is confined in a low-index region permits a very compact sensor (device area about 1200 µm(2)) to be realized, having the minimum detectable refractive index change as low as 10(-5). Silicon-on-Insulator technology has been assumed in sensor design and a very accurate modelling procedure based on Finite Element Method and Coupled Mode Theory has been pointed out. Sensor design and optimization have allowed a very good trade-off between device length and sensitivity. Expected device sensitivity to glucose concentration change in an aqueous solution is of the order of 0.1 g/L.