High-efficiency self-focusing metamaterial grating coupler in silicon nitride with amorphous silicon overlay.

Efficient fiber-chip coupling interfaces are critically important for integrated photonics. Since surface gratings diffract optical signals vertically out of the chip, these couplers can be placed anywhere in the circuit allowing for wafer-scale testing. While state-of-the-art grating couplers have been developed for silicon-on-insulator (SOI) waveguides, the moderate index contrast of silicon nitride (SiN) presents an outstanding challenge for implementing efficient surface grating couplers on this platform. Due to the reduced grating strength, a longer structure is required to radiate the light from the chip which produces a diffracted field that is too wide to couple into the fiber. In this work, we present a novel grating coupler architecture for silicon nitride photonic integrated circuits that utilizes an amorphous silicon (α-Si) overlay. The high refractive index of the α-Si overlay breaks the coupler's vertical symmetry which increases the directionality. We implement subwavelength metamaterial apodization to optimize the overlap of the diffracted field with the optical fiber Gaussian mode profile. Furthermore, the phase of the diffracted beam is engineered to focalize the field into an SMF-28 optical fiber placed 55 µm above the surface of the chip. The coupler was designed using rigorous three-dimensional (3D) finite-difference time-domain (FDTD) simulations supported by genetic algorithm optimization. Our grating coupler has a footprint of 26.8 × 32.7 µm2 and operates in the O-band centered at 1.31 µm. It achieves a high directionality of 85% and a field overlap of 90% with a target fiber mode size of 9.2 µm at the focal plane. Our simulations predict a peak coupling efficiency of - 1.3 dB with a 1-dB bandwidth of 31 nm. The α-Si/SiN grating architecture presented in this work enables the development of compact and efficient optical interfaces for SiN integrated photonics circuits with applications including optical communications, sensing, and quantum photonics.

Long-term outcomes of endoscopic ultrasound-guided laser ablation for liver tumors in the caudate lobe: 5 years of experience.

OBJECTIVES: Liver tumor in the caudate lobe is challenging to treat, partly due to its deep location. Endoscopic ultrasound-guided laser ablation (EUS-LA) is a new attractive option for tumors in high-risk or difficult-to-reach locations. This prospective study investigated the long-term efficacy of EUS-LA for tumors in the caudate lobe, and factors that predict outcomes. METHODS: From June 2016 to July 2021, twenty consecutive patients (aged 56.95 ± 10.06 years) with 25 caudate lobe tumors (15.64 ± 6.37 mm) underwent EUS-LA. Treatment outcomes were assessed and predictive factors were calculated via univariate and multivariate analyses. RESULTS: Twenty-five tumors achieved complete ablation after the first or second session of EUS-LA. The treatment effectiveness was 100%. During a median follow up of 27 months (3-60), four tumors (16%) developed local tumor progression and 15 patients (75%) experienced intrahepatic distant recurrence. According to univariate and multivariate analyses, the significant prognostic factor of local tumor progression was tumor size >2 cm (p = 0.047). Significant prognostic factors of intrahepatic distant recurrence were: tumor number, alpha-fetoprotein level, and total bilirubin level (p = 0.020, 0.019, 0.010, respectively). No adverse events related to EUS-LA were observed. CONCLUSION: EUS-LA is a viable, safe, and effective treatment option for patients with liver tumor in the caudate lobe. Tumor size >2 cm increases the risk of post-procedural local tumor progression. Intrahepatic tumor number, and pretreatment alpha-fetoprotein level and total bilirubin level are associated with intrahepatic distant recurrence. REGISTRATION: Clinicaltrials.gov, ID: NCT02816944(June 29, 2016).

Fabrication error tolerant broadband mode converters and their working principles.

Computational inverse design techniques have shown potential to become reliable means for designing compact nanophotonic devices without compromising the performance. Much effort has been made to reduce the computation cost involved in the optimization process and obtain final designs that are robust to fabrication imperfections. In this work, we experimentally demonstrate TE0-TE1 and TE1-TE3 mode converters (MCs) on the silicon-on-insulator platform designed using the computationally efficient shape optimization method. These MCs have mode conversion efficiencies above 95%, and the insertion loss ranges from 0.3 dB to 1 dB over a wavelength span of 80 nm ranging from 1.5 µm to 1.58 µm. Maximum modal crosstalk found experimentally in the C-band is -19 dB. The conversion efficiency drops at most by 2.2% at 1.55 µm for 10 nm over/under etch, implying good robustness to dimensional variations. We present the mode conversion mechanism of these MCs by studying the simulated electromagnetic field patterns and validate with supportive data. We also demonstrate their performance in the time domain with a 28 Gbps OOK and a 20 GBaud PAM-4 payload transmissions, which supports their utility for high throughput data communications. The open eye diagrams exhibit Q-factors of 8 dB.

Efficient mode exchanger-based silicon photonic switch enabled by inverse design.

A novel and energy efficient mode insensitive switch building block is proposed and experimentally demonstrated on a silicon-on-insulator platform. Based on a Mach-Zehnder interferometer, the switch uses a relatively compact mode insensitive phase shifter which includes a mode exchanger. The novel structure realizes the exact same phase shift for all modes by exchanging the modes midway within the phase shifter. The design approach leads to reduced power consumption otherwise not possible. Switching the first two quasi transverse electric (TE) modes simultaneously consumes 25.6 mW of power, an approximately 30% reduction from previous reported demonstrations. The measured insertion loss is 3.1 dB on average with a worst-case crosstalk of -14.9 dB over a 40 nm optical bandwidth from 1530 nm to 1570 nm. The design methodology enables scalability up to four optical modes.

Deep learning for real-time auxiliary diagnosis of pancreatic cancer in endoscopic ultrasonography.

In recent year, many deep learning have been playing an important role in the detection of cancers. This study aimed to real-timely differentiate a pancreatic cancer (PC) or a non-pancreatic cancer (NPC) lesion via endoscopic ultrasonography (EUS) image. A total of 1213 EUS images from 157 patients (99 male, 58 female) with pancreatic disease were used for training, validation and test groups. Before model training, regions of interest (ROIs) were manually drawn to mark the PC and NPC lesions using Labelimage software. Yolov5m was used as the algorithm model to automatically distinguish the presence of pancreatic lesion. After training the model based on EUS images using YOLOv5, the parameters achieved convergence within 300 rounds (GIoU Loss: 0.01532, Objectness Loss: 0.01247, precision: 0.713 and recall: 0.825). For the validation group, the mAP0.5 was 0.831, and mAP@.5:.95 was 0.512. In addition, the receiver operating characteristic (ROC) curve analysis showed this model seemed to have a trend of more AUC of 0.85 (0.665 to 0.956) than the area under the curve (AUC) of 0.838 (0.65 to 0.949) generated by physicians using EUS detection without puncture, although pairwise comparison of ROC curves showed that the AUC between the two groups was not significant (z= 0.15, p = 0.8804). This study suggested that the YOLOv5m would generate attractive results and allow for the real-time decision support for distinction of a PC or a NPC lesion.

Corrigendum: Antitumor effect and immune response of nanosecond pulsed electric fields in pancreatic cancer.

[This corrects the article DOI: 10.3389/fonc.2020.621092.].

The Safety and Efficacy of Nanosecond Pulsed Electric Field in Patients With Hepatocellular Carcinoma: A Prospective Phase 1 Clinical Study Protocol.

Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Irreversible electroporation (IRE) is an ablative modality that uses high-voltage electrical pulses to permeabilize the cell membrane leading to cell necrosis. Unlike traditional thermal ablation, IRE is hardly affected by the "heat-sink" effect and can prevent damage of the adjacent vital structures. Nanosecond pulsed electric field (nsPEF) is a new IRE technique using ultra-short pulses (nanosecond duration), can not only penetrate the cell membranes, but also act on the organelles. Sufficient preclinical researches have shown that nsPEF can eliminate HCC without damaging vital organs, and elicit potent anti-tumor immune response. Objective: This is the first clinical study to evaluate feasibility, efficacy, and safety of nsPEF for the treatment of HCC, where thermal ablation is unsuitable due to proximity to critical structures. Methods and analysis: We will conduct an open-labeled, single-arm, prospective, multicenter, and objective performance criteria trial. One hundred and ninety-two patients with HCC, in which the tumor is located immediately (<0.5 cm) adjacent to the portal vein, hepatic veins, bile duct, gastrointestinal tract, or diaphragm, will be enrolled among 4 academic medical centers. The primary outcomes are the rate of complete ablation at 1 month and adverse events. Secondary outcomes include technical success, technique efficacy, nsPEF procedural characteristics, local tumor progression, and local progression-free survival. Ethics and dissemination: The trial will be conducted according to the ethical principles of the Declaration of Helsinki and has been approved by the ethics committee of all participating centers. The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences. Conclusions: This study is the Phase 1 clinical trial to evaluate the efficacy and safety of nsPEF in patients with HCC at high-risk locations where thermal ablation is contra-indicated. The results may expand the options and offer an alternative therapy for HCC. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04309747.

Neutrophil membrane-coated nanoparticles for enhanced nanosecond pulsed electric field treatment of pancreatic cancer.

OBJECTIVE: Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Poor prognosis and low survival rates have driven the development of novel therapeutic strategies. Nanosecond pulsed electric field has emerged as a novel, minimal invasive and non-thermal treatment for solid tumors. It is of great significance to study the combination therapy of nsPEF and other treatment strategies for pancreatic cancer. METHODS: We developed neutrophil membrane-wrapped liposomal nanoparticles loaded with gemcitabine (NE/Lip-GEM) and investigated their use as a complementary agent for nsPEF treatment. RESULTS: Our results showed that neutrophil-mediated delivery of liposomal-gemcitabine (NE/Lip-GEM) efficiently inhibited the growth of pancreatic tumors in mice whose has been treated with incomplete nsPEF ablation. CONCLUSIONS: The combination of nsPEF and NE/Lip-GEM may be a promising synergistic strategy for pancreatic cancer therapy.

Deep Eutectic Solvent-Induced In Situ Etching and Phosphorization to Form Nickel Phosphides for Electrooxidation of 5-Hydroxymethylfurfural.

The development of catalysts with relatively high current densities at low potentials for the electrooxidation of 5-hydroxymethylfurfural (HMF) is still challenging. In this study, an in situ deep eutectic solvent (DES) etching phosphorization strategy is developed to prepare nickel phosphides encapsulated in P,O-codoped carbon nanosheets (Ni-P@POC). The DES serves not only as an etchant to extract Ni2+ from the nickel foam, but also as a phosphorus source to form nickel phosphides in situ uniformly embedded in the carbon films to produce a sheet structure. The electrooxidation performance is further greatly improved by implementing an electrochemical activation step to transform Ni-P@POC into NiOOH/Ni-P@POC (t-Ni-P@POC). t-Ni-P@POC exhibits a low onset potential of 1.20 V vs. RHE and a high current density of 200 mA cm-2 at 1.33 V vs. RHE for HMF electrooxidation, outperforming most reported catalysts. The as-developed DES etching phosphorization strategy offers a facile, flexible, and universal route for the design of high-performance catalysts with specific nanostructures.

Athermal echelle grating and tunable echelle grating demultiplexers using a Mach-Zehnder interferometer launch structure.

We present a comparative experimental study of three silicon photonic echelle grating demultiplexers that are integrated with a Mach-Zehnder interferometer (MZI) launch structure. By appropriate choice of the MZI configuration, the temperature induced shift of the demultiplexer channel wavelengths can be suppressed (athermal) or enhanced (super-thermal) or be controlled by an on-chip micro-heater. The latter two configurations allow the channel wavelengths to be actively tuned using lower power than possible by temperature tuning a conventional echelle demultiplexer. In the athermal configuration, the measured channel spectral shift is reduced to less than 10 pm/°C, compared to the 83 pm/°C shift for an unmodified echelle device. In super-thermal operation an enhanced channel temperature tuning rate of 170 pm/°C is achieved. Finally, by modulating the MZI phase with an on-chip heater, the demultiplexer channels can be actively tuned to correct for ambient temperature fluctuations up to 20 °C, using a drive current of less than 20 mA.

Fiber Fabry-Perot astrophotonic correlation spectroscopy for remote gas identification and radial velocity measurements.

We present a novel, to the best of our knowledge, remote gas detection and identification technique based on correlation spectroscopy with a piezoelectric tunable fiber-optic Fabry-Perot filter. We show that the spectral correlation amplitude between the filter transmission window and gas absorption features is related to the gas absorption optical depth, and that different gases can be distinguished from one another using their correlation signal phase. Using a previously captured telluric-corrected high-resolution near-infrared spectrum of Venus, we show that the radial velocity of Venus can be extracted from the phase of higher order harmonic lock-in signals. This correlation spectroscopy technique has applications in the detection and radial velocity determination of weak spectral features in astronomy and remote sensing. We experimentally demonstrate a remote CO2 detection system using a lock-in amplifier, fiber-optic Fabry-Perot filter, and single channel avalanche photodiode.

Efficient Bloch mode calculation of periodic systems with arbitrary geometry and open boundary conditions in the complex wavevector domain.

We show how existing iterative methods can be used to efficiently and accurately calculate Bloch periodic solutions of Maxwell's equations in arbitrary geometries. This is carried out in the complex-wavevector domain using a commercial frequency-domain finite-element solver that is available to the general user. The method is capable of dealing with leaky Bloch mode solutions, and is extremely efficient even for 3D geometries with non-trivial material distributions. We perform independent finite-difference time-domain simulations of Maxwell's equations to confirm our results. This comparison demonstrates that the iterative mode finder is more accurate, since it provides the true solutions in the complex-wavevector domain and removes the need for additional signal processing and fitting. Due to its efficiency, generality and reliability, this technique is well suited for complex and novel design tasks in integrated photonics, and also for a wider range of photonics problems.

Topological inverse design of nanophotonic devices with energy constraint.

In this paper, we introduce an energy constraint to improve topology-based inverse design. Current methods typically place the constraints solely on the device geometry and require many optimization iterations to converge to a manufacturable solution. In our approach the energy constraint directs the optimization process to solutions that best contain the optical field inside the waveguide core medium, leading to more robust designs with relatively larger minimum feature size. To validate our method, we optimize two components: a mode converter (MC) and a wavelength demultiplexer. In the MC, the energy constraint leads to nearly binarized structures without applying independent binarization stage. In the demultiplexer, it also reduces the appearance of small features. Furthermore, the proposed constraint improves the robustness to fabrication imperfections as shown in demultiplexer design. With energy constraint optimization, the corresponding spectrum shifts under ±10 nm dimensional variations are reduced by 17% to 30%. The proposed constraint is unique in simultaneously taking both geometry and electric field into account, opening the door to new ideas and insights to further improve the computationally intensive topology-based optimization process of nanophotonic devices.

Curcumin-loaded nanoMOFs@CMFP: A biological preserving paste with antibacterial properties and long-acting, controllable release.

Food spoilage is one of the biggest concerns for food safety worldwide. Here, we describe the construction of a carrier for biological agents by chemical combination of porous nanoMOFs and carboxymethylated filter paper (CMFP). When curcumin was encapsulated in nanoMOFs@CMFP, they showed the ability to act as super-long-acting food preserving agents with controllable release of curcumin. Although only 22.3% of curcumin was released into water in 600 h, 65.8% was released into PBS in the same time, and the release into PBS could be tuned by adding citric acid at the time of greatest requirement. Furthermore, the chemical stability of curcumin in nanoMOFs@CMFP was >4.9 times greater than for free curcumin. The outstanding antioxidant and antimicrobial activity of curcumin-loaded nanoMOFs@CMFP paste was demonstrated by prolonging the shelf life of pitayas, which illustrates its potential for development as long-acting and stable preserving paste for use in food preservation.

Irreversible electroporation in patients with liver tumours: treated-area patterns with contrast-enhanced ultrasound.

BACKGROUND: Familiarity with post-IRE imaging interpretation is of considerable importance in determining ablation success and detecting recurrence. CEUS can be used to assess the tumour response and characteristics of the ablation zone. It is of clinical interest to describe the ultrasonographic findings of liver tumours after irreversible electroporation (IRE) percutaneous ablation. METHODS: A prospective study of 24 cases of malignant liver tumours (22 cases of primary liver tumours and 2 cases of liver metastases) treated by IRE ablation was conducted. Two inspectors evaluated the ablation zone in a consensus reading performed immediately, 1 day, and 1 month after IRE ablation. The gold standard method, magnetic resonance imaging (MRI), was used to evaluate the effectiveness of the treatment at 1 month. RESULTS: Immediately after IRE ablation and up to 1 month later, the ablation zones gradually changed from hypo-echogenicity to hyper-echogenicity on conventional ultrasound and showed non-enhancement on contrast-enhanced ultrasound (CEUS). One month after IRE ablation, CEUS and MRI results were highly consistent (κ = 0.78, p < 0.05). CONCLUSIONS: We conclude that CEUS may be an effective tool for assessing post-IRE ablation changes after 1 month. CEUS enables the depiction of tumour vascularity in real time and serves as an easy, repeatable method.

Development of a novel melatonin-modified near-infrared fluorescent probe for in vivo hepatocellular carcinoma imaging.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor prognosis. The early identification and precise resection of HCC are essential for improving the prognosis and overall survival of patients. In clinical practice, fluorescence imaging is a powerful technology to identify and remove HCC lesions, but accurate and reliable detection of HCC continues to remain a challenge due to non-specificity and false-positive uptake of probes. To circumvent these problems, it is crucial to design a specific probe for the accurate detection of HCC. Herein, we reported the design and synthesis of an NIR fluorescent probe by conjugating IRDye800CW with melatonin, which plays a significant role in the HCC development. The in vivo imaging revealed that IRDye800-MT was uptake specifically by the HCC tumor with a high tumor-to-background ratio. These results demonstrated that IRDye800-MT might hold clinical potentials for future diagnosis of HCC patients.

Highly efficient optical antenna with small beam divergence in silicon waveguides.

Optical antennas are key components in optical phased arrays for light detection and ranging technology requiring long sensing range and high scanning resolution. To achieve a narrow beam width in the far-field region, antenna lengths of several millimeters or more are required. To date, such long antennas have been impossible to achieve in silicon waveguides because currently demonstrated technologies do not allow accurate control of grating strength. Here, we report on a new type of surface-emitting silicon waveguide with a dramatically increased antenna length of L=3.65mm. This is achieved by using a subwavelength metamaterial waveguide core evanescently coupled with radiative segments laterally separated from the core. This results in a far-field diffracted beam width of 0.025°, which is a record small beam divergence for a silicon photonics surface-emitting device. We also demonstrate that by using a design with L-shaped surface-emitting segments, the radiation efficiency of the antenna can be substantially increased compared to a conventional design, with an efficiency of 72% at the wavelength of 1550 nm.

Spectrum-free integrated photonic remote molecular identification and sensing.

Absorption spectroscopy is widely used in sensing and astronomy to understand remote molecular compositions. However, dispersive techniques require multichannel detection, reducing detection sensitivity while increasing instrument cost when compared to spectrophotometric methods. We present a novel non-dispersive infrared molecular detection and identification scheme that performs spectral correlation optically using a specially tailored integrated silicon ring resonator. We show experimentally that the correlation amplitude is proportional to the number of overlapping ring resonances and gas lines, and that molecular specificity can be achieved from the phase of the correlation signal. This strategy can enable on-chip detection of extremely faint remote spectral signatures.

Photonic temperature and wavelength metrology by spectral pattern recognition.

Spectral pattern recognition is used to measure temperature and generate calibrated wavelength/frequency combs using a single silicon waveguide ring resonator. The ring generates two incommensurate interleaving TE and TM spectral combs that shift independently with temperature to create a spectral pattern that is unique at every temperature. Following an initial calibration, the ring temperature can be determined by recognizing the spectral resonance pattern, and as a consequence, the wavelength of every resonance is also known. Two methods of pattern-based temperature retrieval are presented. In the first method, the ring is locked to a previously determined temperature set-point defined by the coincidence of only two specific TE and TM cavity modes. Based on a prior calibration at the set-point, the ring temperature and hence all resonance wavelengths are then known and the resulting comb can be used as a wavelength calibration reference. In this configuration, all reference comb wavelengths have been reproduced within a 5 pm accuracy across an 80 nm range by using an on-chip micro-heater to tune the ring. For more general photonic thermometry, a spectral correlation algorithm is developed to recognize a resonance pattern across a 30 nm wide spectral window and thereby determine ring temperature continuously to 50 mK accuracy. The correlation method is extended to simultaneously determine temperature and to identify and correct for wavelength calibration errors in the interrogating light source. The temperature and comb wavelength accuracy is limited primarily by the linewidth of the ring resonances, with accuracy and resolution scaling with the ring quality factor.