Reference Arm Research Articles

Ultra-high sensitivity methane gas sensor based on vernier effect in double D-shaped and cryptophane-A film-coated photonic crystal fiber: Design and FEM simulation

Utilization of the vernier effect in fiber optic interferometers represents the latest approach to enhance the sensitivity and resolution in fiber optic sensors. In this paper, the Vernier effect in Sagnac interference (SI) with a double D-shaped photonic crystal fiber (PCF) was proposed for the methane gas sensing. The sensing arm in the SI was composed of a double D-shaped PCF which was coated with cryptophane-A film, while the polarization maintaining photonic crystal fiber (PM-PCF) is used as the reference arm. The sensing arm and the reference arm were cascaded in parallel to generate the Vernier effect. The influence of the structural parameters in the PCF on the sensing performance was analyzed using the finite element method. The sensing fiber uses a double-D structure, so methane gas is more easily in contact with the sensitive film. According to the simulation results, the wavelength sensitivity of the parallel Sagnac loops within the methane gas concentration range of 0–3.5% is as high as 170.58 nm/%, which is 3.14 times that of a single Sagnac loop. The proposed sensor exhibits a significant enhancement in sensitivity compared to the other fiber optic-based methane gas sensors, thereby providing a reference sample for the development of high-sensitivity methane gas sensors.

Novel microspherical fiber Fabry–Pérot interferometer based on the Vernier effect for micro-displacement sensing

A novel optical fiber Fabry–Perot interferometer (FPI) based on the Vernier effect is proposed for micro-displacement sensing. The sensor is composed of an optical fiber microsphere and a section of multimode optical fiber with a flat end surface. The air cavity in the middle is used as the Fabry–Perot cavity. The extinction ratio of the reflection spectrum is significantly improved by the optical fiber microsphere, and the extinction ratio is ∼12 dB. First, a single FPI is tested for micro-displacement. A sensitivity of 2.13 nm/µm and linearity of 99.31% are obtained within the range of 0–1.872 µm via phase demodulation. The fabricated optical fiber FPI is used as the sensing arm and cascaded with the designed analog reference arm. The micro-displacement sensitivity of the sensing arm can be improved to 28.92 nm/µm through the Vernier effect, i.e., 13.58 times that of a single FPI. The fabricated sensor exhibits the characteristics of high sensitivity, contrast, and linearity; a compact structure; and low cost. It can be used for micro-displacement detection. In addition, the analog reference arm is unaffected by the environment, and it can freely adjust sensitivity magnification. Accordingly, it is applicable to micro-displacement detection scenarios under different sensitivity requirements.

A Generic and Effective System Dispersion Compensation Method: Development and Validation in Visible-Light OCT

Compared with optical coherence tomography (OCT) in the near-infrared domain, the visible-light OCT (vis-OCT) system affords a higher axial resolution for discerning subtle pathological changes associated with early diseases. However, the significant material dispersion at the visible-light range leads to a severe problem for dispersion management in vis-OCT systems, which results in a compromised axial resolution. While dispersion compensators (such as prism pairs) are commonly used, a digital method is still highly desirable and has been widely used to compensate for the residual dispersion imbalance between the reference and sample arms in an OCT system. In this paper, we develop a generic approach to effectively compensate for the system dispersion, especially the higher-order dispersion in the vis-OCT system, by using a single arbitrary measurement of the mirror-reflection (SAMMR) method and its resulting phase information. Compared with the previous methods, including the method based on the Taylor series iterative fitting and differential method, the proposed method does not need to extract the dispersion coefficients or use the metric functions and affords a better performance for axial resolution and the signal-to-noise ratio in vis-OCT systems. Its effectiveness is further validated in an OCT system operating in the near-infrared domain.

Trace detection of canine distemper virus based on surface-functionalized optic-fiber Mach–Zehnder interferometer and the Vernier effect

A surface-functionalized cascaded optic-fiber Mach–Zehnder interferometer (MZI) is proposed and fabricated for trace detection of canine distemper virus (CDV). The Vernier effect is formed based on single-mode fiber (SMF)-dislocation single-mode fiber-SMF. The two MZIs serve as the sensing arm and reference arm, respectively. The CDV antibody is modified on the sensing arm to detect CDV antigen, and the surface structure and morphology are analyzed by the atomic force microscope. The sensitivity of the cascaded MZI sensor is about 12 times than that of a single MZI. In the range of 0.1–104 pg ml−1 CDV, the detection limit of the cascaded MZI sensor is 0.1687 pg ml−1, and the response time is 25 min. The sensor also has good temperature, time stability and excellent selectivity. The biosensor has the advantages of low cost, easy preparation, high sensitivity and good selectivity, and has potential application for trace CDV detection.

High-sensitivity fiber optic temperature sensor based on CTFBG-FPI and Vernier effect.

A novel high-sensitivity temperature sensor based on a chirped thin-core fiber Bragg grating Fabry-Perot interferometer (CTFBG-FPI) and the Vernier effect is proposed and demonstrated. With femtosecond laser direct writing technology, two CTFBG-FPIs with different interferometric cavity lengths are inscribed inside a thin-core fiber to form a Vernier effect system. The two FPIs consist of two pairs of CTFBGs with a full width at half maximum (FWHM) of 66.5 nm staggered in parallel. The interferometric cavity lengths of the two FPIs were designed to be 2 mm and 1.98 mm as the reference arm and sensing arm of the sensor, respectively. The temperature sensitivity of this sensor was measured to be -1.084 nm/°C in a range of 40-90°C. This sensor is expected to play a crucial role in precision temperature measurement applications.

Interface self-referenced dynamic full-field optical coherence tomography.

Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as an invaluable live label-free and non-invasive imaging modality able to image subcellular biological structures and their metabolic activity within complex 3D samples. However, D-FFOCT suffers from fringe artefacts when imaging near reflective surfaces and is highly sensitive to vibrations. Here, we present interface Self-Referenced (iSR) D-FFOCT, an alternative configuration to D-FFOCT that takes advantage of the presence of the sample coverslip in between the sample and the objective by using it as a defocused reference arm, thus avoiding the aforementioned artefacts. We demonstrate the ability of iSR D-FFOCT to image 2D fibroblast cell cultures, which are among the flattest mammalian cells.

Collision avoidance analysis of human-robot physical interaction based on null-space impedance control of a dynamic reference arm plane.

When the terminal upper limb rehabilitation robot is used for motion-assisted training, collisions between the manipulator links and the human upper limb may occur due to the null-space self-motion of the redundant manipulator. A null-space impedance control method based on a dynamic reference arm plane is proposed to realize collision avoidance during human-robot physical interaction motion for the collision problem between the manipulator links and the human upper limb. Firstly, a dynamic model and a Cartesian impedance controller of the manipulator are established. Then, the null-space impedance controller of the redundant manipulator is established based on the dynamic reference plane, which manages the null-space self-motion of the redundant manipulator to prevent collision between the manipulator links and the human upper limb. Finally, it is experimentally verified that the method proposed in this paper can effectively manage the null-space self-motion of the redundant manipulator, and thus achieve collision avoidance during the human-robot physical interaction motion. This research has significant potential in improving the safety and feasibility of motion-assisted training with rehabilitation robots.

Free-space interferometer design for optical frequency dissemination and out-of-loop characterization below the 10−21-level

For improving the performance of optical frequency dissemination and the resolution of its out-of-loop (OOL) characterization, we investigate a compact free-space interferometer design in which a monolithic assembly forms the reference arm. Two interferometer designs are realized, and their environmental sensitivity is analyzed based on the properties of the materials involved. We elucidate that in these designs the temperature sensitivities of the out-of-loop signal paths are greater than for the reference arm. As the estimated temperature-variation-induced frequency transfer errors are observed to be the relevant limitation, the out-of-loop characterization signal can be regarded as a trustworthy upper limit of the frequency transfer error to a remote place. We demonstrate a fractional frequency transfer uncertainty and OOL characterization resolution of ≤2.7×10−21 over many measurement runs. With a value of (0.23±1.07)×10−22 the weighted mean offset is significantly below the best reported results so far.

Neoplastic and blood-based biomarkers of response in patients with advanced endometrial cancer: Results from NRG GY012.

5525 Background: NRG GY012 is a randomized, 3-arm phase II study, comparing olaparib (O) and the combination of cediranib and olaparib (CO) to the reference arm cediranib (C) for metastatic pre-treated, endometrial cancer (EC). The trial found a trend towards benefit for CO and no benefit for O compared to C. Archival tumor and prospective blood samples were collected for biomarker analysis. Methods: Targeted next-generation sequencing (BROCA-GO) was used to detect pathogenic variants (PV) and loss of heterozygosity (LOH) in DNA from paired blood and archival cancers. The LOH cut-off was identified at 11% for HRD based on testing ovarian cancers with known HRD. Plasma samples collected at baseline, cycle 2 day 1, and end-of-treatment were analyzed via multiplex ELISA for 25 angiogenic and inflammatory circulating protein biomarkers (Angiome); IL6 was of specific interest. Prognostic associations with PFS and OS were analyzed using proportional hazards models (PhM) stratified by histology and adjusted for treatment assignment. Predictive associations (PFS and OS) were analyzed using PhM stratified by histology and including main effects for both treatment assignment and biomarker group plus an interaction term. Results: In 97 patients (pts) with evaluable tumor, BROCA-GO identified 370 somatic PV; TP53 (61%) was the most commonly mutated gene. PV in homologous recombination repair (HRR) genes were identified in 5 cases (5%). Somatic PVs were identified in BRCA2, RAD51B and PALB2. 1 pt had a germline BRCA1 PV. 2 cases had somatic PV that might restore HRR: 1 case with a somatic BRCA2 PV had somatic PVs in CHD4 and TP53BP1; the TP53BP1 frameshift PV was present only in the recurrent and not primary cancer. LOH was available for 45 cases. LOH high occurred in 16 (35.6%) cases and was exclusive to EC with TP53 mutations (p=0.0003). LOH was not associated with outcome in any of the arms. For the circulating biomarker analysis (N=96), median IL-6 was 4pg/ml. IL-6 levels >4pg/ml were associated with increased risk of progression (HR: 1.59; 95% CI: (1.04-2.42); p-value=0.032). In predictive analyses, pts with IL-6 > 4 pg/ml receiving C or C+O had increased PFS (3.8 mo vs 1.9 mo) and OS (11.9 mo vs 5.7 mo) compared to pts receiving O, the interaction p value did not reach statistical significance. Conclusions: LOH high status was not associated with outcome to O. There were too few cases with HRR PVs to determine their relationship to PARPi response. The restriction of LOH high to cancers with TP53 mutation may suggest that genomic LOH in ECs correlates better with aneuploidy than with HRR function indicating that at least some biomarkers of PARPi response vary between tumor types. IL-6 levels were prognostic of PFS but were not predictive of either OS or PFS for pts receiving C compared to pts receiving O in this small study. Further analysis of the complete Angiome and integration with the BROCA-GO dataset are ongoing. Clinical trial information: NCT03660826 .

A randomized phase II study comparing single-agent olaparib, single-agent cediranib, and the combinations of cediranib/olaparib, olaparib/durvalumab (MEDI4736), cediranib/durvalumab (MEDI4736), and olaparib/AZD5363 (capivasertib) in women with recurrent, persistent, or metastatic endometrial cancer.

TPS5629 Background: Identifying new approaches for the treatment of advanced endometrial cancer (EC) is a priority. A platform study design allows for a faster investigation of novel drug combinations. NRG-GY012 is an ongoing platform study investigating drug combinations with the PARP inhibitor olaparib (O) and the anti-angiogenic agent cediranib (C). Results from the first set of arms established improved PFS for combination cediranib/olaparib over C alone, but did not meet its prespecified statistical significance. In this second set of arms, based on preclinical data, we are investigating the combination of O with an AKT inhibitor (capivasertib), O with durvalumab and C with durvalumab compared to the reference arm of C alone. Methods: This is a multicenter randomized four arm study for patients with recurrent, metastatic or persistent EC. Patients are randomized 1:1:1:1 to cediranib PO 30 mg Daily; olaparib 300 mg PO BID and capivasertib 400mg 4 day on/3 off schedule; olaparib 300 mg PO BID and durvalumab 1500mg q28 days; or the combination of cediranib 20 mg PO Daily 5 days on/2 days and durvalumab 1500mg q28. All treatment cycles are 28 days. Primary endpoint is progression free survival (PFS). The study is powered to detect a doubling in median PFS from 3.6 (based on cediranib alone) to 7.2 months with 90% power, using a one-sided test with α = 0.05 per comparison. Forty patients will be enrolled per arm, with an interim futility analysis planned at 50% information time. Eligibility includes endometroid, serous, and mixed histology EC; at least 1 prior line of chemotherapy (no more than 2 lines for metastatic disease), prior endocrine or immunotherapy alone is allowed; prior treatment with lenvatinib and pembrolizumab is excluded. Archival tumor tissue and blood samples are being collected for translational studies. The study is open across the NRG network; 76 of a planned 168 patients are enrolled to date. Safety analysis at the time of 36 patients enrolled did not demonstrate any new safety signals and the study was approved to continue enrollment. Clinical trial information: NCT03660826 .

Tunable sensitivity microfiber Sagnac loop based on a virtual reference arm for microdisplacement detection

A virtual reference arm-based microfiber Sagnac ring (MFSL) microdisplacement sensor with tunable sensitivity is proposed and demonstrated in this study. We abandon the traditional physical reference arm and build a virtual reference arm to overcome the disadvantage of the physical reference arm being susceptible to environmental influences and to achieve tunable sensitivity. A MFSL with a diameter of 4 μm was fabricated via the winding and tapering process, and a microdisplacement sensitivity of −0.34 nm/μm was obtained in the range of 0–5 μm. Experimental results show that the microdisplacement sensitivity can reach −1.40 nm/μm after cascading the simulated reference arm, which is 4.12 times that of single MFSL. In addition, by changing the parameters of the virtual reference arm without remaking the reference arm, we obtained sensors with sensitivities of −1.74 and −2.30 nm/μm. The sensor has advantages of tunable sensitivity and low cost and has potential applications in microdisplacement measurement.

Treatment of radiation-associated angiosarcoma.

Radiation-associated angiosarcoma is a cutaneous aggressive tumor that is very rare and it represents a specific entity poorly studied in literature. It requires new therapeutic opportunity. The complete surgical resection with negative margins is the mainstay treatment of localized treatment, even though it is difficult to reach in case of diffuse cutaneous infiltration. Adjuvant re-irradiation may improve local control with no benefit demonstrated on survival. Many systemic treatments can be efficient not only in metastatic setting but also in neoadjuvant setting in case of diffuse presentation. These treatments have never been compared to each other; the most efficient regimen remains to be determined, and a high heterogeneity of treatment is observed, even between sarcoma reference centers. Immune therapy represents the most promising treatment under development. At the time of building clinical trial to assess the efficacy of immune therapy, the lack of randomized studies prevents the identification of a strong and consensual reference arm treatment. Given the rarity of the disease, only international collaborative clinical trials may have a chance to include enough patients to draw any conclusion and so will have to counteract the heterogeneity of management.

Determination of birefringence of biological tissues using modified PS-OCT based on the quaternion approach

Introduction: Polarization-sensitive optical coherence tomography (PS-OCT) is a functional extension of standard OCT. PS-OCT systems can be generally categorized into two categories based on the number of input polarization states on the sample: multi-input polarization state (multi-IPS) and single IPS. In addition, each category includes two configurations: fiber-based system and bulk optics-based system. However, there are complex and time-consuming steps to calibrate the polarization states of light among the reference, the sample, and detection arms for fiber-based system. And it is not compact and robust enough for bulk optics-based system.Methods: In the modified SD PS-OCT system with structural symmetry in both arms of the reference and sample, there are no bulk polarization optical elements in both arms of the reference and the sample. A circularly polarized light was used to incident on sample, and Stokes vector of backscattered light was employed to characterize the birefringence of biological tissues based on the quaternion approach, which directly establishes the relationship between Stokes vectors of backscattered light and Jones matrix of the sample.Results and discussion: The new algorithm provides the analytic solution of retardance and fast-axis orientation. To evaluate the performance of the developed system, an eighth-wave plate is used. Then, the polarization properties of the myocardial tissue in vivo are quantitatively reconstructed based on the quaternion approach. The results demonstrated that the proposed method has an advantage over Jones formalism based on a single input state and two polarization input states. In the future, the modified SD PS-OCT could be improved as a common path SD PS-OCT for clinical applications.

Single-shot spatiotemporal plasma density diagnosis using an arbitrary time-wavelength-encoded biprism interferometer

Single-shot ultrafast imaging reveals the transient dynamics of ultrafast phenomena. Herein, we introduce a new approach for capturing ultrafast micron-scale dynamics using an arbitrary time-wavelength-encoded biprism interferometer (TWEBI). In TWEBI, a time-wavelength-encoded pulse train is generated using a set of cascaded frequency-doubling crystals with slightly different phase-matching angles and independent delay lines, which have the advantages of independent temporal resolution, time window, and frame interval parameters. Phase measurement of TWEBI is achieved using a plug-and-play biprism interferometer. In the experiment to capture the transient dynamic of femtosecond laser-induced plasma filament, we demonstrated that the TWEBI setup can capture a total of 12 frames in a single shot, and its effective frame rate is 5 trillion frames per second (Tfps), corresponding to a temporal resolution of 200 fs and a spatial resolution of 4 μm. Moreover, the time window of the TWEBI setup can be adjusted from sub-picosecond to nanosecond timescales. Thus, TWEBI has the advantages of high-precision temporal-spatial resolution, high frame rate, adjustable time window, and no reference arm, thus providing a practical and feasible diagnostic scheme for complex transient dynamics.

On-chip digital holographic interferometry for measuring wavefront deformation in transparent samples.

This paper describes on-chip digital holographic interferometry for measuring the wavefront deformation of transparent samples. The interferometer is based on a Mach-Zehnder arrangement with a waveguide in the reference arm, which allows for a compact on-chip arrangement. The method thus exploits the sensitivity of digital holographic interferometry and the advantages of the on-chip approach, which provides high spatial resolution over a large area, simplicity, and compactness of the system. The method's performance is demonstrated by measuring a model glass sample fabricated by depositing SiO2 layers of different thicknesses on a planar glass substrate and visualizing the domain structure in periodically poled lithium niobate. Finally, the results of the measurement made with the on-chip digital holographic interferometer were compared with those made with a conventional Mach-Zehnder type digital holographic interferometer with lens and with a commercial white light interferometer. The comparison of the obtained results indicates that the on-chip digital holographic interferometer provides accuracy comparable to conventional methods while offering the benefits of a large field of view and simplicity.

Environmental cleaning to prevent hospital-acquired infections on non-intensive care units: a pragmatic, single-centre, cluster randomized controlled, crossover trial comparing soap-based, disinfection and probiotic cleaning

The impact of environmental hygiene on the occurrence of hospital-acquired infections (HAIs) remains a subject of debate. We determined the effect of three different surface-cleaning strategies on the incidence of HAIs. Between June 2017 and August 2018 we conducted a pragmatic, cluster-randomized controlled crossover trial at 18 non-ICU wards in the university hospital of Berlin, Germany. Surfaces in patient rooms on the study wards were routinely cleaned using one of three agents: Soap-based (reference), disinfectant and probiotic. Each strategy was used on each ward for four consecutive months (4m-4m-4m). There was a one-month wash-in period at the beginning of the study and after each change in strategy. The order of strategies used was randomized for each ward. Primary outcome was the incidence of HAIs. The trial was registered with the German Clinical Trials Register, DRKS00012675. 13,896 admitted patients met the inclusion criteria, including 4708 in the soap-based (reference) arm, 4535 in the disinfectant arm and 4653 in the probiotic arm. In the reference group, the incidence density of HAIs was 2.31 per 1000 exposure days. The incidence density was similar in the disinfectant arm 2.21 cases per 1000 exposure days (IRR 0.95; 95% CI 0.69-1.31; p=0.953) and the probiotic arm 2.21 cases per 1000 exposure days (IRR 0.96; 95% CI 0.69-1.32; p=0.955). In non-ICU wards, routine surface disinfection proved not superior to soap-based or probiotic cleaning in terms of HAI prevention. Thus, probiotic cleaning could be an interesting alternative, especially in terms of environmental protection. Federal Ministry of Education and Research of Germany (03Z0818C). Bill and Melinda Gates Foundation (INV-004308).

Fiber-Optic Interferometry and Phase Generation-Based Micro-Vibration Estimating System

This research presents a novel contactless micro-vibration estimating system that combines a Michelson fiber-optic interferometer and phase generation carriers based on calculation of the arc tangent. The system utilizes a narrow-band light source, a coupler, and a non-equilibrium Michelson fiber-optic interferometer to measure micro-vibrations on the surface of an object. One path of the light irradiates the object's surface vertically using an optical-fiber self-focusing lens, while the other path is reflected by a device at the reference arm's optical fiber. The light paths are then coupled, detected by a photoelectric coupler (PD), and processed by a data processing module. Additionally, the data processing module generates carrier waves to control a phase modulator on the interference arm. The resulting measurements are obtained using a phase demodulation technique based on the calculation of arc tangent (ARCTAN). The proposed system exhibits high flexibility, excellent response, and is unaffected by light intensity and visibility drifting, enabling online measurements of contactless micro-vibrations.

Mirror-terminated Mach-Zehnder interferometer based on SiNOI slot and strip waveguides for sensing applications using visible light

In this work, a highly sensitive sensor based on silicon nitride (SiN) waveguide is proposed that can be used for gas sensing using visible light. The whole sensor waveguide uses a silicon dioxide (SiO2) cladding while the sensing arm uses a fluidic cladding such as water. The proposed device is based on loop-mirror terminated (LMT) Mach-Zehnder interferometer (MZI), where the reference arm is exposed to the reference SiO2 medium, while the sensing arm is exposed to the sensing medium leading to a change in the refractive index of the waveguide cladding. The sensor performance is overall optimized by optimizing the design performance of all the components of the structure one by one. The waveguide sensitivity of both strip and slot types is analyzed for gaseous medium in order to compare their sensitivities and select the dimensions of the waveguide that results in the highest device sensitivity. Transverse-electric (TE) polarization is considered in this study for strip waveguide, where a higher sensitivity is founded with respect to the transverse-magnetic (TM) polarization. The field confinement in the slot waveguide in the sensing region is investigated and verified with a mode solver, where the optimum dimensions are obtained using finite difference eigenmode and finite difference time domain solvers. With a sensing arm length of 150 μm only, the proposed sensor achieves a device sensitivity of about 1,320 nm/RIU and a figure-of-merit (FOM) as high as 641 RIU−1 at the wavelength of 650 nm, which is the highest reported FOM up to the author’s knowledge. Higher values of the FOM are possible by employing a longer sensing arm.

Target Velocity Ghost Imaging Using Slice Difference Method.

Ghost imaging is a technique that uses the correlation between reference and signal arms to obtain intensity images of targets. Compared with the existing laser active imaging methods, ghost imaging can improve the signal-to-noise ratio and resolution. In this paper, through the use of the slice difference method, we propose a new scheme that allows a velocity image of moving targets to be obtained. We conduct a complete theoretical analysis and provide a proof-of-principle experiment. The experimental results are in good agreement with those of the theoretical analysis, and a velocity image with 64 × 64 resolution is obtained. This protocol achieves a great increase in the signal-to-noise ratio over what would be achievable using direct imaging. The results show a fully functional instance of velocity imaging, which is a key advancement on the path towards the multi-dimensional information acquisition of moving targets. Our scheme fulfils an urgent need for the detection of moving targets and may thus find use in fields such as target attitude perception and security monitoring.

Remote vectorial vibration sensing based on locally stabilized Mach-Zehnder interferometers using multi-core fiber and optical phase-locking.

We report on remote sensing of vectorial vibration based on locally stabilized Mach-Zehnder interferometers (MZIs) using commercial multi-core fiber (MCF). Hexa-MZIs with a shared common reference arm are constructed by a 7-core MCF to acquire remotely vectorial vibration. A set of corresponding local receivers consisting of optical phase-locked loops (OPLLs) for not only eliminating the impact of environmental perturbations but also maintaining the stable operation and relative stability among the MZIs, allows guaranteed stabilized remote sensing. It moreover ensures a linearized phase detection, and thus an improved sensing sensitivity and dynamic range. This way, by exploiting the symmetrically geometric distribution for the cores of 7-core MCF, the proposed all-fiber design can enable highly precise remote extraction of vibration in a vectorial manner with a simplified remote structure. We achieve vectorial remote sensing for vibrations with ∼0.1076° and ∼0.3603 µm precision for the angle and displacement, respectively, over 10 km.