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Chemoradiotherapy (CRT) followed by consolidation immune checkpoint inhibitors significantly improves survival in unresectable locally advanced non-small cell lung cancer. However, the optimal sequence for CRT and immune checkpoint inhibitors has not yet been established. We investigated the dynamics of peripheral blood immune cells during CRT to determine the best sequence for treatment.Peripheral blood samples were prospectively collected pretreatment, weekly during CRT for 6 weeks, and 1 month posttreatment in 24 patients with locally advanced non-small cell lung cancer who received definitive CRT. Immune cell analysis was performed by flow cytometry. Ex vivo PD-1 blockade assays were performed by IFN-γ intracellular cytokine staining.Lymphopenia was prominently observed during CRT and mostly recovered 1 month post-CRT. Robust proliferation of CD8The findings suggest that earlier administration of PD-1 blockade may be associated with superior efficacy compared with delayed administration after completion of CRT. These findings provide an immunologic rationale for optimal timing of combining immune checkpoint inhibitors with CRT in clinical trials.

The monolayer transition metal dichalcogenides are an emergent semiconductor platform exhibiting rich excitonic physics with coupled spin-valley degree of freedom and optical addressability. Here, we report a new series of low energy excitonic emission lines in the photoluminescence spectrum of ultraclean monolayer WSe2. These excitonic satellites are composed of three major peaks with energy separations matching known phonons, and appear only with electron doping. They possess homogenous spatial and spectral distribution, strong power saturation, and anomalously long population (> 6 $��$s) and polarization lifetimes (> 100 ns). Resonant excitation of the free inter- and intra-valley bright trions leads to opposite optical orientation of the satellites, while excitation of the free dark trion resonance suppresses the satellites photoluminescence. Defect-controlled crystal synthesis and scanning tunneling microscopy measurements provide corroboration that these features are dark excitons bound to dilute donors, along with associated phonon replicas. Our work opens opportunities to engineer homogenous single emitters and explore collective quantum optical phenomena using intrinsic donor-bound excitons in ultraclean 2D semiconductors., to be appear in Nature Communications

Solid-state quantum emitters (QEs) are fundamental in photonic-based quantum information processing. There is strong interest to develop high-quality QEs in III-nitride semiconductors because of their sophisticated manufacturing driven by large and growing applications in optoelectronics, high voltage power transistors, and microwave amplifiers. Here, the generation and direct integration of QEs in an aluminum nitride-based photonic integrated circuit platform is reported. For individual waveguide-integrated QEs, an off-chip count rate exceeding 6 × 104 counts per second (cps; saturation rate >8.6 × 104 cps) is measured at room temperature under continuous-wave (CW) excitation. In an unpatterned thin-film sample, antibunching with g(2)(0) ∼0.08 and photon count rates exceeding 8 × 105 cps (saturation rate >1 × 106 cps) are measured at room temperature under CW excitation. Although spin and detailed optical line width measurements are left for future work, these results already show the potential for high-quality QEs monolithically integrated in a wide range of III-nitride device technologies that would enable new quantum device opportunities and industrial scalability., United States. Army Research Office MURI ((Ab-Initio Solid-State Quantum Materials Grant W911NF-18-1-0431), National Science Foundation (U.S.). Research Advanced by Interdisciplinary Science and Engineering (Grant CHE-1839155), Air Force Research Laboratory. RITA program ( FA8750-16-2-0141), National Research Foundation of Korea (Grants 2015R1A6A3A03020926 and 2018R1D1A1B07043390)

The ability to control excitons in semiconductors underlies numerous proposed applications, from excitonic circuits to energy transport. Two dimensional (2D) semiconductors are particularly promising for room-temperature applications due to their large exciton binding energy and enormous stretchability. Although the strain-induced static exciton flux has been observed in predetermined structures, dynamic control of exciton flux represents an outstanding challenge. Here, we introduce a method to tune the bandgap of suspended 2D semiconductors by applying a local strain gradient with a nanoscale tip. This strain allows us to locally and reversibly shift the exciton energy and to steer the exciton flux over micrometer-scale distances. We anticipate that our result not only marks an important experimental tool but will also open a broad range of new applications from information processing to energy conversion., United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-18-1-0431), National Science Foundation (U.S.). Emerging Frontiers & Multidisciplinary Activities. Quantum Optoelectronics, Magnetoelectronics and Plasmonics in 2-Dimensional Materials Heterostructures (Award Abstract 1542863), CREST (Grant JPMJCR15F3)

Single-photon emitters represent a key component for many quantum technologies, from quantum communication to computation. Atomically thin two-dimensional materials are promising hosts of quantum e...

Quantum emitters capable of producing single photons on-demand with high color purity are the building blocks of emerging schemes in secure quantum communications, quantum computing, and quantum metrology. Such solid-state systems, however, are usually prone to effects of spectral diffusion (SD), i.e., fast modulation of the emission wavelength due to the presence of localized, fluctuating electric fields. Two-dimensional materials are especially vulnerable to SD by virtue of the proximity of the emitters to the outside environment. In this study we report measurements of SD in a single hexagonal boron nitride (hBN) quantum emitter on the nanosecond to second time scales using photon correlation Fourier spectroscopy. We demonstrate that the spectral diffusion dynamics can be modeled by a two-component Gaussian random jump model, suggesting multiple sources of local fluctuations. We provide a lower limit of ∼0.13 for the ratio of the emitter's coherence time (

supplementary information

Two-dimensional van der Waals materials have emerged as promising platforms for solid-state quantum information processing devices with unusual potential for heterogeneous assembly. Recently, bright and photostable single photon emitters were reported from atomic defects in layered hexagonal boron nitride (hBN), but controlling inhomogeneous spectral distribution and reducing multi-photon emission presented open challenges. Here, we demonstrate that strain control allows spectral tunability of hBN single photon emitters over 6 meV, and material processing sharply improves the single photon purity. We observe high single photon count rates exceeding 7 × 106 counts per second at saturation, after correcting for uncorrelated photon background. Furthermore, these emitters are stable to material transfer to other substrates. High-purity and photostable single photon emission at room temperature, together with spectral tunability and transferability, opens the door to scalable integration of high-quality quantum emitters in photonic quantum technologies., Inhomogeneous spectral distribution and multi-photon emission are currently hindering the use of defects in layered hBN as reliable single photon emitters. Here, the authors demonstrate strain-controlled wavelength tuning and increased single photon purity through suitable material processing.

Single photon sources based on atomic defects in layered hexagonal boron nitride (hBN) have emerged as promising solid state quantum emitters with atom-like photophysical and quantum optoelectronic properties. Similar to other atom-like emitters, defect-phonon coupling in hBN governs the characteristic single-photon emission and provides an opportunity to investigate the atomic and electronic structure of emitters as well as the coupling of their spin- and charge-dependent electronic states to phonons. Here, we investigate these questions using photoluminescence excitation (PLE) experiments at T = 4 K on single-photon emitters in multilayer hBN grown by chemical vapor deposition. By scanning up to 250 meV from the zero phonon line (ZPL), we can precisely measure the emitter's coupling efficiency to different phonon modes. Our results show that excitation mediated by the absorption of one in-plane optical phonon increases the emitter absorption probability 10-fold compared to that mediated by acoustic or out-of-plane optical phonons. We perform complementary theoretical predictions by first-principles density-functional theory of four defect candidates for which we calculate prevalent charge states and their spin-dependent coupling to bulk and local phonon modes. We discuss possible hypotheses to overcome the disparity between experimental results and theoretical predictions. Our work illuminates the phonon-coupled dynamics in hBN quantum emitters at cryogenic temperature, with implications more generally for mesoscopic quantum emitter systems in 2D materials, and represents possible applications in solid-state quantum technologies., United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-18-1-0431)

The demonstration of stable quantum emitters in semiconductor transition metal dichalcogenides (TMDs) [1] and insulating hexagonal boron nitride (hBN) [2] has begun to impact the field of integrated quantum optics due to the promising properties of two-dimensional materials, such room-temperature operation, stretchability, heterogeneous device assembly and straightforward integration with photonic circuits. Nevertheless, major questions remain. Single photon emitters (SPEs) in hBN are associated with atom-like defects that confine electronic levels deep within the wide band gap. As recently reported, hBN can host several different families of emitters with emission energy that spans over a large spectral band [3]. On the other hand, quantum emission in TMDs is attributed to individual excitons bound to defects or impurities of the crystal structure. Recently, it has been shown that strain pockets can create potential traps able to confine single excitons producing SPEs with high spatial control [4,5]. Nevertheless, the relation between strain and emission energy is still not fully clear. The lack of a clear understanding of the nature of these defects [6] brings along the challenge of controlling the emission energy and of the deterministic creation of such emitters. These crucial aspects present central problems for developing identical single photon sources and for integration with photonic platforms. We developed a material processing based on ion irradiation and high temperature annealing of exfoliated hBN that sharply improves the single-photon purity with g(2)(0) = 0.08, and brightness with emission rate exceeding 10^7 counts/sec at room temperature. We also showed that the emitters persist material transfer process allowing to integrate them onto different platforms. To investigate the wide span of the emission energy we applied external compressive and tensile strain. Emitters in hBN show different tuning coefficients up to 6 meV per strain unit [7]. Furthermore, we performed photoluminescence excitation experiments at cryogenic temperature on different families of emitters. Our experimental results allow to identify the excited states of these atom-like systems and shine light on the characteristic level structures of the different families of emitters in hBN and can potentially help to reduce the spectral wandering with more efficient resonant excitation. Recently, new methods to develop quantum emitters in monolayer TMDs have been reported [4,5]. They rely on the strain induced by nanostructures in the substrate. This technique allows to create emitters with high spatial resolution. Unfortunately, it is still not possible to engineer the single photon energy with strain since the relation between strain and the emission energy of the localized excitons in TMDs is still not fully understood. To answer this question, we transferred CVD grown WSe2 on a pre-patterned Si3N4 substrate with pillars of 200 nm in diameter. We combined hyperspectral measurements, which allow to locate a single energy emission peak with a spatial resolution of around 10 nm, with strain measurements. Strain is measured optically by resolving in polarization the intensity of the second harmonic signal. This method allows to measure the photoelastic tensor of TMD monolayers and to retrieve the magnitude of biaxial strain with a spatial resolution of ~ 200 nm [8]. The combination of these techniques opens a new way to investigate the correspondence between the strain magnitude created by a nanopatterned substrate and the emission energy of the single photon emitted due to exciton localization in the nanostructures. [1] Perebeinos, V. Nat. Nano. 10, 485 (2015) [2] Tran, T. T., et al. Nat. Nano. 11, 37 (2016) [3] Tran, T. T. et al. ACS Nano 10, 7331 (2016) [4] Branny, A. et al. Nature Comm. 8, 15053 (2017) [5] Palacios-Berraquero, C. et al. Nature Comm. 8, 15093 (2017) [6] Tawfik, S.A. et al. Nanoscale 9, 13575 (2017) [7] Grosso, G., Moon, H, et al., Nature Comm. 8, 705 (2017) [8] L. Mennel, et al. Nature Comm. 9, 516 (2018)

Hexagonal boron nitride (hBN) is an emerging two dimensional material for quantum photonics owing to its large bandgap and hyperbolic properties. Here we report a broad range of multicolor room temperature single photon emissions across the visible and the near infrared spectral ranges from point defects in hBN multilayers. We show that the emitters can be categorized into two general groups, but most likely possess similar crystallographic structure. We further show two approaches for engineering of the emitters using either electron beam irradiation or annealing, and characterize their photophysical properties. The emitters exhibit narrow line widths of sub 10 nm at room temperature, and a short excited state lifetime with high brightness. Remarkably, the emitters are extremely robust and withstand aggressive annealing treatments in oxidizing and reducing environments. Our results constitute the first step towards deterministic engineering of single emitters in 2D materials and hold great promise for the use of defects in boron nitride as sources for quantum information processing and nanophotonics.

Strain engineering is a natural route to control the electronic and optical properties of two-dimensional (2D) materials. Recently, 2D semiconductors have also been demonstrated as an intriguing host of strain-induced quantum-confined emitters with unique valley properties inherited from the host semiconductor. Here, we study the continuous and reversible tuning of the light emitted by such localized emitters in a monolayer tungsten diselenide embedded in a van der Waals heterostructure. Biaxial strain is applied on the emitters via strain transfer from a lead magnesium niobate–lead titanate (PMN-PT) piezoelectric substrate. Efficient modulation of the emission energy of several localized emitters up to 10 meV has been demonstrated on application of a voltage on the piezoelectric substrate. Further, we also find that the emission axis rotates by ∼ 40 ∘ as the magnitude of the biaxial strain is varied on these emitters. These results elevate the prospect of using all electrically controlled devices where the property of the localized emitters in a 2D host can be engineered with elastic fields for an integrated opto-electronics and nano-photonics platform.

We demonstrate a wide-bandgap semiconductor photonics platform based on nanocrystalline aluminum nitride (AlN) on sapphire. This photonics platform guides light at low loss from the ultraviolet (UV) to the visible spectrum. We measure ring resonators with intrinsic quality factor (Q) exceeding 170,000 at 638 nm and Q >20,000 down to 369.5 nm, which shows a promising path for low-loss integrated photonics in UV and visible spectrum. This platform opens up new possibilities in integrated quantum optics with trapped ions or atom-like color centers in solids, as well as classical applications including nonlinear optics and on-chip UV-spectroscopy.

© 2016 Optical Society of America. We demonstrate that strain control of exfoliated hexagonal boron nitride allows spectral tuning of single photon emitters over 6 meV. We propose a material processing that sharply improves the single-photon purity with g(2)(0) = 0.077, and brightness with emission rate exceeding 107counts/sec at saturation.

© 2017 IEEE. Non-classical light sources, such as atoms and atom-like emitters play central roles in many areas of quantum information processing with applications as single photon generators, sources for nonlinearity and quantum memories. Solid-state quantum emitters have attracted growing interest due to the promise of combining remarkable optical properties with the convenience of scalability [1]. In recent years, there has been tremendous progress in developing quantum emitter systems based on crystallographic defects in wide-bandgap semiconductors. Nitrogen vacancies (NV) in diamond were among the first studied systems due to the well-defined optical transitions as well as electronic spin states that can be controlled optically. Quantum spins in diamond are among the most advanced systems in solid state for quantum based technologies such as quantum computing or quantum sensing [2]. Nevertheless, solid-state quantum emitters are not only limited to diamond and efforts to engineer single photon emitters (SPE) based on atom-like defects in scalable system have expanded beyond NV centers in diamond. Similar quantum emitters have been discovered in many other wide-bandgap host materials, including silicon carbide (SiC), III-nitride semiconductors such as gallium nitride (GaN) and aluminum nitride (AlN), and layered materials such as hexagonal boron nitride (hBN) [1]. Here, we will review our recent progress in developing and characterizing new quantum emitters in wide-bandgap semiconductors, and consider their applications as quantum light sources and sensors.

Efficient, on-demand, and robust single photon emitters (SPEs) are important to a wide varity of applications in quantum information processing [1]. Over the past decade, color centers in solid-state systems have emerged as excellent SPEs [2] and have also been shown to provide optical access to internal spin states at room and cyogenic temperatures. Color centers in diamond [3] and silicon carbide [4] are among the most intensively studied SPEs. Recently, other cost-efficient wide-bandgap materials have become attractive as potential host materials. Theoretical calculations show that aluminum nitride (AlN) with a bandgap of 6.015 eV can serve as a stable environment for well isolated SPEs with optically accessible spin states [5].

We report on the development of a highly flexible, thin shape sensor that can be integrated into minimally invasive surgery systems. Three optical fibers are arranged in a triangular shape and epoxy molded to produce a sensor diameter of less than 900 μm, ensuring high-bending operation up to 90°. Each fiber contains four fiber Bragg gratings (FBGs) operating at different wavelengths. With simultaneous detection of all the grating signals, the overall curvatures and torsions are interpolated and used for three-dimensional shape reconstruction. Three FBGs located at the same axial location also enables temperature compensation. Real-time shape monitoring with a sampling rate of 3.74 Hz is realized. The average tip position error was 1.50% of the total sensor length.

Shape tracking using a fiber Bragg grating sensor is a promising tool due to its thin, flexible, and weightless nature. Conventional investigations attached optical fibers with a metal rod which limited the curvature due to its stiffness and increased distance between the center of the fiber and that of the sensor. We fabricated ultrathin flexible shape sensor with 110 mm length and 560 µm diameter. Its low Young's modulus and small diameter makes it suitable for application in minimally invasive surgical robot such as active cannula. The sensor causes only miniscule resistance when the cannula rotates or moves, and allows extra spaces for other surgical tools thanks to its small diameter. After the calibration, the sensor was integrated to the active cannula and overall position of the sensor was tracked. It showed an average error of 3.17 ± 1.21 % of the lengths of the measured nodes from the fixed starting point. The error was comparable to the outer diameter of the cannula, 2.8mm.

In this study, we demonstrate that drug treatments change cardiomyocyte contractile force in vitro. Contractile force was determined by bending deflection of the cantilever end. We quantified the effect of Digoxin, Isoproterenol, and BayK8644, drugs that increase contractile force, on cardiomyocyte contractile forces when grown on the grooved cantilever. We also investigated the effect of Verapamil, which decreases contractile force. We applied Digoxin, Isoproterenol, and BayK8644 on day 8, and Verapamil on day 5. Digoxin, Isoproterenol, and BayK8644 increased cardiomyocyte contractile forces by 19.31%, 9.75%, and 23.81%, respectively. Verapamil decreased the contractile force by 48.06%. In summary, we monitored bending movement with cantilever sensors and concluded that cardiomyocyte contractile force changes in response to various drug treatments.

We described a calibration method for 3-dimensional tip position tracking sensor. This sensor consists of three optical fibers containing multiple fiber Bragg gratings. Each fiber Bragg grating measures a strain at their position as the sensor bends, then curvature and bending direction at the position is calculated. Finally, the position of the sensor tip was calculated from the information. Because the location of each fiber Bragg grating is very important to calculate tip position exactly, compensation to minimize the error caused by fabrication process is inevitable. The sensor was deflected in eight directions, and the position of the sensor tip was measured exactly by the camera with telecentric lens. Next, the deflected distance and tilted angle of the tip position from the original position were calculated by shape sensor. The two data were compared and compensated using simple linear regression analysis. The final error of calibrated single bending system was less than 1%.

Conventional cardiac physiology experiments investigate in vitro beat frequency using cells isolated from adult or neonatal rat hearts. In this study, we show that various cantilever shapes and drug treatments alter cardiomyocyte contraction force in vitro. Four types of cantilevers were used to compare the contractile forces: flat, peg patterned, grooved, and peg and grooved. Contraction force was represented as bending deflection of the cantilever end. The deflections of the flat, peg patterned, grooved, and peg and grooved cantilevers were 24.2 nN, 41.6 nN, 121 nN, and 134.2 nN, respectively. We quantified the effect of drug treatments on cardiomyocyte contractile forces on the grooved cantilever using Digoxin, Isoproterenol, and BayK8644, all of which increase contractile force, and Verapamil, which decreases contractile force. The cardiomyocyte contractile force without drugs decreased 8 days after culture initiation. Thus, we applied Digoxin, Isoproterenol, and BayK8644 at day 8, and Verapamil at day 5. Digoxin, Isoproterenol, and BayK8644 increased the cardiomyocyte contractile forces by 19.31%, 9.75%, and 23.81%, respectively. Verapamil decreased the contraction force by 48.06%. In summary, contraction force changes in response to adhesion surface topology and various types of drug treatments. We observed these changes by monitoring cell alignment, adhesion, morphology, and bending displacement with cantilever sensors.

While retinal implants based on microphotodiode array (MPDA) could achieve great number of channels without an external camera, the absence of proper packaging technology of MPDA has limited their use in chronic implantation. Liquid crystal polymer (LCP) has gained increasing attention as a biomaterial for implantable devices due to its low water absorption rate and low permeability. In this letter, feasibility of LCP film as an encapsulation material of photodiode-based retinal prosthesis was explored. Optical property of LCP was measured to find the film thickness that can guarantee the light transmittance greater than 20%, which was achieved by developing the dry etching process of commercial LCP films to be less than 10 $\mu \text{m}$ . The minimum distinguishable line pitch of the thin LCP encapsulation evaluated by a custom setup with projected grating patterns on CMOS image sensor was 90 $\mu \text{m}$ , which could be equivalent to ideally 1200 channels in macular area of 10 mm2.

A gold-deposited optical fiber sensor system based on surface plasmon resonance (SPR) was developed for optical measurement of neuronal activity. To enhance the sensitivity of localized SPR and to make a precise and safe contact with the cellular membrane, we designed a tapered optical probe of 1μm diameter at the tip of the fiber. By wet etching and gold evaporating processes, pencil-shaped optical probes were successfully fabricated. The SPR system with the sharp optical probe was integrated with a conventional patch clamping system to realize a simultaneous optical and electrical recording on a single neuron. Although the shape of optical signal is not clear due to tiny change of intrinsic optical properties on the neuron, optical and electrical signals were simultaneously changed by capsaicin stimulation. Furthermore, our designed fiber probe can be applicable to localized optical stimulation as well as in vivo optical neuroprosthetic devices.

In this paper, a magnetic bead based immobilization method and pH detection method is applied to the LAPS (light addressable potentiometric sensor) system to detect a pathogenic micro-organism population. Magnetic beads are very small, superparamagnetic particles (0.8 approximately 5.0 microm in diameter) that are able to sustain a magnetic domain under excitation and do not exhibit residual magnetization when the external field is removed. By using magnetic beads as an immobilization method, other bulky and complex method can be alternated. To verify the method, an urease labeled anti-salmonella typhimurium antibody is used to detect a pathogenic micro-organism( S. typhimurium ) population by a bias voltage maximum slope detection.

A parallel guidance endoscopic optical coherence tomography (OCT) system is proposed for minimally invasive internal inspection of inner organs or complex structures for diagnosis. The system is maneuvered to access the target using an active cannulas’ steerable structures. The integration of a specially designed linkage device with the developed system allows the OCT endoscope to scan with enhanced signal-collective performance, while maintaining its tip at a constant distance from the target, as well as expanding the scanning range. The proposed system is integrated with flexible active cannulas, and this prototype is used for testing. The test results show that the device reliably performs for biological samples. Thus, it could be implemented for various types of noninvasive diagnoses in situations involving small entrances or crooked passage to a target.

We propose an intrinsic optical method for in vivo neural recording using optic fiber-based surface plasmon resonance (SPR) phenomena. The fiber-based SPR method is electrical artifact free, labeling free, and feasible for a portable system compared with conventional in vivo neural recording systems. We simultaneously detected SPR signals and electrical neural activity from the rat somatosensory cortex evoked by electrical stimulation on the forepaw. Pharmacological analysis using a voltage-gated sodium channel blocker confirmed the neural origins of the optical signals. This fiber-based SPR system promises the enhanced ability to record in vivo neural activity for the investigation of neurons and their networks.

We demonstrate a wide-bandgap semiconductor photonics platform based on aluminum nitride on sapphire. We measure ring resonators with quality factor >140, 000 at 638 nm and >20, 000 down to 369 nm, which shows a promising path for low-loss integrated photonics in the ultraviolet and visible spectrum.