Soliton microcomb based spectral domain optical coherence tomography

Spectral domain optical coherence tomography (SD-OCT) is a widely used and minimally invaive technique for bio-medical imaging [1]. SD-OCT typically relies on the use of superluminescent diodes (SLD), which provide a low-noise and broadband optical spectrum. Recent advances in photonic chipscale frequency combs [2, 3] based on soliton formation in photonic integrated microresonators provide an chipscale alternative illumination scheme for SD-OCT. Yet to date, the use of such soliton microcombs in OCT has not yet been analyzed. Here we explore the use of soliton microcombs in spectral domain OCT and show that, by using photonic chipscale Si3N4 resonators in conjunction with 1300 nm pump lasers, spectral bandwidths exceeding those of commercial SLDs are possible. We demonstrate that the soliton states in microresonators exhibit a noise floor that is ca. 3 dB lower than for the SLD at identical power, but can exhibit significantly lower noise performance for powers at the milliWatt level. We perform SD-OCT imaging on an ex vivo fixed mouse brain tissue using the soliton microcomb, alongside an SLD for comparison, and demonstrate the principle viability of soliton based SD-OCT. Importantly, we demonstrate that classical amplitude noise of all soliton comb teeth are correlated, i.e. common mode, in contrast to SLD or incoherent microcomb states [4], which should, in theory, improve the image quality. Moreover, we demonstrate the potential for circular ranging, i.e. optical sub-sampling [5, 6], due to the high coherence and temporal periodicity of the soliton state. Taken together, our work indicates the promising properties of soliton microcombs for SD-OCT

Nanophotonic soliton-based microwave synthesizers

Microwave photonic technologies, which upshift the carrier into the optical domain to facilitate the generation and processing of ultrawide-band electronic signals at vastly reduced fractional bandwidths, have the potential to achieve superior performance compared to conventional electronics for targeted functions. For microwave photonic applications such as filters, coherent radars, subnoise detection, optical communications and low-noise microwave generation, frequency combs are key building blocks. By virtue of soliton microcombs, frequency combs can now be built using CMOS compatible photonic integrated circuits, operated with low power and noise, and have already been employed in system-level demonstrations. Yet, currently developed photonic integrated microcombs all operate with repetition rates significantly beyond those that conventional electronics can detect and process, compounding their use in microwave photonics. Here we demonstrate integrated soliton microcombs operating in two widely employed microwave bands, X- and K-band. These devices can produce more than 300 comb lines within the 3-dB-bandwidth, and generate microwave signals featuring phase noise levels below 105 dBc/Hz (140 dBc/Hz) at 10 kHz (1 MHz) offset frequency, comparable to modern electronic microwave synthesizers. In addition, the soliton pulse stream can be injection-locked to a microwave signal, enabling actuator-free repetition rate stabilization, tuning and microwave spectral purification, at power levels compatible with silicon-based lasers (<150 mW). Our results establish photonic integrated soliton microcombs as viable integrated low-noise microwave synthesizers. Further, the low repetition rates are critical for future dense WDM channel generation schemes, and can significantly reduce the system complexity of photonic integrated frequency synthesizers and atomic clocks

Dual chirped micro-comb based parallel ranging at megapixel-line rates

Laser based ranging (LiDAR) - already ubiquitously used in industrial monitoring, atmospheric dynamics, or geodesy - is key sensor technology. Coherent laser ranging, in contrast to time-of-flight approaches, is immune to ambient light, operates continuous wave allowing higher average powers, and yields simultaneous velocity and distance information. State-of-the-art coherent single laser-detector architectures reach hundreds of kilopixel per second rates. While emerging applications such as autonomous driving, robotics, and augmented reality mandate megapixel per second point sampling to support real-time video-rate imaging. Yet, such rates of coherent LiDAR have not been demonstrated. Here we report a swept dual-soliton microcomb technique enabling coherent ranging and velocimetry at megapixel per second line scan measurement rates with up to 64 spectrally dispersed optical channels. It is based on recent advances in photonic chip-based microcombs that offer a solution to reduce complexity both on the transmitter and receiver sides. Multi-heterodyning two synchronously frequency-modulated microcombs yields distance and velocity information of all individual ranging channels on a single receiver alleviating the need for individual separation, detection, and digitization. The reported LiDAR implementation is hardware-efficient, compatible with photonic integration, and demonstrates the significant advantages of acquisition speed afforded by the convergence of optical telecommunication and metrology technologies. We anticipate our research will motivate further investigation of frequency swept microresonator dual-comb approach in the neighboring fields of linear and nonlinear spectroscopy, optical coherence tomography

Voltage-tunable OPO with an alternating dispersion dimer integrated on chip

Optical parametric oscillators enable the conversion of pump light to new frequency bands using nonlinear optical processes. Recent advances in integrated nonlinear photonics have led to create compact, chip-scale sources via Kerr nonlinearity-induced parametric oscillations. While these sources have provided broadband wavelength tuning, the ability to tune the emission wavelength via dynamically altering the dispersion, has not been attained so far. Here we present a voltage-tunable, on-chip integrated optical parametric oscillator based on alternating dispersiondimer, allowing to tune the emission over nearly 20 THz near 1550 nm. Unlike previous approaches, our device eliminates the need for a widely tunable pump laser source and provides efficient pump filtering at the drop port of the auxiliary ring. Integration of this scheme on a chip opens up the possibility of compact and low-cost voltage-tunable parametric oscillators with diverse application possibilities

Massively parallel coherent laser ranging using soliton microcombs

Coherent ranging, also known as frequency-modulated continuous-wave (FMCW) laser based ranging (LIDAR) is currently developed for long range 3D distance and velocimetry in autonomous driving. Its principle is based on mapping distance to frequency, and to simultaneously measure the Doppler shift of reflected light using frequency chirped signals, similar to Sonar or Radar. Yet, despite these advantages, coherent ranging exhibits lower acquisition speed and requires precisely chirped and highly-coherent laser sources, hindering their widespread use and impeding Parallelization, compared to modern time-of-flight (TOF) ranging that use arrays of individual lasers. Here we demonstrate a novel massively parallel coherent LIDAR scheme using a photonic chip-based microcomb. By fast chirping the pump laser in the soliton existence range of a microcomb with amplitudes up to several GHz and sweep rate up to 10 MHz, the soliton pulse stream acquires a rapid change in the underlying carrier waveform, while retaining its pulse-to-pulse repetition rate. As a result, the chirp from a single narrow-linewidth pump laser is simultaneously transferred to all spectral comb teeth of the soliton at once, and allows for true parallelism in FMCW LIDAR. We demonstrate this approach by generating 30 distinct channels, demonstrating both parallel distance and velocity measurements at an equivalent rate of 3 Mpixel/s, with potential to improve sampling rates beyond 150 Mpixel/s and increase the image refresh rate of FMCW LIDAR up to two orders of magnitude without deterioration of eye safety. The present approach, when combined with photonic phase arrays based on nanophotonic gratings, provides a technological basis for compact, massively parallel and ultra-high frame rate coherent LIDAR systems.Comment: 18 pages, 12 Figure

Lithium tantalate electro-optical photonic integrated circuits for high volume manufacturing

Photonic integrated circuits based on Lithium Niobate have demonstrated the vast capabilities afforded by material with a high Pockels coefficient, allowing linear and high-speed modulators operating at CMOS voltage levels for applications ranging from data-center communications and photonic accelerators for AI. However despite major progress, the industrial adoption of this technology is compounded by the high cost per wafer. Here we overcome this challenge and demonstrate a photonic platform that satisfies the dichotomy of allowing scalable manufacturing at low cost, while at the same time exhibiting equal, and superior properties to those of Lithium Niobate. We demonstrate that it is possible to manufacture low loss photonic integrated circuits using Lithium Tantalate, a material that is already commercially adopted for acoustic filters in 5G and 6G. We show that LiTaO3 posses equally attractive optical properties and can be etched with high precision and negligible residues using DUV lithography, diamond like carbon (DLC) as a hard mask and alkaline wet etching. Using this approach we demonstrate microresonators with an intrinsic cavity linewidth of 26.8 MHz, corresponding to a linear loss of 5.6 dB/m and demonstrate a Mach Zehnder modulator with Vpi L = 4.2 V cm half-wave voltage length product. In comparison to Lithium Niobate, the photonic integrated circuits based on LiTaO3 exhibit a much lower birefringence, allowing high-density circuits and broadband operation over all telecommunication bands (O to L band), exhibit higher photorefractive damage threshold, and lower microwave loss tangent. Moreover, we show that the platform supports generation of soliton microcombs in X-Cut LiTaO3 racetrack microresonator with electronically detectable repetition rate, i.e. 30.1 GHz.Comment: 8 pages, 4 figure

Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer

BACKGROUND: Bacillus Calmette Guérin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy. METHODS: Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-γ ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-α and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry. RESULTS: Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-γ release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1. Immunohistochemical analysis and splenocyte restimulation assay revealed that local and systemic immune responses were triggered by intravesical PstS1-immunotherapy. CONCLUSION: Our results demonstrate profound in vitro activation of human immune cells by recombinant PstS1. In addition, intravesical PstS1 immunotherapy induced strong local and systemic immune responses together with substantial anti-tumor activity in a preclinical mouse model. Thus, we have identified recombinant PstS1 antigen as a potent immunotherapeutic drug for cancer therapy

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS- and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer

Roadmap on multimode light shaping

Our ability to generate new distributions of light has been remarkably enhanced in recent years. At the most fundamental level, these light patterns are obtained by ingeniously combining different electromagnetic modes. Interestingly, the modal superposition occurs in the spatial, temporal as well as spatio-temporal domain. This generalized concept of structured light is being applied across the entire spectrum of optics: generating classical and quantum states of light, harnessing linear and nonlinear light-matter interactions, and advancing applications in microscopy, spectroscopy, holography, communication, and synchronization. This Roadmap highlights the common roots of these different techniques and thus establishes links between research areas that complement each other seamlessly. We provide an overview of all these areas, their backgrounds, current research, and future developments. We highlight the power of multimodal light manipulation and want to inspire new eclectic approaches in this vibrant research community.acceptedVersionPeer reviewe