Ultrafast tunable lasers using lithium niobate integrated photonics.

Early works1 and recent advances in thin-film lithium niobate (LiNbO3) on insulator have enabled low-loss photonic integrated circuits2,3, modulators with improved half-wave voltage4,5, electro-optic frequency combs6 and on-chip electro-optic devices, with applications ranging from microwave photonics to microwave-to-optical quantum interfaces7. Although recent advances have demonstrated tunable integrated lasers based on LiNbO3 (refs. 8,9), the full potential of this platform to demonstrate frequency-agile, narrow-linewidth integrated lasers has not been achieved. Here we report such a laser with a fast tuning rate based on a hybrid silicon nitride (Si3N4)-LiNbO3 photonic platform and demonstrate its use for coherent laser ranging. Our platform is based on heterogeneous integration of ultralow-loss Si3N4 photonic integrated circuits with thin-film LiNbO3 through direct bonding at the wafer level, in contrast to previously demonstrated chiplet-level integration10, featuring low propagation loss of 8.5 decibels per metre, enabling narrow-linewidth lasing (intrinsic linewidth of 3 kilohertz) by self-injection locking to a laser diode. The hybrid mode of the resonator allows electro-optic laser frequency tuning at a speed of 12 × 1015 hertz per second with high linearity and low hysteresis while retaining the narrow linewidth. Using a hybrid integrated laser, we perform a proof-of-concept coherent optical ranging (FMCW LiDAR) experiment. Endowing Si3N4 photonic integrated circuits with LiNbO3 creates a platform that combines the individual advantages of thin-film LiNbO3 with those of Si3N4, which show precise lithographic control, mature manufacturing and ultralow loss11,12.

A photonic integrated continuous-travelling-wave parametric amplifier.

The ability to amplify optical signals is of pivotal importance across science and technology typically using rare-earth-doped fibres or gain media based on III-V semiconductors. A different physical process to amplify optical signals is to use the Kerr nonlinearity of optical fibres through parametric interactions1,2. Pioneering work demonstrated continuous-wave net-gain travelling-wave parametric amplification in fibres3, enabling, for example, phase-sensitive (that is, noiseless) amplification4, link span increase5, signal regeneration and nonlinear phase noise mitigation6. Despite great progress7-15, all photonic integrated circuit-based demonstrations of net parametric gain have necessitated pulsed lasers, limiting their practical use. Until now, only bulk micromachined periodically poled lithium niobate (PPLN) waveguide chips have achieved continuous-wave gain16,17, yet their integration with silicon-wafer-based photonic circuits has not been shown. Here we demonstrate a photonic-integrated-circuit-based travelling-wave optical parametric amplifier with net signal gain in the continuous-wave regime. Using ultralow-loss, dispersion-engineered, metre-long, Si3N4 photonic integrated circuits18 on a silicon chip of dimensions 5 × 5 mm2, we achieve a continuous parametric gain of 12 dB that exceeds both the on-chip optical propagation loss and fibre-chip-fibre coupling losses in the telecommunication C band. Our work demonstrates the potential of photonic-integrated-circuit-based parametric amplifiers that have lithographically controlled gain spectrum, compact footprint, resilience to optical feedback and quantum-limited performance, and can operate in the wavelength ranges from visible to mid-infrared and outside conventional rare-earth amplification bands.

Integrated photonics enables continuous-beam electron phase modulation.

Integrated photonics facilitates extensive control over fundamental light-matter interactions in manifold quantum systems including atoms1, trapped ions2,3, quantum dots4 and defect centres5. Ultrafast electron microscopy has recently made free-electron beams the subject of laser-based quantum manipulation and characterization6-11, enabling the observation of free-electron quantum walks12-14, attosecond electron pulses10,15-17 and holographic electromagnetic imaging18. Chip-based photonics19,20 promises unique applications in nanoscale quantum control and sensing but remains to be realized in electron microscopy. Here we merge integrated photonics with electron microscopy, demonstrating coherent phase modulation of a continuous electron beam using a silicon nitride microresonator. The high-finesse (Q0 ≈ 106) cavity enhancement and a waveguide designed for phase matching lead to efficient electron-light scattering at extremely low, continuous-wave optical powers. Specifically, we fully deplete the initial electron state at a cavity-coupled power of only 5.35 microwatts and generate >500 electron energy sidebands for several milliwatts. Moreover, we probe unidirectional intracavity fields with microelectronvolt resolution in electron-energy-gain spectroscopy21. The fibre-coupled photonic structures feature single-optical-mode electron-light interaction with full control over the input and output light. This approach establishes a versatile and highly efficient framework for enhanced electron beam control in the context of laser phase plates22, beam modulators and continuous-wave attosecond pulse trains23, resonantly enhanced spectroscopy24-26 and dielectric laser acceleration19,20,27. Our work introduces a universal platform for exploring free-electron quantum optics28-31, with potential future developments in strong coupling, local quantum probing and electron-photon entanglement.

Massively parallel coherent laser ranging using a soliton microcomb.

Coherent ranging, also known as frequency-modulated continuous-wave (FMCW) laser-based light detection and ranging (lidar)1 is used for long-range three-dimensional distance and velocimetry in autonomous driving2,3. FMCW lidar maps distance to frequency4,5 using frequency-chirped waveforms and simultaneously measures the Doppler shift of the reflected laser light, similar to sonar or radar6,7 and coherent detection prevents interference from sunlight and other lidar systems. However, coherent ranging has a lower acquisition speed and requires precisely chirped8 and highly coherent5 laser sources, hindering widespread use of the lidar system and impeding parallelization, compared to modern time-of-flight ranging systems that use arrays of individual lasers. Here we demonstrate a massively parallel coherent lidar scheme using an ultra-low-loss photonic chip-based soliton microcomb9. By fast chirping of the pump laser in the soliton existence range10 of a microcomb with amplitudes of up to several gigahertz and a sweep rate of up to ten megahertz, a rapid frequency change occurs in the underlying carrier waveform of the soliton pulse stream, but the pulse-to-pulse repetition rate of the soliton pulse stream is retained. As a result, the chirp from a single narrow-linewidth pump laser is transferred to all spectral comb teeth of the soliton at once, thus enabling parallelism in the FMCW lidar. Using this approach we generate 30 distinct channels, demonstrating both parallel distance and velocity measurements at an equivalent rate of three megapixels per second, with the potential to improve sampling rates beyond 150 megapixels per second and to increase the image refresh rate of the FMCW lidar by up to two orders of magnitude without deterioration of eye safety. This approach, when combined with photonic phase arrays11 based on nanophotonic gratings12, provides a technological basis for compact, massively parallel and ultrahigh-frame-rate coherent lidar systems.

Monolithic piezoelectric control of soliton microcombs.

High-speed actuation of laser frequency1 is critical in applications using lasers and frequency combs2,3, and is a prerequisite for phase locking, frequency stabilization and stability transfer among optical carriers. For example, high-bandwidth feedback control of frequency combs is used in optical-frequency synthesis4, frequency division5 and optical clocks6. Soliton microcombs7,8 have emerged as chip-scale frequency comb sources, and have been used in system-level demonstrations9,10. Yet integrated microcombs using thermal heaters have limited actuation bandwidths11,12 of up to 10 kilohertz. Consequently, megahertz-bandwidth actuation and locking of microcombs have only been achieved with off-chip bulk component modulators. Here we demonstrate high-speed soliton microcomb actuation using integrated piezoelectric components13. By monolithically integrating AlN actuators14 on ultralow-loss Si3N4 photonic circuits15, we demonstrate voltage-controlled soliton initiation, tuning and stabilization with megahertz bandwidth. The AlN actuators use 300 nanowatts of power and feature bidirectional tuning, high linearity and low hysteresis. They exhibit a flat actuation response up to 1 megahertz-substantially exceeding bulk piezo tuning bandwidth-that is extendable to higher frequencies by overcoming coupling to acoustic contour modes of the chip. Via synchronous tuning of the laser and the microresonator, we exploit this ability to frequency-shift the optical comb spectrum (that is, to change the comb's carrier-envelope offset frequency) and make excursions beyond the soliton existence range. This enables a massively parallel frequency-modulated engine16,17 for lidar (light detection and ranging), with increased frequency excursion, lower power and elimination of channel distortions resulting from the soliton Raman self-frequency shift. Moreover, by modulating at a rate matching the frequency of high-overtone bulk acoustic resonances18, resonant build-up of bulk acoustic energy allows a 14-fold reduction of the required driving voltage, making it compatible with CMOS (complementary metal-oxide-semiconductor) electronics. Our approach endows soliton microcombs with integrated, ultralow-power and fast actuation, expanding the repertoire of technological applications of microcombs.

Integrated turnkey soliton microcombs.

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2-9. Such soliton microcombs10 have been applied to spectroscopy11-13, the search for exoplanets14,15, optical frequency synthesis16, time keeping17 and other areas10. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs18,19. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si3N4 resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.

In Situ Polymerization-Mediated Antigen Presentation.

Activating antigen-presenting cells is essential to generate adaptive immunity, while the efficacy of conventional activation strategies remains unsatisfactory due to suboptimal antigen-specific priming. Here, in situ polymerization-mediated antigen presentation (IPAP) is described, in which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto the surface of dendritic cells in vivo through co-deposition with dopamine. The resulting chemically bound nanovaccines can promote antigen presentation by elevating macropinocytosis-based cell uptake and reducing lysosome-related antigen degradation. IPAP is able to prolong the duration of antigen reservation in the injection site and enhance subsequent accumulation in the draining lymph nodes, thereby eliciting robust antigen-specific cellular and humoral immune responses. IPAP is also applicable for different antigens and capable of circumventing the disadvantages of complicated preparation and purification. By implementation with ovalbumin, IPAP induces a significant protective immunity against ovalbumin-overexpressing tumor cell challenge in a prophylactic murine model. The use of the SARS-CoV-2 Spike protein S1 subunit also remarkably increases the production of S1-specific immunoglobulin G in mice. IPAP offers a unique strategy for stimulating antigen-presenting cells to boost antigen-specific adaptive responses and proposes a facile yet versatile method for immunization against various diseases.

Dual-Antigen-Displaying Nanovaccines Elicit Synergistic Immunoactivation for Treating Cancer and Preventing Infectious Complications.

As one of the most common complications, infection causes the majority of mortality in cancer patients. However, therapeutic strategies that can simultaneously suppress tumors and protect patients from infection have been rarely reported. Here, the use of dual-antigen-displaying nanovaccines (DADNs) is described to elicit synergistic immunoactivation for treating cancer and preventing infectious complications. DADNs are prepared by wrapping immunoadjuvant-loaded nanoparticles with a hybrid coating, which is fused from cell membranes that are separately genetically engineered to express tumor and infectious pathogenic antigens. Due to the presence of a dual-antigen combination, DADNs are able to promote the maturation of dendritic cells and more importantly to trigger cross-presentation of both combined antigens. During in vivo investigations, we find that DADNs can reverse immunosuppression by stimulating tumor-associated antigen-specific T-cell responses, resulting in significantly delayed tumor growth in mice. These nanovaccines also elicit effective protective immunity against tumor challenges and induce robust production of pathogenic antigen-specific immunoglobulin G antibody in a prophylactic study. This work offers a unique approach to develop dual-mode vaccines, which are promising for synchronously treating cancer and preventing infection.

Towards efficient broadband parametric conversion in ultra-long Si3N4 waveguides.

Broadband continuous-wave parametric gain and efficient wavelength conversion is an important functionality to bring on-chip. Recently, meter-long silicon nitride waveguides have been utilized to obtain continuous-traveling-wave parametric gain, establishing the great potential of photonic-integrated-circuit-based parametric amplifiers. However, the effect of spiral structure on the performance and achievable bandwidth of such devices have not yet been studied. In this work, we investigate the efficiency-bandwidth performance in up to 2 meter-long waveguides engineered for broadband operation. Moreover, we analyze the conversion efficiency fluctuations that have been observed in meter-long Si3N4 waveguides and study the use of temperature control to limit the fluctuations.

Architecture for integrated RF photonic downconversion of electronic signals.

Electronic analog to digital converters (ADCs) are running up against the well-known bit depth versus bandwidth trade off. Towards this end, radio frequency (RF) photonic-enhanced ADCs have been the subject of interest for some time. Optical frequency comb technology has been used as a workhorse underlying many of these architectures. Unfortunately, such designs must generally grapple with size, weight, and power (SWaP) concerns, as well as frequency ambiguity issues which threaten to obscure critical spectral information of detected RF signals. In this work, we address these concerns via an RF photonic downconverter with potential for easy integration and field deployment by leveraging a novel, to the best of our knowledge, hybrid microcomb/electro-optic comb design.

Crown Ether-Based Ion Transporters in Bilayer Membranes.

Bilayer membranes that enhance the stability of the cell are essential for cell survival, separating and protecting the interior of the cell from its external environment. Membrane-based channel proteins are crucial for sustaining cellular activities. However, dysfunction of these proteins would induce serial channelopathies, which could be substituted by artificial ion channel analogs. Crown ethers (CEs) are widely studied in the area of artificial ion channels owing to their intrinsic host-guest interaction with different kinds of organic and inorganic ions. Other advantages such as lower price, chemical stability, and easier modification also make CE a research hotspot in the field of synthetic transmembrane nanopores. And numerous CEs-based membrane-active synthetic ion channels were designed and fabricated in the past decades. Herein, the recent progress of CEs-based synthetic ion transporters has been comprehensively summarized in this review, including their design principles, functional mechanisms, controllable properties, and biomedical applications. Furthermore, this review has been concluded by discussing the future opportunities and challenges facing this research field. It is anticipated that this review could offer some inspiration for the future fabrication of novel CEs-derived ion transporters with more advanced structures, properties, and practical applications.

Rehmannia Glutinosa Polysaccharide Regulates Bone Marrow Microenvironment via HIF-1α/NF-κB Signaling Pathway in Aplastic Anemia Mice.

Aplastic anemia (AA), a rare disorder, is associated with bone marrow microenvironment (BMM). Presently, AA treatment is of great difficulty. This study aimed to explore the mechanism of action of Rehmannia glutinosa polysaccharide (RGP) in AA. Busulfan was used to induce AA in BALB/c mice; blood cell count and Ray's Giemsa staining were used to assess the severity of hematopoietic failure; HE was performed to assess the pathological state of the marrow cavity; ELISA was performed to assess IL-4, IL-10, IL-6, IL-12, IL-1ß, TNF-α, MCP-1, VEGF, and EPO; and WB was performed to evaluate the effects of RGP on the HIF-1α/NF-κB signaling. Significant downregulation of hemocyte levels in the blood and nucleated cells in the bone marrow was reversed by RGP and Cyclosporine A (CA). Compared with the AA group, dilating blood sinusoids, inflammation, hematopoiesis, decreased bone marrow cells and megakaryocytes were alleviated by RGP and CA, and the HIF-1α/NF-κB signaling was inhibited too. Notably, RGP was more effective when used in combination with CA. In this study, we established a relationship between BMM and the HIF-1α/NF-κB signaling pathway and found that RGP regulates BMM by suppressing the activation of the HIF-1α/NF-κB signaling. Thus, RGP exerts a pharmacological effect on AA.

Current Advances of Atomically Dispersed Metal-Centered Nanozymes for Tumor Diagnosis and Therapy.

Nanozymes, which combine enzyme-like catalytic activity and the biological properties of nanomaterials, have been widely used in biomedical fields. Single-atom nanozymes (SANs) with atomically dispersed metal centers exhibit excellent biological catalytic activity due to the maximization of atomic utilization efficiency, unique metal coordination structures, and metal-support interaction, and their structure-activity relationship can also be clearly investigated. Therefore, they have become an emerging alternative to natural enzymes. This review summarizes the examples of nanocatalytic therapy based on SANs in tumor diagnosis and treatment in recent years, providing an overview of material classification, activity modulation, and therapeutic means. Next, we will delve into the therapeutic mechanism of SNAs in the tumor microenvironment and the advantages of synergistic multiple therapeutic modalities (e.g., chemodynamic therapy, sonodynamic therapy, photothermal therapy, chemotherapy, photodynamic therapy, sonothermal therapy, and gas therapy). Finally, this review proposes the main challenges and prospects for the future development of SANs in cancer diagnosis and therapy.

Single-Molecule Observation of Selenoenzyme Intermediates in a Semisynthetic Seleno-α-Hemolysin Nanoreactor.

The development of monitoring methods to capture short-lived intermediates is crucial for kinetic mechanism validation of enzymatic reaction steps. In this work, a semisynthetic selenoenzyme nanoreactor was constructed by introducing the unnatural amino acid (Sec) into the lumen of the α-hemolysin (αHL) nanopore. This nanoreactor not only created a highly confined space to trap the enzyme-substrate complex for a highly efficient antioxidant activity but also provided a single channel to characterize a series of selenoenzyme intermediates in the whole catalytic cycle through electrochemical analysis. In particular, the unstable intermediate of SeOH can be clearly detected by the characteristic blocking current. The duration time corresponding to the lifetime of each intermediate that stayed within the nanopore was also determined. This label-free approach showed a high detection sensitivity and temporal-spatial resolution to scrutinize a continuous enzymatic process, which would facilitate uncovering the mysteries of selenoenzyme catalysis at the single-molecule level.

Polarization selective ultra-broadband wavelength conversion in silicon nitride waveguides.

We experimentally demonstrate broadband degenerate continuous-wave four-wave mixing in long silicon nitride (Si3N4) waveguides for operation both in the telecommunication L-band and the thulium band near 2 µm by leveraging polarization dependence of the waveguide dispersion. Broadband conversion is typically demonstrated in short milimeter long waveguides as the bandwidth is linked to the interaction length. This makes it challenging to simultaneously push bandwidth and efficiency, imposing stringent constraints on dispersion engineering. In this work, we show conversion bandwidths larger than 150 nm in the L-band when pumping in the transverse magnetic (TM) mode and larger than 120 nm at 2 µm when using transverse electric excitation, despite the use of 0.5 m long waveguides. In addition, we also show how extreme polarization selectivity can be leveraged in a single waveguide to enable switchable distant phase-matching based on higher-order dispersion. Relying on this approach, we demonstrate the selective conversion of light from the telecom band to the O-band for TM polarization or to the mid-infrared light up to 2.5 µm in TE. Our experiments are in excellent agreement with simulations, showing the high potential of the platform for broadband and distant conversion beyond the telecom band.

Unimolecular Helix-Based Transmembrane Nanochannel with a Smallest Luminal Cavity of 1 Å Expressing High Proton Selectivity and Transport Activity.

Natural protein channels have evolved with exquisite structures to transport ions selectively and rapidly. Learning from nature to construct biomimetic artificial channels is always challenging. Herein we present a unimolecular transmembrane proton channel by quinoline-derived helix, which exhibited highly selective and ultrafast proton transport behaviors. This helix-based channel possesses a small luminal cavity of 1 Å in diameter, which could efficiently reject the permeation of cations, anions or water molecules but only permits the translocation of protons owing to the size effect. The proton flow rate exceeded 107 H+ s-1 channel-1 and reached the same magnitude with gramicidin A. Mechanism investigation revealed that the directionally arrayed NH-chain inside the synthetic channel played a pivotal role during the proton flux. This work not only presented a helix-based channel with the smallest observable nanopore, but also unveiled an unexplored pathway for realizing efficient transport of protons via the consecutive NH-chain.

Low-Loss Integrated Nanophotonic Circuits with Layered Semiconductor Materials.

Monolayer transition-metal dichalcogenides with direct bandgaps are emerging candidates for optoelectronic devices, such as photodetectors, light-emitting diodes, and electro-optic modulators. Here we report a low-loss integrated platform incorporating molybdenum ditelluride monolayers with silicon nitride photonic microresonators. We achieve microresonator quality factors >3 × 106 in the telecommunication O- to E-bands. This paves the way for low-loss, hybrid photonic integrated circuits with layered semiconductors, not requiring heterogeneous wafer bonding.

Recent Development of Polydopamine Anti-Bacterial Nanomaterials.

Polydopamine (PDA), as a mussel-inspired material, exhibits numerous favorable performance characteristics, such as a simple preparation process, prominent photothermal transfer efficiency, excellent biocompatibility, outstanding drug binding ability, and strong adhesive properties, showing great potential in the biomedical field. The rapid development of this field in the past few years has engendered substantial progress in PDA antibacterial materials. This review presents recent advances in PDA-based antimicrobial materials, including the preparation methods and antibacterial mechanisms of free-standing PDA materials and PDA-based composite materials. Furthermore, the urgent challenges and future research opportunities for PDA antibacterial materials are discussed.

Design of Cyclic Peptide-Based Nanospheres and the Delivery of siRNA.

In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2'-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy.

Flexible Single-Chain-Heteropolymer-Derived Transmembrane Ion Channels with High K+ Selectivity and Tunable pH-Gated Characteristics.

A series of single-chain random heteropolymer (RHP)-derived artificial ion channels with both high K+ selectivity and controllable pH-gated behaviors were fabricated by a facile "one-pot" polymerization method. The benzo-18-crown-6 moieties appended on lateral chains of RHPs can form ion-permeable nanopores and transport K+ over Na+ through the lipid bilayers. The ion permeation selectivity was significantly enhanced by incorporating a cholesterol group to serve as a membrane anchor. Interestingly, similar to natural gated protein channels, on-off switchable characteristics were also realized by integrating an additional acid-sensitive alkylamine group into the RHP-derived channel. The unique design strategies have endowed the RHP-derived ion channels with facile synthetic procedures, desirable membrane compatibility, high K+ selectivity, and tunable pH-gated properties. This work provides an entry point for future design of novel functional nanochannels.