Development of wafer-scale multifunctional nanophotonic neural probes for brain activity mapping.

Optical techniques, such as optogenetic stimulation and functional fluorescence imaging, have been revolutionary for neuroscience by enabling neural circuit analysis with cell-type specificity. To probe deep brain regions, implantable light sources are crucial. Silicon photonics, commonly used for data communications, shows great promise in creating implantable devices with complex optical systems in a compact form factor compatible with high volume manufacturing practices. This article reviews recent developments of wafer-scale multifunctional nanophotonic neural probes. The probes can be realized on 200 or 300 mm wafers in commercial foundries and integrate light emitters for photostimulation, microelectrodes for electrophysiological recording, and microfluidic channels for chemical delivery and sampling. By integrating active optical devices to the probes, denser emitter arrays, enhanced on-chip biosensing, and increased ease of use may be realized. Silicon photonics technology makes possible highly versatile implantable neural probes that can transform neuroscience experiments.

Photonic neural probe enabled microendoscopes for light-sheet light-field computational fluorescence brain imaging.

Significance: Light-sheet fluorescence microscopy is widely used for high-speed, high-contrast, volumetric imaging. Application of this technique to in vivo brain imaging in non-transparent organisms has been limited by the geometric constraints of conventional light-sheet microscopes, which require orthogonal fluorescence excitation and collection objectives. We have recently demonstrated implantable photonic neural probes that emit addressable light sheets at depth in brain tissue, miniaturizing the excitation optics. Here, we propose a microendoscope consisting of a light-sheet neural probe packaged together with miniaturized fluorescence collection optics based on an image fiber bundle for lensless, light-field, computational fluorescence imaging. Aim: Foundry-fabricated, silicon-based, light-sheet neural probes can be packaged together with commercially available image fiber bundles to form microendoscopes for light-sheet light-field fluorescence imaging at depth in brain tissue. Approach: Prototype microendoscopes were developed using light-sheet neural probes with five addressable sheets and image fiber bundles. Fluorescence imaging with the microendoscopes was tested with fluorescent beads suspended in agarose and fixed mouse brain tissue. Results: Volumetric light-sheet light-field fluorescence imaging was demonstrated using the microendoscopes. Increased imaging depth and enhanced reconstruction accuracy were observed relative to epi-illumination light-field imaging using only a fiber bundle. Conclusions: Our work offers a solution toward volumetric fluorescence imaging of brain tissue with a compact size and high contrast. The proof-of-concept demonstrations herein illustrate the operating principles and methods of the imaging approach, providing a foundation for future investigations of photonic neural probe enabled microendoscopes for deep-brain fluorescence imaging in vivo.

Implantable photonic neural probes with 3D-printed microfluidics and applications to uncaging.

Advances in chip-scale photonic-electronic integration are enabling a new generation of foundry-manufacturable implantable silicon neural probes incorporating nanophotonic waveguides and microelectrodes for optogenetic stimulation and electrophysiological recording in neuroscience research. Further extending neural probe functionalities with integrated microfluidics is a direct approach to achieve neurochemical injection and sampling capabilities. In this work, we use two-photon polymerization 3D printing to integrate microfluidic channels onto photonic neural probes, which include silicon nitride nanophotonic waveguides and grating emitters. The customizability of 3D printing enables a unique geometry of microfluidics that conforms to the shape of each neural probe, enabling integration of microfluidics with a variety of existing neural probes while avoiding the complexities of monolithic microfluidics integration. We demonstrate the photonic and fluidic functionalities of the neural probes via fluorescein injection in agarose gel and photoloysis of caged fluorescein in solution and in fixed brain tissue.

Microcantilever-integrated photonic circuits for broadband laser beam scanning.

Laser beam scanning is central to many applications, including displays, microscopy, three-dimensional mapping, and quantum information. Reducing the scanners to microchip form factors has spurred the development of very-large-scale photonic integrated circuits of optical phased arrays and focal plane switched arrays. An outstanding challenge remains to simultaneously achieve a compact footprint, broad wavelength operation, and low power consumption. Here, we introduce a laser beam scanner that meets these requirements. Using microcantilevers embedded with silicon nitride nanophotonic circuitry, we demonstrate broadband, one- and two-dimensional steering of light with wavelengths from 410 nm to 700 nm. The microcantilevers have ultracompact ~0.1 mm2 areas, consume ~31 to 46 mW of power, are simple to control, and emit a single light beam. The microcantilevers are monolithically integrated in an active photonic platform on 200-mm silicon wafers. The microcantilever-integrated photonic circuits miniaturize and simplify light projectors to enable versatile, power-efficient, and broadband laser scanner microchips.

Clostridium butyricum Prevents Dysbiosis and the Rise in Blood Pressure in Spontaneously Hypertensive Rats.

Hypertension is accompanied by dysbiosis and a decrease in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria. However, there is no report to examine the role of C. butyricum in blood pressure regulation. We hypothesized that a decrease in the relative abundance of SCFA-producing bacteria in the gut was the cause of spontaneously hypertensive rats (SHR)-induced hypertension. C. butyricum and captopril were used to treat adult SHR for six weeks. C. butyricum modulated SHR-induced dysbiosis and significantly reduced systolic blood pressure (SBP) in SHR (p < 0.01). A 16S rRNA analysis determined changes in the relative abundance of the mainly SCFA-producing bacteria Akkermansia muciniphila, Lactobacillus amylovorus, and Agthobacter rectalis, which increased significantly. Total SCFAs, and particularly butyrate concentrations, in the SHR cecum and plasma were reduced (p < 0.05), while C. butyricum prevented this effect. Likewise, we supplemented SHR with butyrate for six weeks. We analyzed the flora composition, cecum SCFA concentration, and inflammatory response. The results showed that butyrate prevented SHR-induced hypertension and inflammation, and the decline of cecum SCFA concentrations (p < 0.05). This research revealed that increasing cecum butyrate concentrations by probiotics, or direct butyrate supplementation, prevented the adverse effects of SHR on intestinal flora, vascular, and blood pressure.

Thermo-Optic Phase Shifter with Interleaved Suspended Design for Power Efficiency and Speed Adjustment.

Conventional thermo-optic devices-which can be broadly categorized to that with and without a thermal isolation trench-typically come with a tradeoff between thermal tuning efficiency and tuning speed. Here, we propose a method that allows us to directly define the tradeoff using a specially designed thermo-optic phase shifter with an interleaved isolation trench. With the design, the tuning efficiency and speed can be precisely tailored simply by controlling the duty ratio (suspended length over total heater length) of the suspended design. Phase shifters are one of the main components in photonic-integrated circuits, and having phase shifters with a flexible design approach may enable the wide adoption of photonic applications such as an optical neural network and LiDAR.

Monolithically integrated, broadband, high-efficiency silicon nitride-on-silicon waveguide photodetectors in a visible-light integrated photonics platform.

Visible and near-infrared spectrum photonic integrated circuits are quickly becoming a key technology to address the scaling challenges in quantum information and biosensing. Thus far, integrated photonic platforms in this spectral range have lacked integrated photodetectors. Here, we report silicon nitride-on-silicon waveguide photodetectors that are monolithically integrated in a visible light photonic platform on silicon. Owing to a leaky-wave silicon nitride-on-silicon design, the devices achieved a high external quantum efficiency of >60% across a record wavelength span from λ ~ 400 nm to ~640 nm, an opto-electronic bandwidth up to 9 GHz, and an avalanche gain-bandwidth product up to 173 ± 30 GHz. As an example, a photodetector was integrated with a wavelength-tunable microring in a single chip for on-chip power monitoring.

Resource-efficient high-dimensional subspace teleportation with a quantum autoencoder.

Quantum autoencoders serve as efficient means for quantum data compression. Here, we propose and demonstrate their use to reduce resource costs for quantum teleportation of subspaces in high-dimensional systems. We use a quantum autoencoder in a compress-teleport-decompress manner and report the first demonstration with qutrits using an integrated photonic platform for future scalability. The key strategy is to compress the dimensionality of input states by erasing redundant information and recover the initial states after chip-to-chip teleportation. Unsupervised machine learning is applied to train the on-chip autoencoder, enabling the compression and teleportation of any state from a high-dimensional subspace. Unknown states are decompressed at a high fidelity (~0.971), obtaining a total teleportation fidelity of ~0.894. Subspace encodings hold great potential as they support enhanced noise robustness and increased coherence. Laying the groundwork for machine learning techniques in quantum systems, our scheme opens previously unidentified paths toward high-dimensional quantum computing and networking.

Power-efficient silicon nitride thermo-optic phase shifters for visible light.

We demonstrate power-efficient, thermo-optic, silicon nitride waveguide phase shifters for blue, green, and yellow wavelengths. The phase shifters operated with low power consumption due to a suspended structure and multi-pass waveguide design. The devices were fabricated on 200-mm silicon wafers using deep ultraviolet lithography as part of an active visible-light integrated photonics platform. The measured power consumption to achieve a π phase shift (averaged over multiple devices) was 0.78, 0.93, 1.09, and 1.20 mW at wavelengths of 445, 488, 532, and 561 nm, respectively. The phase shifters were integrated into Mach-Zehnder interferometer switches, and 10 - 90% rise(fall) times of about 570(590) µs were measured.

Two-dimensional multi-layered SiN-on-SOI optical phased array with wide-scanning and long-distance ranging.

Silicon based optoelectronic integrated optical phased array is attractive owing to large-dense integration, large scanning range and CMOS compatibility. In this paper, we design and fabricate a SiN-on-SOI two-dimensional optical phased array chip. We demonstrate a two-dimensional scanning range of 96°×14.4° and 690 mW peak power of the main lobe. Additionally, we set up the time of flight (ToF) and frequency-modulated continuous-wave (FMCW) ranging systems by using this optical phased array chip, and achieve the objects detection at the range of 20 m in the ToF system and 109 m in the FMCW system, respectively.

Low-loss broadband bi-layer edge couplers for visible light.

Low-loss broadband fiber-to-chip coupling is currently challenging for visible-light photonic-integrated circuits (PICs) that need both high confinement waveguides for high-density integration and a minimum feature size above foundry lithographical limit. Here, we demonstrate bi-layer silicon nitride (SiN) edge couplers that have ≤ 4 dB/facet coupling loss with the Nufern S405-XP fiber over a broad optical wavelength range from 445 to 640 nm. The design uses a thin layer of SiN to expand the mode at the facet and adiabatically transfers the input light into a high-confinement single-mode waveguide (150-nm thick) for routing, while keeping the minimum nominal lithographic feature size at 150 nm. The achieved fiber-to-chip coupling loss is about 3 to 5 dB lower than that of single-layer designs with the same waveguide confinement and minimum feature size limitation.

Investigation and demonstration of a high-power handling and large-range steering optical phased array chip.

The optical power handling of an OPA scanning beam determines its targeted detection distance. So far, a limited number of investigations have been conducted on the restriction of the beam power. To the best of our knowledge, we for the first time in this paper explore the ability of the silicon photonics based OPA circuit for the high power application. A 64-channel SiN-Si based one-dimensional (1D) OPA chip has been designed to handle high beam power to achieve large scanning range. The chip was fabricated on the standard silicon photonics platform. The main lobe power of our chip can reach 720 mW and its peak side-lobe level (PSLL) is -10.33 dB. We obtain a wide scanning range of 110° in the horizontal direction at 1550 nm wavelength, with a compressed longitudinal divergence angle of each scanning beam of 0.02°.

Colonization of Clostridium butyricum in Rats and Its Effect on Intestinal Microbial Composition.

Gut microorganisms participate in many physiological processes. In particular, Clostridium butyricum can modulate gut microorganisms and treat diseases. The colonization and persistence of strains in the gut contribute to beneficial effects, and the colonization by C. butyricum in the gut is currently unknown. We investigated the total intestinal contents of C. butyricum at 12 h, 24 h, 48 h, and four and six days using real-time reverse transcription-PCR, after oral administration of C. butyricum to rats for seven consecutive days. We assessed the bacterial community structure using Illumina MiSeq sequencing. The results showed that C. butyricum was mainly colonized in the colon. The total content of C. butyricum in the gut increased significantly at 12 h after administration. Exogenous C. butyricum could still be detected in the gut six days after administration. Administration of C. butyricum significantly enhanced gut microbial diversity. The relative abundance of short-chain fatty acid-producing bacterial genera was shown to be higher than that of the control group, and treatment with C. butyricum elevated Firmicutes and diminished Bacteroidetes phyla compared with to the control group. These findings laid the foundation for the study of probiotic colonization capacity and the improvement of microflora for the prevention of gut diseases.

Unidirectional large-scale waveguide grating with uniform radiation for optical phased array.

Two novel waveguide gratings for optical phased array transmitters are investigated. By offsetting the grating structures along the waveguide on the upper and lower surfaces of the silicon nitride (Si3N4) waveguide, the dual-level chain and dual-level fishbone structures can achieve 95% of unidirectional radiation with a single Si3N4 layer by design. With apodized perturbation along the gratings, both structures can achieve uniform radiation without compromising the unidirectional radiation performance. In experiment, both demonstrate ∼ 80-90% unidirectionality. With further analysis, it is found that the dual-level fishbone structure is more feasible and robust to process variations in uniform radiation.

Implantable photonic neural probes for light-sheet fluorescence brain imaging.

Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200-mm-diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed, in vitro, and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 µ m for propagation distances up to 300 µ m in free space. Imaging areas were as large as ≈ 240 µ m × 490 µ m in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals.

Visible-light silicon nitride waveguide devices and implantable neurophotonic probes on thinned 200 mm silicon wafers.

We present passive, visible light silicon nitride waveguides fabricated on ≈ 100 µm thick 200 mm silicon wafers using deep ultraviolet lithography. The best-case propagation losses of single-mode waveguides were ≤ 2.8 dB/cm and ≤ 1.9 dB/cm over continuous wavelength ranges of 466-550 nm and 552-648 nm, respectively. In-plane waveguide crossings and multimode interference power splitters are also demonstrated. Using this platform, we realize a proof-of-concept implantable neurophotonic probe for optogenetic stimulation of rodent brains. The probe has grating coupler emitters defined on a 4 mm long, 92 µm thick shank and operates over a wide wavelength range of 430-645 nm covering the excitation spectra of multiple opsins and fluorophores used for brain stimulation and imaging.

Thermal annealing study of the mid-infrared aluminum nitride on insulator (AlNOI) photonics platform.

Aluminum nitride on insulator (AlNOI) photonics platform has great potential for mid-infrared applications thanks to the large transparency window, piezoelectric property, and second-order nonlinearity of AlN. However, the deployment of AlNOI platform might be hindered by the high propagation loss. We perform thermal annealing study and demonstrate significant loss improvement in the mid-infrared AlNOI photonics platform. After thermal annealing at 400°C for 2 hours in ambient gas environment, the propagation loss is reduced by half. Bend loss and taper coupling loss are also investigated. The performance of multimode interferometer, directional coupler, and add/drop filter are improved in terms of insertion loss, quality factor, and extinction ratio. Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction spectroscopy suggest the loss improvement is mainly attributed to the reduction of extinction coefficient in the silicon dioxide cladding. Apart from loss improvement, appropriate thermal annealing also helps in reducing thin film stress.

Aluminum nitride on insulator (AlNOI) platform for mid-infrared photonics.

We report an aluminum nitride on insulator platform for mid-infrared (MIR) photonics applications beyond 3 µm. Propagation loss and bending loss are studied, while functional devices such as directional couplers, multimode interferometers, and add/drop filters are demonstrated with high performance. The complementary metal-oxide-semiconductor-compatible aluminum nitride offers advantages ranging from a large transparency window, high thermal and chemical resistance, to piezoelectric tunability and three-dimensional integration capability. This platform can have synergy with other photonics platforms to enable novel applications for sensing and thermal imaging in MIR.

Wavelength-Flattened Directional Coupler Based Mid-Infrared Chemical Sensor Using Bragg Wavelength in Subwavelength Grating Structure.

In this paper, we report a compact wavelength-flattened directional coupler (WFDC) based chemical sensor featuring an incorporated subwavelength grating (SWG) structure for the mid-infrared (MIR). By incorporating a SWG structure into directional coupler (DC), the dispersion in DC can be engineered to allow broadband operation which is advantageous to extract spectroscopic information for MIR sensing analysis. Meanwhile, the Bragg reflection introduced by the SWG structure produces a sharp trough at the Bragg wavelength. This sharp trough is sensitive to the surrounding refractive index (RI) change caused by the existence of analytes. Therefore, high sensitivity can be achieved in a small footprint. Around fivefold enhancement in the operation bandwidth compared to conventional DC is achieved for 100% coupling efficiency in a 40 µm long WFDC experimentally. Detection of dichloromethane (CH2Cl2) in ethanol (C2H5OH) is investigated in a SWG-based WFDC sensor 136.8 µm long. Sensing performance is studied by 3D finite-difference time domain (FDTD) simulation while sensitivity is derived by computation. Both RI sensing and absorption sensing are examined. RI sensing reveals a sensitivity of -0.47% self-normalized transmitted power change per percentage of CH2Cl2 concentration while 0.12% change in the normalized total integrated output power is realized in the absorption sensing. As the first demonstration of the DC based sensor in the MIR, our device has the potential for tertiary mixture sensing by utilizing both changes in the real and imaginary part of RI. It can also be used as a broadband building block for MIR application such as spectroscopic sensing system.

Efficient and broadband subwavelength grating coupler for 3.7 µm mid-infrared silicon photonics integration.

A grating coupler is an essential building block for compact and flexible photonics integration. In order to meet the increasing demand of mid-infrared (MIR) integrated photonics for sensitive chemical/gas sensing, we report a silicon-on-insulator (SOI) based MIR subwavelength grating coupler (SWGC) operating in the 3.7 µm wavelength range. We provide the design guidelines of a uniform and apodized SWGC, followed by numerical simulations for design verification. We experimentally demonstrate both types of SWGC. The apodized SWGC enables high coupling efficiency of -6.477 dB/facet with 3 dB bandwidth of 199 nm, whereas the uniform SWGC shows larger 3dB bandwidth of 263.5 nm but slightly lower coupling efficiency of -7.371 dB/facet.