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We have designed, fabricated, and characterized implantable silicon neural probes with nanophotonic grating emitters that focus the emitted light at a specified distance above the surface of the probe for spatially precise optogenetic targeting of neurons. Using the holographic principle, we designed gratings for wavelengths of 488 and 594 nm, targeting the excitation spectra of the optogenetic actuators Channelrhodopsin-2 and Chrimson, respectively. The measured optical emission pattern of these emitters in non-scattering medium and tissue matched well with simulations. To our knowledge, this is the first report of focused spots with the size scale of a neuron soma in brain tissue formed from implantable neural probes.
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Neurônios , Optogenética , Fótons , Optogenética/métodos , Optogenética/instrumentação , Neurônios/fisiologia , Animais , Próteses e Implantes , Silício/químicaRESUMO
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.
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Encéfalo , Encéfalo/fisiologia , Humanos , Animais , Mapeamento Encefálico/instrumentação , Neurônios/fisiologia , Neurônios/citologia , Silício/química , Nanotecnologia/instrumentação , Optogenética/instrumentaçãoRESUMO
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.
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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.
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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.
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Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO could sense DA in the 3D printed neural network with a detection limit of 0.137 µM. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.
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Bioimpressão , Técnicas Biossensoriais , Óxido de Zinco , Humanos , Dopamina , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
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.
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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.
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Implantable silicon neural probes with integrated nanophotonic waveguides can deliver patterned dynamic illumination into brain tissue at depth. Here, we introduce neural probes with integrated optical phased arrays and demonstrate optical beam steering in vitro. Beam formation in brain tissue is simulated and characterized. The probes are used for optogenetic stimulation and calcium imaging.
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Optogenética , Silício , Encéfalo/diagnóstico por imagemRESUMO
We report multicore fibers (MCFs) with 10 and 16 linearly distributed cores with single-mode operation in the visible spectrum. The average propagation loss of the cores is 0.06â dB/m at λ = 445â nm and < 0.03â dB/m at wavelengths longer than 488â nm. The low inter-core crosstalk and nearly identical performance of the cores make these MCFs suitable for spatial division multiplexing in the visible spectrum. As a proof-of-concept application, one of the MCFs was coupled to an implantable neural probe to spatially address light-emitting gratings on the probe.
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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.
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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.
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We propose a new paradigm for dense functional imaging of brain activity to surmount the limitations of present methodologies. We term this approach "integrated neurophotonics"; it combines recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics. This approach has the potential to enable lens-less functional imaging from within the brain itself to achieve dense, large-scale stimulation and recording of brain activity with cellular resolution at arbitrary depths. We perform a computational study of several prototype 3D architectures for implantable probe-array modules that are designed to provide fast and dense single-cell resolution (e.g., within a 1-mm3 volume of mouse cortex comprising â¼100,000 neurons). We describe progress toward realizing integrated neurophotonic imaging modules, which can be produced en masse with current semiconductor foundry protocols for chip manufacturing. Implantation of multiple modules can cover extended brain regions.
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Encéfalo/diagnóstico por imagem , Neuroimagem Funcional/métodos , Neurônios/patologia , Imagem Óptica/métodos , Animais , Encéfalo/patologia , Encéfalo/fisiologia , Simulação por Computador , Sistemas Computacionais , Neuroimagem Funcional/instrumentação , Procedimentos Analíticos em Microchip , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Imagem Óptica/instrumentação , Óptica e Fotônica , OptogenéticaRESUMO
Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real-time neurosurgical guidance tool. We present, to our knowledge, the first full-field swept-source optical coherence tomography system operating near a wavelength of 1310 nm. The proof-of-concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.
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Algoritmos , Tomografia de Coerência Óptica , Encéfalo/diagnóstico por imagem , NeuroimagemRESUMO
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.
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A polarization-independent grating coupler is proposed and demonstrated in a 3-layer silicon nitride-on-silicon photonic platform. Polarization independent coupling was made possible by the supermodes and added degrees of geometric freedom unique to the 3-layer photonic platform. The grating was designed via optimization algorithms, and the simulated peak coupling efficiency was -2.1 dB with a 1 dB polarization dependent loss (PDL) bandwidth of 69 nm. The fabricated grating couplers had a peak coupling efficiency of -4.8 dB with 1 dB PDL bandwidth of over 100 nm.
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We correct two minor errors in the manuscript. The effective diameter of the ring modulator should be 62.5 µm rather than 65 µm. The factor, g, in the FOM for comparing between the O- and C-band results should be 0.83 instead of 0.7.
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We present a three-layer silicon nitride on silicon platform for constructing very large photonic integrated circuits. Efficient interlayer transitions are enabled by the close spacing between adjacent layers, while ultra-low-loss crossings are enabled by the large spacing between the topmost and bottommost layers. We demonstrate interlayer taper transitions with losses < 0.15 dB for wavelengths spanning from 1480 nm to 1620 nm. Our overpass waveguide crossings exhibit insertion loss < 2.1 mdB and crosstalk below -56 dB in the wavelength range between 1480 nm and 1620 nm with losses as low as 0.28 mdB. Our platform architecture is suited to meet the demands of large-scale photonic circuits which contain hundreds of crossings.
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Backscattering in integrated photonic waveguides can significantly impact the performance of optical systems. However, it has not been extensively studied in the literature and measurements on waveguides fabricated in production foundry processes are particularly lacking in view of their importance to technology. Here we experimentally measure and analyze distributed backscattering in various production O-band silicon photonic waveguides. We find the measured backscattering to scale from -18 to -36 dB/mm. Measured trends across waveguide geometry and polarization are consistent with stochastic defects on waveguide sidewalls being the dominant source of distributed backscattering in production Si waveguides. For production SiNx waveguides, both sidewall and cladding defects need to be considered to fit measured trends.
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We demonstrate U-shaped silicon PN junctions for energy efficient Mach-Zehnder modulators and ring modulators in the O-band. This type of junction has an improved modulation efficiency compared to existing PN junction geometries, has low losses, and supports high-speed operation. The U-shaped junctions were fabricated in an 8" silicon photonics platform, and they were incorporated in travelling-wave Mach-Zehnder modulators and microring modulators. For the high-bandwidth Mach-Zehnder modulator, the DC VπL at -0.5 V bias was 4.6 V·mm. It exhibited a 3dB bandwidth of 13 GHz, and eye patterns at up to 24 Gb/s were observed. A VπL as low as ~2.6 V·mm at a -0.5 V bias was measured in another device. The ring modulator tuning efficiency was 40 pm·V-1 between 0 V and -0.5 V bias. It had a 3-dB bandwidth of 13.5 GHz and open eye patterns at up to 13 Gb/s were measured. This type of PN junctions can be easily fabricated without extra masks and can be incorporated into generic silicon photonics platforms.