The ultra-thin, minimally invasive surface electrode array NeuroWeb for probing neural activity.

Electrophysiological recording technologies can provide valuable insights into the functioning of the central and peripheral nervous systems. Surface electrode arrays made of soft materials or implantable multi-electrode arrays with high electrode density have been widely utilized as neural probes. However, neither of these probe types can simultaneously achieve minimal invasiveness and robust neural signal detection. Here, we present an ultra-thin, minimally invasive neural probe (the "NeuroWeb") consisting of hexagonal boron nitride and graphene, which leverages the strengths of both surface electrode array and implantable multi-electrode array. The NeuroWeb open lattice structure with a total thickness of 100 nm demonstrates high flexibility and strong adhesion, establishing a conformal and tight interface with the uneven mouse brain surface. In vivo electrophysiological recordings show that NeuroWeb detects stable single-unit activity of neurons with high signal-to-noise ratios. Furthermore, we investigate neural interactions between the somatosensory cortex and the cerebellum using transparent dual NeuroWebs and optical stimulation, and measure the times of neural signal transmission between the brain regions depending on the pathway. Therefore, NeuroWeb can be expected to pave the way for understanding complex brain networks with optical and electrophysiological mapping of the brain.

Label-free adaptive optics single-molecule localization microscopy for whole zebrafish.

Specimen-induced aberration has been a major factor limiting the imaging depth of single-molecule localization microscopy (SMLM). Here, we report the application of label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging. The proposed system measures complex tissue aberrations from intrinsic reflectance rather than fluorescence emission and physically corrects the wavefront distortion more than three-fold stronger than the previous limit. This enables us to resolve sub-diffraction morphologies of cilia and oligodendrocytes in whole zebrafish as well as dendritic spines in thick mouse brain tissues at the depth of up to 102 µm with localization number enhancement by up to 37 times and localization precision comparable to aberration-free samples. The proposed approach can expand the application range of SMLM to whole zebrafish that cause the loss of localization number owing to severe tissue aberrations.

Exploiting volumetric wave correlation for enhanced depth imaging in scattering medium.

Imaging an object embedded within a scattering medium requires the correction of complex sample-induced wave distortions. Existing approaches have been designed to resolve them by optimizing signal waves recorded in each 2D image. Here, we present a volumetric image reconstruction framework that merges two fundamental degrees of freedom, the wavelength and propagation angles of light waves, based on the object momentum conservation principle. On this basis, we propose methods for exploiting the correlation of signal waves from volumetric images to better cope with multiple scattering. By constructing experimental systems scanning both wavelength and illumination angle of the light source, we demonstrated a 32-fold increase in the use of signal waves compared with that of existing 2D-based approaches and achieved ultrahigh volumetric resolution (lateral resolution: 0.41 [Formula: see text], axial resolution: 0.60 [Formula: see text]) even within complex scattering medium owing to the optimal coherent use of the broad spectral bandwidth (225 nm).

Computational conjugate adaptive optics microscopy for longitudinal through-skull imaging of cortical myelin.

Myelination processes are closely related to higher brain functions such as learning and memory. While their longitudinal observation has been crucial to understanding myelin-related physiology and various brain disorders, skull opening or thinning has been required to secure clear optical access. Here we present a high-speed reflection matrix microscope using a light source with a wavelength of 1.3 µm to reduce tissue scattering and aberration. Furthermore, we develop a computational conjugate adaptive optics algorithm designed for the recorded reflection matrix to optimally compensate for the skull aberrations. These developments allow us to realize label-free longitudinal imaging of cortical myelin through an intact mouse skull. The myelination processes of the same mice were observed from 3 to 10 postnatal weeks to the depth of cortical layer 4 with a spatial resolution of 0.79 µm. Our system will expedite the investigations on the role of myelination in learning, memory, and brain disorders.

Through-skull brain imaging in vivo at visible wavelengths via dimensionality reduction adaptive-optical microscopy.

Compensation of sample-induced optical aberrations is crucial for visualizing microscopic structures deep within biological tissues. However, strong multiple scattering poses a fundamental limitation for identifying and correcting the tissue-induced aberrations. Here, we introduce a label-free deep-tissue imaging technique termed dimensionality reduction adaptive-optical microscopy (DReAM) to selectively attenuate multiple scattering. We established a theoretical framework in which dimensionality reduction of a time-gated reflection matrix can attenuate uncorrelated multiple scattering while retaining a single-scattering signal with a strong wave correlation, irrespective of sample-induced aberrations. We performed mouse brain imaging in vivo through the intact skull with the probe beam at visible wavelengths. Despite the strong scattering and aberrations, DReAM offered a 17-fold enhancement of single scattering-to-multiple scattering ratio and provided high-contrast images of neural fibers in the brain cortex with the diffraction-limited spatial resolution of 412 nanometers and a 33-fold enhanced Strehl ratio.

Optical transfer function of time-gated coherent imaging in the presence of a scattering medium.

Optical imaging of objects embedded within scattering media such as biological tissues suffers from the loss of resolving power. In our previous work, we proposed an approach called collective accumulation of single scattering (CASS) microscopy that attenuates this detrimental effect of multiple light scattering by combining the time-gated detection and spatial input-output correlation. In the present work, we perform a rigorous theoretical analysis on the effect of multiple light scattering to the optical transfer function of CASS microscopy. In particular, the spatial frequency-dependent signal to noise ratio (SNR) is derived depending on the intensity ratio of the single- and multiple-scattered waves. This allows us to determine the depth-dependent resolving power. We conducted experiments using a Siemens star-like target having various spatial frequency components and supported the theoretical derived SNR spectra. Our study provides a theoretical framework for understanding the effect of multiple light scattering in high-resolution and deep-tissue optical imaging.

Near-field transmission matrix microscopy for mapping high-order eigenmodes of subwavelength nanostructures.

As nanoscale photonic devices are densely integrated, multiple near-field optical eigenmodes take part in their functionalization. Inevitably, these eigenmodes are highly multiplexed in their spectra and superposed in their spatial distributions, making it extremely difficult for conventional near-field scanning optical microscopy (NSOM) to address individual eigenmodes. Here, we develop a near-field transmission matrix microscopy for mapping the high-order eigenmodes of nanostructures, which are invisible with conventional NSOM. At an excitation wavelength where multiple modes are superposed, we measure the near-field amplitude and phase maps for various far-field illumination angles, from which we construct a fully phase-referenced far- to near-field transmission matrix. By performing the singular value decomposition, we extract orthogonal near-field eigenmodes such as anti-symmetric mode and quadruple mode of multiple nano-slits whose gap size (50 nm) is smaller than the probe aperture (150 nm). Analytic model and numerical mode analysis validated the experimentally observed modes.

Label-free neuroimaging in vivo using synchronous angular scanning microscopy with single-scattering accumulation algorithm.

Label-free in vivo imaging is crucial for elucidating the underlying mechanisms of many important biological systems in their most native states. However, the applicability of existing modalities has been limited to either superficial layers or early developmental stages due to tissue turbidity. Here, we report a synchronous angular scanning microscope for the rapid interferometric recording of the time-gated reflection matrix, which is a unique matrix characterizing full light-specimen interaction. By applying single scattering accumulation algorithm to the recorded matrix, we removed both high-order sample-induced aberrations and multiple scattering noise with the effective aberration correction speed of 10,000 modes/s. We demonstrated in vivo imaging of whole neural network throughout the hindbrain of the larval zebrafish at a matured stage where physical dissection used to be required for conventional imaging. Our method will expand the scope of applications for optical imaging, where fully non-invasive interrogation of living specimens is critical.

Author Correction: Maximizing energy coupling to complex plasmonic devices by injecting light into eigenchannels.

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Maximizing energy coupling to complex plasmonic devices by injecting light into eigenchannels.

Surface plasmon polaritons have attracted broad attention in the optoelectronics field due to their ability to merge nanoscale electronics with high-speed optical communication. As the complexity of optoelectronic devices increases to meet various needs, this integration has been hampered by the low coupling efficiency of light to plasmonic modes. Here we present a method to maximize the coupling of far-field optical waves to plasmonic waves for arbitrarily complex devices. The method consists of experimentally identifying the eigenchannels of a given nanostructure and shaping the wavefront of incident light to a particular eigenchannel that maximizes the generation of plasmonic waves. Our proposed approach increases the coupling efficiency almost four-fold with respect to the uncontrolled input. Our study will help to facilitate the integration of electronics and photonics.

Control of randomly scattered surface plasmon polaritons for multiple-input and multiple-output plasmonic switching devices.

Merging multiple microprocessors with high-speed optical networks has been considered a promising strategy for the improvement of overall computation power. However, the loss of the optical communication bandwidth is inevitable when interfacing between optical and electronic components. Here we present an on-chip plasmonic switching device consisting of a two-dimensional (2D) disordered array of nanoholes on a thin metal film that can provide multiple-input and multiple-output channels for transferring information from a photonic to an electronic platform. In this device, the surface plasmon polaritons (SPPs) generated at individual nanoholes become uncorrelated on their way to the detection channel due to random multiple scattering. We exploit this decorrelation effect to use individual nanoholes as independent antennas, and demonstrated that more than 40 far-field incident channels can be delivered simultaneously to the SPP channels, an order of magnitude improvement over conventional 2D patterned devices.