Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 μm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 μm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes’ mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

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Double-layer flexible neuronal probe with closely spaced electrodes for high-density in-vivo brain recordings

10.1101/2020.10.15.341263 ◽

2020 ◽

Author(s):

Sara Pimenta ◽

José A. Rodrigues ◽

Francisca Machado ◽

João F. Ribeiro ◽

Marino J. Maciel ◽

...

Keyword(s):

Double Layer ◽

Signal To Noise Ratio ◽

Brain Activity ◽

Low Cost ◽

Flexible Substrate ◽

High Density ◽

Composition Analysis ◽

Mouse Cortex ◽

Flexible Probe

AbstractFlexible probes for brain activity recordings are an attractive emerging approach that reduces mechanical mismatch between probe and neuronal tissue, thus minimizing the risk of brain damage or glial scaring. Although promising, flexible probes still present some technical challenges namely: i) how to overcome probe buckling during brain insertion given its intrinsically low mechanical rigidity; ii) how to fabricate closely spaced electrode configurations for high density recordings by standard lithography techniques in the flexible substrate. Here, we present a new flexible probe based solely on standard and low-cost lithography processes, which has closely spaced 10 μm diameter gold electrode sites on a polyimide substrate with inter-site distances of only 5 μm. By using a double-layer design and fabrication approach we were able to accommodate closely spaced electrode sites at two different depths from probe surface while also providing additional stiffening, just sufficient to prevent probe buckling during brain insertion. Detailed probe characterization through metrology of structural and electrical properties and chemical composition analysis, as well as functional assessment through in vivo high-density recordings of neuronal activity in the mouse cortex, confirmed the viability of this new fabrication approach and that this probe can be used for obtaining high quality brain recordings with excellent signal-to-noise ratio (SNR).

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High fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo

10.1101/2020.01.26.920256 ◽

2020 ◽

Cited By ~ 1

Author(s):

Michael E. Xie ◽

Yoav Adam ◽

Linlin Z. Fan ◽

Urs L. Böhm ◽

Ian Kinsella ◽

...

Keyword(s):

Signal To Noise Ratio ◽

Nonnegative Matrix ◽

Matrix Decomposition ◽

High Signal ◽

High Fidelity ◽

Correlated Noise ◽

Promising Tool ◽

Mouse Cortex ◽

Recent Developments

AbstractThe ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved high signal to noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise that present analysis challenges, namely light scattering, out-of-focus sources, motion, and blood flow. We present a novel signal extraction methodology, Spike-Guided Penalized Matrix Decomposition-Nonnegative Matrix Factorization (SGPMD-NMF), which resolves supra- and sub-threshold voltages with high fidelity, even in the presence of correlated noise. The method incorporates biophysical constraints (shared soma profiles for spiking and subthreshold dynamics) and optical constraints (smoother spatial profiles from defocused vs. in-focus sources) to cleave signal from background. We validated the pipeline using simulated and composite datasets with realistic noise properties. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon, mouse cortex expressing SomArchon or Voltron, and zebrafish spine expressing zArchon1.

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Hybrid Multisite Silicon Neural Probe with Integrated Flexible Connector for Interchangeable Packaging

Sensors ◽

10.3390/s21082605 ◽

2021 ◽

Vol 21 (8) ◽

pp. 2605

Author(s):

Ashley Novais ◽

Carlos Calaza ◽

José Fernandes ◽

Helder Fonseca ◽

Patricia Monteiro ◽

...

Keyword(s):

Fabrication Process ◽

High Signal ◽

Wafer Level ◽

Neural Probes ◽

Insertion Force ◽

Precise Integration ◽

Flexible Cable ◽

Flexible Polymer ◽

Hybrid Silicon

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).

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High-speed high-resolution laser diode-based photoacoustic microscopy for in vivo microvasculature imaging

Visual Computing for Industry Biomedicine and Art ◽

10.1186/s42492-020-00067-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Xiufeng Li ◽

Victor T C Tsang ◽

Lei Kang ◽

Yan Zhang ◽

Terence T W Wong

Keyword(s):

High Resolution ◽

High Speed ◽

High Performance ◽

Continuous Wave ◽

Signal To Noise Ratio ◽

Cost Effective ◽

High Signal ◽

Photoacoustic Microscopy ◽

Mouse Ear

AbstractLaser diodes (LDs) have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy (PAM). However, the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously. In this paper, we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD, operating at a pulsed mode, with a repetition rate of 30 kHz, as an excitation source. A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio. By optimizing the optical system, a high lateral resolution of 4.8 μm has been achieved. In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.

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Methods for Voltage-Sensitive Dye Imaging of Rat Cortical Activity With High Signal-to-Noise Ratio

Journal of Neurophysiology ◽

10.1152/jn.01169.2006 ◽

2007 ◽

Vol 98 (1) ◽

pp. 502-512 ◽

Cited By ~ 81

Author(s):

Michael T. Lippert ◽

Kentaroh Takagaki ◽

Weifeng Xu ◽

Xiaoying Huang ◽

Jian-Young Wu

Keyword(s):

Dynamic Range ◽

Signal To Noise Ratio ◽

Field Potential ◽

High Sensitivity ◽

High Dynamic Range ◽

High Signal ◽

Blue Dye ◽

Voltage Sensitive Dye ◽

Imaging Device

We describe methods to achieve high sensitivity in voltage-sensitive dye (VSD) imaging from rat barrel and visual cortices in vivo with the use of a blue dye RH1691 and a high dynamic range imaging device (photodiode array). With an improved staining protocol and an off-line procedure to remove pulsation artifact, the sensitivity of VSD recording is comparable with that of local field potential recording from the same location. With this sensitivity, one can record from ∼500 individual detectors, each covering an area of cortical tissue 160 μm in diameter (total imaging field ∼4 mm in diameter) and a temporal resolution of 1,600 frames/s, without multiple-trial averaging. We can record 80–100 trials of intermittent 10-s trials from each imaging field before the VSD signal reduces to one half of its initial amplitude because of bleaching and wash-out. Taken together, the methods described in this report provide a useful tool for visualizing evoked and spontaneous waves from rodent cortex.

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Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage

10.26434/chemrxiv.13699222.v1 ◽

2021 ◽

Author(s):

Yipu Wang ◽

Dong Mei ◽

Xinyi Zhang ◽

Da-Hui Qu ◽

Ju Mei ◽

...

Keyword(s):

High Performance ◽

Ex Vivo ◽

Early Stage ◽

Signal To Noise Ratio ◽

High Signal ◽

In Vivo Detection ◽

Different Strains ◽

Aβ Fibrils

With increase of social aging, Alzheimer's disease (AD) has been one of the serious diseases threatening human health. The occurrence of Aβ fibrils or plaques is recognized as the hallmark of AD. Currently, optical imaging has stood out to be a promising technique for the imaging of Aβ fibrils/plaques and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, and aggregation-caused quenching (ACQ) effect, the clinically used gold-standard optical probes such as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective enough in the early diagnosis of AD in vivo. Herein, we put forward an “all-in-one” design principle and demonstrate its feasibility in developing high-performance fluorescent probes which are specific to Aβ fibrils/plaques and promising for super-early in-vivo diagnosis of AD. As a proof of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD, is developed by taking the specificity, BBB penetration ability, deep-tissue penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD is constituted by connecting the electron-donating and accepting moieties through single bonds and tagging with a propanesulfonate tail, giving rise to the NIR fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like structure, which in turn result in high binding-affinity and excellent specificity to Aβ fibrils/plaques, satisfactory ability to penetrate BBB and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging capability. In-vitro, ex-vivo, and in-vivo <a>identifying of Aβ fibrils/plaques</a> in different strains of mice indicate that AIE-CNPy-AD holds the universality to the detection of Aβ fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely distributed Aβ fibrils/plaques in very young AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest mice to have Aβ deposits in brains, suggesting its great potential in diagnosis and intervention of AD at a super-early stage.

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Wind Turbine Noise Reduction from Seismological Data

10.5194/egusphere-egu21-4907 ◽

2021 ◽

Author(s):

Janis Heuel ◽

Wolfgang Friederich

Keyword(s):

Signal To Noise Ratio ◽

Low Cost ◽

Computational Cost ◽

Noise Signal ◽

Noise Model ◽

Threshold Function ◽

High Signal ◽

Time Data ◽

Negative Effects ◽

Before And After

Over the last years, installations of wind turbines (WTs) increased worldwide. Owing to negative effects on humans, WTs are often installed in areas with low population density. Because of low anthropogenic noise, these areas are also well suited for sites of seismological stations. As a consequence, WTs are often installed in the same areas as seismological stations. By comparing the noise in recorded data before and after installation of WTs, seismologists noticed a substantial worsening of station quality leading to conflicts between the operators of WTs and earthquake services.In this study, we compare different techniques to reduce or eliminate the disturbing signal from WTs at seismological stations. For this purpose, we selected a seismological station that shows a significant correlation between the power spectral density and the hourly windspeed measurements. Usually, spectral filtering is used to suppress noise in seismic data processing. However, this approach is not effective when noise and signal have overlapping frequency bands which is the case for WT noise. As a first method, we applied the continuous wavelet transform (CWT) on our data to obtain a time-scale representation. From this representation, we estimated a noise threshold function (Langston & Mousavi, 2019) either from noise before the theoretical P-arrival (pre-noise) or using a noise signal from the past with similar ground velocity conditions at the surrounding WTs. Therefore, we installed low cost seismometers at the surrounding WTs to find similar signals at each WT. From these similar signals, we obtain a noise model at the seismological station, which is used to estimate the threshold function. As a second method, we used a denoising autoencoder (DAE) that learns mapping functions to distinguish between noise and signal (Zhu et al., 2019).In our tests, the threshold function performs well when the event is visible in the raw or spectral filtered data, but it fails when WT noise dominates and the event is hidden. In these cases, the DAE removes the WT noise from the data. However, the DAE must be trained with typical noise samples and high signal-to-noise ratio events to distinguish between signal and interfering noise. Using the threshold function and pre-noise can be applied immediately on real-time data and has a low computational cost. Using a noise model from our prerecorded database at the seismological station does not improve the result and it is more time consuming to find similar ground velocity conditions at the surrounding WTs.

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Internally Modulated Chirped Pulse Based Direct Detection Type φ-OTDR System with High Signal-to-Noise Ratio and Low Cost

Chinese Journal of Lasers ◽

10.3788/cjl201946.0806003 ◽

2019 ◽

Vol 46 (8) ◽

pp. 0806003

Author(s):

李鲁川 Luchuan Li ◽

卢斌 Bin Lu ◽

王校 Xiao Wang ◽

梁嘉靖 Jiajing Liang ◽

郑汉荣 Hanrong Zheng ◽

...

Keyword(s):

Direct Detection ◽

Signal To Noise Ratio ◽

Low Cost ◽

High Signal ◽

Signal To Noise ◽

Chirped Pulse ◽

Noise Ratio

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Sequential average segmented microscopy for high signal-to-noise ratio motion-artifact-free in vivo heart imaging

Biomedical Optics Express ◽

10.1364/boe.4.002095 ◽

2013 ◽

Vol 4 (10) ◽

pp. 2095 ◽

Cited By ~ 12

Author(s):

Claudio Vinegoni ◽

Sungon Lee ◽

Paolo Fumene Feruglio ◽

Pasquina Marzola ◽

Matthias Nahrendorf ◽

...

Keyword(s):

Signal To Noise Ratio ◽

Motion Artifact ◽

High Signal ◽

Signal To Noise ◽

Heart Imaging ◽

Noise Ratio

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Upconversion Nanoparticles Decorated with Polysialic Acid for Solid Tumors Visualization In Vivo

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672921020034 ◽

2021 ◽

Author(s):

P. A. Demina ◽

N. V. Sholina ◽

R. A. Akasov ◽

D. A. Khochenkov ◽

A. V. Nechaev ◽

...

Keyword(s):

Solid Tumors ◽

Near Infrared ◽

Signal To Noise Ratio ◽

Polysialic Acid ◽

Lymphatic Drainage ◽

Circulation Time ◽

High Signal ◽

Upconversion Nanoparticles ◽

Nonspecific Protein Adsorption

Abstract Upconversion nanoparticles (UCNPs) are a promising nanoplatform for bioreagent formation for in vivo imaging, which emit UV and blue light under the action of near-infrared radiation, providing deep tissue penetration and maintaining a high signal-to-noise ratio. In the case of solid tumor visualization, the UCNP surface functionalization is required to ensure a long circulation time, biocompatibility, and non-toxicity. The effective UCNP accumulation in the solid tumors is determined by the disturbed architecture of the vascular network and lymphatic drainage. This work demonstrates an approach to the UCNP biofunctionalization with endogenous polysialic acid for in vivo bioreagent formation. Bioreagents possess a low level of nonspecific protein adsorption and macrophage uptake, which allow the prolongation of the circulation time in the bloodstream up to 3 h. This leads to an intense photoluminescent signal in the tumor.

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