scholarly journals Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo

2021 ◽  
Author(s):  
Antje Kilias ◽  
Yu-Tao Lee ◽  
Ulrich P Froriep ◽  
Charlotte Sielaff ◽  
Dominik Moser ◽  
...  
Keyword(s):  
Unit Activity ◽  
Soft Materials ◽  
Tissue Response ◽  
Electrical Performance ◽  
Fixation Method ◽  
Probe Design ◽  
Rear Side ◽  
Tissue Reactions

Abstract Objective. Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes. Approach. We report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-µm-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e. grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse for in vivo recordings of freely behaving animals. Main results. Probes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiological in vivo recordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone. Significance. The innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a µm-precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-µm-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

scholarly journals Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo

2021 ◽  
Author(s):  
Antje Kilias ◽  
Yu-Tao Lee ◽  
Ulrich P. Froriep ◽  
Dominik Moser ◽  
Tobias Holzhammer ◽  
...  
Keyword(s):  
Unit Activity ◽  
Soft Materials ◽  
Tissue Response ◽  
Electrical Performance ◽  
Fixation Method ◽  
Probe Design ◽  
Rear Side ◽  
Tissue Reactions

Objective: Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes. Approach: We report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-μm-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse for in vivo recordings of freely behaving animals. Main results: Probes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiological in vivo recordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone. Significance: The innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-μm-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

Anti-Adhesive Finishing of Temporary Implant Surfaces by a Plasma-Fluorocarbon-Polymer

2014 ◽  
Vol 783-786 ◽  
pp. 1238-1243 ◽  
Author(s):  
Birgit Finke ◽  
Holger Testrich ◽  
Henrike Rebl ◽  
Barbara Nebe ◽  
Rainer Bader ◽  
...  
Keyword(s):  
Photoelectron Spectroscopy ◽  
Trauma Surgery ◽  
Titanium Implant ◽  
Tissue Response ◽  
Rf Discharge ◽  
Water Contact ◽  
Capacitively Coupled ◽  
Fluorocarbon Polymer ◽  
Tissue Reactions

Titanium implant surfaces should ideally be designed to support the subsequent clinical application. Therefore temporarily used implants have to fulfill both the mechanical stabilization of the bone stock and furthermore in trauma surgery the disintegration into the bone because the implant should be removed after fracture healing. The anti-adhesive plasma-fluorocarbon-polymer (PFP) films were synthesized using two different low-pressure plasma sources, the 2.45 GHz microwave (mw) and the 13.56 MHz capacitively coupled radio-frequency (rf) discharge in a mixture of the precursor octafluoropropane (C3F8) and hydrogen (H2). The film properties were characterized using X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, water contact angle measurements, and abrasive strength tests. Cell adhesion and spreading of human osteoblasts were clearly reduced on these PFP surfaces. First in vivo data on the biocompatibility of the PFP films deposited in the rf-discharge demonstrate that the local inflammatory tissue response for PFP coating was comparable to controls, while a PFP coating deposited in mw plasma induced stronger tissue reactions.

Open-architecture Neural Probes Reduce Cellular Encapsulation

2006 ◽  
Vol 926 ◽  
Author(s):  
John Seymour ◽  
Daryl Kipke
Keyword(s):  
Flexible Substrate ◽  
Neuronal Loss ◽  
Cell Encapsulation ◽  
Tissue Response ◽  
Open Architecture ◽  
Probe Design ◽  
Sprague Dawley ◽  
Neural Probes ◽  
Cord Injury

ABSTRACTIntracortical microelectrodes currently have the greatest potential for achieving a functional neural prosthesis in patients with neurodegenerative diseases or spinal cord injury. Device efficacy is lacking in long-term performance as seen in both chronological histology and biopotential recording studies.Some researchers have shown that small single polymer fibers (less than 7-μm diameter) do not induce an encapsulation layer in the rat subcutis so we have extended this concept to neural probe design. In this experiment we investigated the brain-tissue response of polymer probes with 4-μm feature sizes that are capable of withstanding insertion forces when penetrating the rat neocortex. This polymer probe has both a stiff penetrating shank (70-μm by 42-μm) and fine polymer structures (4-μm by 5-μm) that extend laterally from the shank. Our testing verifies that despite a flexible substrate and small dimensions, these devices are mechanically robust and practical as neural probes. We developed a microfabrication process using SU-8 and parylene to create the relatively thick probe shank and thin lateral arms.In vivo testing was conducted on seven Sprague-Dawley rats. These parylene devices were chronically implanted in the motor cortex for 4-weeks and then imaged using fluorescence microscopy. Cellular encapsulation and neuronal loss were assessed using a Hoechst counterstain and the immunomarker NeuN (neuronal nuclei).The tissue reactivity immediately around the fine-feature structures is greatly reduced, showing mild cell encapsulation (90±68% increase) relative to the probe shank (460±320% increase). Neuronal loss was only (21±25%) out to 25-μm relative to significant loss around the probe shank (47±19%). Additionally, laminin+, fibronectin+, and Ox42+ tissue often showed greater intensity and thickness at the shank, indicating that the dense scar formation typical of cortical implants was mitigated around the fine lateral structure.These results suggest that using MEMS-based microfabrication to create sub-cellular structures will significantly reduce encapsulation, which should extend the longevity of neural probes. We also believe this concept could be beneficial to any implantable sensor capable of scaled geometries.

scholarly journals Long-term in-vivo recording performance of flexible penetrating microelectrode arrays

2021 ◽  
Vol 18 (6) ◽  
pp. 066018
Author(s):  
Jae-Won Jang ◽  
Yoo Na Kang ◽  
Hee Won Seo ◽  
Boil Kim ◽  
Han Kyoung Choe ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Microelectrode Arrays ◽  
High Signal ◽  
Robotic Arms ◽  
Single Neuron Recording ◽  
Tissue Reactions ◽  
Physical Degradation ◽  
Silicon Based

Abstract Objective. Neural interfaces are an essential tool to enable the human body to directly communicate with machines such as computers or prosthetic robotic arms. Since invasive electrodes can be located closer to target neurons, they have advantages such as precision in stimulation and high signal-to-noise ratio (SNR) in recording, while they often exhibit unstable performance in long-term in-vivo implantation because of the tissue damage caused by the electrodes insertion. In the present study, we investigated the electrical functionality of flexible penetrating microelectrode arrays (FPMAs) up to 3 months in in-vivo conditions. Approach. The in-vivo experiment was performed by implanting FPMAs in five rats. The in-vivo impedance as well as the action potential (AP) amplitude and SNR were analyzed over weeks. Additionally, APs were tracked over time to investigate the possibility of single neuron recording. Main results. It was observed that the FPMAs exhibited dramatic increases in impedance for the first 4 weeks after implantation, accompanied by decreases in AP amplitude. However, the increase/decrease in AP amplitude was always accompanied by the increase/decrease in background noise, resulting in quite consistently maintained SNRs. After 4 weeks of implantation, we observed two distinctive issues regarding long-term implantation, each caused by chronic tissue responses or by the delamination of insulation layer. The results demonstrate that the FPMAs successfully recorded neuronal signals up to 12 weeks, with very stably maintained SNRs, reduced by only 16.1% on average compared to the first recordings, although biological tissue reactions or physical degradation of the FPMA were present. Significance. The fabricated FPMAs successfully recorded intracortical signals for 3 months. The SNR was maintained up to 3 months and the chronic function of FPMA was comparable with other silicon based implantable electrodes.

scholarly journals The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response

2019 ◽  
Vol 20 (8) ◽  
pp. 1969 ◽  
Author(s):  
Dominik Sieger ◽  
Tadas Korzinskas ◽  
Ole Jung ◽  
Sanja Stojanovic ◽  
Sabine Wenisch ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Bone Substitute ◽  
Tissue Response ◽  
Control Group ◽  
L929 Cells ◽  
High Doses ◽  
Tissue Reactions ◽  
Inflammatory Macrophages

Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties.

Bone tissue response to biodegradable polymers used for intra medullary fracture fixation: A long-term in vivo study in sheep femora

Biomaterials ◽  
1999 ◽  
Vol 20 (2) ◽  
pp. 121-128 ◽  
Author(s):  
M. van der Elst ◽  
C.P.A.T. Klein ◽  
J.M. de Blieck-Hogervorst ◽  
P. Patka ◽  
H.J.Th.M. Haarman
Keyword(s):  
Bone Tissue ◽  
Biodegradable Polymers ◽  
Fracture Fixation ◽  
Tissue Response ◽  
In Vivo Study

In Vitro and In Vivo Surface Reactivity of Various Calcium Phosphate Coatings Deposited Using Electrostatic Spray Deposition (ESD)

2006 ◽  
Vol 309-311 ◽  
pp. 607-610
Author(s):  
Sander C.G. Leeuwenburgh ◽  
Joop G.C. Wolke ◽  
M.C. Siebers ◽  
J. Schoonman ◽  
John A. Jansen
Keyword(s):  
Calcium Phosphate ◽  
Fibrous Tissue ◽  
Tissue Response ◽  
Specific Chemical ◽  
Phosphate Coatings ◽  
Time Periods ◽  
Tissue Reactions ◽  
Calcium Phosphate Coatings

The dissolution and precipitation behavior of various porous, ESD-derived calcium phosphate coatings was investigated a) in vitro after soaking in Simulated Body Fluid (SBF) for several time periods (2, 4, 8, and 12 weeks), and b) in vivo after subcutaneous implantation in the back of goats for identical time periods. At the end of these studies, the physicochemical properties of the coated substrates were characterized by means of Scanning Electron Microscopy (SEM), XRay Diffraction (XRD), Fourier-Transform InfraRed spectroscopy (FTIR) and Energy Dispersive Spectroscopy (EDS). Moreover, part of the implants was prepared for light microscopical evaluation of the tissue response. In vitro, a highly bioactive behavior was observed for all ESD-coatings, characterized by the deposition of a thick and homogeneous carbonate hydroxyapatite precipitation layer on top of the porous coatings. Regarding the in vivo study, no adverse tissue reactions (toxic effects/inflammatory cells) were observed using light microscopy, and all coatings became surrounded by a thin, dense fibrous tissue capsule after implantation. The ESD-coatings degraded gradually at a dissolution rate depending on the specific chemical phase, thereby enabling synthesis of CaP coatings with a tailored degradation rate.

scholarly journals Soft, Conductive, Brain-Like, Coatings at Tips of Microelectrodes Improve Electrical Stability under Chronic, In Vivo Conditions

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 761
Author(s):  
Arati Sridharan ◽  
Jit Muthuswamy
Keyword(s):  
Unit Activity ◽  
Electrochemical Impedance ◽  
Neural Interfaces ◽  
Electrical Performance ◽  
Electrical Stability ◽  
Neural Recordings ◽  
Soft Interfaces ◽  
Impedance Characteristics ◽  
Silicone Coatings

Several recent studies have reported improved histological and electrophysiological outcomes with soft neural interfaces that have elastic moduli ranging from 10 s of kPa to hundreds of MPa. However, many of these soft interfaces use custom fabrication processes. We test the hypothesis that a readily adoptable fabrication process for only coating the tips of microelectrodes with soft brain-like (elastic modulus of ~5 kPa) material improves the long-term electrical performance of neural interfaces. Conventional tungsten microelectrodes (n = 9 with soft coatings and n = 6 uncoated controls) and Pt/Ir microelectrodes (n = 16 with soft coatings) were implanted in six animals for durations ranging from 5 weeks to over 1 year in a subset of rats. Electrochemical impedance spectroscopy was used to assess the quality of the brain tissue–electrode interface under chronic conditions. Neural recordings were assessed for unit activity and signal quality. Electrodes with soft, silicone coatings showed relatively stable electrical impedance characteristics over 6 weeks to >1 year compared to the uncoated control electrodes. Single unit activity recorded by coated electrodes showed larger peak-to-peak amplitudes and increased number of detectable neurons compared to uncoated controls over 6–7 weeks. We demonstrate the feasibility of using a readily translatable process to create brain-like soft interfaces that can potentially overcome variable performance associated with chronic rigid neural interfaces.

scholarly journals Long-term in vivo Monitoring of Gliotic Sheathing of Ultrathin Entropic Coated Brain Microprobes with Fiber-based Optical Coherence Tomography

2020 ◽  
Author(s):  
Ian Dryg ◽  
Yijing Xie ◽  
Michael Bergmann ◽  
Gerald Urban ◽  
William Shain ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Primary Source ◽  
Brain Parenchyma ◽  
Tissue Response ◽  
Neuron Activity ◽  
Optical Coherence ◽  
Current State ◽  
Animal Monitoring

AbstractMicrofabricated neuroprosthetic devices have made possible important observations on neuron activity; however, long-term high-fidelity recording performance of these devices has yet to be realized. Tissue-device interactions appear to be a primary source of lost recording performance. The current state of the art for visualizing the tissue response surrounding brain implants in animals is Immunohistochemistry + Confocal Microscopy, which is mainly performed after sacrificing the animal. Monitoring the tissue response as it develops could reveal important features of the response which may inform improvements in electrode design. Optical Coherence Tomography (OCT), an imaging technique commonly used in ophthalmology, has already been adapted for imaging of brain tissue. Here, we use OCT to achieve real-time, in vivo monitoring of the tissue response surrounding chronically implanted neural devices. The employed tissue-response-provoking implants are coated with a plasma-deposited nanofilms, which have been demonstrated as a biocompatible and anti-inflammatory interface for indwelling devices. We evaluate the method by comparing the OCT results to traditional histology qualitatively and quantitatively. The differences in OCT signal across the implantation period between the plasma group and the control reveal that the Parylene-type coating of otherwise rigid brain probes (glass and silicon) does not improve the glial encapsulation in the brain parenchyma.

scholarly journals Comparison of macroscopic resorption time for a self-locking device and suture material in ovarian pedicle ligation in dogs

2019 ◽  
Vol 184 (15) ◽  
pp. 478-478 ◽  
Author(s):  
Matheus Roberto da Mota Costa ◽  
André Lacerda de Abreu Oliveira ◽  
Leonardo Waldstein de Moura Vidal ◽  
Renato Moran Ramos ◽  
Ingrid de Oliveira Campos ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Suture Material ◽  
Tissue Reaction ◽  
Equivalent Material ◽  
Surgical Ligation ◽  
Tissue Reactions ◽  
Ovarian Pedicle

A resorbable self-locking device (LigaTie) was developed to enable safe and easy surgical ligation of blood vessels. The aim of this study was to compare the long-term in vivo resorption of the device to a commercially available suture of equivalent material (Maxon) following ovarian pedicle ligation. After ovariohysterectomy follow-up ultrasound examinations were performed monthly on 21 dogs ligated with the device and 22 dogs ligated with the suture material until no hyperechoic remnants, acoustic shadowing or local tissue reactions were detected. In both groups, the ovarian pedicles gradually decreased in size. Ligation material was considered macroscopically resorbed when ultrasound showed no signs of the device or suture, ovarian pedicle or tissue reaction. Macroscopic resorption had occurred without signs of complications and was complete by four months for sutures and 5.5 months for the device. The results show that resorption time in vivo for the resorbable self-locking device is mildly longer than suture of the same material and that no complications of device resorption were detected, supporting that the resorbable self-locking device is safe for in vivo use.

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