RESUMEN
This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode's enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.
Asunto(s)
Diamante , Prótesis Neurales , Diamante/química , Impedancia Eléctrica , Materiales Biocompatibles/química , Humanos , Electrodos , TemperaturaRESUMEN
L-tryptophan is an amino acid that is essential to the metabolism of humans. Therefore, there is a high interest for its detection in biological fluids including blood, urine, and saliva for medical studies, but also in food products. Towards this goal, we report on a new electrochemiluminescence (ECL) method for L-tryptophan detection involving the in situ production of hydrogen peroxide at the surface of boron-doped diamond (BDD) electrodes. We demonstrate that the ECL response efficiency is directly related to H2O2 production at the electrode surface and propose a mechanism for the ECL emission of L-tryptophan. After optimizing the analytical conditions, we show that the ECL response to L-tryptophan is directly linear with concentration in the range of 0.005 to 1 µM. We achieved a limit of detection of 0.4 nM and limit of quantification of 1.4 nM in phosphate buffer saline (PBS, pH 7.4). Good selectivity against other indolic compounds (serotonin, 3-methylindole, tryptamine, indole) potentially found in biological fluids was observed, thus making this approach highly promising for quantifying L-tryptophan in a broad range of aqueous matrices of interest.
Asunto(s)
Boro , Diamante , Técnicas Electroquímicas , Electrodos , Mediciones Luminiscentes , Triptófano , Triptófano/química , Triptófano/análisis , Boro/química , Diamante/química , Técnicas Electroquímicas/métodos , Mediciones Luminiscentes/métodos , Humanos , Límite de Detección , Técnicas Biosensibles/métodos , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/químicaRESUMEN
Early, rapid and non-invasive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for the prevention and control of coronavirus disease 2019 (COVID-19). COVID-19 mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In the current study, an experimental protocol using an electronic-nose ('e-nose') for attempting to identify a specific respiratory imprint in COVID-19 patients was optimized. Thus the analytical performances of the Cyranose®, a commercial e-nose device, were characterized under various controlled conditions. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. A statistical data analysis was applied to e-nose sensor response using common statistical analysis algorithms in an attempt to demonstrate the possibility to detect the presence of low concentrations of spiked acetone and nonanal in the breath samples of a healthy volunteer. Cyranose®reveals a possible detection of low concentrations of these two compounds, in particular of 25 ppm nonanal, a possible marker of SARS-CoV-2 in the breath.
Asunto(s)
COVID-19 , Compuestos Orgánicos Volátiles , Humanos , SARS-CoV-2 , Pruebas Respiratorias/métodos , Nariz Electrónica , Biomarcadores/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
A new method for the determination of skatole present in porcine adipose tissue samples utilizing the electrochemiluminescence of skatole is presented. It has been observed that oxygen radicals produced at a high cathodic voltage can react with oxidized skatole to create an excited intermediate molecule that then relaxes, generating peak photon emission at around 480 nm. A strong electrochemiluminescence or electrogenerated chemiluminescence (ECL) signal using boron-doped diamond (BDD) electrodes was observed optimally when a reduction potential of -1.8 V was applied, held for 40 s, before holding an oxidation potential of 0.8 V for 10 s. Using this principle, a calibration curve using known concentrations of skatole showed good linearity (range 0.025-2 µM) and a very low detection limit (LOD, 0.7 nM). A method that demonstrates for the first time an approach that utilizes this ECL reaction, and has the potential to be developed into an analytical device for use in the slaughterhouse, has been developed. This was achieved by extracting skatole out of the porcine adipose tissues into acetonitrile - giving an extraction efficiency of 67.6%. This method was then validated by analyzing the skatole content of 33 pig fat samples that had been previously tested using a standard technique, high-performance liquid chromatography (HPLC), containing a range of concentrations (0.02-2.58 µg/g). This ECL method exhibited excellent reliability and correlation with HPLC, giving a R2 coefficient of 0.911, thus demonstrating the potential for this method to be developed for an on-line skatole detector.
Asunto(s)
Diamante , Escatol , Tejido Adiposo/química , Animales , Electrodos , Reproducibilidad de los Resultados , Escatol/análisis , PorcinosRESUMEN
When implantable recording devices for brain or neural electrical activity are designed, the number of available materials for electrodes is quite limited. The material must be biocompatible with respect to ISO10993, its electrochemical properties must remain stable and the response of cells or tissues can be mitigated, especially on the glial scar. This involves electrode characterization pre- implantation and impedance spectroscopy during chronic implantation, in order to evaluate both electrode properties and performance. This study was aimed at a comparison of the long-term behavior of a nanostructured boron-doped diamond (BDD) with a nanostructured Platinum Iridium (PtIr) electrode. Firstly, a batch of cortical grids with bare and modified contacts (2â¯mm in diameter) was engineered for implantation. Secondly a miniature swine model was developed. This study highlighted the predominant role of electrode surface roughness on the quality of recordings. Rough PtIr contacts and BDD coated ones showed comparable behavior after three-month implantation with a slight increase of the modulus of the impedance and a tissue capsule. Nevertheless, immunohistochemistry analysis did not exhibit either a toxic or irritation reaction. With regard to biocompatibility, promising long term results are shown for both materials.
Asunto(s)
Materiales Biocompatibles/química , Boro/química , Diamante/química , Electrodos Implantados , Nanoestructuras/química , Animales , Materiales Biocompatibles/efectos adversos , Boro/efectos adversos , Encéfalo/ultraestructura , Diamante/efectos adversos , Espectroscopía Dieléctrica , Técnicas Electroquímicas , Electrodos Implantados/efectos adversos , Proteína Ácida Fibrilar de la Glía/análisis , Nanoestructuras/efectos adversos , Nanoestructuras/ultraestructura , Porcinos , Porcinos EnanosRESUMEN
This paper reports on the development of an autonomous instrument based on an array of eight resonant microcantilevers for vapor detection. The fabricated sensors are label-free devices, allowing chemical and biological functionalization. In this work, sensors based on an array of silicon and synthetic diamond microcantilevers are sensitized with polymeric films for the detection of analytes. The main advantage of the proposed system is that sensors can be easily changed for another application or for cleaning since the developed gas cell presents removable electrical connections. We report the successful application of our electronic nose approach to detect 12 volatile organic compounds. Moreover, the response pattern of the cantilever arrays is interpreted via principal component analysis (PCA) techniques in order to identify samples.
RESUMEN
Nanocrystalline Boron doped Diamond proved to be a very attractive material for neural interfacing, especially with the retina, where reduce glia growth is observed with respect to other materials, thus facilitating neuro-stimulation over long terms. In the present study, we integrated diamond microelectrodes on a polyimide substrate and investigated their performances for the development of neural prosthesis. A full description of the microfabrication of the implants is provided and their functionalities are assessed using cyclic voltammetry and electrochemical impedance spectroscopy. A porous structure of the electrode surface was thus revealed and showed promising properties for neural recording or stimulation. Using the flexible implant, we showed that is possible to follow in vivo the evolution of the electric contact between the diamond electrodes and the retina over 4months by using electrochemical impedance spectroscopy. The position of the implant was also monitored by optical coherence tomography to corroborate the information given by the impedance measurements. The results suggest that diamond microelectrodes are very good candidates for retinal prosthesis.
Asunto(s)
Materiales Biocompatibles/química , Boro/química , Diamante/química , Animales , Espectroscopía Dieléctrica , Modelos Animales de Enfermedad , Técnicas Electroquímicas , Electrodos Implantados , Microelectrodos , Microscopía Electrónica de Rastreo , Porosidad , Ratas , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología , Tomografía de Coherencia Óptica , Prótesis VisualesRESUMEN
Two retinal implants have recently received the CE mark and one has obtained FDA approval for the restoration of useful vision in blind patients. Since the spatial resolution of current vision prostheses is not sufficient for most patients to detect faces or perform activities of daily living, more electrodes with less crosstalk are needed to transfer complex images to the retina. In this study, we modelled planar and three-dimensional (3D) implants with a distant ground or a ground grid, to demonstrate greater spatial resolution with 3D structures. Using such flexible 3D implant prototypes, we showed that the degenerated retina could mould itself to the inside of the wells, thereby isolating bipolar neurons for specific, independent stimulation. To investigate the in vivo biocompatibility of diamond as an electrode or an isolating material, we developed a procedure for depositing diamond onto flexible 3D retinal implants. Taking polyimide 3D implants as a reference, we compared the number of neurones integrating the 3D diamond structures and their ratio to the numbers of all cells, including glial cells. Bipolar neurones were increased whereas there was no increase even a decrease in the total cell number. SEM examinations of implants confirmed the stability of the diamond after its implantation in vivo. This study further demonstrates the potential of 3D designs for increasing the resolution of retinal implants and validates the safety of diamond materials for retinal implants and neuroprostheses in general.
Asunto(s)
Diamante/química , Electrodos Implantados , Ensayo de Materiales/métodos , Modelos Biológicos , Retina/fisiología , Prótesis Visuales , Animales , Estimulación Eléctrica , Fondo de Ojo , Procesamiento de Imagen Asistido por Computador , Microscopía Confocal , Microscopía Electrónica de Rastreo , Docilidad , Diseño de Prótesis , Ratas , Células Bipolares de la Retina/citologíaRESUMEN
The electrode material is a key element in the design of long-term neural implants and neuroprostheses. To date, the ideal electrode material offering high longevity, biocompatibility, low-noise recording and high stimulation capabilities remains to be found. We show that 3D-nanostructured boron doped diamond (BDD), an innovative material consisting in a chemically stable material with a high aspect ratio structure obtained by encapsulation of a carbon nanotube template within two BDD nanolayers, allows neural cell attachment, survival and neurite extension. Further, we developed arrays of 20-µm-diameter 3D-nanostructured BDD microelectrodes for neural interfacing. These microelectrodes exhibited low impedances and low intrinsic recording noise levels. In particular, they allowed the detection of low amplitude (10-20 µV) local-field potentials, single units and multiunit bursts neural activity in both acute whole embryonic hindbrain-spinal cord preparations and long-term hippocampal cell cultures. Also, cyclic voltammetry measurements showed a wide potential window of about 3 V and a charge storage capacity of 10 mC.cm(-2), showing high potentiality of this material for neural stimulation. These results demonstrate the attractiveness of 3D-nanostructured BDD as a novel material for neural interfacing, with potential applications for the design of biocompatible neural implants for the exploration and rehabilitation of the nervous system.
Asunto(s)
Boro , Diamante , Microelectrodos , Prótesis Neurales , Animales , Materiales Biocompatibles , Hipocampo/citología , Ratones , Médula Espinal/citologíaRESUMEN
Retinal prostheses aim at restoring vision in patients blind from photoreceptor degeneration by electrically stimulating the residual retinal tissue. Currently, the most efficient implants are either inserted in the subretinal space or on the vitreal side of the retina (epi-retinal). Although the residual tissue can partly degenerate, it was shown that acute stimulation of residual neurones can induce visual percepts. Recently, a clinical trial with the epiretinal Argus2 device (60 electrodes) from the company 2nd Sight enabled most patients to orient and find light targets, some even reading words. This device has received a CE mark. Surprisingly, when the subretinal implant from the company Retina Implant AG displaying many more electrodes (1500 electrodes) was evaluated in clinical trials, the patient visual performances were fairly similar. The restored visual performances of the patients demonstrate that blind patients can recover some visual function when their residual retina is properly stimulated. However, the resolution is not yet sufficient to perform complex tasks such as autonomous locomotion, face identification or text reading. Several challenges remain to generate an increase in pixel density corresponding to the increase in electrode number and density. These challenges include the stimulation modality, the tissue/implant interface design, the electrode materials, and the visual information encoder. This review will discuss these great challenges after introducing the major clinical results.
Asunto(s)
Ceguera/terapia , Células Fotorreceptoras/fisiología , Regeneración/fisiología , Degeneración Retiniana/fisiopatología , Degeneración Retiniana/terapia , Visión Ocular/fisiología , Ceguera/fisiopatología , Humanos , Prótesis e Implantes/tendencias , Diseño de Prótesis/métodos , Diseño de Prótesis/tendencias , Retina/fisiología , Retina/fisiopatologíaRESUMEN
We report herein an innovative electrochemical (EC) technique based on boron doped diamond (BDD) microelectrodes which enable the fast determination of uric acid (UA) concentrations in urine. On the basis of fast cyclic voltammetry (CV), the technique was assessed in human urine samples and compared successfully using routine spectrophotometric diagnosis. The approach relies on the use of BDD's superior properties such as low background current, low adsorption of species, long-term stability, and antifouling capabilities using electrochemical reactivation. Moreover, the article also describes an in situ activation technique, where the electrodes were reactivated within human urine, thereby opening the way toward automatic quantification of UA with in situ cleaning. The time taken to quantify UA concentration and cleaning remains below 0.5 s. Two analytic models were derived, based on different concentrations of ascorbic acid (AA) and uric acid, consisting of 2 s order calibration curves. Solving the second order equation enables the direct estimation of UA concentration, and values demonstrated good accuracy when compared with spectrophotometric measurements.
Asunto(s)
Técnicas Biosensibles , Boro/química , Diamante/química , Electroquímica , Microelectrodos , Ácido Úrico/orina , Automatización , HumanosRESUMEN
We report on the fabrication and characterization of an 8 × 8 multichannel Boron Doped Diamond (BDD) ultramicro-electrode array (UMEA). The device combines both the assets of microelectrodes, resulting from conditions in mass transport from the bulk solution toward the electrode, and of BDD's remarkable intrinsic electrochemical properties. The UMEAs were fabricated using an original approach relying on the selective growth of diamond over pre-processed 4 inches silicon substrates. The prepared UMEAs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the electrodes have exhibited a very fast electrode transfer rate (k(0)) up to 0.05 cm·s(-1) (in a fast redox couple) and on average, a steady state limiting current (in a 0.5 M potassium chloride aqueous solution containing 1 mM Fe(CN)(6)(4-) ion at 100 mV·s(-1)) of 1.8 nA. The UMEAs are targeted for electrophysiological as well as analytical applications.
RESUMEN
Resonant microcantilevers have demonstrated that they can play an important role in the detection of chemical and biological agents. Molecular interactions with target species on the mechanical microtransducers surface generally induce a change of the beam's bending stiffness, resulting in a shift of the resonance frequency. In most biochemical sensor applications, cantilevers must operate in liquid, even though damping deteriorates the vibrational performances of the transducers. Here we focus on diamond-based microcantilevers since their transducing properties surpass those of other materials. In fact, among a wide range of remarkable features, diamond possesses exceptional mechanical properties enabling the fabrication of cantilever beams with higher resonant frequencies and Q-factors than when made from other conventional materials. Therefore, they appear as one of the top-ranked materials for designing cantilevers operating in liquid media. In this study, we evaluate the resonator sensitivity performances of our diamond microcantilevers using grafted carboxylated alkyl chains as a tool to investigate the subtle changes of surface stiffness as induced by electrostatic interactions. Here, caproic acid was immobilized on the hydrogen-terminated surface of resonant polycrystalline diamond cantilevers using a novel one-step grafting technique that could be also adapted to several other functionalizations. By varying the pH of the solution one could tune the -COO(-)/-COOH ratio of carboxylic acid moieties immobilized on the surface, thus enabling fine variations of the surface stress. We were able to probe the cantilevers resonance frequency evolution and correlate it with the ratio of -COO(-)/-COOH terminations on the functionalized diamond surface and consequently the evolution of the electrostatic potential over the cantilever surface. The approach successfully enabled one to probe variations in cantilevers bending stiffness from several tens to hundreds of millinewtons/meter, thus opening the way for diamond microcantilevers to direct sensing applications in liquids. The evolution of the diamond surface chemistry was also investigated using X-ray photoelectron spectroscopy.