Polarization Induced Electro-Functionalization of Pore Walls: A Contactless Technology.

This review summarizes recent advances in micro- and nanopore technologies with a focus on the functionalization of pores using a promising method named contactless electro-functionalization (CLEF). CLEF enables the localized grafting of electroactive entities onto the inner wall of a micro- or nano-sized pore in a solid-state silicon/silicon oxide membrane. A voltage or electrical current applied across the pore induces the surface functionalization by electroactive entities exclusively on the inside pore wall, which is a significant improvement over existing methods. CLEF's mechanism is based on the polarization of a sandwich-like silicon/silicon oxide membrane, creating electronic pathways between the core silicon and the electrolyte. Correlation between numerical simulations and experiments have validated this hypothesis. CLEF-induced micro- and nanopores functionalized with antibodies or oligonucleotides were successfully used for the detection and identification of cells and are promising sensitive biosensors. This technology could soon be successfully applied to planar configurations of pores, such as restrictions in microfluidic channels.

Enhanced Bipolar Electrochemistry at Solid-State Micropores: Demonstration by Wireless Electrochemiluminescence Imaging.

Bipolar electrochemistry (BPE) is a powerful method based on the wireless polarization of a conductive object that induces the asymmetric electroactivity at its two extremities. A key physical limitation of BPE is the size of the conductive object because the shorter the object, the larger is the potential necessary for sufficient polarization. Micrometric and nanometric objects are thus extremely difficult to address by BPE due to the very high potentials required, in the order of tens of kV or more. Herein, the synergetic actions of BPE and of planar micropores integrated in a microfluidic device lead to the spatial confinement of the potential drop at the level of the solid-state micropore, and thus to a locally enhanced polarization of a bipolar electrode. Electrochemiluminescence (ECL) is emitted in half of the electroactive micropore and reveals the asymmetric polarization in this spatial restriction. Micrometric deoxidized silicon electrodes located in the micropore are polarized at a very low potential (7 V), which is more than 2 orders of magnitude lower compared to the classic bipolar configurations. This behavior is intrinsically associated with the unique properties of the micropores, where the sharp potential drop is focused. The presented approach offers exciting perspectives for BPE of micro/nano-objects, such as dynamic BPE with objects passing through the pores or wireless ECL-emitting micropores.

Probing the functional impact of sub-retinal prosthesis.

Retinal prostheses are promising tools for recovering visual functions in blind patients but, unfortunately, with still poor gains in visual acuity. Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models. Here, we provide a systematic comparison between visual and prosthetic activations of the rat primary visual cortex (V1). We established a precise V1 mapping as a functional benchmark to demonstrate that sub-retinal implants activate V1 at the appropriate position, scalable to a wide range of visual luminance, but with an aspect-ratio and an extent much larger than expected. Such distorted activation profile can be accounted for by the existence of two sources of diffusion, passive diffusion and activation of ganglion cells' axons en passant. Reverse-engineered electrical pulses based on impedance spectroscopy is the only solution we tested that decreases the extent and aspect-ratio, providing a promising solution for clinical applications.

Endoventricular Deep Brain Stimulation of the Third Ventricle: Proof of Concept and Application to Cluster Headache.

BACKGROUND: The third ventricle (3rd V) is surrounded by centers related to satiety, homeostasis, hormones, sleep, memory, and pain. Stimulation of the wall of the 3rd V could be useful to treat disorders related to dysfunction of the hypothalamus. OBJECTIVE: To assess safety and efficacy of endoventricular electrical stimulation of the hypothalamus using a floating deep brain stimulation (DBS) lead laid on the floor of the 3rd V to treat refractory cluster headaches (CH). METHODS: Seven patients, aged 24 to 60 years, experiencing chronic CH (mean chronic duration 5.8 ± 2.5 years) were enrolled in this pilot, prospective, open study assessing the safety and potential efficacy of chronic DBS of the 3rd V. Number of attacks was collected during baseline and was compared with those occurring at 3, 6, and 12 months postoperation. Any side effects that occurred during or after surgery were reported. Effect on mood was assessed using the Hospital Anxiety and Depression scale during baseline and at 6 and 12 months postoperation. RESULTS: Insertion of the lead into the posterior 3rd V and chronic stimulation was feasible and safe in all patients. The voltage ranged from 0.9 to 2.3 volts. The most common side effect was transient trembling vision during stimulation. At 12 months, 3 of 7 patients were pain free, 2 had 90% improvement, 1 of 7 had 75% improvement, and 1 of 7 was not significantly improved. CONCLUSION: This proof of concept demonstrates the feasibility, safety, and potential efficacy of 3rd V DBS using an endoventricular road that could be applied to treat various diseases involving hypothalamic areas. ABBREVIATIONS: CCH, chronic cluster headacheCH, cluster headacheDBS, deep brain stimulationHAD, hospital anxiety depressionONS, occipital nerve stimulationPAG, periaqueductal gray matterPH, posterior hypothalamusPVG, periventricular gray matter3rd V, third ventricle.

Design and development of an impedimetric-based system for the remote monitoring of home-based dialysis patients.

A key clinical challenge is to determine the desired 'dry weight' of a patient in order to terminate the dialysis procedure at the optimal moment and thus avoid the effects of over- and under-hydration. It has been found that the effects of haemodialysis on patients can be conveniently monitored using whole-body bioimpedance measurements. The identified need of assessing the hydrational status of patients undergoing haemodialysis at home gave rise to the present Dialydom (DIALYse à DOMicile) project. The aim of the project is to develop a convenient miniaturised impedance monitoring device for localised measurements (on the calf) in order to estimate an impedimetric hydrational index of the home-based patient, and to transmit this and other parameters to a remote clinical site. Many challenges must be overcome to develop a robust and valid home-based device. Some of these are presented in the paper.

Modular architecture of a multi-frequency electrical impedance tomography system: design and implementation.

Electrical impedance tomography (EIT) provides means of imaging the electrical properties distribution of biological tissues and fluids while impedance spectroscopy (IS) allows measuring their frequency response in a more global way. Both require precise and well-integrated instrumentation. In this work, we propose a modular architecture of a multi-frequency EIT (MfEIT) system which has capabilities in implementing both IS and MfEIT. First, IS performance is assessed in vivo using a cuff electrode implanted around the rodent cervical vagus nerve. Second, MfEIT performance is evaluated in vitro based on saline phantom experiments. Overall system allows addressing a wide range of applications and proves effective both in vitro and in vivo.

Post-implantation impedance spectroscopy of subretinal micro-electrode arrays, OCT imaging and numerical simulation: towards a more precise neuroprosthesis monitoring tool.

OBJECTIVE: Previous studies have shown that single-frequency impedance measurements could provide useful information about the distance between the neuroprosthesis and the retina. This work investigates the use of impedance spectroscopy in monitoring subretinal implantations of flexible micro-electrode arrays and focuses on determining what is governing impedance profiles. APPROACH: In this study, we use impedance spectroscopy together with optical coherence tomography imaging and numerical simulation to quantitatively evaluate the constituent elements of measured impedance. MAIN RESULTS: We show the existence of specific impedance spectrum profiles for retinal detection and retinal detachment that are in good agreement with numerical simulations. These simulations suggest that monopolar impedance is mainly influenced by the subretinal space. Numerical simulations also provide a quantitative prediction of the lateral spread of current density in the vicinity of the measuring contact as a function of retina-electrode distance. SIGNIFICANCE: In general, our results point to the need for scanning a large frequency range for impedance measurements since capacitive and resistive regimes are strongly dependent on retina-electrode proximity. We believe that these results will contribute to a better understanding of electrical stimulation in neuroprostheses and ultimately improve their efficiency.

Electrochemically induced maskless metal deposition on micropore wall.

By applying an external electric field across a micropore via an electrolyte, metal ions in the electrolyte can be reduced locally onto the inner wall of the micropore, which was fabricated in a silica-covered silicon membrane. This maskless metal deposition on the silica surface is a result of the pore membrane polarization in the electric field.

Polarization-induced local pore-wall functionalization for biosensing: from micropore to nanopore.

The use of biological-probe-modified solid-state pores in biosensing is currently hindered by difficulties in pore-wall functionalization. The surface to be functionalized is small and difficult to target and is usually chemically similar to the bulk membrane. Herein, we demonstrate the contactless electrofunctionalization (CLEF) approach and its mechanism. This technique enables the one-step local functionalization of the single pore wall fabricated in a silica-covered silicon membrane. CLEF is induced by polarization of the pore membrane in an electric field and requires a sandwich-like composition and a conducting or semiconducting core for the pore membrane. The defects in the silica layer of the micropore wall enable the creation of an electric pathway through the silica layer, which allows electrochemical reactions to take place locally on the pore wall. The pore diameter is not a limiting factor for local wall modification using CLEF. Nanopores with a diameter of 200 nm fabricated in a silicon membrane and covered with native silica layer have been successfully functionalized with this method, and localized pore-wall modification was obtained. Furthermore, through proof-of-concept experiments using ODN-modified nanopores, we show that functionalized nanopores are suitable for translocation-based biosensing.

Self-arraying of charged levitating droplets.

Diamagnetic levitation of water droplets in air is a promising phenomenon to achieve contactless manipulation of chemical or biochemical samples. This noncontact handling technique prevents contaminations of samples as well as provides measurements of interaction forces between levitating reactors. Under a nonuniform magnetic field, diamagnetic bodies such as water droplets experience a repulsive force which may lead to diamagnetic levitation of a single or few micro-objects. The levitation of several repulsively charged picoliter droplets was successfully performed in a ~1 mm(2) adjustable flat magnetic well provided by a centimeter-sized cylindrical permanent magnet structure. Each droplet position results from the balance between the centripetal diamagnetic force and the repulsive Coulombian forces. Levitating water droplets self-organize into satellite patterns or thin clouds, according to their charge and size. Small triangular lattices of identical droplets reproduce magneto-Wigner crystals. Repulsive forces and inner charges can be measured in the piconewton and the femtocoulomb ranges, respectively. Evolution of interaction forces is accurately followed up over time during droplet evaporation.