Xiaohong Sui

In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation

BackgroundEpiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined.MethodsA novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina.ResultsThe substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex.ConclusionWe provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate.

Characterization of evoked tactile sensation in forearm amputees with transcutaneous electrical nerve stimulation.

OBJECTIVE The goal of this study is to characterize the phenomenon of evoked tactile sensation (ETS) on the stump skin of forearm amputees using transcutaneous electrical nerve stimulation (TENS). APPROACH We identified the projected finger map (PFM) of ETS on the stump skin in 11 forearm amputees, and compared perceptual attributes of the ETS in nine forearm amputees and eight able-bodied subjects using TENS. The profile of perceptual thresholds at the most sensitive points (MSPs) in each finger-projected area was obtained by modulating current amplitude, pulse width, and frequency of the biphasic, rectangular current stimulus. The long-term stability of the PFM and the perceptual threshold of the ETS were monitored in five forearm amputees for a period of 11 months. MAIN RESULTS Five finger-specific projection areas can be independently identified on the stump skin of forearm amputees with a relatively long residual stump length. The shape of the PFM was progressively similar to that of the hand with more distal amputation. Similar sensory modalities of touch, pressure, buzz, vibration, and numb below pain sensation could be evoked both in the PFM of the stump skin of amputees and in the normal skin of able-bodied subjects. Sensory thresholds in the normal skin of able-bodied subjects were generally lower than those in the stump skin of forearm amputees, however, both were linearly modulated by current amplitude and pulse width. The variation of the MSPs in the PFM was confined to a small elliptical area with 95% confidence. The perceptual thresholds of thumb-projected areas were found to vary less than 0.99 × 10(-2) mA cm(-2). SIGNIFICANCE The stable PFM and sensory thresholds of ETS are desirable for a non-invasive neural interface that can feed back finger-specific tactile information from the prosthetic hand to forearm amputees.

A simulation of current focusing and steering with penetrating optic nerve electrodes.

OBJECTIVE Current focusing and steering are both widely used to shape the electric field and increase the number of distinct perceptual channels in neural stimulation, yet neither technique has been used for an optic nerve (ON)-based visual prosthesis. In order to evaluate the effects of current focusing and steering in penetrative stimulation, we built an integrated computational model to simulate and investigate the influence of stimulating parameters on ON fibre recruitment. APPROACH Finite element models with extremely fine meshes were first established to compute the 3D electric potential distribution under different stimulating parameters. Then the external electric potential was fed to randomized multi-compartment cable models to predict the distribution of fibres generating an action potential. Finally a statistical process was conducted to quantify the recruitment region. MAIN RESULTS The simulation results show that a two-electrode mode is superior to a three-electrode mode in current steering. The three-electrode mode performs poorly in current focusing, albeit the localized recruitment from both configurations implies that current focusing might be unnecessary in penetrative ON stimulation. SIGNIFICANCE This study provides useful information for the optimized design of penetrating ON electrodes and stimulating strategies. The Monte Carlo style computation paradigm is designed to simulate neural responses of an ensemble of ON fibres, which can be immediately transferred to other similar problems.

Phantom finger perception evoked with transcutaneous electrical stimulation for sensory feedback of prosthetic hand

This paper reports a pilot study to explore the plausibility of using the phenomenon of phantom finger perception (PFP) in amputees to develop sensory feedback for prosthetic hand. PFP can be aroused by touching a specific part of the skin in the stump area of amputees. We hypothesized that transcutaneous electrical stimulation (TES) can evoke the similar PFP in amputees with electrodes placed at the same skin area. We tested this hypothesis in subjects with distal amputation at the forearm above the wrist. The areas of PFP on the stump skin of amputee subjects were first identified and labeled by manually touching the skin. Electrical stimulation was then applied to the same area with surface electrode. The subjects reported that the corresponding finger was touched with electrical stimulation, and gradation of sensation with increased strength of stimulation current was perceived in a similar way as reported in normal subjects. Peripheral nerve sprouting into the receptors in stump skin after amputation is speculated as the neural mechanism of PFP. Preliminary results support the hypothesis that PFP evoked by TES can be utilized to establish a direct sensory feedback from the fingers of prosthetic hand to the amputee.

Evaluation of a MEMS-Based Dual Metal-Layer Thin-Film Microelectrode Array for Suprachoroidal Electrical Stimulation

A double metal-layer thin-film platinum microelectrode array was fabricated for implantation between sclera and choroid based on MEMS processing techniques and photosensitive polyimide material. The array was composed of 60 stimulating sites (6 × 10) and four selectable returning electrodes. The diameter of each stimulating electrode was 350 μm with a center-to-center spacing of 750 μm. The transient voltage responses of the electrode to current pulse stimulation indicated a charge-injection capacity greater than 52.1 μC/cm2. Acute in vivo animal experiments showed that the implicit time of electrically evoked potentials (EEPs) was 17.09 ± 1.45 ms at a threshold current of 25.55 ± 5.43 μA for a full-row of simultaneously stimulated electrodes (i.e. current applied simultaneously to each of the 10 electrodes). Individual electrode stimulation threshold was 48.57 ± 6.90 μA. The corresponding threshold charge densities were 13.28 ± 2.82 μC/cm2 and 25.24 ± 3.59 μC/cm2, respectively. The spatial spread of the maximally recorded P1 response in the EEPs indicated a correspondence between the retinal stimulation site and the focal response location in the cortex. This method of array fabrication is suitable for acute suprachoroidal stimulation, and has a potential use for the fabrication of a visual prosthesis.

Visual Prosthesis for Optic Nerve Stimulation

The C-Sight visual prosthesis is based on optical nerve stimulation with a penetrating electrode array. A silicon-based microprobe by MEMS process techniques and Pt–Ir microwire arrays by electrochemical etching were fabricated in our project. Noise and impedance analyses were applied to optimize the electrode configuration. A multichannel microcurrent neural electrical stimulator and an implantable CMOS-based micro-camera were developed for neural stimulation and image acquisition, respectively, with a DSP-based system processing the captured image. Electrical evoked potentials (EEPs) from rabbit models were recorded using multichannel stainless-steel screws mounted on the primary visual cortex. The mean charge threshold density was 20.99 ± 5.52 μC/cm2 considering the exposed surface of the stimulating electrode. Current threshold decreased as the pulse duration of the stimulus increased while the corresponding charge threshold increased. The amplitude of P1 increased when the pulse duration increased from 0.4 to 1.0 ms while the latency of P1 changed little. Experiments also showed that different distribution maps of EEPs were elicited by different pairs of stimulating electrodes. The stimulating electrode pair along the axis of the optic nerve elicited cortical responses with much lower thresholds than that perpendicular to the axis of the optic nerve. The visual prosthesis with stimulating electrodes the penetrating into the optic nerve has been validated in animal experiments.

Cortical response of the projected-thumb tactile sensation under TENS by MEG

The existence of projected finger territories (PFTs) near the stump provides an essential way to realize the tactile sensation of lost fingers by transcutaneous electrical nerve stimulation (TENS). After amputation, the somatosensory cortex corresponding to lost fingers might be invaded by other cortical areas due to cortical plasticity. However, it was seldom observed how the amputees could feel the projected or lost finger tactile sensation in the cerebral cortex under TENS. To answer this question, by using magnetoencephalography (MEG), we investigated the cortical response under TENS of the projected thumb territory and normal thumb with 2 Hz current pulses. One subject with long-term left forearm amputation was recruited. The temporal and spatial characteristics of the activated cortical magnetic signals were analyzed. The Equivalent Current Dipoles (ECDs) corresponding to the strongest strength were mapped in the cerebral cortex, and the current density distribution were clearly illustrated. We found that the latencies at the maximum ECD strength were 60 ± 1.41 ms for the projected thumb and 46 ± 1.25 ms for the normal counterpart. The strongest ECD corresponding to projected thumb was located in the central sulcus near the mirror location of the normal thumb counterpart. And the response strengths of projected thumb cortex were stronger than normal thumb counterpart.

Effects of stratum corneum and conductive gel properties on sensory afferents recruitment by 3D TENS computational modeling

Incorporation of tactile sensory feedback by non-invasive transcutaneous electrical nerve stimulation (TENS) is potentially helpful for a prosthetic hand to accomplish dexterous manipulation. As for TENS through surface electrode, the stimulating current flows directly through the conductive gel and the stratum corneum (SC) layers to activate the tactile afferent nerve fibers. In our study the specific modulation effect of recruiting afferent nerve fibers in the two layers was investigated by establishing a 3D finite element model of the forearm. The results showed that both decreasing the gel thickness and increasing the gel resistivity improved the electrical stimulation sensitivity for electrotactile feedback, which would be beneficial to lower the threshold current of TENS. Meanwhile, decreasing the SC resistivity was also beneficial to improve the electrical stimulation sensitivity, but the variations of the normal SC thickness had negligible influence on the sensitivity. On one hand, these results gave us a specific guidance for choosing appropriate property parameters for conductive gel. On the other hand, both the thickness and resistivity of SC were susceptible to age, gender, and physical conditions etc., so it was significant for us to comprehend specific modulation effect under variation of SC properties.

A Flexible Thin-film Microelectrode for Optic-Nerve Visual Prosthesis

A novel 16-channel flexible thin-film microelectrode was fabricated for optic-nerve visual prosthesis by MEMS (Micro Electromechanical System) technology. It was encapsulated by medical-grade silicone adhesive and suitable for chronic stabilization in-vivo. Testing results in-vitro showed that average impedance of each channel was 100kΩ at 1kHz and that the microelectrode had good biocompatibility with the optic-nerve glial cells. Proper surgery was adopted to implant the microelectrode in the optic-nerve dura.

Discrimination and Recognition of Phantom Finger Sensation Through Transcutaneous Electrical Nerve Stimulation

Tactile sensory feedback would make a significant contribution to the state-of-the-art prosthetic hands for achieving dexterous manipulation over objects. Phantom finger sensation, also called referred sensation of lost fingers, can be noninvasively evoked by transcutaneous electrical nerve stimulation (TENS) of the phantom finger territories (PFTs) near the stump for upper-limb amputees. As such, intuitive sensations pertaining to lost fingers could be non-invasively generated. However, the encoding of stimulation parameters into tactile sensations that can be intuitively interpreted by the users remains a significant challenge. Further, how discriminative such artificial tactile sensation with TENS of the PFTs is still unknown. In this study, we systematically characterized the tactile discrimination across different phantom fingers on the stump skin by TENS among six subjects. Charge-balanced and biphasic stimulating current pulses were adopted. The pulse amplitude (PA), the pulse frequency (PF) and the pulse width (PW) were modulated to evaluate the detection threshold, perceived touch intensity, and the just-noticeable difference (JND) of the phantom finger sensation. Particularly, the recognition of phantom fingers under simultaneous stimulation was assessed. The psychophysical experiments revealed that subjects could discern fine variations of stimuli with comfortable sensation of phantom fingers including D1 (phantom thumb), D2 (phantom index finger), D3 (Phantom middle finger), and D5 (Phantom pinky finger). With respect to PA, PF, and PW modulations, the detection thresholds across the four phantom fingers were achieved by the method of constant stimuli based on a two-alternative forced-choice (2AFC) paradigm. For each modulation, the perceived intensity, which was indexed by skin indentations on the contralateral intact finger pulp, reinforced gradually with enhancing stimuli within lower-intensity range. Particularly, the curve of the indentation depth vs. PF almost reached a plateau with PF more than 200 Hz. Moreover, the performance of phantom finger recognition deteriorated with the increasing number of phantom fingers under simultaneous TENS. For one, two and four stimulating channels, the corresponding recognition rate of an individual PFT were respective 85.83, 67.67, and 46.44%. The results of the present work would provide direct guidelines regarding the optimization of stimulating strategies to deliver artificial tactile sensation by TENS for clinical applications.