Electrotactile Communication via Matrix Electrode Placed on the Torso Using Fast Calibration, and Static vs. Dynamic Encoding.

Electrotactile stimulation is a technology that reproducibly elicits tactile sensations and can be used as an alternative channel to communicate information to the user. The presented work is a part of an effort to develop this technology into an unobtrusive communication tool for first responders. In this study, the aim was to compare the success rate (SR) between discriminating stimulation at six spatial locations (static encoding) and recognizing six spatio-temporal patterns where pads are activated sequentially in a predetermined order (dynamic encoding). Additionally, a procedure for a fast amplitude calibration, that includes a semi-automated initialization and an optional manual adjustment, was employed and evaluated. Twenty subjects, including twelve first responders, participated in the study. The electrode comprising the 3 × 2 matrix of pads was placed on the lateral torso. The results showed that high SRs could be achieved for both types of message encoding after a short learning phase; however, the dynamic approach led to a statistically significant improvement in messages recognition (SR of 93.3%), compared to static stimulation (SR of 83.3%). The proposed calibration procedure was also effective since in 83.8% of the cases the subjects did not need to adjust the stimulation amplitude manually.

Design of a photoelectrochemical lab-on-a-chip immunosensor based on enzymatic production of quantum dots in situ.

In this work we report the development and validation of a photoelectrochemical immunosensor on the basis of alkaline phosphatase (ALP)-linked immunoassay for the detection of human serum albumin as a model analyte. In this biosensor, oriented immobilization of capture antibodies on aminated polystyrene was achieved via physical adsorption. After the interaction with the analyte, ALP immobilised on the surface through the sandwich immunoassay catalyses the hydrolysis of sodium thiophosphate (TP) to hydrogen sulphide (H2S) which in the presence of cadmium ions yields CdS quantum dots (QDs). The electrical current is generated in the course of the photoelectrochemical process (PEC) during irradiation of the CdS QDs with a UV LED (365 nm) on home-made screen-printed carbon electrodes modified with a conductive polymer. Reaction time, steps and volumes were optimized for the miniaturization of the process in order to develop a lab-on-a-chip platform. The microfluidic system was designed with optimised parameters to fabricate the immunosensor combining the immunoassay with PEC detection. The final system presents a sensitivity comparable to that of the commercial kit thanks to the signal amplification enabled by the enzymatic growth of CdS QDs in situ. This photoelectrochemical immunosensing strategy potentially opens up a new avenue for the detection of a wide range of analytes of interest due to the universal and effective enzymatic signal amplification method. Moreover, the developed bioanalytical device allows for a great reduction of time and reagents compared to exiting commercial assays, making it suitable for point-of-care applications.

Smart Protocols for Physical Therapy of Foot Drop Based on Functional Electrical Stimulation: A Case Study.

Functional electrical stimulation (FES) is used for treating foot drop by delivering electrical pulses to the anterior tibialis muscle during the swing phase of gait. This treatment requires that a patient can walk, which is mostly possible in the later phases of rehabilitation. In the early phase of recovery, the therapy conventionally consists of stretching exercises, and less commonly of FES delivered cyclically. Nevertheless, both approaches minimize patient engagement, which is inconsistent with recent findings that the full rehabilitation potential could be achieved by an active psycho-physical engagement of the patient during physical therapy. Following this notion, we proposed smart protocols whereby the patient sits and ankle movements are FES-induced by self-control. In six smart protocols, movements of the paretic ankle were governed by the non-paretic ankle with different control strategies, while in the seventh voluntary movements of the paretic ankle were used for stimulation triggering. One stroke survivor in the acute phase of recovery participated in the study. During the therapy, the patient's voluntary ankle range of motion increased and reached the value of normal gait after 15 sessions. Statistical analysis did not reveal the differences between the protocols in FES-induced movements.

High-throughput roll-to-roll production of polymer biochips for multiplexed DNA detection in point-of-care diagnostics.

Roll-to-roll UV nanoimprint lithography has superior advantages for high-throughput manufacturing of micro- or nano-structures on flexible polymer foils with various geometries and configurations. Our pilot line provides large-scale structure imprinting for cost-effective polymer biochips (4500 biochips/hour), enabling rapid and multiplexed detections. A complete high-volume process chain of the technology for producing structures like µ-sized, triangular optical out-couplers or capillary channels (width: from 1 µm to 2 mm, height: from 200 nm up to 100 µm) to obtain biochips (width: 25 mm, length: 75 mm, height: 100 µm to 1.5 mm) was described. The imprinting process was performed with custom-developed resins on polymer foils with resin thicknesses ranging between 125-190 µm. The produced chips were tested in a commercial point-of-care diagnostic system for multiplexed DNA analysis of methicillin resistant Staphylococcus aureus (e.g., mecA, mecC gene detections). Specific target DNA capturing was based on hybridisation between surface bound DNA probes and biotinylated targets from the sample. The immobilised biotinylated targets subsequently bind streptavidin-horseradish peroxidase conjugates, which in turn generate light upon incubation with a chemiluminescent substrate. To enhance the light out-coupling thus to improve the system performance, optical structures were integrated into the design. The limits-of-detection of mecA (25 bp) for chips with and without structures were calculated as 0.06 and 0.07 µM, respectively. Further, foil-based chips with fluidic channels were DNA functionalised in our roll-to-roll micro-array spotter following the imprinting. This straightforward approach of sequential imprinting and multiplexed DNA functionalisation on a single foil was also realised for the first time. The corresponding foil-based chips were able to detect mecA gene DNA sequences down to a 0.25 µM concentration.

PVA Cryogel as model hydrogel for iontophoretic transdermal drug delivery investigations. Comparison with PAA/PVA and PAA/PVP interpenetrating networks.

The use of polyvinyl alcohol (PVA) cryogel as a model hydrogel for iontophoretic transdermal investigations is proposed. Due to the excellent combination of its properties, it could be used for evaluating iontophoretic transdermal delivery of variety of drugs, regardless of pKa, pH or presence of auxiliary ions. Applicability of PVA Cryogel for drug delivery purposes was compared to those of polyacrylic acid/polyvinyl alcohol (PAA/PVA) and polyacrylic acid/polyvinylpyrrolidone (PAA/PVP) adhesive interpenetrating networks. Swelling properties of PVA Cryogel were shown to be almost independent on pH and NaCl concentration, while swelling of PAA-based gels was significantly affected. Addition of PVA and PVP to PAA decreased swelling degrees and increased adhesivity and compression moduli. Iontophoretic experiments were performed using a donor gel/skin/receptor gel configuration; current density and delivery duration were varied. Dexamethasone sodium phosphate was used as model drug molecule. PVA Cryogel was used for investigating the influence of NaCl concentration, which can alter the amount of current carried by the drug ions and, therefore, the delivery rate. By using PVA Cryogel it was possible to easily determine the amount of drug permeated through the skin into the receptor gel, the amount retained by the skin and the amount remained in the donor hydrogel. Decreasing NaCl concentration in PVA Cryogel resulted in higher total amounts of drug delivered and significantly enhanced drug permeation through the lower layers of the skin into the receptor hydrogel.

Novel multi-pad functional electrical stimulation in stroke patients: A single-blind randomized study.

BACKGROUND: Foot drop is common gait impairment after stroke. Functional electrical stimulation (FES) of the ankle dorsiflexor muscles during the swing phase of gait can help correcting foot drop. OBJECTIVE: To evaluate efficacy of additional novel FES system to conventional therapy in facilitating motor recovery in the lower extremities and improving walking ability after stroke. METHODS: Sixteen stroke patients were randomly allocated to the FES group (FES therapy plus conventional rehabilitation program) (n = 8), and control group (conventional rehabilitation program) n = 8. FES was delivered for 30 min during gait to induce ankle plantar and dorsiflexion. MAIN OUTCOME MEASURES: gait speed using 10 Meter Walk Test (10 MWT), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS) and modified Barthel Index (MBI). RESULTS: Results showed a significant increase in gait speed in FES group (p < 0.001), higher than the minimal detected change. The FES group showed improvement in functional independence in the activities of daily living, motor recovery and gait performance. CONCLUSIONS: The findings suggest that novel FES therapy combined with conventional rehabilitation is more effective on walking speed, mobility of the lower extremity, balance disability and activities of daily living compared to a conventional rehabilitation program only.

A decision support system for electrode shaping in multi-pad FES foot drop correction.

BACKGROUND: Functional electrical stimulation (FES) can be applied as an assistive and therapeutic aid in the rehabilitation of foot drop. Transcutaneous multi-pad electrodes can increase the selectivity of stimulation; however, shaping the stimulation electrode becomes increasingly complex with an increasing number of possible stimulation sites. We described and tested a novel decision support system (DSS) to facilitate the process of multi-pad stimulation electrode shaping. The DSS is part of a system for drop foot treatment that comprises a custom-designed multi-pad electrode, an electrical stimulator, and an inertial measurement unit. METHODS: The system was tested in ten stroke survivors (3-96 months post stroke) with foot drop over 20 daily sessions. The DSS output suggested stimulation pads and parameters based on muscle twitch responses to short stimulus trains. The DSS ranked combinations of pads and current amplitudes based on a novel measurement of the quality of the induced movement and classified them based on the movement direction (dorsiflexion, plantar flexion, eversion and inversion) of the paretic foot. The efficacy of the DSS in providing satisfactory pad-current amplitude choices for shaping the stimulation electrode was evaluated by trained clinicians. The range of paretic foot motion was used as a quality indicator for the chosen patterns. RESULTS: The results suggest that the DSS output was highly effective in creating optimized FES patterns. The position and number of pads included showed pronounced inter-patient and inter-session variability; however, zones for inducing dorsiflexion and plantar flexion within the multi-pad electrode were clearly separated. The range of motion achieved with FES was significantly greater than the corresponding active range of motion (p < 0.05) during the first three weeks of therapy. CONCLUSIONS: The proposed DSS in combination with a custom multi-pad electrode design covering the branches of peroneal and tibial nerves proved to be an effective tool for producing both the dorsiflexion and plantar flexion of a paretic foot. The results support the use of multi-pad electrode technology in combination with automatic electrode shaping algorithms for the rehabilitation of foot drop. TRIAL REGISTRATION: This study was registered at the Current Controlled Trials website with ClinicalTrials.gov ID NCT02729636 on March 29, 2016.

Computational and experimental model of transdermal iontophorethic drug delivery system.

The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery.

Multichannel Electrotactile Feedback With Spatial and Mixed Coding for Closed-Loop Control of Grasping Force in Hand Prostheses.

Providing somatosensory feedback to the user of a myoelectric prosthesis is an important goal since it can improve the utility as well as facilitate the embodiment of the assistive system. Most often, the grasping force was selected as the feedback variable and communicated through one or more individual single channel stimulation units (e.g., electrodes, vibration motors). In the present study, an integrated, compact, multichannel solution comprising an array electrode and a programmable stimulator was presented. Two coding schemes (15 levels), spatial and mixed (spatial and frequency) modulation, were tested in able-bodied subjects, psychometrically and in force control with routine grasping and force tracking using real and simulated prosthesis. The results demonstrated that mixed and spatial coding, although substantially different in psychometric tests, resulted in a similar performance during both force control tasks. Furthermore, the ideal, visual feedback was not better than the tactile feedback in routine grasping. To explain the observed results, a conceptual model was proposed emphasizing that the performance depends on multiple factors, including feedback uncertainty, nature of the task and the reliability of the feedforward control. The study outcomes, specific conclusions and the general model, are relevant for the design of closed-loop myoelectric prostheses utilizing tactile feedback.

Integrated and flexible multichannel interface for electrotactile stimulation.

OBJECTIVE: The aim of the present work was to develop and test a flexible electrotactile stimulation system to provide real-time feedback to the prosthesis user. The system requirements were to accommodate the capabilities of advanced multi-DOF myoelectric hand prostheses and transmit the feedback variables (proprioception and force) using intuitive coding, with high resolution and after minimal training. APPROACH: We developed a fully-programmable and integrated electrotactile interface supporting time and space distributed stimulation over custom designed flexible array electrodes. The system implements low-level access to individual stimulation channels as well as a set of high-level mapping functions translating the state of a multi-DoF prosthesis (aperture, grasping force, wrist rotation) into a set of predefined dynamic stimulation profiles. The system was evaluated using discrimination tests employing spatial and frequency coding (10 able-bodied subjects) and dynamic patterns (10 able-bodied and 6 amputee subjects). The outcome measure was the success rate (SR) in discrimination. MAIN RESULTS: The more practical electrode with the common anode configuration performed similarly to the more usual concentric arrangement. The subjects could discriminate six spatial and four frequency levels with SR >90% after a few minutes of training, whereas the performance significantly deteriorated for more levels. The dynamic patterns were intuitive for the subjects, although amputees showed lower SR than able-bodied individuals (86% ± 10% versus 99% ± 3%). SIGNIFICANCE: The tests demonstrated that the system was easy to setup and apply. The design and resolution of the multipad electrode was evaluated. Importantly, the novel dynamic patterns, which were successfully tested, can be superimposed to transmit multiple feedback variables intuitively and simultaneously. This is especially relevant for closing the loop in modern multifunction prostheses. Therefore, the proposed system is convenient for practical applications and can be used to implement sensory perception training and/or closed-loop control of myoelectric prostheses, providing grasping force and proprioceptive feedback.

Numerical simulation of iontophoresis in the drug delivery system.

The architecture and composition of stratum corneum act as barriers and limit the diffusion of most drug molecules and ions. Much effort has been made to overcome this barrier and it can be seen that iontophoresis has shown a good effect. Iontophoresis represents the application of low electrical potential to increase the transport of drugs into and across the skin or tissue. Iontophoresis is a noninvasive drug delivery system, and therefore, it is a useful alternative to drug transportation by injection. In this study, we present a numerical model and effects of electrical potential on the drug diffusion in the buccal tissue and the stratum corneum. The initial numerical results are in good comparison with experimental observation. We demonstrate that the application of an applied voltage can greatly improve the efficacy of localized drug delivery as compared to diffusion alone.

Relationship Between Electromyographic Signal Amplitude and Thickness Change of the Trunk Muscles in Patients With and Without Low Back Pain.

OBJECTIVES: To compare the relative thickness change of the transversal abdominal (TrA) and lumbar multifidus (LM) muscles during activation in individuals with and without low back pain (LBP), and to establish a relationship between surface electromyography (sEMG) signal amplitude and the relative thickness change of the corresponding muscle during clinically relevant activity, with preferential activation of TrA/LM. MATERIALS AND METHODS: Thirty-seven pain-free participants and 36 LBP patients were assessed by ultrasound for thickness changes of TrA and LM and by sEMG for changes of electrical activity of the same muscles. sEMG is done with wireless LUMBIA system. The position of the sEMG sensors and activation maneuvers were chosen carefully. RESULTS: Significant group effect was found for relative thickness change of TrA (F1,142=60.69, P<0.0001) and LM (F1,142=36.01, P<0.0001). We found significant correlations between relative thickness change of TrA and sEMG signal amplitude on both sides for LBP (r=0.46 to 0.63, P<0.05) and pain-free patients (r=0.43-0.47, P<0.05). The correlation between LM thickness change and sEMG was significant in pain-free participants for both sides (r=0.36 to 0.38 P<0.05), and right LM in LBP participants (r=0.43, P<0.05), but not for LM in LBP group (r=0.16, P=0.351). DISCUSSION: US and sEMG measurements can be used for objective TrA/LM assessment. Correlation results suggest that the relative change of the muscle thickness could be used as the indicator of the muscle activity. Insight into the activity of TrA/LM in pain-free individuals and LBP patients during and after painful episodes may clarify the role of functional abnormalities of these muscles in LBP.

Multi-pad electrode for effective grasping: design.

We designed a new surface multi-pad electrode for the electrical stimulation of the forearm that is effective in controlling functional grasp in hemiplegic patients. The electrode shape and size were designed on the basis of the surface stimulation map of the forearm, determined from measurements in seven hemiplegic patients who had limited or absent voluntary movements of the fingers, thumb and wrist. The stimulation map for each patient was assessed with a conventional set of single pad Pals Platinum electrodes. Since the sites for the stimulation varied greatly between patients, the end result was a rather large multi-pad electrode. Modulating multi-pad electrode size, shape, position and individual pad stimulation parameters allows us to accommodate the diversity of the neural tissues in patients that need to be activated for functional grasp. This also allows asynchronous activation of different portions of the muscle and dynamic adaptation of the stimulation sites to appropriate underlying tissues during functional use. The validity of the determined stimulation map was tested in the same group of hemiplegic patients. The selected set of active pads resulted in fully functional and reproducible palmar and lateral grasps similar to healthy-like grasps.

A multi-pad electrode based functional electrical stimulation system for restoration of grasp.

BACKGROUND: Functional electrical stimulation (FES) applied via transcutaneous electrodes is a common rehabilitation technique for assisting grasp in patients with central nervous system lesions. To improve the stimulation effectiveness of conventional FES, we introduce multi-pad electrodes and a new stimulation paradigm. METHODS: The new FES system comprises an electrode composed of small pads that can be activated individually. This electrode allows the targeting of motoneurons that activate synergistic muscles and produce a functional movement. The new stimulation paradigm allows asynchronous activation of motoneurons and provides controlled spatial distribution of the electrical charge that is delivered to the motoneurons. We developed an automated technique for the determination of the preferred electrode based on a cost function that considers the required movement of the fingers and the stabilization of the wrist joint. The data used within the cost function come from a sensorized garment that is easy to implement and does not require calibration. The design of the system also includes the possibility for fine-tuning and adaptation with a manually controllable interface. RESULTS: The device was tested on three stroke patients. The results show that the multi-pad electrodes provide the desired level of selectivity and can be used for generating a functional grasp. The results also show that the procedure, when performed on a specific user, results in the preferred electrode configuration characteristics for that patient. The findings from this study are of importance for the application of transcutaneous stimulation in the clinical and home environments.

Adsorption characteristics of stoichiometric and nonstoichiometric molecular polyelectrolyte complexes on silicon oxynitride surfaces.

Adsorption properties of stoichiometric and nonstoichiometric polyelectrolyte complexes (PECs) have been investigated by means of dual polarization interferometry (DPI) and X-ray photoelectron spectroscopy (XPS). Poly(sodium styrenesulfonate) (NaPSS) of molecular weight 4300 g/mol was used as polyanion, and two bottle-brush copolymers possessing different molar ratios of the cationic segment methacryloxyethyltrimethylammonium chloride (METAC) and the nonionic segment poly(ethylene oxide) methyl ether methacrylate (PEO(45)MEMA) were used as polycations. They are referred to as PEO(45)MEMA:METAC-25 and PEO(45)MEMA:METAC-50, where the last digits denote the mol % of charged main-chain segments. The time evolution of the adsorbed amount, thickness, and refractive index of the PEC layers were determined in aqueous solution using DPI. We demonstrate that cationic, uncharged, and negatively charged complexes adsorb to negatively charged silicon oxynitride and that maximum adsorption is achieved when small amounts of PSS are present in the complexes. The surface composition of the adsorbed PEC layers was estimated from XPS measurements that demonstrated very low content of NaPSS. On the basis of these data, the PEC adsorption mechanism is discussed and the competition between PSS and negative surface sites for association with the cationic polyelectrolyte is identified as a key issue.

Adsorption characteristics of brush polyelectrolytes on silicon oxynitride revealed by dual polarization interferometry.

Adsorption properties of bottle-brush polyelectrolytes have been investigated using dual polarization interferometry (DPI), which provides real time monitoring of adsorbed layer thickness and refractive index. The adsorption on silicon oxynitride was carried out from aqueous solution with no added inorganic salt, and the adsorbed polyelectrolyte layer was subsequently rinsed with NaCl solutions of increasing concentration. The bottle-brush polyelectrolytes investigated in this study have different ratios of permanent cationic charged segments and uncharged PEO side chains. Both the cationic groups and the PEO side chains have affinity for silica-like surfaces, and thus contribute to the adsorption process that becomes rather complex. Adsorption properties in water, responses to changes in ionic strength of the surrounding medium, adsorption kinetics and the layer structure are all strongly dependent on the ratio between backbone charges and side chains. The results are interpreted in terms of competitive adsorption of segments with different chemical nature. The adsorption kinetics is relatively fast, taking only tens to hundreds of seconds when adsorbed from dilute 100 ppm solutions. The DPI technique was found to be suitable for studying such rapid adsorption processes, including determination of the initial adsorption kinetics. We expect that the effects observed in this study are of general importance for synthetic and biological polymers carrying segments of different nature.

Lumbar stimulation belt for therapy of low-back pain.

We developed the STIMBELT, an electrical stimulation system that comprises a lumbar belt with up to eight pairs of embedded electrodes and an eight-channel electronic stimulator. The STIMBELT is an assistive system for the treatment of low-back pain (LBP). We describe here technical details of the system and summarize the results of its application in individuals with subacute and chronic LBP. The direct goals of the treatment were to relieve pain, reduce muscle spasms, increase strength and range of motion, and educate individuals with LBP in reducing the chances of its reoccurrence. The outcome measures include: a Visual Analogue Scale (VAS), the Oswestry LBP Disability Questionnaire, the Short Form (SF)-12 health survey, and the Manual Muscle Test. The results indicate significant benefits for individuals who use the STIMBELT in addition to the conventional therapy as opposed to only the conventional therapy.

Numerically simulated pH-induced reactivation of catalytic activity of horseradish peroxidase.

A model mechanism that accounts for the experimentally observed pH-dependent enhancement of enzymatic activity of horseradish peroxidase through the catalase-like pathway is proposed. Predictions of the model are tested against a number of experimental results to confirm that kinetic constants used in the numerical simulation are correctly chosen and that the model can be used to emulate the reaction between horseradish peroxidase and hydrogen peroxide in a wide range of conditions.

Multi-field surface electrode for selective electrical stimulation.

We designed a 24-field array and an on-line control box that selects which and how many of 24 fields will conduct electrical charge during functional electrical stimulation. The array was made using a conductive microfiber textile, silver two-component adhesive, and the conductive ink imprint on the polycarbonate. The control box comprised 24 switches that corresponded one-to-one to the fields on the array. Each field could be made conductive or nonconductive by simple pressing of the corresponding push-button type switch on the control box. We present here representative results of the selectivity of the new electrode measured in three tetraplegic patients during functional electrical stimulation of the forearm. The task was to generate finger flexion and extension with minimal interference of the wrist movement during lateral and palmar grasps. Therapists determined the appropriate pattern that lead to effective grasping, lasting on average 5 min per stimulation channel in the first session. This optimal conductive pattern (size and shape) provided effective finger flexion and extension with minimal wrist flexion/extension and ulnar/radial deviations (<10 degrees). The optimal size and shape of the electrode in all cases had a branched pattern. The selection of the optimal stimulation site was achieved without moving the electrode. The size and shape were reproducible in the same subject from session to session, yet were different from subject to subject. The optimal electrode size and shape changed when subjects pronated and supinated their forearm. The control box includes a program that can dynamically change the number and sites of the conductive fields; hence, it is feasible to use this during functional movements. Subjects learned how to determine the optimal electrode pattern; hence, these electrodes could be effective for home usage.