Aim: Multisegmental gastrointestinal (GI) dysmotilities, such as chronic intestinal pseudo-obstruction, may lead to life-threatening events. The interdisciplinary INTAKT project is developing wirelessly communicating GI devices for intelligent sensor technology and electrostimulation-based motility modulation. However, a concrete vision of clinical implementation has not been previously described. Methods: An interdisciplinary team of surgeons, gastroenterologists, biologists, engineers, veterinarians and product designers developed a clinical scenario based on pre-clinical experiments, contextual analysis and usage scenarios. Results: The surgical experiences of our previous studies with conventional open, laparoscopic and robotic setups were analyzed. Patient selection, a surgical strategy and perioperative management are described in detail. Conclusion: Further technological solutions may enable first-in-human trials according to our protocol.

Abstract Background Remarkable work has been recently introduced to enhance the usage of Electromyography (EMG) signals in operating prosthetic arms. Despite the rapid advancements in this field, providing a reliable, naturalistic myoelectric prosthesis remains a significant challenge. Other challenges include the limited number of allowed movements, lack of simultaneous, continuous control and the high computational power that could be needed for accurate decoding. In this study, we propose an EMG-based multi-Kalman filter approach to decode arm kinematics; specifically, the elbow angle (θ), wrist joint horizontal (X) and vertical (Y) positions in a continuous and simultaneous manner. Results Ten subjects were examined from which we recorded arm kinematics and EMG signals of the biceps, triceps, lateral and anterior deltoid muscles corresponding to a randomized set of movements. The performance of the proposed decoder is assessed using the correlation coefficient (CC) and the normalized root-mean-square error (NRMSE) computed between the actual and the decoded kinematic. Results demonstrate that when training and testing the decoder using same-subject data, an average CC of 0.68 ± 0.1, 0.67 ± 0.12 and 0.64 ± 0.11, and average NRMSE of 0.21 ± 0.06, 0.18 ± 0.03 and 0.24 ± 0.07 were achieved for θ, X, and Y, respectively. When training the decoder using the data of one subject and decoding the data of other subjects, an average CC of 0.61 ± 0.19, 0.61 ± 0.16 and 0.48 ± 0.17, and an average NRMSE of 0.23 ± 0.07, 0.2 ± 0.05 and 0.38 ± 0.15 were achieved for θ, X, and Y, respectively. Conclusions These results suggest the efficacy of the proposed approach and indicates the possibility of obtaining a subject-independent decoder.

Need Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. Technical Solution A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. Proof of Concept Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. Next Steps Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. Conclusion We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.

Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs.

Einleitung Patienten mit multisegmentalen gastrointestinalen Motilitätsstörungen, wie beispielsweise der Gastroparese mit Slow-Transit-Obstipation oder der Chronischen Intestinalen Pseudoobsstruktion (CIPO) leiden unter eingeschränkter Lebensqualität, Nebenwirkungen aktueller Therapien und ausgedehnten Resektionen.

Abstract We present the first results of work towards a foil-based epiretinal prosthesis that can stimulate retinal cells. The prosthesis receives trigger signals and energy in the form of high intensity infrared radiation. Array-like silicon photodiodes with attached thin film electrodes convert the received infrared light into electrical stimulation signals, which are intended to stimulate ganglion cells. The photodiodes are arranged like stones in a mosaic on an only 10 µm thin and thus flexible polymer foil. Like this, the prosthesis can adapt to the curved shape of the eye and will have close contact with the retina. The photodiode array is fabricated on silicon wafers. Etched trenches guarantee the electrical separation between the individual photodiodes and pixels. Spectral sensitivities of backside-illuminated photodiodes were measured for wafers thinned to different thicknesses. The thin polymer foil is realized by spin coating polyimide on the photodiode array followed by imidization. Via holes are etched into the polyimide film for contacting the pads of the photodiodes. First spin coating tests were performed using silicon wafers without photodiodes but with metal pads and with etched trenches to simulate the gap between individual photodiodes. Although the thickness of the spin-coated polyimide layer was very inhomogeneous, we succeeded in realizing vias for connecting contact pads by thin film gold tracks crossing deep trenches. The realized via holes had inclined sidewalls as desired. Electrical measurements showed sufficient electrical contact between two connected pads.

This paper reports on the evaluation of recurrent and convolutional neural networks as real-time grasp phase classifiers for future control of neuroprostheses for people with high spinal cord injury. A field-programmable gate array has been chosen as an implementation platform due to its form factor and ability to perform parallel computations, which are specific for the selected neural networks. Three different phases of two grasp patterns and the additional open hand pattern were predicted by means of surface Electromyography (EMG) signals (i.e. Seven classes in total). Across seven healthy subjects, CNN (Convolutional Neural Networks) and RNN (Recurrent Neural Networks) had a mean accuracy of 85.23% with a standard deviation of 4.77% and 112 µs per prediction and 83.30% with a standard deviation of 4.36% and 40 µs per prediction, respectively.

Background: The aim of this study was to address the vision of wireless theranostic devices distributed along the gastrointestinal (GI) tract by defining design requirements, developing prototype mock-ups, and establishing a minimally invasive surgical approach for the implantation process.Methods: Questionnaires for contextual analysis and use case scenarios addressing the technical issues of an implantable GI device, a possible scenario for implantation, preparation and calibration of a device, and therapeutic usage by professionals and patients were completed and discussed by an interdisciplinary team of surgeons, engineers, and product designers. Two acute porcine experiments were conducted with a robotic surgical system under general anaesthesia.Results: A variety of requirements for the design and implantation of implantable devices for modulating GI motility were defined. Five prototype implant mock-ups were three-dimensional (3D)-printed from black polymer material (width 22.32 mm, height 7.66 mm) and successfully implanted on the stomach, duodenum, jejunum, ileum, and colon using the robotic surgical system, without any complications.Conclusions: Our study shows the development and successful pre-clinical evaluation of a reliable device design with a minimally invasive implantation approach. Several stages of device development, including pre-clinical tests, characterisation of clinical requirements, regulatory affairs, and marketing issues should be managed side by side.

Background:Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree of tissue trauma. We evaluated a minimally invasive surgical approach using a robotic surgical system to perform electromyographic (EMG) recordings and ES of several porcine GI segments, comparing these data to an open surgical approach by laparotomy.Materials and Methods:In 5 acute porcine experiments, we placed multiple electrodes on the stomach, duodenum, jejunum, ileum, and colon. Three experiments were performed with a median laparotomy and 2 others using a robotic platform. Multichannel EMGs were recorded, and ES was sequentially delivered with 4 ES parameters to the 5 target segments. We calculated pre- and poststimulatory spikes per minute (Spm) and performed a statistical Poisson analysis.Results:Electrode placement was achieved in all cases without complications. Increased technical and implantation time were required to achieve the robotic electrode placement, but invasiveness was markedly reduced in comparison to the conventional approach. The highest calculated (c)Spm values were found in the poststimulatory period of the small bowel with both the conventional and robotic approaches. Six of the 20 Poisson test results in the open setup reached statistical significance and 12 were significant in the robotic experiments.Conclusions:The robotic setup was less invasive, revealed more consistent effects of multilocular ES in several GI segments, and is a promising option for future preclinical and clinical studies of GI motility disorders.

Despite previous studies on the restoration of tactile sensation to the fingers and the hand, there are no examples of use of the routed sensory information to finely control a prosthestic hand in complex grasp and manipulation tasks. Here, it is shown that force and slippage sensations can be elicited in an amputee by means of biologically inspired slippage detection and encoding algorithms, supported by a stick-slip model of the performed grasp. A combination of cuff and intraneural electrodes was implanted for 11 weeks in a young woman with hand amputation and was shown to provide close-to-natural force and slippage sensations, paramount for substantially improving manipulative skills with the prosthesis. Evidence is provided about the improvement of the participant's grasping and manipulation capabilities over time resulting from neural feedback. The elicited tactile sensations enabled the successful fulfillment of fine grasp and manipulation tasks with increasing complexity. Grasp performance was quantitatively assessed by means of instrumented objects and a purposely developed metrics. Closed-loop control capabilities enabled by the neural feedback were compared with those achieved without feedback. Further, the work demonstrates that the described amelioration of motor performance in dexterous tasks had as central neurophysiological correlates changes in motor cortical plasticity and that such changes were not of purely motor origin, but were the effect of a strong and persistent drive of the sensory feedback.

New regulations for medical products complicate research projects for new application fields and translation of innovative product ideas to refundable medical products becomes a high economic risk. All this demands for a CE-marked platform, which offers the possibility to access the recorded data online or even directly the hardware during research applications, to bridge the gap. This paper describes how a CE-marked medical product can be extended by different interfaces to enable basic research or simplify first proof-of-concept studies thus optimizing prototype development in research projects, simplifying the documentation process and reducing the risk for market access.

Gastrointestinale (GI) Motilitätsstörungen können den gesamten Verdauungstrakt betreffen. Eine vielversprechende diagnostische und therapeutische Option für medikamentös-refraktäre Störungen bieten die Elektromyografie (EMG) mit multilokulärer elektrischer Stimulation (ES). Grundlegende Experimente wurden bisher mittels konventioneller Laparotomie durchgeführt.

BACKGROUND/AIMS:Motility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocular sensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate the effects of adjustable ES on poststimulatory spike activities in 5 GI segments.METHODS:Six acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or 1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needle and hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance by Poisson analysis.RESULTS:Post-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of 24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required a pulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Five reaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X), and 27.5% non-significant responses (type 0).CONCLUSIONS:Multilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automated electromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

Networks of distributed interactive micro-implants could enhance the treatment of otoneurological conditions such as tinnitus or restore impaired complex physiological/ motor functions such as gastrointestinal motility or grasping. For this, an electrical stimulation of neural and muscular tissue is a key prerequisite. Challenges in the development of such interactive micro-implants are the complex human-machine interface, the wireless power supply, and the long-term stability of implants as well as secure and safe signal transmission. This paper addresses all these topics as well as the ethical, legal and social implications of smart implant networks in general. First achievements of the German innovation cluster INTAKT will be presented.

Objective. We propose, design and test a novel thin-film multichannel electrode that can be used for both recording from and stimulating a muscle in acute implants. Approach. The system is built on a substrate of polyimide and contains 12 recording and three stimulation sites made of platinum. The structure is 420 µm wide, 20 µm thick and embeds the recording and stimulation contacts on the two sides of the polyimide over an approximate length of 2 cm. We show representative applications in healthy individuals as well as tremor patients. The designed system was tested by a psychometric characterization of the stimulation contacts in six tremor patients and three healthy individuals determining the perception threshold and current limit as well as the success rate in discriminating elicited sensations (electrotactile feedback). Also, we investigated the possibility of using the intramuscular electrode for reducing tremor in one patient by electrical stimulation delivered with timing based on the electromyographic activity recorded with the same electrode. Main results. In the tremor patients, the current corresponding to the perception threshold and the current limit were 0.7  ±  0.2 and 1.4  ±  0.7 mA for the wrist flexor muscles and 0.4  ±  0.2 and 1.5  ±  0.7 mA for the extensors. In one patient, closed-loop stimulation resulted in a decrease of the tremor power  >50%. In healthy individuals the perception threshold and current limits were 0.9  ±  0.6 and 2.1  ±  0.6 mA for the extensor carpi radialis muscle. The subjects could distinguish four or six stimulation patterns (two or three stimulation sites  ×  two stimulation current amplitudes) with true positive rate  >80% (two subjects) and  >60% (one subject), respectively. Significance. The proposed electrode provides a compact multichannel interface for recording electromyogram and delivering electrical stimulation in applications such as neuroprostheses for tremor suppression and closed-loop myoelectric prostheses.

A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

Different complex physiological functions might be restored by means of distributed active implants. Wireless communication between the implants, on the one hand, and an external control unit, on the other hand, is necessary to synchronize electrical stimulation of neural and muscular tissue. Seventeen project partners from industries, universities, healthcare providers and research organizations closely cooperate in the framework of the BMBF Innovation Cluster “Interactive Implants (INTAKT)”. The goal of this cluster is to develop and evaluate networks of distributed implants. Challenges of the project include complex interaction between humans and technology, wireless power supply, long-term stability of implants as well as secure and safe signal transmission [1].