Human gait-labeling uncertainty and a hybrid model for gait segmentation.

Motion capture systems are widely accepted as ground-truth for gait analysis and are used for the validation of other gait analysis systems. To date, their reliability and limitations in manual labeling of gait events have not been studied. Objectives: Evaluate manual labeling uncertainty and introduce a hybrid stride detection and gait-event estimation model for autonomous, long-term, and remote monitoring. Methods: Estimate inter-labeler inconsistencies by computing the limits-of-agreement. Develop a hybrid model based on dynamic time warping and convolutional neural network to identify valid strides and eliminate non-stride data in inertial (walking) data collected by a wearable device. Finally, detect gait events within a valid stride region. Results: The limits of inter-labeler agreement for key gait events heel off, toe off, heel strike, and flat foot are 72, 16, 24, and 80 ms, respectively; The hybrid model's classification accuracy for stride and non-stride are 95.16 and 84.48%, respectively; The mean absolute error for detected heel off, toe off, heel strike, and flat foot are 24, 5, 9, and 13 ms, respectively, when compared to the average human labels. Conclusions: The results show the inherent labeling uncertainty and the limits of human gait labeling of motion capture data; The proposed hybrid-model's performance is comparable to that of human labelers, and it is a valid model to reliably detect strides and estimate the gait events in human gait data. Significance: This work establishes the foundation for fully automated human gait analysis systems with performances comparable to human-labelers.

Real-Time Gait Phase Detection on Wearable Devices for Real-World Free-Living Gait.

Detecting gait phases with wearables unobtrusively and reliably in real-time is important for clinical gait rehabilitation and early diagnosis of neurological diseases. Due to hardware limitations of microcontrollers in wearable devices (e.g., memory and computation power), reliable real-time gait phase detection on the microcontrollers remains a challenge, especially for long-term real-world free-living gait. In this work, a novel algorithm based on a reduced support vector machine (RSVM) and a finite state machine (FSM) is developed to address this. The RSVM is developed by exploiting the cascaded K-means clustering to reduce the model size and computation time of a standard SVM by 88% and a factor of 36, with only minor degradation in gait phase prediction accuracy of around 4%. For each gait phase prediction from the RSVM, the FSM is designed to validate the prediction and correct misclassifications. The developed algorithm is implemented on a microcontroller of a wearable device and its real-time (on the fly) classification performance is evaluated by twenty healthy subjects walking along a predefined real-world route with uncontrolled free-living gait. It shows a promising real-time performance with an accuracy of 91.51%, a sensitivity of 91.70%, and a specificity of 95.77%. The algorithm also demonstrates its robustness with varying walking conditions.

Integrated Pedal System for Data Driven Rehabilitation.

We present a system capable of providing visual feedback for ergometer training, allowing detailed analysis and gamification. The presented solution can easily upgrade any existing ergometer device. The system consists of a set of pedals with embedded sensors, readout electronics and wireless communication modules and a tablet device for interaction with the users, which can be mounted on any ergometer, transforming it into a full analytical assessment tool with interactive training capabilities. The methods to capture the forces and moments applied to the pedal, as well as the pedal's angular position, were validated using reference sensors and high-speed video capture systems. The mean-absolute error (MAE) for load is found to be 18.82 N, 25.35 N, 0.153 Nm for Fx, Fz and Mx respectively and the MAE for the pedal angle is 13.2°. A fully gamified experience of ergometer training has been demonstrated with the presented system to enhance the rehabilitation experience with audio visual feedback, based on measured cycling parameters.

An Intelligent In-Shoe System for Gait Monitoring and Analysis with Optimized Sampling and Real-Time Visualization Capabilities.

The deterioration of gait can be used as a biomarker for ageing and neurological diseases. Continuous gait monitoring and analysis are essential for early deficit detection and personalized rehabilitation. The use of mobile and wearable inertial sensor systems for gait monitoring and analysis have been well explored with promising results in the literature. However, most of these studies focus on technologies for the assessment of gait characteristics, few of them have considered the data acquisition bandwidth of the sensing system. Inadequate sampling frequency will sacrifice signal fidelity, thus leading to an inaccurate estimation especially for spatial gait parameters. In this work, we developed an inertial sensor based in-shoe gait analysis system for real-time gait monitoring and investigated the optimal sampling frequency to capture all the information on walking patterns. An exploratory validation study was performed using an optical motion capture system on four healthy adult subjects, where each person underwent five walking sessions, giving a total of 20 sessions. Percentage mean absolute errors (MAE%) obtained in stride time, stride length, stride velocity, and cadence while walking were 1.19%, 1.68%, 2.08%, and 1.23%, respectively. In addition, an eigenanalysis based graphical descriptor from raw gait cycle signals was proposed as a new gait metric that can be quantified by principal component analysis to differentiate gait patterns, which has great potential to be used as a powerful analytical tool for gait disorder diagnostics.

Programmable Locomotion Mechanisms of Nanowires with Semihard Magnetic Properties Near a Surface Boundary.

We report on the simplest magnetic nanowire-based surface walker that is able to change its propulsion mechanism near a surface boundary as a function of the applied rotating magnetic field frequency. The nanowires are made of CoPt alloy with semihard magnetic properties synthesized by means of template-assisted galvanostatic electrodeposition. The semihard magnetic behavior of the nanowires allows for programming their alignment with an applied magnetic field as they can retain their magnetization direction after premagnetizing them. By engineering the macroscopic magnetization, the nanowires' speed and locomotion mechanism are set to tumbling, precession, or rolling depending on the frequency of an applied rotating magnetic field. Also, we present a mathematical analysis that predicts the translational speed of the nanowire near the surface, showing a very good agreement with experimental results. Interestingly, the maximal speed is obtained at an optimal frequency (∼10 Hz), which is far below the theoretical step-out frequency (∼345 Hz). Finally, vortices are found by tracking polystyrene microbeads, trapped around the CoPt nanowire, when they are propelled by precession and rolling motion.

Protective coatings for intraocular wirelessly controlled microrobots for implantation: Corrosion, cell culture, and in vivo animal tests.

Diseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This article investigates the use of polypyrrole- and gold-coated cobalt-nickel microrobots. While gold has been used in ocular implants, no ocular implantation involving polypyrrole is reported, despite its well-established biocompatibility properties. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after 2 weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 836-845, 2017.

Multisegmented FeCo/Cu nanowires: electrosynthesis, characterization, and magnetic control of biomolecule desorption.

In this paper, we report on the synthesis of FeCo/Cu multisegmented nanowires by means of pulse electrodeposition in nanoporous anodic aluminum oxide arrays supported on silicon chips. By adjustment of the electrodeposition conditions, such as the pulse scheme and the electrolyte, alternating segments of Cu and ferromagnetic FeCo alloy can be fabricated. The segments can be built with a wide range of lengths (15-150 nm) and exhibit a close-to-pure composition (Cu or FeCo alloy) as suggested by energy-dispersive X-ray mapping results. The morphology and the crystallographic structure of different nanowire configurations have been assessed thoroughly, concluding that Fe, Co, and Cu form solid solution. Magnetic characterization using vibrating sample magnetometry and magnetic force microscopy reveals that by introduction of nonmagnetic Cu segments within the nanowire architecture, the magnetic easy axis can be modified and the reduced remanence can be tuned to the desired values. The experimental results are in agreement with the provided simulations. Furthermore, the influence of nanowire magnetic architecture on the magnetically triggered protein desorption is evaluated for three types of nanowires: Cu, FeCo, and multisegmented FeCo15nm/Cu15nm. The application of an external magnetic field can be used to enhance the release of proteins on demand. For fully magnetic FeCo nanowires the applied oscillating field increased protein release by 83%, whereas this was found to be 45% for multisegmented FeCo15nm/Cu15nm nanowires. Our work suggests that a combination of arrays of nanowires with different magnetic configurations could be used to generate complex substance concentration gradients or control delivery of multiple drugs and macromolecules.

Electroforming of implantable tubular magnetic microrobots for wireless ophthalmologic applications.

Magnetic tubular implantable micro-robots are batch fabricated by electroforming. These microdevices can be used in targeted drug delivery and minimally invasive surgery for ophthalmologic applications. These tubular shapes are fitted into a 23-gauge needle enabling sutureless injections. Using a 5-degree-of-freedom magnetic manipulation system, the microimplants are conveniently maneuvered in biological environments. To increase their functionality, the tubes are coated with biocompatible films and can be successfully filled with drugs.

Microrobots: a new era in ocular drug delivery.

INTRODUCTION: Ocular microrobots have the potential to change the way in which we treat a variety of diseases at the anterior and the posterior segments of the eye. Wireless manipulation and positioning of drug delivery magnetic millimeter and submillimeter platforms into the eye constitute a potential route for minimally invasive targeted therapy. However, the field is still in its infancy and faces challenges related to the fabrication, control an interaction with complex biological environments. AREAS COVERED: This review briefly introduces the complex anatomy and physiology of the eye, which renders limitations to the current treatments of ocular diseases. The topical administration of eye drops, intravitreal injections and drug delivery implants is briefly mentioned together with their drawbacks. The authors also analyze the minimally invasive microrobotic approach as an alternative method and report the recent advancements in the fabrication, control, manipulation and drug delivery. EXPERT OPINION: Although microrobotics is a young field, a significant amount of work has been developed to face different challenges related to the minimally invasive manipulation of microdevices in the eye. Current research is already at the state of in vivo testing for systems and their biocompatibility. It is expected that the general concepts acquired will soon be applied for specific interventions, especially for posterior eye pathologies.

Mobility experiments with microrobots for minimally invasive intraocular surgery.

PURPOSE: To investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye. METHODS: A system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments. RESULTS: The developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye. CONCLUSIONS: Intravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

Chitosan electrodeposition for microrobotic drug delivery.

A method to functionalize steerable magnetic microdevices through the co-electrodeposition of drug loaded chitosan hydrogels is presented. The characteristics of the polymer matrix have been investigated in terms of fabrication, morphology, drug release and response to different environmental conditions. Modifications of the matrix behavior could be achieved by simple chemical post processing. The system is able to load and deliver 40-80 µg cm(-2) of a model drug (Brilliant Green) in a sustained manner with different profiles. Chitosan allows a pH responsive behavior with faster and more efficient release under slightly acidic conditions as can be present in tumor or inflamed tissue. A prototype of a microrobot functionalized with the hydrogel is presented and proposed for the treatment of posterior eye diseases.

In vitro oxygen sensing using intraocular microrobots.

We present a luminescence oxygen sensor integrated with a wireless intraocular microrobot for minimally-invasive diagnosis. This microrobot can be accurately controlled in the intraocular cavity by applying magnetic fields. The microrobot consists of a magnetic body susceptible to magnetic fields and a sensor coating. This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence material and polystyrene as a supporting matrix, and it can be wirelessly excited and read out by optical means. The sensor works based on quenching of luminescence in the presence of oxygen. The excitation and emission spectrum, response time, and oxygen sensitivity of the sensor were characterized using a spectrometer. A custom device was designed and built to use this sensor for intraocular measurements with the microrobot. Due to the intrinsic nature of luminescence lifetimes, a frequency-domain lifetime measurement approach was used. An alternative sensor design with increased performance was demonstrated by using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP nanospheres.

Oxygen sensing using microrobots.

We present a luminescence oxygen sensor incorporated in a wireless intraocular microrobot for minimally-invasive diagnosis. This microrobot can be accurately controlled in the intraocular cavity by applying magnetic fields. The microrobot consists of a magnetic body susceptible to magnetic fields and a sensor coating. This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence material and polystyrene as a supporting matrix, and it can be wirelessly excited and read out by optical means. The sensor works based on quenching of luminescence in the presence of oxygen. The excitation and emission spectrum, response time, and oxygen sensitivity of the sensor were characterized using a spectrometer. A custom device was designed and built to use this sensor for intraocular measurements with the microrobot. Due to the intrinsic nature of luminescence lifetimes, a frequency-domain lifetime measurement approach was employed. An alternative sensor implementation using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP was successfully demonstrated with nanospheres to increase sensor performance.