An Optical Sensor for Measuring Displacement between Parallel Surfaces.

An optoelectronic sensor was developed to measure the in-plane displacement between two parallel surfaces. This sensor used a photodetector, which was placed on one of the parallel surfaces, to measure the intensity of the red (R), green (G), blue (B), and white/clear (C) light spectra of a broad-spectrum light that was reflected off a color grid on the opposing surface. The in-plane displacement between these two surfaces caused a change in the reflected RGB and C light intensity, allowing the prediction of the displacement direction and magnitude by using a polynomial regression prediction algorithm to convert the RGB and C light intensity to in-plane displacement. Results from benchtop experiments showed that the sensor can achieve accurate displacement predictions with a coefficient of determination R2 > 0.97, a root mean squared error (RMSE) < 0.3 mm, and a mean absolute error (MAE) < 0.36 mm. By measuring the in-plane displacement between two surfaces, this sensor can be applied to measure the shear of a flexible layer, such as a shoe's insole or the lining of a limb prosthesis. This sensor would allow slippage detection in wearable devices such as orthotics, prostheses, and footwear to quantify the overfitting or underfitting of these devices.

An Optoelectronics-Based Compressive Force Sensor with Scalable Sensitivity.

There is an increasing need to accurately measure compressive force for biomedical and industrial applications. However, this need has not been fully addressed, as many sensors are bulky, have high power requirements, and/or are susceptible to electromagnetic interference. This paper presents an optoelectronics-based force sensor that can overcome the limitations of many sensors in the market. The sensor uses a light emitting diode (LED) to transmit visible broad-spectrum light into a photoresistor through an optically clear spacer on top of an elastomeric medium. In the absence of an external force, the light path is mostly blocked by the opaque elastomeric medium. Under a compressive force, the clear spacer compresses the elastomer, moving itself into the light path, and thus increasing the overall light transmission. The amount of light received by the photoresistor is used to quantify compressive force based on elastomer displacement/compression and a priori knowledge of elastomer stiffness. This sensing scheme was tested under eight different configurations: two different sized sensors with four types of elastomers per size (20A neoprene, 30A neoprene, 50A neoprene, and 75A styrene-butadiene rubber (SBR)). All configurations measured force with R2 > 0.97, RMSE < 1.9 N, and sensitivity values ranging from 17 to 485 N/V. This sensing scheme provides a low-cost, low-power method for accurate force sensing with a wide force range.

Magnetoelastic Monitoring System for Tracking Growth of Human Mesenchymal Stromal Cells.

Magnetoelastic sensors, which undergo mechanical resonance when interrogated with magnetic fields, can be functionalized to measure various physical quantities and chemical/biological analytes by tracking their resonance behaviors. The unique wireless and functionalizable nature of these sensors makes them good candidates for biological sensing applications, from the detection of specific bacteria to tracking force loading inside the human body. In this study, we evaluate the viability of magnetoelastic sensors based on a commercially available magnetoelastic material (Metglas 2826 MB) for wirelessly monitoring the attachment and growth of human mesenchymal stromal cells (hMSCs) in 2D in vitro cell culture. The results indicate that the changes in sensor resonance are linearly correlated with cell quantity. Experiments using a custom-built monitoring system also demonstrated the ability of this technology to collect temporal profiles of cell growth, which could elucidate key stages of cell proliferation based on acute features in the profile. Additionally, there was no observed change in the morphology of cells after they were subjected to magnetic and mechanical stimuli from the monitoring system, indicating that this method for tracking cell growth may have minimal impact on cell quality and potency.

Implantable biosensors for musculoskeletal health.

PURPOSE: A healthy musculoskeletal system requires complex functional integration of bone, muscle, cartilage, and connective tissues responsible for bodily support, motion, and the protection of vital organs. Conditions or injuries to musculoskeeltal tissues can devastate an individual's quality of life. Some conditions that are particularly disabling include severe bone and muscle injuries to the extremities and amputations resulting from unmanageable musculoskeletal conditions or injuries. Monitoring and managing musculoskeletal health is intricate because of the complex mechanobiology of these interconnected tissues. METHODS: For this article, we reviewed literature on implantable biosensors related to clinical data of the musculoskeletal system, therapeutics for complex bone injuries, and osseointegrated prosthetics as example applications. RESULTS: As a result, a brief summary of biosensors technologies is provided along with review of noteworthy biosensors and future developments needed to fully realize the translational benefit of biosensors for musculoskeletal health. CONCLUSIONS: Novel implantable biosensors capable of tracking biophysical parameters in vivo are highly relevant to musculoskeletal health because of their ability to collect clinical data relevant to medical decisions, complex trauma treatment, and the performance of osseointegrated prostheses.

Effects of osteogenic ambulatory mechanical stimulation on early stages of BMP-2 mediated bone repair.

Purpose: Mechanical loading of bone defects through rehabilitation is a promising approach to stimulate repair and reduce nonunion risk; however, little is known about how therapeutic mechanical stimuli modulate early-stage repair before mineralized bone formation. The objective of this study was to investigate the early effects of osteogenic loading on cytokine expression and angiogenesis during the first 3 weeks of BMP-2 mediated segmental bone defect repair.Materials and Methods: A rat model of BMP-2 mediated bone defect repair was subjected to an osteogenic mechanical loading protocol using ambulatory rehabilitation and a compliant, load-sharing fixator with an integrated implantable strain sensor. The effect of fixator load-sharing on local tissue strain, angiogenesis, and cytokine expression was evaluated.Results: Using sensor readings for local measurements of boundary conditions, finite element simulations showed strain became amplified in remaining soft tissue regions between 1 and 3 weeks (Week 3: load-sharing: -1.89 ± 0.35% and load-shielded: -1.38 ± 0.35% vs. Week 1: load-sharing: -1.54 ± 0.17%; load-shielded: -0.76 ± 0.06%). Multivariate analysis of cytokine arrays revealed that load-sharing significantly altered expression profiles in the defect tissue at 2 weeks compared to load-shielded defects. Specifically, loading reduced VEGF (p = 0.052) and increased CXCL5 (LIX) levels. Subsequently, vascular volume in loaded defects was reduced relative to load-shielded defects but similar to intact bone at 3 weeks. Endochondral bone repair was also observed histologically in loaded defects at 3 weeks.Conclusions: Together, these results demonstrate that moderate ambulatory strains previously shown to stimulate bone regeneration significantly alter early angiogenic and cytokine signaling and may promote endochondral ossification.

Magnetoelastic Sensor Optimization for Improving Mass Monitoring.

Magnetoelastic sensors, typically made of magnetostrictive and magnetically-soft materials, can be fabricated from commercially available materials into a variety of shapes and sizes for their intended applications. Since these sensors are wirelessly interrogated via magnetic fields, they are good candidates for use in both research and industry, where detection of environmental parameters in closed and controlled systems is necessary. Common applications for these sensors include the investigation of physical, chemical, and biological parameters based on changes in mass loading at the sensor surface which affect the sensor's behavior at resonance. To improve the performance of these sensors, optimization of sensor geometry, size, and detection conditions are critical to increasing their mass sensitivity and detectible range. This work focuses on investigating how the geometry of the sensor influences its resonance spectrum, including the sensor's shape, size, and aspect ratio. In addition to these factors, heterogeneity in resonance magnitude was mapped for the sensor surface and the effect of the magnetic bias field strength on the resonance spectrum was investigated. Analysis of the results indicates that the shape of the sensor has a strong influence on the emergent resonant modes. Reducing the size of the sensor decreased the sensor's magnitude of resonance. The aspect ratio of the sensor, along with the bias field strength, was also observed to affect the magnitude of the signal; over or under biasing and aspect ratio extremes were observed to decrease the magnitude of resonance, indicating that these parameters can be optimized for a given shape and size of magnetoelastic sensor.

Modern Electrode Technologies for Ion and Molecule Sensing.

In high concentrations, ionic species can be toxic in the body, catalyzing unwanted bioreactions, inhibiting enzymes, generating free radicals, in addition to having been associated with diseases like Alzheimer's and cancer. Although ionic species are ubiquitous in the environment in trace amounts, high concentrations of these metals are often found within industrial and agricultural waste runoff. Therefore, it remains a global interest to develop technologies capable of quickly and accurately detecting trace levels of ionic species, particularly in aqueous environments that naturally contain other competing/inhibiting ions. Herein, we provide an overview of the technologies that have been developed, including the general theory, design, and benefits/challenges associated with ion-selective electrode technologies (carrier-doped membranes, carbon-based varieties, enzyme inhibition electrodes). Notable variations of these electrodes will be highlighted, and a brief overview of associated electrochemical techniques will be given.

Wireless Technologies for Implantable Devices.

Wireless technologies are incorporated in implantable devices since at least the 1950s. With remote data collection and control of implantable devices, these wireless technologies help researchers and clinicians to better understand diseases and to improve medical treatments. Today, wireless technologies are still more commonly used for research, with limited applications in a number of clinical implantable devices. Recent development and standardization of wireless technologies present a good opportunity for their wider use in other types of implantable devices, which will significantly improve the outcomes of many diseases or injuries. This review briefly describes some common wireless technologies and modern advancements, as well as their strengths and suitability for use in implantable medical devices. The applications of these wireless technologies in treatments of orthopedic and cardiovascular injuries and disorders are described. This review then concludes with a discussion on the technical challenges and potential solutions of implementing wireless technologies in implantable devices.

Implantable Sensors for Regenerative Medicine.

The translation of many tissue engineering/regenerative medicine (TE/RM) therapies that demonstrate promise in vitro are delayed or abandoned due to reduced and inconsistent efficacy when implemented in more complex and clinically relevant preclinical in vivo models. Determining mechanistic reasons for impaired treatment efficacy is challenging after a regenerative therapy is implanted due to technical limitations in longitudinally measuring the progression of key environmental cues in vivo. The ability to acquire real-time measurements of environmental parameters of interest including strain, pressure, pH, temperature, oxygen tension, and specific biomarkers within the regenerative niche in situ would significantly enhance the information available to tissue engineers to monitor and evaluate mechanisms of functional healing or lack thereof. Continued advancements in material and fabrication technologies utilized by microelectromechanical systems (MEMSs) and the unique physical characteristics of passive magnetoelastic sensor platforms have created an opportunity to implant small, flexible, low-power sensors into preclinical in vivo models, and quantitatively measure environmental cues throughout healing. In this perspective article, we discuss the need for longitudinal measurements in TE/RM research, technical progress in MEMS and magnetoelastic approaches to implantable sensors, the potential application of implantable sensors to benefit preclinical TE/RM research, and the future directions of collaborative efforts at the intersection of these two important fields.

A wireless, passive magnetoelastic force-mapping system for biomedical applications.

A wireless, passive force­mapping system based on changes in magnetic permeability of soft, amorphous Metglas 2826MB strips is presented for long-term force/stress monitoring on biomedical devices. The presented technology is demonstrated for use in lower-limb prosthetics to ensure proper postoperative fitting by providing real-time monitoring of the force distribution at the body-prosthesis interface. The sensor system consisted of a force-sensitive magnetoelastic sensing strip array that monitored applied loading as an observed change in the peak amplitude of the measured magnetic higher-order harmonic signal of each array element. The change in higher-order harmonic signal is caused by the change in the magnetic permeability of the sensing strips that corresponds to an increase in strip magnetization. After loading, the measured higher-order harmonic signals were fed into an algorithm to determine the applied forces, allowing for determination of the real-time loading profile at the body prosthesis interface.

In vitromagnetohydrodynamics system for modulating cell migration.

Fluid shear stress (FSS) is an important parameter that regulates various cell functions such as proliferation and migration. While there are a number of techniques to generate FSSin vitro, many of them require physical deformation or movement of solid objects to generate the fluid shear, making it difficult to decouple the effects of FSS and mechanical strains. This work describes the development of a non-mechanical means to generate fluid flow and FSS in a 2Din vitrosetting. This was accomplished with a magnetohydrodynamic (MHD) pump, which creates liquid flow by generating a Lorentz force through the interaction between an electric field and an orthogonal magnetic field. The MHD pump system presented here consisted of trapezoidal prism-shaped magnets, a pair of platinum electrodes, and a modified petri dish. The system was validated and tested on anin vitrowound model, which is based on analyzing the migration of fibroblast cells through an artificially created scratch on a confluent cell culture surface. Experiments were performed to a control group, an electric field only group, and a group that was subject to fluid flow with the application of both electric field and magnetic field. Results show that fibroblast cells that experienced fluid shear have higher wound closure rate compared to the control group and the electric field only group. The data shows that the MHD pump can be a great tool to study FSSin vitro. Furthermore, due to its fluid flow generation without mechanical force, this system can be adapted and implemented to study the role of FSS and electric field on wound healingin vivo.

Early Resistance Rehabilitation Improves Functional Regeneration Following Segmental Bone Defect Injury.

Mechanical loading is integral to bone development and repair. The application of mechanical loads through rehabilitation are regularly prescribed as a clinical aide following severe bone injuries. However, current rehabilitation regimens typically involve long periods of non-loading and rely on subjective patient feedback, leading to muscle atrophy and soft tissue fibrosis. While many pre-clinical studies have focused on unloading, ambulatory loading, or direct mechanical compression, rehabilitation intensity and its impact on the local strain environment and subsequent bone healing have largely not been investigated. This study combines implantable strain sensors and subject-specific finite element models in a pre-clinical rodent model with a defect size on the cusp of critically-sized. Animals were enrolled in either high or low intensity rehabilitation one week post injury to investigate how rehabilitation intensity affects the local mechanical environment and subsequent functional bone regeneration. The high intensity rehabilitation animals were given free access to running wheels with resistance, which increased local strains within the regenerative niche by an average of 44% compared to the low intensity (no-resistance) group. Finite element modeling demonstrated that resistance rehabilitation significantly increased compressive strain by a factor of 2.0 at week 1 and 4.45 after 4 weeks of rehabilitation. The resistance rehabilitation group had significantly increased regenerated bone volume and higher bone bridging rates than its sedentary counterpart (bone volume: 22.00 mm3 ± 4.26 resistance rehabilitation vs 8.00 mm3 ± 2.27 sedentary; bridging rates: 90% resistance rehabilitation vs 50% sedentary). In addition, animals that underwent resistance running had femurs with improved mechanical properties compared to those left in sedentary conditions, with failure torque and torsional stiffness values matching their contralateral, intact femurs (stiffness: 0.036 Nm/deg ± 0.006 resistance rehabilitation vs 0.008 Nm/deg ± 0.006 sedentary). Running on a wheel with no resistance rehabilitation also increased bridging rates (100% no resistance rehabilitation vs 50% sedentary). Analysis of bone volume and von Frey suggest no-resistance rehabilitation may improve bone regeneration and hindlimb functionality. These results demonstrate the potential for early resistance rehabilitation as a rehabilitation regimen to improve bone regeneration and functional recovery.

A Wireless Embedded Sensor based on Magnetic Higher-order Harmonic Fields: Application to Liquid Pressure Monitoring.

A wireless sensor based on the magnetoelastic, magnetically soft ferromagnetic alloy was constructed for remote measurement of pressure in flowing fluids. The pressure sensor was a rectangular strip of ferromagnetic alloy Fe(40)Ni(38)Mo(4)B(18) adhered on a solid polycarbonate substrate and protected by a thin polycarbonate film. Upon excitation of a time-varying magnetic field through an excitation coil, the magnetically soft sensor magnetized and produced higher-order harmonic fields, which were detected through a detection coil. Under varying pressures, the sensor's magnetoelastic property caused a change in its magnetization, altering the amplitudes of the higher-order harmonic fields. A theoretical model was developed to describe the effect of pressure on the sensor's higher order harmonic fields. Experimental observations showed the 2(nd) order harmonic field generated by the pressure sensor was correlated to the surrounding fluid pressure, consistent with the theoretical results. Furthermore, it was demonstrated that the sensor exhibited good repeatability and stability with minimal drift. Sensors with smaller dimensions were shown to have greater sensitivity but lower pressure range as compared to their larger counterparts. Since the sensor signal was also dependent on the location of the sensor with respect to the excitation/detection coil, a calibration algorithm was developed to eliminate signal variations due to the changing sensor location. Because of its wireless and passive nature, this sensor is useful for continuous and long-term monitoring of pressure at inaccessible areas. For example, sensors with these capabilities are suitable to be used in biomedical applications where permanent implantation and long-term monitoring are needed.

Wireless sensor enables longitudinal monitoring of regenerative niche mechanics during rehabilitation that enhance bone repair.

Mechanical loads exerted on the skeleton during activities such as walking are important regulators of bone repair, but dynamic biomechanical signals are difficult to measure inside the body. The inability to measure the mechanical environment in injured tissues is a significant barrier to developing integrative regenerative and rehabilitative strategies that can accelerate recovery from fracture, segmental bone loss, and spinal fusion. Here we engineered an implantable strain sensor platform and longitudinally measured strain across a bone defect in real-time throughout rehabilitation. The results showed that load-sharing permitted by a load-sharing fixator initially delivered a two-fold increase in deformation magnitude, subsequently increased mineralized bridging by nearly three-fold, and increased bone formation by over 60%. These data implicate a critical role for early mechanical cues on the long term healing response as strain cycle magnitude at 1 week (before appreciable healing occurred) had a significant positive correlation with the long-term bone regeneration outcomes. Furthermore, we found that sensor readings correlated with the status of healing, suggesting a role for strain sensing as an X-ray-free healing assessment platform. Therefore, non-invasive strain measurements may possess diagnostic potential to evaluate bone repair and reduce clinical reliance on current radiation-emitting imaging methods. Together, this study demonstrates a promising framework to quantitatively develop and exploit mechanical rehabilitation strategies that enhance bone repair.

Magnetoelastic galfenol as a stent material for wirelessly controlled degradation rates.

The gold standard of care for coronary artery disease, a leading cause of death for in the world, is balloon angioplasty in conjunction with stent deployment. However, implantation injuries and long-term presence of foreign material often promotes significant luminal tissue growth, leading to a narrowing of the artery and severely restricted blood flow. A promising method to mitigate this process is the use of biodegradable metallic stents, but thus far they have either degraded too slowly (iron) or disappeared prematurely (magnesium). The present work investigates the use of a unique type of magnetic material, galfenol (iron-gallium), for postoperative wireless control of stent degradation rates. Due to its magnetoelastic property, galfenol experiences longitudinal micron-level elongations when exposed to applied magnetic fields, allowing generation of a microstirring effect that affect its degradation behavior. In vitro indirect cytotoxicity tests on primary rat aortic smooth muscle cells indicated that galfenol byproducts must be concentrated approximately seven times from collected 60 day degradation medium to cause ∼15% of death from all cells. Surface and cross-sectional characterization of the material indicate that galfenol (Fe80 Ga20 ) degradation rates (∼0.55% per month) are insufficient for stenting applications. While this material may not be ideal for comprising the entire stent, there is potential for use in combination with other materials. Furthermore, the ability to control degradation rates postimplantation opens new possibilities for biodegradable stents; additional magnetoelastic materials should be investigated for use in stenting applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 232-241, 2019.

Implantable Biosensors for Real-time Strain and Pressure Monitoring.

Implantable biosensors were developed for real-time monitoring of pressure and strain in the human body. The sensor, which was wireless and passive, consisted of a soft magnetic material and a permanent magnet. When exposed to a low frequency AC magnetic field, the soft magnetic material generated secondary magnetic fields that also included the higher-order harmonic modes. Parameters of interest were determined by measuring the changes in the pattern of these higher-order harmonic fields, which was achieved by changing the intensity of a DC magnetic field generated by a permanent magnet. The DC magnetic field, or the biasing field, was altered by changing the separation distance between the soft magnetic material and the permanent magnet. For pressure monitoring, the permanent magnet was placed on the membrane of an airtight chamber. Changes in the ambient pressure deflected the membrane, altering the separation distance between the two magnetic elements and thus the higher-order harmonic fields. Similarly, the soft magnetic material and the permanent magnet were separated by a flexible substrate in the stress/strain sensor. Compressive and tensile forces flexed the substrate, changing the separation distance between the two elements and the higher-order harmonic fields. In the current study, both stress/strain and pressure sensors were fabricated and characterized. Good stability, linearity and repeatability of the sensors were demonstrated. This passive and wireless sensor technology may be useful for long term detection of physical quantities within the human body as a part of treatment assessment, disease diagnosis, or detection of biomedical implant failures.

Clinical potential of implantable wireless sensors for orthopedic treatments.

INTRODUCTION: Implantable wireless sensors have been used for real-time monitoring of chemicals and physical conditions of bones, tendons and muscles to diagnose and study orthopedic diseases and injuries. Due to the importance of these sensors in orthopedic care, a critical review, which not only analyzes the underlying technologies but also their clinical implementations and challenges, will provide a landscape view on their current state and their future clinical role. AREAS COVERED: By conducting an extensive literature search and following the leaders of orthopedic implantable wireless sensors, this review covers the battery-powered and battery-free wireless implantable sensor technologies, and describes their implementation for hips, knees, spine, and shoulder stress/strain monitoring. Their advantages, limitations, and clinical challenges are also described. EXPERT COMMENTARY: Currently, implantable wireless sensors are mostly limited for scientific investigations and demonstrative experiments. Although rapid advancement in sensors and wireless technologies will push the reliability and practicality of these sensors for clinical realization, regulatory constraints and financial viability in medical device industry may curtail their continuous adoption for clinical orthopedic applications. In the next five years, these sensors are expected to gain increased interest from researchers, but wide clinical adoption is still unlikely.

Control of cellular adhesion and myofibroblastic character with sub-micrometer magnetoelastic vibrations.

The effect of sub-cellular mechanical loads on the behavior of fibroblasts was investigated using magnetoelastic (ME) materials, a type of material that produces mechanical vibrations when exposed to an external magnetic AC field. The integration of this functionality into implant surfaces could mitigate excessive fibrotic responses to many biomedical devices. By changing the profiles of the AC magnetic field, the amplitude, duration, and period of the applied vibrations was altered to understand the effect of each parameter on cell behavior. Results indicate fibroblast adhesion depends on the magnitude and total number of applied vibrations, and reductions in proliferative activity, cell spreading, and the expression of myofibroblastic markers occur in response to the vibrations induced by the ME materials. These findings suggest that the subcellular amplitude mechanical loads produced by ME materials could potentially remotely modulate myofibroblastic activity and limit undesirable fibrotic development.

A Wireless, Passive Sensor for Quantifying Packaged Food Quality.

This paper describes the fabrication of a wireless, passive sensor based on aninductive-capacitive resonant circuit, and its application for in situ monitoring of thequality of dry, packaged food such as cereals, and fried and baked snacks. The sensor ismade of a planar inductor and capacitor printed on a paper substrate. To monitor foodquality, the sensor is embedded inside the food package by adhering it to the package'sinner wall; its response is remotely detected through a coil connected to a sensor reader. Asfood quality degrades due to increasing humidity inside the package, the paper substrateabsorbs water vapor, changing the capacitor's capacitance and the sensor's resonantfrequency. Therefore, the taste quality of the packaged food can be indirectly determined bymeasuring the change in the sensor's resonant frequency. The novelty of this sensortechnology is its wireless and passive nature, which allows in situ determination of foodquality. In addition, the simple fabrication process and inexpensive sensor material ensure alow sensor cost, thus making this technology economically viable.

A Wireless Sensor for Real-Time Monitoring of Tensile Force on Sutured Wound Sites.

A new wireless sensor was designed, fabricated, and applied for in situ monitoring of tensile force at a wound site. The sensor was comprised of a thin strip of magnetoelastic material with its two ends connected to suture threads for securing the sensor across a wound repair site. Since the sensor was remotely interrogated by applying an ac magnetic field and capturing the resulting magnetic field, it did not require direct wire connections to an external device or internal battery for long-term use. Due to its magnetoelastic property, the application of a tensile force changed the magnetic permeability of the sensor, altering the amplitude of the measured magnetic field. This study presents two sensor designs: one for high and one for low-force ranges. A sensor was fabricated by directly adhering the magnetoelastic strip to the suture. This sensor showed good sensitivity at low force, but its response saturated at about 1.5 N. To monitor high tensile force, the magnetoelastic strip was attached to a metal strip for load sharing. The suture thread was attached to the both ends of the metal strip so only a fraction of the applied force was directed to the sensor, allowing it to exhibit good sensitivity even at 44.5 N. The sensor was applied to two ex vivo models: a sutured section of porcine skin and a whitetail deer Achilles tendon. The results demonstrate the potential for in vivo force monitoring at a wound repair site.