Implantable sensors for regenerative medicine

In vivo, real-time measurement of local environmental parameters such as strain, pressure, temperature, pH, oxygen tension and specific biomarkers can be valuable for regenerative medicine research and therapies. Wireless implantable sensors are an attractive approach for certain regenerative medicine applications due to its relative simplicity and low cost. Presented here are such two implantable sensors. The first sensor is based on a miniature wireless sensor network that can digitize physical and chemical parameters and continuously stream measurements to a nearby receiver via a 2-way communication protocol. With the incorporation of a strain gauge, this sensor platform was applied to record mechanical loading at an internal fixation plate across a segmental femoral critical-size defect of a rat. The second sensor is based on a wireless, passive (battery-less) capacitive-inductive (LC) sensor. This sensor is being developed for detection of bone infection associated with orthopedic implants by monitoring local temperature variations.https://digitalcommons.mtu.edu/techtalks/1038/thumbnail.jp

Temperature, Stress, and Corrosive Sensing Apparatus Utilizing Harmonic Response of Magnetically Soft Sensor Element (s)

A temperature sensing apparatus including a sensor element made of a magnetically soft material operatively arranged within a first and second time-varying interrogation magnetic field, the first time-varying magnetic field being generated at a frequency higher than that for the second magnetic field. A receiver, remote from the sensor element, is engaged to measure intensity of electromagnetic emissions from the sensor element to identify a relative maximum amplitude value for each of a plurality of higher-order harmonic frequency amplitudes so measured. A unit then determines a value for temperature (or other parameter of interst) using the relative maximum harmonic amplitude values identified. In other aspects of the invention, the focus is on an apparatus and technique for determining a value for of stress condition of a solid analyte and for determining a value for corrosion, using the relative maximum harmonic amplitude values identified. A magnetically hard element supporting a biasing field adjacent the magnetically soft sensor element can be included

Fabrication of biocompatible, vibrational magnetoelastic materials for controlling cellular adhesion

This paper describes the functionalization of magnetoelastic (ME) materials with Parylene-C coating to improve the surface reactivity to cellular response. Previous study has demonstrated that vibrating ME materials were capable of modulating cellular adhesion when activated by an externally applied AC magnetic field. However, since ME materials are not inherently biocompatible, surface modifications are needed for their implementation in biological settings. Here, the long-term stability of the ME material in an aqueous and biological environment is achieved by chemical-vapor deposition of a conformal Parylene-C layer, and further functionalized by methods of oxygen plasma etching and protein adsorption. In vitro cytotoxicity measurement and characterization of the vibrational behavior of the ME materials showed that Parylene-C coatings of 10 µm or greater could prevent hydrolytic degradation without sacrificing the vibrational behavior of the ME material. This work allows for long-term durability and functionality of ME materials in an aqueous and biological environment and makes the potential use of this technology in monitoring and modulating cellular behavior at the surface of implantable devices feasible

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

Design, fabrication, and implementation of a wireless, passive implantable pressure sensor based on magnetic higher-order harmonic fields

A passive and wireless sensor was developed for monitoring pressure in vivo. Structurally, the pressure sensor, referred to as the magneto-harmonic pressure sensor, is an airtight chamber sealed with an elastic pressure membrane. A strip of magnetically-soft material is attached to the bottom of the chamber and a permanent magnet strip is embedded inside the membrane. Under the excitation of an externally applied AC magnetic field, the magnetically-soft strip produces a higher-order magnetic signature that can be remotely detected with an external receiving coil. As ambient pressure varies, the pressure membrane deflects, altering the separation distance between the magnetically-soft strip and the permanent magnet. This shifts the higher-order harmonic signal, allowing for detection of pressure change as a function of harmonic shifting. The wireless, passive nature of this sensor technology allows for continuous long-term pressure monitoring, particularly useful for biomedical applications such as monitoring pressure in aneurysm sac and sphincter of Oddi. In addition to demonstrating its pressure sensing capability, an animal model was used to investigate the efficacy and feasibility of the pressure sensor in a biological environment

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

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 sensors, which are 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

Application of sub-micrometer vibrations to mitigate bacterial adhesion

As a prominent concern regarding implantable devices, eliminating the threat of opportunistic bacterial infection represents a significant benefit to both patient health and device function. Current treatment options focus on chemical approaches to negate bacterial adhesion, however, these methods are in some ways limited. The scope of this study was to assess the efficacy of a novel means of modulating bacterial adhesion through the application of vibrations using magnetoelastic materials. Magnetoelastic materials possess unique magnetostrictive property that can convert a magnetic field stimulus into a mechanical deformation. In vitro experiments demonstrated that vibrational loads generated by the magnetoelastic materials significantly reduced the number of adherent bacteria on samples exposed to Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus suspensions. These experiments demonstrate that vibrational loads from magnetoelastic materials can be used as a post-deployment activated means to deter bacterial adhesion and device infection

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression1,2, is known for its association with fasting glucose levels3,4. The evidence of an association with T2D for PEPD5 and HNF4A6,7 has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D

Multi-parameter sensing with a single magnetoelastic sensor by applying loads on the null locations of multiple resonant modes

© 2016 IOP Publishing Ltd. Magnetoelastic sensors are mass sensitive sensors commonly used for stress and pressure measurement, as well as chemical and biological monitoring when combined with a functionalized coating. Magnetoelastic sensors are typically made of free-standing, rectangular strips of magnetoelastic materials that exhibit longitudinal, extensional vibrations due to the excitation of magnetic fields. A single magnetoelastic sensor is generally used to monitor one parameter since only the fundamental resonant frequency is measured. Multiple-parameter sensing in close proximity has previously been achieved by using multiple magnetoelastic sensors of different dimensions and tracking their resonant frequencies independently. However, this requires a large surface area and inconvenient layout of dissimilarly shaped sensors. This paper presents a technique for monitoring multiple parameters with a single magnetoelastic sensor by applying separate mass loads at the null points (points of zero vibration) of multiple resonant modes. Applying a load at a null location does not affect the corresponding resonant mode but alters the resonant frequencies of other modes. Therefore, by isolating the variables of interest to multiple null points and simultaneously measuring the resonant frequency shifts of related resonant modes, the masses at each null location can be calculated. Results showed that changing the coverage at a null location along the width of the sensor can be used to minimize the loading effect on the corresponding resonant mode. In contrast, changing the lengthwise coverage can maximize the loading effect on other resonant modes, thus increasing the mass sensitivity of the sensor. Furthermore, simultaneously applying loads to null points of multiple resonant modes had a nearly additive effect, allowing detection of multiple parameters with a single magnetoelastic sensor