The alteration of the hydrostatic pressure gradient in the human body has been associated with changes in human physiology, including abnormal blood flow, syncope, and visual impairment. The focus of this study was to evaluate changes in the resonant frequency of a wearable electromagnetic resonant skin patch sensor during simulated physiological changes observed in aerospace applications. Simulated microgravity was induced in eight healthy human participants (n = 8), and the implementation of lower body negative pressure (LBNP) countermeasures was induced in four healthy human participants (n = 4). The average shift in resonant frequency was −13.76 ± 6.49 MHz for simulated microgravity with a shift in intracranial pressure (ICP) of 9.53 ± 1.32 mmHg, and a shift of 8.80 ± 5.2097 MHz for LBNP with a shift in ICP of approximately −5.83 ± 2.76 mmHg. The constructed regression model to explain the variance in shifts in ICP using the shifts in resonant frequency (R2 = 0.97) resulted in a root mean square error of 1.24. This work demonstrates a strong correlation between sensor signal response and shifts in ICP. Furthermore, this study establishes a foundation for future work integrating wearable sensors with alert systems and countermeasure recommendations for pilots and astronauts.

In the human body, maintaining the core body temperature (CBT) is vital to ensure proper cellular and body functions. The temperature of 37 degrees C (98 degrees F) is the well-established baseline for CBT, but significant deviations to under 35 degrees C (95 degrees F) or over 40 degrees C (104 degrees F) can result in several health complications. If unnoticed in spaceflight, astronauts CBT could reach dangerously high levels when doing physically challenging tasks such as spacewalking or exercise. Therefore, a real-time multi-physiological parameter sensing system is needed to noninvasively monitor the status of crew members in space. The purpose of this paper is to test a novel temperature sensor developed by integrating thin sheets of polyvinylidene fluoride (PVDF), a temperature dependent dielectric material, into the sensor system designed as a substrate. This substrate interacts with the electromagnetic field created by the spiral sensor to result in a quantitative temperature monitoring sensor with a resolution of 1 degrees C.

Wearable dielectric elastomer actuators (DEAs) have been greatly considered for development of biomedical devices. In particular, a DEA cuff device has the capability of minimizing venous system disorders that occur in the lower limbs such as orthostatic intolerance (OI) and deep-vein thrombosis which are a result of substantial blood pooling. Recent works have shown that DEAs could regulate and even enhance venous blood flow return. This wearable technology orders a new light, low-cost, compliant, and simple countermeasure which could be safely and comfortably worn that includes mobility. In addition, it may supplement or even provide an alternative solution to exercise and medication. This work presents the design, model, and characterization of the DEA cuff device design that is capable of generating significant pressure change. A rolled DEA strip was actuated over a simulated muscle-artery apparatus using a periodic voltage input, and fluid pressure change was directly observed. A force sensitive resistor sensor was used to achieve a more precise pressure measurement. Performance analysis was conducted through frequency response analysis. The results provide a framework for implementing dynamic modelling and control to allow various forms of actuation input.

Modern wearable devices show promising results in terms of detecting vital bodily signs from the wrist. However, there remains a considerable need for a device that can conform to the human body’s variable geometry to accurately detect those vital signs and to understand health better. Flexible radio frequency (RF) resonators are well poised to address this need by providing conformable bio-interfaces suitable for different anatomical locations. In this work, we develop a compact wearable RF biosensor that detects multisite hemodynamic events due to pulsatile blood flow through noninvasive tissue–electromagnetic (EM) field interaction. The sensor consists of a skin patch spiral resonator and a wearable transceiver. During resonance, the resonator establishes a strong capacitive coupling with layered dielectric tissues due to impedance matching. Therefore, any variation in the dielectric properties within the near-field of the coupled system will result in field perturbation. This perturbation also results in RF carrier modulation, transduced via a demodulator in the transceiver unit. The main elements of the transceiver consist of a direct digital synthesizer for RF carrier generation and a demodulator unit comprised of a resistive bridge coupled with an envelope detector, a filter, and an amplifier. In this work, we build and study the sensor at the radial artery, thorax, carotid artery, and supraorbital locations of a healthy human subject, which hold clinical significance in evaluating cardiovascular health. The carrier frequency is tuned at the resonance of the spiral resonator, which is 34.5 ± 1.5 MHz. The resulting transient waveforms from the demodulator indicate the presence of hemodynamic events, i.e., systolic upstroke, systolic peak, dicrotic notch, and diastolic downstroke. The preliminary results also confirm the sensor’s ability to detect multisite blood flow events noninvasively on a single wearable platform.

Shoulder injury is one of the most common phenomena that occurs for astronauts when they are training for space flight. During training, astronauts are required to wear a full space suit, known as the extravehicular mobility unit (EMU). The major component of the EMU that attributes to shoulder injury is the hard upper torso (HUT). This component is primarily comprised of a rigid fiberglass shell with metal scye bearing joints. Placement of the scye bearing joints for the shoulders does not allow for enough range of motion, which can lead to rotator cuff tears. Additionally, shoulder injury also occurs when donning the suit and training in the Neutral Buoyancy Laboratory (NBL). The EMU currently does not contain any provision to account for this biomechanical interference to adjust for optimum range of motion. The objective of this paper is to propose a novel detection scheme using a wearable electromagnetic resonant spiral sensor that could allow for a quantitative value of proximity between the shoulder and the metallic scye bearing joint of the HUT. The presence of the liquid cooling and ventilation garment (LCVG) is also investigated in the environment to validate that accuracy of proximity detection is still achieved. Optimal location for the wearable proximity sensor would be on top the LCVG around the shoulder joint where the scye bearing joints are more likely to meet the shoulder. The first study investigated the ability of the wearable proximity sensor to detect the distance from an aluminum sheet (representing the scye bearing joint) with no LCVG present, while the second study incorporated the wearable proximity sensor on top of the LCVG for a simulated suit environment. Four scenarios were performed with two wearable proximity sensors, resonating at different frequencies, placed in an environment with and without the LCVG. Ten repeated tests were used to train and an additional ten tests to validate a regression learning algorithm to predict the distance for each scenario. Experimental results indicated that the wearable proximity sensors in both the open air and with the LCVG have enough accuracy to provide a root mean square error (RMSE) of approximately 1 mm or less. This accuracy is sufficient for use in the space suit to provide quantitative information for suit fit. The use of this proximity detection scheme incorporated into the suit will offer previously unknown information regarding suit fit, while also influencing optimum fit for future suit generations.

Non-intrusive monitoring of blood flow parameters is vital for obtaining physiological and pathophysiological information pertaining to dynamic cardiovascular events and is feasible to achieve via non-invasive, conformal, wearable technologies. Here, we present a proof-of-concept of a fully integrated, high frequency (bandwidth 40 MHz), electromagnetic sensing device for monitoring limb hemodynamics and morphology associated with blood flow. The sensing architecture integrates a novel radio frequency (RF) skin patch resonator embedded with a coplanar outer loop antenna and a scalable, standalone wireless readout hardware based on standing wave ratio (SWR) bridge. The resonator itself is a copper-based open circuit planar Archimedean spiral with a rectangular cross-sectional area, chemically etched on a flexible polyimide substrate. The readout hardware is developed exploiting off-the-shelf components, fabricated on the top of a rigid FR4 substrate. The proposed readout circuit can measure resonant frequency of an RLC network. When energized by the external oscillating RF field via loop antenna, the resonator produces an electromagnetic field response which can be perturbed by dielectric variation inside its field boundary. Through leveraging this principle, the in-vitro experimental results from the benchtop models suggest that the resonator's RF attributes such as resonant frequency shift and magnitude variation of reflection coefficient due to fluid volume displacement can be successfully detected through the proposed hardware architecture. Hence, the system could be an alternative to the conventional, multimodal, non-invasive wearable sensing with an unprecedented capability of ubiquitous fluid phenomena detection from multiple sites of the human body.

This work presents a preliminary evaluation of a complete wearable radiofrequency (RF, 40 MHz bandwidth) readout device for a novel electromagnetic skin patch sensor to monitor health parameters associated with shifts in biofluid volume. The skin patch sensor consists of a continuous trace of copper configured into a square planar spiral surrounded by an embedded coplanar outer loop antenna. When an incident RF wave from the loop antenna impinges upon the planar spiral, the coupled system exhibits a multiband resonant response. The readout system connected to the sensor comprises of an RF signal generator, resistive reflectometer, RF power detector, and a microcontroller unit with an inbuilt 10-bit ADC and a blue-tooth transceiver. During continuous wave sweeping, the recorded response from the sensor was transmitted wirelessly to the host computer for further post-processing and data interpretation. Results: Experimental results demonstrated that the developed prototype could successfully detect resonant frequency of an NFC tag-based fixed resonator and a fluid volume shift of 0 to 600 mL in an in-vitro beaker study using the multiband planar spiral skin patch sensor. The outcomes were further validated against the similar findings from a commercial benchtop vector network analyzer (VNA). Conclusion: This RF readout device provides a wearable alternative to current methods for analyzing the resonant response from the sensor system under different dielectric conditions for biomedical applications including measurement of limb hemodynamics, detect changes in intracranial and ventricular stroke volume, and cardiac function.

The interconnected porous structures that mimic the extracellular matrix support cell growth in tissue engineering. Nanofibers generated by electrospinning can act as a vehicle for therapeutic cell delivery to a neural lesion. The incorporation of carbon nanomaterials with excellent electrical conductivity in nanofibers is an attractive aspect for design of a nanodevice for neural tissue regeneration. In this study, nanoscaffolds were created by electrospinning poly(ε-caprolactone) (PCL) and three different types of carbon nanomaterials, which are carbon nanotubes, graphene, and fullerene. The component of carbon nanomaterials in nanofibers was confirmed by Fourier transform infrared spectroscopy. The fiber diameter was determined by scanning electron microscopy, and it was found that the diameter varied depending on the type of nanomaterial in the fibers. The incorporation of carbon nanotubes and graphene in the PCL fibers increased the contact angle significantly, while the incorporation of fullerene reduced the contact angle significantly. Incorporation of CNT, fullerene, and graphene in the PCL fibers increased dielectric constant. Astrocytes isolated from neonatal rats were cultured on PCL-nanomaterial nanofibers. The cell viability assay showed that the PCL-nanomaterial nanofibers were not toxic to the cultured astrocytes. The immunolabeling showed the growth and morphology of astrocytes on nanofiber scaffolds. SEM was performed to determine the cell attachment and interaction with the nanoscaffolds. This study indicates that PCL nanofibers containing nanomaterials are biocompatible and could be used for cell and drug delivery into the nervous system.

Injectable thermosensitive hydrogels have been widely investigated for drug delivery systems. Chitosan (CH) is one of the most abundant natural polymers, and its biocompatibility and biodegradability make it a favorable polymer for thermosensitive hydrogel formation. The addition of nanoparticles can improve its drug release behavior, remote actuation capability, and biological interactions. Carbon nanotubes (CNTs) have been studied for the use in drug delivery systems, and they can act as drug delivery vehicles to improve the delivery of different types of therapeutic agents. In this work, carbon nanotubes were incorporated into a thermosensitive and injectable hydrogel formed by chitosan and β-glycerophosphate (β-GP) (CH−β-GP–CNTs). The hybrid hydrogels loaded with methotrexate (MTX) were liquid at room temperature and became a solidified gel at body temperature. A number of tests including scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction were utilized to characterize the MTX-loaded CH−β-GP–CNT hybrid hydrogels. The cell viability (alamarBlue) assay showed that hydrogels containing CNT (0.1%) were not toxic to the 3T3 cells. In vitro MTX release study revealed that CNT-containing hydrogels (with 0.1% CNT) demonstrated a decreased MTX releasing rate compared with control hydrogels without CNT. The cultured MCF-7 breast cancer cells were used to evaluate the efficacy of CH−β-GP–CNT hybrid hydrogels delivering MTX on the control of tumor cell growth. Results demonstrated that CNT (0.1%) in the hydrogel enhanced the MTX antitumor function. Our study indicates that a thermosensitive CH−β-GP–CNT hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of MTX.

Objective: The objectives of this study were to design and develop an open-circuit electromagnetic resonant skin patch sensor, characterize the fluid volume and resonant frequency relationship, and investigate the sensor's ability to measure limb hemodynamics and pulse volume waveform features. Methods: The skin patch was designed from an open-circuit electromagnetic resonant sensor comprised of a single baseline trace of copper configured into a square planar spiral which had a self-resonating response when excited by an external radio frequency sweep. Using a human arm phantom with a realistic vascular network, the sensor's performance to measure limb hemodynamics was evaluated. Results: The sensor was able to measure pulsatile blood flow which registered as shifts in the sensor's resonant frequencies. The time-varying waveform pattern of the resonant frequency displayed a systolic upstroke, a systolic peak, a dicrotic notch, and a diastolic down stroke. The resonant frequency waveform features and peak systolic time were validated against ultrasound pulse wave Doppler. A statistical correlation analysis revealed a strong correlation (R-2 = 0.99) between the resonant sensor peak systolic time and the pulse wave Doppler peak systolic time. Conclusion: The sensor was able to detect pulsatile flow, identify hemodynamic waveform features, and measure heart rate with 98% accuracy. Significance: The open-circuit resonant sensor design leverages the architecture of a thin planar spiral which is passive (does not require batteries), robust and lightweight (does not have electrical components or electrical connections), and may be able to wirelessly monitor cardiovascular health and limb hemodynamics.

Elevated intracranial fluid volume can drive intracranial pressure increases, which can potentially result in numerous neurological complications or death. This study’s focus was to develop a passive skin patch sensor for the head that would non-invasively measure cranial fluid volume shifts. The sensor consists of a single baseline component configured into a rectangular planar spiral with a self-resonant frequency response when impinged upon by external radio frequency sweeps. Fluid volume changes (10 mL increments) were detected through cranial bone using the sensor on a dry human skull model. Preliminary human tests utilized two sensors to determine feasibility of detecting fluid volume shifts in the complex environment of the human body. The correlation between fluid volume changes and shifts in the first resonance frequency using the dry human skull was classified as a second order polynomial with R2 = 0.97. During preliminary and secondary human tests, a ≈24 MHz and an average of ≈45.07 MHz shifts in the principal resonant frequency were measured respectively, corresponding to the induced cephalad bio-fluid shifts. This electromagnetic resonant sensor may provide a non-invasive method to monitor shifts in fluid volume and assist with medical scenarios including stroke, cerebral hemorrhage, concussion, or monitoring intracranial pressure.

This paper focuses on the development of a passive, lightweight skin patch sensor that can measure fluid volume changes in the heart in a non-invasive, point-of-care setting. The wearable sensor is an electromagnetic, self-resonant sensor configured into a specific pattern to formulate its three passive elements (resistance, capacitance, and inductance). In an animal model, a bladder was inserted into the left ventricle (LV) of a bovine heart, and fluid was injected using a syringe to simulate stoke volume (SV). In a human study, to assess the dynamic fluid volume changes of the heart in real time, the sensor frequency response was obtained from a participant in a 30° head-up tilt (HUT), 10° HUT, supine, and 10° head-down tilt positions over time. In the animal model, an 80-mL fluid volume change in the LV resulted in a downward frequency shift of 80.16 kHz. In the human study, there was a patterned frequency shift over time which correlated with ventricular volume changes in the heart during the cardiac cycle. Statistical analysis showed a linear correlation ${R} ^{2} = 0.98$ and 0.87 between the frequency shifts and fluid volume changes in the LV of the bovine heart and human participant, respectively. In addition, the patch sensor detected heart rate in a continuous manner with a 0.179% relative error compared to electrocardiography. These results provide promising data regarding the ability of the patch sensor to be a potential technology for SV monitoring in a non-invasive, continuous, and non-clinical setting.

This paper focuses on the development of a passive, lightweight skin patch sensor that can measure fluid volume changes in the heart in a non-invasive, point-of-care setting. The wearable sensor is an electromagnetic, self-resonant sensor configured into a specific pattern to formulate its three passive elements (resistance, capacitance, and inductance). In an animal model, a bladder was inserted into the left ventricle (LV) of a bovine heart, and fluid was injected using a syringe to simulate stoke volume (SV). In a human study, to assess the dynamic fluid volume changes of the heart in real time, the sensor frequency response was obtained from a participant in a 30° head-up tilt (HUT), 10° HUT, supine, and 10° head-down tilt positions over time. In the animal model, an 80-mL fluid volume change in the LV resulted in a downward frequency shift of 80.16 kHz. In the human study, there was a patterned frequency shift over time which correlated with ventricular volume changes in the heart during the cardiac cycle. Statistical analysis showed a linear correlation ${R} ^{2} = 0.98$ and 0.87 between the frequency shifts and fluid volume changes in the LV of the bovine heart and human participant, respectively. In addition, the patch sensor detected heart rate in a continuous manner with a 0.179% relative error compared to electrocardiography. These results provide promising data regarding the ability of the patch sensor to be a potential technology for SV monitoring in a non-invasive, continuous, and non-clinical setting.

Peripheral artery disease (PAD) is a condition caused by atherosclerotic blockages in the arteries supplying the lower limbs and is characterized by ischemia of the leg, progressive myopathy, and increased risk of limb loss. The affected leg muscles undergo significant changes of their biochemistry and metabolism including variations in the levels of many key proteins, lipids, and nucleotides. The mechanisms behind these changes are poorly understood. The objective of this study was to correlate the severity of the PAD disease stage and associated hemodynamic limitation (determined by the ankle brachial index, ABI) in the legs of the patients with alterations in the biochemistry of chronically ischemic leg muscle as determined by ATR‐Fourier transform infrared micro‐spectroscopy. Muscle (gastrocnemius) biopsies were collected from 13 subjects including four control patients (ABI≥0.9), five claudicating patients (0.4 ≤ ABI<0.9), and four critical limb ischemia (CLI) patients (ABI<0.4). Slide mounted specimens were analyzed by ATR‐Fourier transform infrared micro‐spectroscopy. An analysis of variance and a partial least squares regression model were used to identify significant differences in spectral peaks and correlate them with the ABI. The spectra revealed significant differences (P < 0.05) across control, claudicating, and CLI patients in the fingerprint and functional group regions. Infrared microspectroscopic probing of ischemic muscle biopsies demonstrates that PAD produces significant and unique changes to muscle biochemistry in comparison to control specimens. These distinctive biochemical profiles correlate with disease progression and may provide insight and direction for new targets in the diagnosis and therapy of muscle degeneration in PAD.

Background Peripheral artery disease (PAD) is a vascular disease caused by atherosclerosis, resulting in decreased blood flow to the lower extremities. The ankle-brachial index (ABI) is a standard PAD diagnostic test but only identifies reduced blood flow based on blood pressure differences. The early signs of PAD manifest themselves not only at a clinical level but also at an elemental and biochemical level. However, the biochemical and elemental alterations to PAD muscle are not well understood. The objective of this study was to compare fundamental changes in intracellular elemental compositions between control, claudicating, and critical limb ischemia muscle tissue. Materials and methods Gastrocnemius biopsies from three subjects including one control (ABI ≥ 0.9), one claudicating (0.4 ≤ ABI < 0.9), and one critical limb ischemia patient (ABI < 0.4) were evaluated using a scanning electron microscope and energy dispersive X-ray spectroscopy to quantify differences in elemental compositions. Spectra were collected for five myofibers per specimen. An analysis of variance was performed to identify significant differences in muscle elemental compositions. Results This study revealed that intracellular magnesium and calcium were lower in PAD compared with control myofibers, whereas sulfur was higher. Magnesium and calcium are antagonistic, meaning, if magnesium concentrations go down calcium concentrations should go up. However, our findings do not support this antagonism in PAD. Our analysis found decreases in sodium and potassium, in PAD myofibers. Conclusions These findings may provide insight into the pathologic mechanisms that may operate in ischemic muscle and aid in the development of specialized preventive and rehabilitative treatment plans for PAD patients.

Background: The aim of this study was to develop a non-invasive mobile skin patch sensor – applied like an adhesive bandage which could potentially measure left-ventricular stroke volume (LVSV). Methods: The sensor was designed from a single baseline component comprised of a trace of copper

Chitosan has the ability to make injectable thermosensitive hydrogels which has been highly investigated for drug delivery applications. The addition of nanoparticles is one way to increase the mechanical strength of thermosensitive chitosan hydrogel and subsequently and control the burst release of drug. Graphene nanoparticles have shown unique mechanical, optical and electrical properties which can be exploited for biomedical applications, especially in drug delivery. This study, have focused on the mechanical properties of a thermosensitive and injectable hybrid chitosan hydrogel incorporated with graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) have been used for morphological and chemical characterization of graphene infused chitosan hydrogels. The cell viability and cytotoxicity of graphene-contained hydrogels were analyzed using the alamarBlue® technique. In-vitro methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as well. As a last step, to evaluate their efficiency as a cancer treatment delivery system, an in vitro anti-tumor test was also carried out using MCF-7 breast cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of methotrexate. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2381-2390, 2017.

The use of nanomaterials and nanostructures have been revolutionizing the advancements of science and technology in various engineering and medical fields. As an example, Carbon Nanotubes (CNTs) have been extensively used for the improvement of mechanical, thermal, electrical, magnetic, and deteriorative properties of traditional composite materials for applications in high-performance structures. The exceptional materials properties of CNTs (i.e., mechanical, magnetic, thermal, and electrical) have introduced them as promising candidates for reinforcement of traditional composites. Most structural configurations of CNTs provide superior material properties; however, their geometrical shapes can deliver different features and characteristics. As one of the unique geometrical configurations, helical CNTs have a great potential for improvement of mechanical, thermal, and electrical properties of polymeric resin composites. The coil spring shape of these CNTs give them the capability to withstand high loads and considerable deformations that can be recovered, upon unloading. In addition, due to their helical shape, the entanglement of these CNTs with each other and the polymeric crosslinked molecular chains is much higher compared to the straight CNTs. Therefore, they can potentially absorb more impact loads and deliver higher resilience and flexibility in composites. One of the main issues for using these nanomaterials in composites is the uniform dispersion of these nanoparticles in the matrix system, besides their poor interface properties. This research reports a method for functionalization of helical CNTs (HCNTs) and investigates the effects of processing parameters, which can influence the effectiveness of the proposed chemical functionalization methods. The proposed method uses a refluxing process with a strong acidic solution; here, the effects of molarity and temperature, as two influential parameters, were investigated. For characterization of the functionalized helical CNTs, X-ray diffraction spectroscopy (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), visual dispersion inspection, and Scanning Electron Microscopy (SEM) methods were used. According to the results, all functionalization processes were successful in increasing the attachment of functional groups to the surface of helical CNTs that resulted in better dispersion of helical CNTs in Dl water. The increase in molarity (M) of the acidic solution beyond 3M resulted a higher dispersion rate and a lower crystallinity. In the case of using a high-reflux temperature, helical CNTs which were processed with a 3M or 16M acids displayed a substantial increase in the solubility compared to the ones which were refluxed at a low temperature.

Cancer is a group of diseases that may start in any body-organ such as breast; it involves abnormal cell growth and spreads to the entire body and the cancer patient may die. Mammography is a familiar method to detect breast cancer of human body. But the disadvantage of a typical mammography technique is of poor contrast; so that, micro calcifications can be overlooked by doctors while using mammograms. In this work, we propose a novel computer-assisted technique to assess mammogram images for breast cancer treatment using some commonly available tools. Our proposed methodology selects suspicious areas on images, hidden attributes are extracted from those selected areas, analyzes the extracted values, and assess the images as benign or malignant based on the extracted values. This work is used by Mammogram images from the Digital Database for Screening Mammogram (DDSM) and Mammographic Image Analysis Society (MIAS). Matrix Laboratory (MATLAB) tool is used to extract the feature values from the images. According to the experimental results, the proposed technique shows potential to accurately analyze the suspicious regions into benign and malignant. We believe that is because the suspicious regions are converted into equivalent numeric values. We plan to extend the proposed image analysis technique to study three-dimensional (3D) medical imaging.