Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin.

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

An Optical Signal Simulator for the Characterization of Photoplethysmographic Devices.

(1) Background: An optical simulator able to provide a repeatable signal with desired characteristics as an input to a photoplethysmographic (PPG) device is presented in order to compare the performance of different PPG devices and also to test the devices with PPG signals available in online databases. (2) Methods: The optical simulator consists of an electronic board containing a photodiode and LEDs at different wavelengths in order to simulate light reflected by the body; the PPG signal taken from the chosen database is reproduced by the electronic board, and the board is used to test a wearable PPG medical device in the form of earbuds. (3) Results: The PPG device response to different average and peak-to-peak signal amplitudes is shown in order to assess the device sensitivity, and the fidelity in tracking the actual heart rate is also investigated. (4) Conclusions: The developed optical simulator promises to be an affordable, flexible, and reliable solution to test PPG devices in the lab, allowing the testing of their actual performances thanks to the possibility of using PPG databases, thus gaining useful and significant information before on-the-field clinical trials.

All-nanofiber-based, ultrasensitive, gas-permeable mechanoacoustic sensors for continuous long-term heart monitoring.

The prolonged and continuous monitoring of mechanoacoustic heart signals is essential for the early diagnosis of cardiovascular diseases. These bodily acoustics have low intensity and low frequency, and measuring them continuously for long periods requires ultrasensitive, lightweight, gas-permeable mechanoacoustic sensors. Here, we present an all-nanofiber mechanoacoustic sensor, which exhibits a sensitivity as high as 10,050.6 mV Pa-1 in the low-frequency region (<500 Hz). The high sensitivity is achieved by the use of durable and ultrathin (2.5 µm) nanofiber electrode layers enabling a large vibration of the sensor during the application of sound waves. The sensor is ultralightweight, and the overall weight is as small as 5 mg or less. The devices are mechanically robust against bending, and show no degradation in performance even after 1,000-cycle bending. Finally, we demonstrate a continuous long-term (10 h) measurement of heart signals with a signal-to-noise ratio as high as 40.9 decibels (dB).

Survey on Energy Harvesting for Biomedical Devices: Applications, Challenges and Future Prospects for African Countries.

Self-powered biomedical devices, which are the new vision of Internet Of Things (IOT) healthcare, are facing many technical and application challenges. Many research works have reported biomedical devices and self-powered applications for healthcare, along with various strategies to improve the monitoring time of self-powered devices or to eliminate the dependence on electrochemical batteries. However, none of these works have especially assessed the development and application of healthcare devices in an African context. This article provides a comprehensive review of self-powered devices in the biomedical research field, introduces their applications for healthcare, evaluates their status in Africa by providing a thorough review of existing biomedical device initiatives and available financial and scientific cooperation institutions in Africa for the biomedical research field, and highlights general challenges for implementing self-powered biomedical devices and particular challenges related to developing countries. The future perspectives of the aforementioned research field are provided, as well as an architecture for improving this research field in developing countries.

Advances in Functionalization of Bioresorbable Nanomembranes and Nanoparticles for Their Use in Biomedicine.

Bioresorbable nanomembranes (NMs) and nanoparticles (NPs) are powerful polymeric materials playing an important role in biomedicine, as they can effectively reduce infections and inflammatory clinical patient conditions due to their high biocompatibility, ability to physically interact with biomolecules, large surface area, and low toxicity. In this review, the most common bioabsorbable materials such as those belonging to natural polymers and proteins for the manufacture of NMs and NPs are reviewed. In addition to biocompatibility and bioresorption, current methodology on surface functionalization is also revisited and the most recent applications are highlighted. Considering the most recent use in the field of biosensors, tethered lipid bilayers, drug delivery, wound dressing, skin regeneration, targeted chemotherapy and imaging/diagnostics, functionalized NMs and NPs have become one of the main pillars of modern biomedical applications.

Novel Material Optimization Strategies for Developing Upgraded Abdominal Meshes.

Over 20 million hernias are operated on globally per year, with most interventions requiring mesh reinforcement. A wide range of such medical devices are currently available on the market, most fabricated from synthetic polymers. Yet, searching for an ideal mesh is an ongoing process, with continuous efforts directed toward developing upgraded implants by modifying existing products or creating innovative systems from scratch. In this regard, this review presents the most frequently employed polymers for mesh fabrication, outlining the market available products and their relevant characteristics, further focusing on the state-of-the-art mesh approaches. Specifically, we mainly discuss recent studies concerning coating application, nanomaterials addition, stem cell seeding, and 3D printing of custom mesh designs.

Transparent and Highly Flexible Hierarchically Structured Polydimethylsiloxane Surfaces Suppress Bacterial Attachment and Thrombosis Under Static and Dynamic Conditions.

The surface fouling of biomedical devices has been an ongoing issue in healthcare. Bacterial and blood adhesion in particular, severely impede the performance of such tools, leading to poor patient outcomes. Various structural and chemical modifications have been shown to reduce fouling, but all existing strategies lack the combination of physical, chemical, and economic traits necessary for widespread use. Herein, a lubricant infused, hierarchically micro- and nanostructured polydimethylsiloxane surface is presented. The surface is easy to produce and exhibits the high flexibility and optical transparency necessary for incorporation into various biomedical tools. Tests involving two clinically relevant, priority pathogens show up to a 98.5% reduction in the biofilm formation of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. With blood, the surface reduces staining by 95% and suppresses thrombin generation to background levels. Furthermore, the surface shows applicability within applications such as catheters, extracorporeal circuits, and microfluidic devices, through its effectiveness in dynamic conditions. The perfusion of bacterial media shows up to 96.5% reduction in bacterial adhesion. Similarly, a 95.8% reduction in fibrin networks is observed following whole blood perfusion. This substrate stands to hold high applicability within biomedical systems as a means to prevent fouling, thus improving performance.

Revisiting the Analysis of Radiative Mid-Range Wireless Link for Pacemakers.

The development of a wireless link for biomedical applications requires an accurate estimation of the delivered power to implanted devices. In particular, a variety of mid-range applications in the biomedical area have gained significant attention. An appropriate method for the mid-range wireless link is required to implement a continuous wireless link through human tissue. Even though formulas used in this work are all based on previous works, this paper presents an implementation of the diverse formulas for the mid-range wireless link of an implanted antenna used for a pacemaker system based on the understanding on radiation properties varied with the distances from the antenna. The formulas based on input far-field data are successfully applied to compute the power transmission for the implanted devices, whose range includes radiative near-field and far-field regions. The wireless link for a pacemaker system is evaluated through using a patch antenna immersed with different depths of human tissue. A comparison of the computed and measured results shows an excellent agreement where the validity of the evaluation is demonstrated.

Venture Capital Investment in Orthopaedics: Has the Landscape Changed over the Past Two Decades (2000-2019)?

Background. Innovations in orthopaedic technologies often require significant funding. Although an increasing trend has been observed for third-party investments in other medical fields, no study has examined the influence of venture capital (VC) funding in orthopaedics. Therefore, this study analyzed trends in VC investments related to the field of orthopaedic surgery, as well as the characteristics of recipients of these investments. Methods. Venture capital investments into orthopaedic-related businesses were reviewed from 2000 to 2019 using Capital IQ, a proprietary intelligence platform documenting financial investments. Metrics categorized were investments by year, investment amount, and subspecialty domain as per the American Academy Orthopaedic Surgeons website. The compound annual growth rate (CAGR) for both quantity and dollar amount of investments was calculated over the study period and the two decade-long periods (2000-2009 and 2010-2019). Results. Over two decades, 673 VC investments took place, involving a total of US$3.5 billion. Both the number and dollar value of investments were greater in the second decade (440, US$1.9 billion), compared to the first decade (233, US$1.6 billion). Both quantity and dollar amount of VC investments grew over the first decade, with a CAGR 9.53% and 4.97%, respectively. However, investment growth declined in the latter decade. The largest and most frequent investments took place within spine surgery and adult reconstruction. Conclusion. An initially rising trend in VC investment in orthopaedic-related businesses may have plateaued over the past decade. These findings may have important implications for continued investment into orthopaedic innovations and collaboration between the surgical community and private sector.

Graphene-Based Antimicrobial Biomedical Surfaces.

Biomedical application of graphene derivatives have been intensively studied in last decade. With the exceptional structural, thermal, electrical, and mechanical properties, these materials have attracted immense attention of biomedical scientists to utilize graphene derivatives in biomedical devices to improve their performance or to achieve desired functions. Surfaces of graphene derivatives including graphite, graphene, graphene oxide and reduce graphene oxide have been demonstrated to pave an excellent platform for antimicrobial behavior, enhanced biocompatibility, tissue engineering, biosensors and drug delivery. This review focuses on the recent advancement in the research of biomedical devices with the coatings or highly structured polymer nanocomposite surfaces of graphene derivatives for antimicrobial activity and sterile surfaces comprising an entirely new class of antibacterial materials. Overall, we aim to highlight on the potential of these materials, current understanding and knowledge gap in the antimicrobial behavior and biocompatibility to be utilized of their coatings to prevent the cross infections.

Investigation on Wireless Link for Medical Telemetry Including Impedance Matching of Implanted Antennas.

The development of biomedical devices benefits patients by offering real-time healthcare. In particular, pacemakers have gained a great deal of attention because they offer opportunities for monitoring the patient's vitals and biological statics in real time. One of the important factors in realizing real-time body-centric sensing is to establish a robust wireless communication link among the medical devices. In this paper, radio transmission and the optimal characteristics for impedance matching the medical telemetry of an implant are investigated. For radio transmission, an integral coupling formula based on 3D vector far-field patterns was firstly applied to compute the antenna coupling between two antennas placed inside and outside of the body. The formula provides the capability for computing the antenna coupling in the near-field and far-field region. In order to include the effects of human implantation, the far-field pattern was characterized taking into account a sphere enclosing an antenna made of human tissue. Furthermore, the characteristics of impedance matching inside the human body were studied by means of inherent wave impedances of electrical and magnetic dipoles. Here, we demonstrate that the implantation of a magnetic dipole is advantageous because it provides similar impedance characteristics to those of the human body.

Interactive Fluid Coupling Effects of Non-Neighbouring Members.

Broadband, multi-functional and parallel-processing devices are often built on coupled oscillators or arrays of resonators. Different length scales and applications determine the dominating coupling mechanism of the device. In this paper we investigate the effects of interactive fluid coupling between members of a one-dimensional array wherein only one member is actuated. We are specifically interested in studying the influence of non-neighbouring members in small-size arrays comprising of three and five members for different Reynolds numbers and gap widths between members. Our model and analysis is based on the Navier-Stokes equation for incompressible flow which is solved using a boundary integral technique resulting in the hydrodynamic coupling matrix through which added mass and damping effects are inferred. Results clearly suggest that non-neighbouring members play a significant role for most typical array configurations and therefore cannot be ignored. In particular, arrays with more than three members must account for the behaviour of such a device with all member interactions. Thus, predicting the performance of most new and emerging technologies such as sensors and biomedical devices is determined by array effects rather than local, nearest neighbour influences.

Molecularly Imprinted Polymers (MIPs) in Sensors for Environmental and Biomedical Applications: A Review.

Molecular imprinted polymers are custom made materials with specific recognition sites for a target molecule. Their specificity and the variety of materials and physical shapes in which they can be fabricated make them ideal components for sensing platforms. Despite their excellent properties, MIP-based sensors have rarely left the academic laboratory environment. This work presents a comprehensive review of recent reports in the environmental and biomedical fields, with a focus on electrochemical and optical signaling mechanisms. The discussion aims to identify knowledge gaps that hinder the translation of MIP-based technology from research laboratories to commercialization.

Skin-Mountable Biosensors and Therapeutics: A Review.

Miniaturization of electronic components and advances in flexible and stretchable materials have stimulated the development of wearable health care systems that can reflect and monitor personal health status by health care professionals. New skin-mountable devices that offer seamless contact onto the human skin, even under large deformations by natural motions of the wearer, provide a route for both high-fidelity monitoring and patient-controlled therapy. This article provides an overview of several important aspects of skin-mountable devices and their applications in many medical settings and clinical practices. We comprehensively describe various transdermal sensors and therapeutic systems that are capable of detecting physical, electrophysiological, and electrochemical responses and/or providing electrical and thermal therapies and drug delivery services, and we discuss the current challenges, opportunities, and future perspectives in the field. Finally, we present ways to protect the embedded electronic components of skin-mountable devices from the environment by use of mechanically soft packaging materials.

Microfabricaton of microfluidic check valves using comb-shaped moving plug for suppression of backflow in microchannel.

This study reports on an efficient microscale one-way valve system that combines the physical properties of photopolymerized microstructures and viscoelastic microchannels to rectify flows with low Reynolds numbers. The comb-shaped moving plug in the microchannel prevented backflow in the closed state to ensure that the microchannel remained completely blocked in the closed state, but allowed forward flow in the open state. This microfluidic check valve was microfabricated using the combination of the soft lithography and the releasing methods with the use of a double photoresist layer to create microchannels and free-moving comb-shaped microstructures, respectively. As a result, the microfluidic check valves elicited average high-pressure differences as much as 10.75 kPa between the backward and forward flows at low Reynolds numbers of the order of 0.253, thus demonstrating efficient rectification of microfluids. This study supports the use of rectification systems for the development of biomedical devices, such as drug delivery, micropumps, and lab-on-a-chip, by allowing unidirectional flow.

A Wearable Fiberless Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Mice.

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultra-small low-power CMOS camera as a 2D detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements (R2 ≥ 0.80, p < 10-5). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source-detector configuration allows for varied probing depths up to ~8 mm, which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

A methodological inter-comparison study on the detection of surface contaminant sodium dodecyl sulfate applying ambient- and vacuum-based techniques.

Biomedical devices are complex products requiring numerous assembly steps along the industrial process chain, which can carry the potential of surface contamination. Cleanliness has to be analytically assessed with respect to ensuring safety and efficacy. Although several analytical techniques are routinely employed for such evaluation, a reliable analysis chain that guarantees metrological traceability and quantification capability is desirable. This calls for analytical tools that are cascaded in a sensible way to immediately identify and localize possible contamination, both qualitatively and quantitatively. In this systematic inter-comparative approach, we produced and characterized sodium dodecyl sulfate (SDS) films mimicking contamination on inorganic and organic substrates, with potential use as reference materials for ambient techniques, i.e., ambient mass spectrometry (AMS), infrared and Raman spectroscopy, to reliably determine amounts of contamination. Non-invasive and complementary vibrational spectroscopy techniques offer a priori chemical identification with integrated chemical imaging tools to follow the contaminant distribution, even on devices with complex geometry. AMS also provides fingerprint outputs for a fast qualitative identification of surface contaminations to be used at the end of the traceability chain due to its ablative effect on the sample. To absolutely determine the mass of SDS, the vacuum-based reference-free technique X-ray fluorescence was employed for calibration. Convex hip liners were deliberately contaminated with SDS to emulate real biomedical devices with an industrially relevant substance. Implementation of the aforementioned analytical techniques is discussed with respect to combining multimodal technical setups to decrease uncertainties that may arise if a single technique approach is adopted. Graphical abstract ᅟ.

A Bootstrapped Comparator-Switched Active Rectifying Circuit for Wirelessly Powered Integrated Miniaturized Energy Sensing Systems.

Human life expectancy has gradually increased in part through rapid advances in technology, including the development and use of wearable and implantable biomedical electronic devices and sensing monitors. A new architecture is proposed in this paper to replace the traditional diode circuit implementation in wireless power supply systems applied to the above-mentioned devices and monitors. By achieving near-ideal power transistor switching and leveraging the characteristics of conventional diodes to prevent reverse current, the proposed approach greatly improves the performance of the energy harvester in power conversion. The MOS harvester used in the uninterrupted permanent wireless near-field power supply described here for use in biomedical systems was designed and verified using the Taiwan Semiconductor Manufacturing Company (TSMC) standard 180-nm process, achieving performance results of Voltage conversion efficiency (VCE) = 73.55-95.12% and Power conversion efficiency (PCE) = 80.36-90.08% with the output load (0.1-1 kΩ) under 3.3 V ac input with an overall area of 1.189 mm2. These results are expected to create an important technical niche for new "green-energy" miniaturized energy sensing systems including cutting edge wirelessly powered biomedical electronics applications.

Candidate Polyurethanes Based on Castor Oil (Ricinus communis), with Polycaprolactone Diol and Chitosan Additions, for Use in Biomedical Applications.

Polyurethanes are widely used in the development of medical devices due to their biocompatibility, degradability, non-toxicity and chemical versatility. Polyurethanes were obtained from polyols derived from castor oil, and isophorone diisocyanate, with the incorporation of polycaprolactone-diol (15% w/w) and chitosan (3% w/w). The objective of this research was to evaluate the effect of the type of polyol and the incorporation of polycaprolactone-diol and chitosan on the mechanical and biological properties of the polyurethanes to identify the optimal ones for applications such as wound dressings or tissue engineering. Polyurethanes were characterized by stress-strain, contact angle by sessile drop method, thermogravimetric analysis, differential scanning calorimetry, water uptake and in vitro degradation by enzymatic processes. In vitro biological properties were evaluated by a 24 h cytotoxicity test using the colorimetric assay MTT and the LIVE/DEAD kit with cell line L-929 (mouse embryonic fibroblasts). In vitro evaluation of the possible inflammatory effect of polyurethane-based materials was evaluated by means of the expression of anti-inflammatory and proinflammatory cytokines expressed in a cellular model such as THP-1 cells by means of the MILLIPLEX® MAP kit. The modification of polyols derived from castor oil increases the mechanical properties of interest for a wide range of applications. The polyurethanes evaluated did not generate a cytotoxic effect on the evaluated cell line. The assessed polyurethanes are suggested as possible candidate biomaterials for wound dressings due to their improved mechanical properties and biocompatibility.

Gendered Innovation in Health and Medicine.

Excellence in research requires careful attention to sex and gender analysis. The Gendered Innovations project, initiated in 2009, develops state-of-the-art methods of sex and gender analysis for basic and applied research. This chapter reviews recent developments in cardiovascular disease for (1) analyzing sex, (2) analyzing gender, and (3) policy initiatives.