ABSTRACT
Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.
Subject(s)
Electromyography , Electronics, Medical , Nanostructures , Pliability , Polymers , Prostheses and Implants , Wearable Electronic Devices , Humans , Nanostructures/chemistry , Polymers/chemistry , Skin , Monitoring, Physiologic , Electronics, Medical/instrumentation , Electronics, Medical/methods , Electromyography/instrumentationABSTRACT
A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.
Subject(s)
Absorbable Implants , Electric Stimulation Therapy , Animals , Drug Delivery Systems , Electronics, Medical , Radio Waves , Rats , Wireless TechnologyABSTRACT
Medical electronic endoscope is one of the indispensable tools in medical diagnosis and treatment. With the development of science and technology, electronic endoscope has higher safety and accuracy than traditional optical endoscope. Due to the sophisticated construction and high price, hospitals spend a lot of money on maintenance every year. In order to prolong the working life of electronic endoscope, reduce the incidence of artificial failure and save hospital costs, this study made a retrospective analysis on the common faults of electronic endoscope, and summarized the maintenance strategies for reference.
Subject(s)
Electronics, Medical , Endoscopes , Retrospective StudiesABSTRACT
This study introduced the current testing content and standards of ECG medical electronic instruments, combined with actual clinical needs, and discussed the comprehensive verification and evaluation protocol for ECG medical electronic instruments. The protocol mainly includes hardware performance testing, automatic diagnostic function testing and clinical application evaluation. The protocol emphasizes the clinical practicality and importance of the comprehensive verification and evaluation program, and provides a reference for the institutions involved in the program.
Subject(s)
Electrocardiography , Electronics, Medical , Reference StandardsABSTRACT
BACKGROUND: Private sector malaria programmes contribute to government-led malaria elimination strategies in Cambodia, Lao PDR, and Myanmar by increasing access to quality malaria services and surveillance data. However, reporting from private sector providers remains suboptimal in many settings. To support surveillance strengthening for elimination, a key programme strategy is to introduce electronic surveillance tools and systems to integrate private sector data with national systems, and enhance the use of data for decision-making. During 2013-2017, an electronic surveillance system based on open source software, District Health Information System 2 (DHIS2), was implemented as part of a private sector malaria case management and surveillance programme. The electronic surveillance system covered 16,000 private providers in Myanmar (electronic reporting conducted by 200 field officers with tablets), 710 in Cambodia (585 providers reporting through mobile app), and 432 in Laos (250 providers reporting through mobile app). METHODS: The purpose of the study was to document the costs of introducing electronic surveillance systems and mobile reporting solutions in Cambodia, Lao PDR, and Myanmar, comparing the cost in different operational settings, the cost of introduction and maintenance over time, and assessing the affordability and financial sustainability of electronic surveillance. The data collection methods included extracting data from PSI's financial and operational records, collecting data on prices and quantities of resources used, and interviewing key informants in each setting. The costing study used an ingredients-based approach and estimated both financial and economic costs. RESULTS: Annual economic costs of electronic surveillance systems were $152,805 in Laos, $263,224 in Cambodia, and $1,310,912 in Myanmar. The annual economic cost per private provider surveilled was $82 in Myanmar, $371 in Cambodia, and $354 in Laos. Cost drivers varied depending on operational settings and number of private sector outlets covered in each country; whether purchased or personal mobile devices were used; and whether electronic (mobile) reporting was introduced at provider level or among field officers who support multiple providers for case reporting. CONCLUSION: The study found that electronic surveillance comprises about 0.5-1.5% of national malaria strategic plan cost and 7-21% of surveillance budgets and deemed to be affordable and financially sustainable.
Subject(s)
Case Management/economics , Electronics, Medical/economics , Epidemiological Monitoring , Population Surveillance/methods , Private Sector/statistics & numerical data , Cambodia , Humans , Laos , Malaria/epidemiology , Myanmar , Private Sector/economicsABSTRACT
OBJECTIVE: The purpose this study was to investigate the reliability of a handheld myotonometer in measuring the mechanical properties of the neck and orofacial muscles in asymptomatic individuals. METHODS: The study included 16 healthy participants. The mechanical properties (frequency, decrement, stiffness, relaxation time, and creep) of the selected muscles were measured with a MyotonPRO myotonometer (Mumeetria Ltd, Tallinn, Estonia). The sternocleidomastoid, upper trapezius, cervical extensor, and masseter muscles were selected to determine the reliability of the device. Measurements were performed by 2 examiners to determine interrater reliability; for intrarater reliability, an examiner repeated the measurements 1 week after the first measurements. RESULTS: The results revealed moderate to excellent intrarater and interrater reliability (intraclass correlation coefficients: 0.50-0.95) in measuring muscle mechanic properties. The standard error of measurement in the tested muscles ranged from 0.3 to 0.8 Hz for frequency, from 7.4 to 20.9 N/m for stiffness, from 0.1 to 0.2 for decrement, and from 0.8 to 1.4 ms for relaxation time. The minimum detectable change ranged from 0.8 to 2.2 Hz for frequency, from 20.5 to 57.9 N/m for stiffness, from 0.2 to 0.6 for decrement, from 2.2 to 3.9 ms for relaxation time, and from 0.2 to 0.3 for creep. In addition, the coefficients of variation were below 9.1% for all the assessed parameters. CONCLUSION: The obtained results demonstrate that the MyotonPRO device is a reliable and repeatable tool to quantify the frequency, stiffness, decrement, relation time, and creep of the neck and orofacial muscles in asymptomatic individuals.
Subject(s)
Electronics, Medical/instrumentation , Neck Muscles/physiology , Superficial Back Muscles/physiology , Adult , Humans , Male , Manometry/standards , Middle Aged , Observer Variation , Reproducibility of Results , Young AdultABSTRACT
Wearable sensors play a crucial role in realizing personalized medicine, as they can continuously collect data from the human body to capture meaningful health status changes in time for preventive intervention. However, motion artifacts and mechanical mismatches between conventional rigid electronic materials and soft skin often lead to substantial sensor errors during epidermal measurement. Because of its unique properties such as high flexibility and conformability, flexible electronics enables a natural interaction between electronics and the human body. In this Account, we summarize our recent studies on the design of flexible electronic devices and systems for physical and chemical monitoring. Material innovation, sensor design, device fabrication, system integration, and human studies employed toward continuous and noninvasive wearable sensing are discussed. A flexible electronic device typically contains several key components, including the substrate, the active layer, and the interface layer. The inorganic-nanomaterials-based active layer (prepared by a physical transfer or solution process) is shown to have good physicochemical properties, electron/hole mobility, and mechanical strength. Flexible electronics based on the printed and transferred active materials has shown great promise for physical sensing. For example, integrating a nanowire transistor array for the active matrix and a conductive pressure-sensitive rubber enables tactile pressure mapping; tactile-pressure-sensitive e-skin and organic light-emitting diodes can be integrated for instantaneous pressure visualization. Such printed sensors have been applied as wearable patches to monitor skin temperature, electrocardiograms, and human activities. In addition, liquid metals could serve as an attractive candidate for flexible electronics because of their excellent conductivity, flexibility, and stretchability. Liquid-metal-enabled electronics (based on liquid-liquid heterojunctions and embedded microchannels) have been utilized to monitor a wide range of physiological parameters (e.g., pulse and temperature). Despite the rapid growth in wearable sensing technologies, there is an urgent need for the development of flexible devices that can capture molecular data from the human body to retrieve more insightful health information. We have developed a wearable and flexible sweat-sensing platform toward real-time multiplexed perspiration analysis. An integrated iontophoresis module on a wearable sweat sensor could enable autonomous and programmed sweat extraction. A microfluidics-based sensing system was demonstrated for sweat sampling, sensing, and sweat rate analysis. Roll-to-roll gravure printing allows for mass production of high-performance flexible chemical sensors at low cost. These wearable and flexible sweat sensors have shown great promise in dehydration monitoring, cystic fibrosis diagnosis, drug monitoring, and noninvasive glucose monitoring. Future work in this field should focus on designing robust wearable sensing systems to accurately collect data from the human body and on large-scale human studies to determine how the measured physical and chemical information relates to the individual's specific health conditions. Further research in these directions, along with the large sets of data collected via these wearable and flexible sensing technologies, will have a significant impact on future personalized healthcare.
Subject(s)
Electronics, Medical/instrumentation , Monitoring, Physiologic/instrumentation , Pliability , Wearable Electronic Devices , Equipment Design , Humans , Skin Physiological Phenomena , Sweat/chemistryABSTRACT
A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.
Subject(s)
Biosensing Techniques , Electronics, Medical , Health , Patient-Specific Modeling , Circadian Rhythm/physiology , Electronics, Medical/instrumentation , Humans , Inflammation/diagnosis , Insulin/metabolism , Insulin Resistance , Oxygen/metabolism , Partial Pressure , Precision Medicine , Radiation , Reproducibility of ResultsABSTRACT
BACKGROUND: There is a pressing need for policy makers to demonstrate progress made on investments in prevention, but few examples of monitoring systems capable of tracking population-level prevention policies and programs and their implementation. In New South Wales, Australia, the scale up of childhood obesity prevention programs to over 6000 childcare centres and primary schools is monitored via an electronic monitoring system, "PHIMS". METHODS: Via a focussed ethnography with all 14 health promotion implementation teams in the state, we set out to explore what aspects of program implementation are captured via PHIMS, what aspects are not, and the implications for future IT implementation monitoring systems as a result. RESULTS: Practitioners perform a range of activities in the context of delivering obesity prevention programs, but only specific activities are captured via PHIMS. PHIMS thereby defines and standardises certain activities, while non-captured activities can be considered as "extra" work by practitioners. The achievement of implementation targets is influenced by multi-level contextual factors, with only some of the factors accounted for in PHIMS. This evidences incongruencies between work done, recorded and, therefore, recognised. CONCLUSIONS: While monitoring systems cannot and should not capture every aspect of implementation, better accounting for aspects of context and "extra" work involved in program implementation could help illuminate why implementation succeeds or fails. Failure to do so may result in policy makers drawing false conclusions about what is required to achieve implementation targets. Practitioners, as experts of context, are well placed to assist policy makers to develop accurate and meaningful implementation targets and approaches to monitoring.
Subject(s)
Electronics, Medical , Health Plan Implementation , Health Promotion , Pediatric Obesity/prevention & control , Anthropology, Cultural , Child , Humans , New South Wales , Policy Making , SchoolsABSTRACT
BACKGROUND: The disproportionately high prevalence of HIV among men who have sex with men (MSM) is a global concern. Despite the increasing utilization of electronic health (eHealth) technology in the delivery of HIV prevention interventions, few studies have systematically explored its effectiveness and association with various intervention characteristics. OBJECTIVE: This study aimed to conduct a meta-analysis of the effectiveness of eHealth technology-based interventions for promoting HIV-preventive behaviors among MSM and to determine effectiveness predictors within a framework integrating design and implementation features. METHODS: A systematic literature search using terms related to eHealth technology, HIV, the MSM population, and an experimental study design was performed using 5 databases (ie, MEDLINE, PsycINFO, EMBASE, Web of Science, and ProQuest Dissertations & Theses) and other sources (eg, bibliographies of relevant reviews and JMIR Publications). First, primary meta-analyses were conducted to estimate the effectiveness of eHealth interventions (d+) in changing 3 HIV-preventive behaviors among MSM: unprotected anal intercourse (UAI), HIV testing, and multiple sex partnership (MSP). Moderation analyses were then conducted to examine a priori effectiveness predictors including behavioral treatment components (eg, theory use, tailoring strategy use, navigation style, and treatment duration), eHealth technology components (eg, operation mode and modality type), and intervention adherence. RESULTS: A total of 46 studies were included. The overall effect sizes at end point were small but significant for all outcomes (UAI: d+=-.21, P<.001; HIV testing: d+=.38, P<.001; MSP: d+=-.26, P=.02). The intervention effects on UAI were significantly larger when compared with preintervention groups than with concurrent groups. Greater UAI reductions were associated with the increased use of tailoring strategies, provision of feedback, and tunneling navigation in interventions with a concurrent group, whereas reductions were associated with the use of self-paced navigation in interventions with a preintervention group. Greater uptake of HIV testing was associated with longer treatment duration; computer-mediated communication; and the use of messaging, social media, or a combined technology modality. Higher intervention adherence consistently predicted larger effects on UAI and HIV testing. CONCLUSIONS: This study provided empirical evidence for the effectiveness of eHealth interventions in promoting HIV-preventive behaviors among MSM. Features of treatment content and eHealth technology might best predict the intervention effects on UAI and HIV testing, respectively. Most importantly, intervention adherence tended to play an important role in achieving better effectiveness. The findings could help inform the development of efficacious interventions for HIV prevention in the future.
Subject(s)
Electronics, Medical/methods , HIV Infections/prevention & control , Homosexuality, Male/statistics & numerical data , Humans , MaleABSTRACT
Safe quality control of radiotherapy treatments lies in reliable dosimetric sensors. Currently, ionization chambers and solid-state diodes along with electrometers as readout systems are accomplishing this task. In this work, we present a well-known and low-cost semiconductor sensor, the light-dependent resistor (LDR), as an alternative to the existing sensing devices for dosimetry. To demonstrate this, a complete characterization of the response to radiation of commercial LDRs has been conducted in terms of sensitivity, reproducibility and thermal correction under different bias voltages. Irradiation sessions have been applied under the common conditions in radiotherapy treatments using a hospital linear accelerator. Moreover, the same electrometer used for the ionization chamber has also been successfully used for LDRs. In comparison with the sensitivity achieved for the ionization chamber (0.2 nC/cGy at 400 V bias voltage), higher sensitivities have been measured for the proposed LDRs, ranging from 0.24 to 1.04 nC/cGy at bias voltages from 30 to 150 V, with a reproducibility uncertainty among samples of around 10%. In addition, LDR temperature dependence has been properly modeled using the simple thermistor model so that an easy thermal drift correction of dose measurements can be applied. Therefore, experimental results show that LDRs can be a reliable alternative to dosimetric sensors with the advantages of low size, affordable cost and the fact that it could be adopted with minimal changes in routine dosimetry quality control since the same readout system is fully compatible.
Subject(s)
Electronics, Medical/instrumentation , Radiometry/instrumentation , Radiotherapy Dosage , Electrical Equipment and Supplies , Electronics, Medical/standards , Equipment Design , Light , Models, Biological , Sensitivity and Specificity , TemperatureABSTRACT
Polymer-based electronics with low bending stiffnesses and high flexibility, including recently reported macroporous syringe-injectable mesh electronics, have shown substantial promise for chronic studies of neural circuitry in the brains of live animals. A central challenge for exploiting these highly flexible materials for in vivo studies has centered on the development of efficient input/output (I/O) connections to an external interface with high yield, low bonding resistance, and long-term stability. Here we report a new paradigm applied to the challenging case of injectable mesh electronics that exploits the high flexibility of nanoscale thickness two-sided metal I/O pads that can deform and contact standard interface cables in high yield with long-term electrical stability. First, we describe the design and facile fabrication of two-sided metal I/O pads that allow for contact without regard to probe orientation. Second, systematic studies of the contact resistance as a function of I/O pad design and mechanical properties demonstrate the key role of the I/O pad bending stiffness in achieving low-resistance stable contacts. Additionally, computational studies provide design rules for achieving high-yield multiplexed contact interfacing in the case of angular misalignment such that adjacent channels are not shorted. Third, the in vitro measurement of 32-channel mesh electronics probes bonded to interface cables using the direct contact method shows a reproducibly high yield of electrical connectivity. Finally, in vivo experiments with 32-channel mesh electronics probes implanted in live mice demonstrate the chronic stability of the direct contact interface, enabling consistent tracking of single-unit neural activity over at least 2 months without a loss of channel recording. The direct contact interfacing methodology paves the way for scalable long-term connections of multiplexed mesh electronics neural probes for neural recording and modulation and moreover could be used to facilitate a scalable interconnection of other flexible electronics in biological studies and therapeutic applications.
Subject(s)
Electronics, Medical/instrumentation , Animals , Electrodes, Implanted , Equipment Design , Injections , Mice , Pliability , SyringesABSTRACT
The unique structure and mechanical properties of syringe-injectable mesh electronics have enabled seamless tissue integration and stable chronic recording of the activities of the same neurons on a year scale. Here, we report studies of a series of structural and mechanical mesh electronics design variations that allow injection using needles at least 4-fold smaller than those previously reported to minimize the footprint during injection of the electronics in soft matter and tissue. Characterization of new ultraflexible two-dimensional (2D) and one-dimensional (1D) probes has demonstrated reproducible injection of the newly developed mesh electronics designs via needles as small as 100 µm in inner diameter (ID) with reduced injection volumes. In vitro hydrogel and in vivo mouse brain studies have shown that ultraflexible 2D and 1D probes maintain their structural integrity and conformation post-injection after being transferred through the reduced diameter needles. In addition, analysis of the variation of the post-injection mesh cross sections suggests a smaller degree of tissue deformation and relaxation with decreasing needle diameters. The capability to implement rational design for mesh electronic probes that can be delivered via much smaller diameter needles should open up new opportunities for integration of electronics with tissue and soft matter in fundamental and translational studies.
Subject(s)
Biomimetic Materials/administration & dosage , Electronics, Medical/instrumentation , Pliability , Animals , Biomimetic Materials/chemistry , Brain/physiology , Equipment Design , Injections , Mice , Needles , Neurons/physiology , Prostheses and ImplantsABSTRACT
The eRPS system for medical device registration of National Medical Products Administration was officially launched on June 24, 2019. This paper focused on the following two aspects of the electronic declaration process of medical device regulatory agencies in the whole world:one is whether the electronic submission format is consistent, the other is whether the electronic submission path is convenient. Suggestions are put forward for the next nationwide implementation of the electronic submission so as to speed up the process of the electronization of medical device evaluation in China.
Subject(s)
Electronics, Medical , ChinaABSTRACT
Multifunctional devices for modulation and probing of neuronal activity during free behavior facilitate studies of functions and pathologies of the nervous system. Probes composed of stiff materials, such as metals and semiconductors, exhibit elastic and chemical mismatch with the neural tissue, which is hypothesized to contribute to sustained tissue damage and gliosis. Dense glial scars have been found to encapsulate implanted devices, corrode their surfaces, and often yield poor recording quality in long-term experiments. Motivated by the hypothesis that reducing the mechanical stiffness of implanted probes may improve their long-term reliability, a variety of probes based on soft materials have been developed. In addition to enabling electrical neural recording, these probes have been engineered to take advantage of genetic tools for optical neuromodulation. With the emergence of optogenetics, it became possible to optically excite or inhibit genetically identifiable cell types via expression of light-sensitive opsins. Optogenetics experiments often demand implantable multifunctional devices to optically stimulate, deliver viral vectors and drugs, and simultaneously record electrophysiological signals from the specified cells within the nervous system. Recent advances in microcontact printing and microfabrication techniques have equipped flexible probes with microscale light-emitting diodes (µLEDs), waveguides, and microfluidic channels. Complementary to these approaches, fiber drawing has emerged as a scalable route to integration of multiple functional features within miniature and flexible neural probes. The thermal drawing process relies on the fabrication of macroscale models containing the materials of interest, which are then drawn into microstructured fibers with predefined cross-sectional geometries. We have recently applied this approach to produce fibers integrating conductive electrodes for extracellular recording of single- and multineuron potentials, low-loss optical waveguides for optogenetic neuromodulation, and microfluidic channels for drug and viral vector delivery. These devices allowed dynamic investigation of the time course of opsin expression across multiple brain regions and enabled pairing of optical stimulation with local pharmacological intervention in behaving animals. Neural probes designed to interface with the spinal cord, a viscoelastic tissue undergoing repeated strain during normal movement, rely on the integration of soft and flexible materials to avoid injury and device failure. Employing soft substrates, such as parylene C and poly-(dimethylsiloxane), for electrode and µLED arrays permitted stimulation and recording of neural activity on the surface of the spinal cord. Similarly, thermally drawn flexible and stretchable optoelectronic fibers that resemble the fibrous structure of the spinal cord were implanted without any significant inflammatory reaction in the vicinity of the probes. These fibers enabled simultaneous recording and optogenetic stimulation of neural activity in the spinal cord. In this Account, we review the applications of multifunctional fibers and other integrated devices for optoelectronic probing of neural circuits and discuss engineering directions that may facilitate future studies of nerve repair and accelerate the development of bioelectronic medical devices.
Subject(s)
Bioengineering/instrumentation , Neurosciences/instrumentation , Optical Fibers , Animals , Electronics, Medical , HumansABSTRACT
Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh nanoelectronics into rodent brains. First, we describe the design of ultraflexible mesh nanoelectronics with size features and mechanical properties similar to brain tissue and a novel syringe-injection methodology that allows the mesh nanoelectronics to be precisely delivered to targeted brain regions in a minimally invasive manner. Next, we discuss time-dependent histology studies showing seamless and stable integration of mesh nanoelectronics within brain tissue on at least one year scales without evidence of chronic immune response or glial scarring characteristic of conventional implants. Third, armed with facile input/output interfaces, we describe multiplexed single-unit recordings that demonstrate stable tracking of the same individual neurons and local neural circuits for at least 8 months, long-term monitoring and stimulation of the same groups of neurons, and following changes in individual neuron activity during brain aging. Moving forward, we foresee substantial opportunities for (1) continued development of mesh nanoelectronics through, for example, broadening nanodevice signal detection modalities and taking advantage of tissue-like properties for selective cell targeting and (2) exploiting the unique capabilities of mesh nanoelectronics for tackling critical scientific and medical challenges such as understanding and potentially ameliorating cell and circuit level changes associated with natural and pathological aging, as well as using mesh nanoelectronics as active tissue scaffolds for regenerative medicine and as neuroprosthetics for monitoring and treating neurological diseases.
Subject(s)
Electrical Equipment and Supplies , Electronics, Medical/instrumentation , Electronics, Medical/methods , Tissue Engineering/methods , Animals , Brain/metabolism , Humans , Mice , Neurons/metabolism , Primates , RatsABSTRACT
Future electronics will take on more important roles in people's lives. They need to allow more intimate contact with human beings to enable advanced health monitoring, disease detection, medical therapies, and human-machine interfacing. However, current electronics are rigid, nondegradable and cannot self-repair, while the human body is soft, dynamic, stretchable, biodegradable, and self-healing. Therefore, it is critical to develop a new class of electronic materials that incorporate skinlike properties, including stretchability for conformable integration, minimal discomfort and suppressed invasive reactions; self-healing for long-term durability under harsh mechanical conditions; and biodegradability for reducing environmental impact and obviating the need for secondary device removal for medical implants. These demands have fueled the development of a new generation of electronic materials, primarily composed of polymers and polymer composites with both high electrical performance and skinlike properties, and consequently led to a new paradigm of electronics, termed "skin-inspired electronics". This Account covers recent important advances in skin-inspired electronics, from basic material developments to device components and proof-of-concept demonstrations for integrated bioelectronics applications. To date, stretchability has been the most prominent focus in this field. In contrast to strain-engineering approaches that extrinsically impart stretchability into inorganic electronics, intrinsically stretchable materials provide a direct route to achieve higher mechanical robustness, higher device density, and scalable fabrication. The key is the introduction of strain-dissipation mechanisms into the material design, which has been realized through molecular engineering (e.g., soft molecular segments, dynamic bonds) and physical engineering (e.g., nanoconfinement effect, geometric design). The material design concepts have led to the successful demonstrations of stretchable conductors, semiconductors, and dielectrics without sacrificing their electrical performance. Employing such materials, innovative device design coupled with fabrication method development has enabled stretchable sensors and displays as input/output components and large-scale transistor arrays for circuits and active matrixes. Strategies to incorporate self-healing into electronic materials are the second focus of this Account. To date, dynamic intermolecular interactions have been the most effective approach for imparting self-healing properties onto polymeric electronic materials, which have been utilized to fabricate self-healing sensors and actuators. Moreover, biodegradability has emerged as an important feature in skin-inspired electronics. The incorporation of degradable moieties along the polymer backbone allows for degradable conducting polymers and the use of bioderived materials has led to the demonstration of biodegradable functional devices, such as sensors and transistors. Finally, we highlight examples of skin-inspired electronics for three major applications: prosthetic e-skins, wearable electronics, and implantable electronics.
Subject(s)
Electronics, Medical/instrumentation , Polymers/chemistry , Biodegradable Plastics/chemistry , Humans , Mechanical Phenomena , Prostheses and Implants , Transistors, Electronic , Wearable Electronic DevicesABSTRACT
The field of bioelectronics involves the fascinating interplay between biology and human-made electronics. Applications such as tissue engineering, biosensing, drug delivery, and wearable electronics require biomimetic materials that can translate the physiological and chemical processes of biological systems, such as organs, tissues. and cells, into electrical signals and vice versa. However, the difference in the physical nature of soft biological elements and rigid electronic materials calls for new conductive or electroactive materials with added biomimetic properties that can bridge the gap. Soft electronics that utilize organic materials, such as conjugated polymers, can bring many important features to bioelectronics. Among the many advantages of conjugated polymers, the ability to modulate the biocompatibility, solubility, functionality, and mechanical properties through side chain engineering can alleviate the issues of mechanical mismatch and provide better interface between the electronics and biological elements. Additionally, conjugated polymers, being both ionically and electrically conductive through reversible doping processes provide means for direct sensing and stimulation of biological processes in cells, tissues, and organs. In this Account, we focus on our recent progress in molecular engineering of conjugated polymers with tunable biomimetic properties, such as biocompatibility, responsiveness, stretchability, self-healing, and adhesion. Our approach is general and versatile, which is based on functionalization of conjugated polymers with long side chains, commonly polymeric or biomolecules. Applications for such materials are wide-ranging, where we have demonstrated conductive, stimuli-responsive antifouling, and cell adhesive biointerfaces that can respond to external stimuli such as temperature, salt concentration, and redox reactions, the processes that in turn modify and reversibly switch the surface properties. Furthermore, utilizing the advantageous chemical, physical, mechanical and functional properties of the grafts, we progressed into grafting of the long side chains onto conjugated polymers in solution, with the vision of synthesizing solution-processable conjugated graft copolymers with biomimetic functionalities. Examples of the developed materials to date include rubbery and adhesive photoluminescent plastics, biomolecule-functionalized electrospun biosensors, thermally and dually responsive photoluminescent conjugated polymers, and tunable self-healing, adhesive, and stretchable strain sensors, advanced functional biocidal polymers, and filtration membranes. As outlined in these examples, the applications of these biomimetic, conjugated polymers are still in the development stage toward truly printable, organic bioelectronic devices. However, in this Account, we advocate that molecular engineering of conjugated polymers is an attractive approach to a versatile class of organic electronics with both ionic and electrical conductivity as well as mechanical properties required for next-generation bioelectronics.
Subject(s)
Biomimetic Materials/chemistry , Polymers/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biomimetic Materials/chemical synthesis , Chemical Engineering , Electric Conductivity , Electronics, Medical/methods , Pliability , Polymers/chemical synthesis , Wearable Electronic DevicesABSTRACT
BACKGROUND: Some methodologies used for evaluating sweat production and antiperspirants are of a stationary aspect, that is, most often performed under warm (38°C) but resting conditions in a rather short period of time. The aim is to develop an electronic sensor apt at continuously recording sweat excretion, in vivo, during physical exercises, exposure to differently heated environments, or any other stimuli that may provoke sweat excretion. MATERIAL AND METHODS: A sensor (20 cm2 ) is wrapped under a double-layered textile pad. Fixed onto the armpits, these two arrays of electrodes are connected to electronic system through an analog multiplexer. A microcontroller is used to permanently record changes in the conductance between two electrodes during exposure of subjects to different sweat-inducing conditions or to assess the efficacy of applied aluminum hydrochloride (ACH)-based roll-ons at two concentrations (5% and 15%). RESULTS: In vitro calibration, using a NaCl 0.5% solution, allows changes in mV to be related with progressively increased volumes. In vivo, results show that casual physical exercise leads to sweat excretions much higher than in warm environment (37 or 45°C). Only, an exposure to a 50°C environment induced comparable sweat excretion. In this condition, sweat excretions were found similar in both armpits and both genders. Decreased sweat excretions were recorded following applications of ACH, with a dose effect. CONCLUSION: Developing phases of this new approach indicate that usual method or guidelines used to determine sweat excretions in vivo do not reflect true energy expenditure processes. As a consequence, they probably over-estimate the efficacy of antiperspirant agents or formulae.
Subject(s)
Exercise/physiology , Hot Temperature/adverse effects , Sweat/metabolism , Sweating/physiology , Adolescent , Adult , Antiperspirants/chemistry , Axilla/physiology , Electric Conductivity , Electrodes, Implanted , Electronics, Medical/instrumentation , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Materials that can serve as long-lived barriers to biofluids are essential to the development of any type of chronic electronic implant. Devices such as cardiac pacemakers and cochlear implants use bulk metal or ceramic packages as hermetic enclosures for the electronics. Emerging classes of flexible, biointegrated electronic systems demand similar levels of isolation from biofluids but with thin, compliant films that can simultaneously serve as biointerfaces for sensing and/or actuation while in contact with the soft, curved, and moving surfaces of target organs. This paper introduces a solution to this materials challenge that combines (i) ultrathin, pristine layers of silicon dioxide (SiO2) thermally grown on device-grade silicon wafers, and (ii) processing schemes that allow integration of these materials onto flexible electronic platforms. Accelerated lifetime tests suggest robust barrier characteristics on timescales that approach 70 y, in layers that are sufficiently thin (less than 1 µm) to avoid significant compromises in mechanical flexibility or in electrical interface fidelity. Detailed studies of temperature- and thickness-dependent electrical and physical properties reveal the key characteristics. Molecular simulations highlight essential aspects of the chemistry that governs interactions between the SiO2 and surrounding water. Examples of use with passive and active components in high-performance flexible electronic devices suggest broad utility in advanced chronic implants.