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Early detection and monitoring of chronic wounds using low-cost, omniphobic paper-based smart bandages
Abstract
The growing socio-economic burden of chronic skin wounds requires the development of new automated and non-invasive analytical systems capable of wirelessly monitoring wound status. This work describes the low-cost fabrication of single-use, omniphobic paper-based smart bandages (OPSBs) designed to monitor the status of open chronic wounds and to detect the formation of pressure ulcers. OPSBs are lightweight, flexible, breathable, easy to apply, and disposable by burning. A reusable wearable potentiostat was fabricated to interface with the OPSB simply by attaching it to the back of the bandage. The wearable potentiostat and the OPSB can be used to simultaneously quantify pH and uric acid levels at the wound site, and wirelessly report wound status to the user or medical personnel. Additionally, the wearable potentiostat and the OPSBs can be used to detect, in an in-vivo mouse model, the formation of pressure ulcers even before the pressure-induced tissue damage becomes visible, using impedance spectroscopy. Our results demonstrate the feasibility of using inexpensive single-use OPSBs and a reusable, wearable potentiostat that can be easily sterilized and attached to a new OPSB during the dressing change, to provide long term wound progression data to guide treatment decisions.
Supplementary resources (2)
... (D) A high stretchable serpentine like pH sensor fabricated using laser carbonization of PANI [63]. (E)The fabrication process of the omniphobic paper-based smart bandages (OPSB) [64]. (F)An automated smart bandage for pH sensing and antibiotic drug release [65]. ...
... (Reproduced from Refs. [34,36,[61][62][63][64][65][66][67] with permissions from Wiley online library, Elsevier, ACS publications, pubs.rsc.org and Nature). ...
... Cost-effective methods enable continuous monitoring while not dramatically increasing the financial load on patients. In this context, Pal et al. [64] developed a low-cost omniphobic paper-based smart bandage (OPSB) for continuous and wireless monitoring of pH of open wounds (Fig. 3E). The pH sensing element consisted of a pair of Ag/AgCl electrode separated by a layer of the pH-sensitive Ag/PANI composition and printed on an omniphobic paper. ...
Chronic wounds are among the major healthcare issues affecting millions of people worldwide with high rates of morbidity, losses of limbs and mortality. Microbial infection in wounds is a severe problem that can impede healing of chronic wounds. Accurate, timely and early detection of infections, and real time monitoring of various wound healing biomarkers related to infection can be significantly helpful in the treatment and care of chronic wounds. However, clinical methodologies of periodic assessment and care of wounds require physical visit to wound care clinics or hospitals and time-consuming frequent replacement of wound dressing patches, which also often adversely affect the healing process. Besides, frequent replacements of wound dressings are highly expensive, causing a huge amount of burden on the national health care systems. Smart bandages have emerged to provide in situ physiochemical surveillance in real time at the wound site. These bandages integrate smart sensors to detect the condition of wound infection based on various parameters, such as pH, temperature and oxygen level in the wound which reduces the frequency of changing the wound dressings and its associated complications. These devices can continually monitor the healing process, paving the way for tailored therapy and improved quality of patient's life. In this review, we present an overview of recent advances in biosensors for real time monitoring of pH, temperature, and oxygen in chronic wounds in order to assess infection status. We have elaborated the recent progress in quantitative monitoring of several biomarkers important for assessing wounds infection status and its detection using smart biosensors. The review shows that real-time monitoring of wound status by quantifying specific biomarkers, such as pH, temperature and tissue oxygenation to significantly aid the treatment and care of chronic infected wounds.
... range, 50 sometimes rising to pH 10, due in part to the proliferation of bacteria. [55][56][57][58] Large differentials in wound pH can therefore provide an early alert of infection, making pH a key parameter in wound healing and characterisation. 59 Many sensors are currently available with potential to detect the level of pH in wounds. ...
... Pal et al. at Purdue University developed an omniphobic paper-based smart bandage (OPSB) that wirelessly monitors wound parameters. 57 Sub-bandage pressure is measured using a high-precision impedance analyser (AD5933, Analog Devices Inc., US), while wound pH and uric acid levels are quantified electrochemically using a detachable and rechargeable potentiostat (LMP91000, Texas Inst. Inc., US), powered by a rechargeable battery. ...
... It also discusses the potential of artificial intelligence (AI) and machine learning to change, inform and improve wound care management. Detachable and rigid printed circuit boards A promising advancement observed with the sensors in this review 57,62,86,88,91,92 has been the achievement of conformality and flexibility, which is clearly a prerequisite for components in close contact with painful wounds. Although conformality has been demonstrated in these sensors, the electronic circuitry, with its surface-mounted components, is primarily a rigid construction. ...
Hard-to-heal wounds are a common side-effect of diabetes, obesity, pressure ulcers and age-related vascular diseases, the incidences of which are growing worldwide. The increasing financial burden of hard-to-heal wounds on global health services has provoked technological research into improving wound diagnostics and therapeutics via 'smart' dressings, within which elements such as microelectronic sensors, microprocessors and wireless communication radios are embedded. This review highlights the progress being made by research groups worldwide in producing 'smart' wound device prototypes. Significant advances have been made, for example, flexible substrates have replaced rigid circuit boards, sensors have been printed on commercial wound dressing materials and wireless communication has been demonstrated. Challenges remain, however, in the areas of power supply, disposability, low-profile components, multiparametric sensing and seamless device integration in commercial wound dressings.
... Furthermore, paper is intrinsically flexible, porosity, breathable, biocompatible, and biodegradable making its promising and versatile platforms in wearable sensors development (Mahadeva et al., 2015) . In the last decade, the studies on paper-based wearable sensors have grown substantially, aiming to collect a variety of information, including for biomarker detections (Gong and Sinton, 2017b) (Pal et al., 2018). In these devices, paper can serve as either breathable and biocompatible supporting substrates or active materials. ...
... This device was developed to contain all elements needed, where the thread allows red blood cell sampling and separation, while the paper microfluidic device for conditioning, biorecognition, and colorimetric transduction of pH and urea via a smartphone. In addition, a paper-based wearable smart bandage has been developed for the detection of pH, uric acid, and potassium ferricyanide in human open wounds, where carbon and screen-printed silver/silver chloride inks are used as working, counter, and reference electrodes, respectively (Pal et al., 2018). ...
Paper-based sensors have received increasing attention in the last decade, their use has spread to various application fields, such as clinical diagnostic, food safety, environmental monitoring, etc. Feature inherent to on-side detection is suitable to be used as point-of-care (POC) testing, including avoided sampling, sample preparation, and laborious procedure in the classical clinical lab, which is undoubtedly driving many developments of this lab-on-paper technology. The detection of biomarkers that are related to human health conditions has to play important role in the indication of the risk of diseases. In this review, the development of paper-based sensors for the detection of important biomarkers is presented. The also emphasis on recognition elements, such as chromophores/fluorophores, plasmonic nanoparticles, metal nanoclusters, etc., used to serve suitable selectivity and sensitivity. The performance of paper-based sensors using various techniques, including optical and electrochemical and other detection techniques are addressed. Furthermore, their limitations and prospects are discussed. The review also highlights cutting-edge technologies for further enhancement in the sensor performances for biomarkers detection.
... Chronic wounds, however, tend to have neutral and basic pH in the range of 7.15-8.90 [40] and even reach pH of 10 in the case of bacterial infection [41,42,43,44]. Therefore, tracking skin pH during wound healing provides reliable information about the healing process and early symptoms of non-healing or infection trajectory [39,40,45,46,47]. ...
... This fabricated smart dress is a real example of efficient integration between electronic technologies and medical science. The other advantages of these fabricated systems are presented as follows: (i) low cost, flexible, breathable, lightweight, and reusable structure; (ii) compatible with mass-scale production techniques, such as spray deposition or roll-to-roll printing [43]. ...
In spite of remarkable progress in the field of wound curation, treatment of chronic wounds remains a challenge for medical services. The constant rise in the number of patients with chronic wounds and their related financial burden has caused concern for the healthcare system. The complicated and dynamic nature of chronic wounds has increased the curation time and difficulty of wound healing with conventional bandages. Efficient healing of these wounds requires new bandages with the ability of real-time monitoring, data analysis, and drug delivery, which protect the wound against infection and accelerate the treatment process. The recent development of smartphone applications and digital equipment in medicine provides an opportunity for significant improvement in wound care through the incorporation of “smart” technologies into clinical practice. The focus of this review is to provide an overview of the current status of smartphones and digital technology in the management of wounds.
... nA/µM. Similarly, a uric acid biosensor was embroidered on a gauze wound dressing [ Figure 6B] for quantitative measurement of the wound marker [67] . The threads embroidered as working and counter electrodes were dipped in carbon ink, and the reference electrode thread was dipped in Ag/AgCl ink. ...
... (C) Calibration plot of generated current vs. uric acid concentration. Reproduced with permission [67] . Copyright 2017, Elsevier. ...
Wound healing is one of the most complex processes in the human body, supported by many cellular events that are tightly coordinated to repair the wound efficiently. Chronic wounds have potentially life-threatening consequences. Traditional wound dressings come in direct contact with wounds to help them heal and avoid further complications. However, traditional wound dressings have some limitations. These dressings do not provide real-time information on wound conditions, leading clinicians to miss the best time for adjusting treatment. Moreover, the current diagnosis of wounds is relatively subjective. Wearable electronics have become a unique platform to potentially monitor wound conditions in a continuous manner accurately and even to serve as accelerated healing vehicles. In this review, we briefly discuss the wound status with some objective parameters/biomarkers influencing wound healing, followed by the presentation of various novel wearable devices used for monitoring wounds and accelerating wound healing. We further summarize the associated device working principles. This review concludes by highlighting some major challenges in wearable devices toward wound healing that need to be addressed by the research community.
... To circumvent this problem, coating substances that modify the cellulose surface chemistry have been reported, making the paper omniphobic (wetting resistant), maintaining mechanical flexibility, strength, and breathing paper properties [33a, 34]. Pal et al. [35] modified Whatman 1 chromatographic filter paper with fluorinated alkyltrichlorosilane to produce an omniphobic surface. The use of the silane causes chemical changes in the cellulose fibers making the paper omniohinic, but there is no block of the pores paper, preserving its breathability. ...
... Another example is the work reported by Pal et al. [35]. They proposed a detection system based on omniphobic paper and commercially available bandages. ...
In this mini‐review, we present the main advances in the development of wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discuss some key challenges for higher performance in this field. We also present an overview of the application of paper as a smart substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, we conclude this mini‐review by highlighting the future advances in wearable sensors and diagnostics by coupling real‐time and on‐body measurements to multiplexed detection of different biomarkers in a simultaneous way, reducing the cost and time of classical analysis, to provide a fast and complete overall of physiological conditions to the wearer.
... In another study, omniphobic paper-based smart bandages were designed to monitor the pH of chronic wounds and the formation of pressure ulcers. 249 Ag/AgCl electrodes were printed on the omniphobic paper and a layer of Ag/polyaniline emeraldine base (PANi-EB) mixture was used to separate the electrodes. Because ...
... The results indicated that this device can be applied to qualify the pH range of 5.5 to 8.5 in the wound site. 249 A wearable flexible intelligent bandage was reported to be able to detect not only temperature, pH, but also can electronically release drugs to eliminate bacterial proliferation. 250 An NPWT device is composed of a vacuum source, drainage tubing, and dressing ( Figure 5). ...
Wound healing is a complex process that is critical in restoring the skin's barrier function. This process can be interrupted by numerous diseases resulting in chronic wounds that represent a major medical burden. Such wounds fail to follow the stages of healing and are often complicated by a pro‐inflammatory milieu attributed to increased proteinases, hypoxia, and bacterial accumulation. The comprehensive treatment of chronic wounds is still regarded as a significant unmet medical need due to the complex symptoms caused by the metabolic disorder of the wound microenvironment. As a result, several advanced medical devices, such as wound dressings, wearable wound monitors, negative pressure wound therapy devices, and surgical sutures, have been developed to correct the chronic wound environment and achieve skin tissue regeneration. Most medical devices encompass a wide range of products containing natural (e.g., chitosan, keratin, casein, collagen, hyaluronic acid, alginate, and silk fibroin) and synthetic (e.g., polyvinyl alcohol, polyethylene glycol, poly[lactic‐co‐glycolic acid], polycaprolactone, polylactic acid) polymers, as well as bioactive molecules (e.g., chemical drugs, silver, growth factors, stem cells, and plant compounds). This review addresses these medical devices with a focus on biomaterials and applications, aiming to deliver a critical theoretical reference for further research on chronic wound healing.
... It was estimated that health services in 2012 spent £5.1 billion on costs associated with wound care management 6 which provided a compelling case for improvement in the current standard of wound dressings not only to reduce healthcare costs but also to improve patient quality of life 7 . However, better and effective means of reporting quantitative information about the wound condition in real time is required to inform and guide treatment decisions as improved wound care will deliver improved public health and healthcare costs 8,9 . ...
... For the first time in literature, this research presents a unique approach to integrate protein sensors in fabric which improves the sensors durability, comfort, flexibility and wearability and performance within specification. Although a similar approach was presented recently 8,45 , where screen printed electrodes (SPEs) were printed on a paper and placed inside a bandage but measure pH and uric acid to monitor chronic wounds. ...
This article focuses on the design and fabrication of flexible textile-based protein sensors to be embedded in wound dressings. Chronic wounds require continuous monitoring to prevent further complications and to determine the best course of treatment in the case of infection. As proteins are essential for the progression of wound healing, they can be used as an indicator of wound status. Through measuring protein concentrations, the sensor can assess and monitor the wound condition continuously as a function of time. The protein sensor consists of electrodes that are directly screen printed using both silver and carbon composite inks on polyester nonwoven fabric which was deliberately selected as this is one of the common backing fabric types currently used in wound dressings. These sensors were experimentally evaluated and compared to each other by using albumin protein solution of pH 7. A comprehensive set of cyclic voltammetry measurements was used to determine the optimal sensor design the measurement of protein in solution. As a result, the best sensor design is comprised of silver conductive tracks but a carbon layer as the working and counter electrodes at the interface zone. This design prevents the formation of silver dioxide and protects the sensor from rapid decay, which allows for the recording of consecutive measurements using the same sensor. The chosen printed protein sensor was able to detect bovine serum albumin at concentrations ranging from 30 to 0.3 mg/mL with a sensitivity of 0.0026μA/M. Further testing was performed to assess the sensor’s ability to identify BSA from other interferential substances usually present in wound fluids and the results show that it can be distinguishable.
... Therefore, to eliminate this complication, uric acid biosensors in the form of adhesive plasters were developed by Kassal et al. [70] developed uric acid biosensors in the form of adhesive plasters to monitor the progress of the wound in real-time (Fig. 5a). Uric acid concentration is correlated with the healing process at the wound site [71] (Fig. 5b). ...
... The skin is periodically subjected to mechanical stress due to body movements. The new tattoo sensor is made to withstand such [70] (Permission from Elsevier), (b) early detection and monitoring of chronic wounds using omniphobic paper-based smart bandages [71] (Permission from Elsevier) deformation by incorporating finely dispersed carbon fibers. The tattoo electrode is then modified with a receptor layer and a reagent layer to give it the selectively detect a wide range of analytes [78]. ...
Biosensors and chemical sensors for healthcare applications are garnering interest due to their potential to provide continuous and real‐time physiological information, chemical information, and noninvasive measurements of biochemical markers in human biofluids, such as tears, saliva, sweat, interstitial fluid, and human volatiles. Recent developments have focused on electrochemical biosensors and monitoring of metabolites, proteins, chemicals, and bacteria. The measurement of biophysical quantities of the human body has been studied in healthcare and medicine. Many flexible, wearable, and detachable sensors have been developed and commercialized to monitor relevant parameters in sports, healthcare, and medicine. Here, we introduce many challenges regarding the integration of sensors and biosensors into the monitoring of biological and chemical information for the internet of things (IoT) in healthcare. IoT sensors are set to improve quality of life (QoL) and living standards. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
... For instance, quantifying the pH and uric acid levels of open chronic wounds is important for monitoring the status of healing and recovery. The signals of these two target biomarkers, as reported by Pal et al., [98] can be detected as current change (in a unit of μA) duo to the uric acid oxidation reaction, and resistance change (in a unit of ohm) due to reversible variations of emeraldine salt (ES) form and emeraldine base (EB) form of polyaniline. Using omniphobic paper-based smart bandages (OPSBs), the authors achieved status monitoring by printing conductive carbon and polyaniline inks as electrodes ( Figure 4e). ...
... Reproduced with permission. [98] Copyright 2018, Elsevier. f ) An eyeglasses-based wearable system for tear biomarkers analysis, including alcohol, vitamins, and glucose. ...
Wearable sensing electronic systems (WSES) are becoming a fundamental platform to construct smart and intelligent networks for broad applications. Various physiological data are readily collected by the WSES, including biochemical, biopotential, and biophysical signals from human bodies. However, understanding these sensing data, such as feature extractions, recognitions, and classifications, is largely restrained because of the insufficient capacity when using conventional data processing techniques. Recent advances in sensing performance and system-level operation quality of the WSES are expedited with the assistance of machine learning (ML) algorithms. Here, the state-of-the-art of the ML-assisted WSES is summarized with emphasis on how the accurate perceptions on physiological signals under different algorithms paradigm augment the performance of the WSES for diverse applications. Concretely, ML algorithms that are frequently implemented in the WSES studies are first synopsized. Then broad applications of ML-assisted WSES with strengthened functions are discussed in the following sections, including intelligent physiological signals monitoring, disease diagnosis, on-demand treatments, assistive devices, human–machine interface, and multiple sensations-based virtual and augmented reality. Finally, challenges confronted for the ML-assisted WSES are addressed.
... It was estimated that health services in 2012 spent £5.1 billion on costs associated with wound care management 5 which provides a compelling case for improvement in the current standard of wound dressings not only to reduce healthcare costs but also to improve patient quality of life 6 . However, better and effective means of reporting quantitative information about the wound condition in real time is required to inform and guide treatment decisions as improved wound care will deliver improved public health and healthcare costs 7,8 . ...
... The different stages of screen printing the carbon electrodes (A) interface layer, (B) Silver, (C) Carbon, The best fit line parameters of oxidation peak measurements6The flexibility of the SPE design (C) printed on textiles The oxidation peak observed after repeating the experiment twice using the three screen printed sensor designsConclusionThe sensor was fabricated using the screen printing technique and consisted of four layers: an interface layer, silver electrodes, carbon conducting interface area and an encapsulation layer. The sensor relied on quantifying the protein concentration by7The silver containing SPEs after use (A) silver only based SPE and (B) Silver and Carbon SPE Measurements obtained when testing a sample of 30 mg/ml of BSA solutions on the third SPE design and conducting three cycles on the three types of fabrics ...
This article focuses on the design and fabrication of flexible textile-based protein sensors to be embedded in wound dressings. Chronic wounds require continuous monitoring to prevent further complications and to determine the best course of treatment in the case of infection. As proteins are essential for the progression of wound healing, they can be used as an indicator of wound status. Through measuring protein concentrations, the sensor can assess and monitor the wound condition continuously as a function of time. The protein sensor consists of electrodes that are directly screen printed using both silver and carbon composite inks on polyester nonwoven fabric which was deliberately selected as this is one of the common backing fabrics currently used in wound dressings. Three sensor designs were investigated to determine if any were suitable for protein detection. These sensors were experimentally evaluated and compared to each other by using albumin protein in phosphate buffered saline (PBS). A comprehensive set of cyclic voltammetry measurements were used to determine the optimal sensor design to provide the measurement of protein in solution. The best sensor was comprised of only silver conductive ink present to form the tracks outside the interface zone and a carbon only layer in the working and counter electrodes at the interface zone. This design prevents the formation of silver dioxide and protects the sensor from rapid decay, which allows for the recording of consecutive measurements using the same sensor. The chosen printed protein sensor was able to detect BSA at varying concentrations ranging from 30-0.3 mg/ml with a sensitivity of 0.0026µA/M.
... [89,90] Figure 4A,B demonstrates a paper-based pH sensor with Ag/PANi-emeraldine base composites, capable of transition into emeraldine salt form with increased conductivity in response to pH drop. [91] The fabricated electrodes were integrated with a potentiostat and a commercially available bandage. In addition, the PANi impedances showed a frequencyindependent behavior at 10-100 kHz when the device was applied on wound extrude models ( Figure 4C). ...
... Colorimetric approaches by incorporating with pH sensitive dyes (e.g., universal indicators and phenol red) have also enabled visualized pH sensing. [95,93] [91] Copyright 2018, Elsevier. D) Schematic of a UA sensor design. ...
Chronic wounds are a major healthcare issue and can adversely affect the lives of millions of patients around the world. The current wound management strategies have limited clinical efficacy due to labor‐intensive lab analysis requirements, need for clinicians’ experiences, long‐term and frequent interventions, limiting therapeutic efficiency and applicability. The growing field of flexible bioelectronics enables a great potential for personalized wound care owing to its advantages such as wearability, low‐cost, and rapid and simple application. Herein, recent advances in the development of wearable bioelectronics for monitoring and management of chronic wounds are comprehensively reviewed. First, the design principles and the key features of bioelectronics that can adapt to the unique wound milieu features are introduced. Next, the current state of wound biosensors and on‐demand therapeutic systems are summarized and highlighted. Furthermore, the design criteria of the integrated closed loop devices are discussed. Finally, the future perspectives and challenges in wearable bioelectronics for wound care are discussed.
... These may or may not include battery based operation. For example solutions that use battery are listed as [2], [3], [14]- [19]. More recently near field communication (NFC) has been demonstrated as an effective means for powering the electronics [7], [20]- [22], and avoid batteries [23]. ...
In this paper,
SkinAid
, a battery-free, low-cost, robust, and user-friendly smart bandage for electrochemical monitoring and sensing of chronic wounds is proposed. The working principle of the bandage is based on direct frequency modulation of a tri-electrode electrochemical sensing of wound data. The electronics and biotelemetry links were realized using low-cost manufacturing process of textile embroidery onto fabric substrate. The transmitter was represented by a bedsheet with novel corrugated crossed-dipole made of
Elektrisola-7
embroidered onto gauze fabric. An input RF signal of 1 W was transmitted at 462 MHz from the bedsheet to the all-textile bandage featuring a rectifying circuit, a voltage-controlled oscillator (VCO), an electrochemical sensor, and a 915-MHz dipole for re-transmission of the modulated wound data. We demonstrate that for wound fluid emulated by various uric acid concentrations from 0.2 mM to 1.2 mM, corresponding modulated frequency varies from 1090 MHz to 1145 MHz for signals captured at 25 cm away from the bandage. For pH modulation ranging from 2 to 10, the corresponding modulated frequency was between 800 MHz and 830 MHz for signals received at more than 6 feet away from the bandage. For quick and reliable assessment, two empirical models were developed for the direct frequency modulation as a function of uric acid and pH. To the best of our knowledge, this is the first time an all-textile (fabric-integrated), battery-free and wirelessly powered smart bandage have been proposed for wound monitoring. This result can be used as a first step in developing RFID-type, battery-free, and low-cost 5 G/6 G smart bandages using millimeterwave and terahertz frequencies where the bedsheet can be host to a MIMO-aided beamforming.
... www.nature.com/scientificreports/ Specifically, in consideration of the aforementioned softness and hygienic issues, commercially available fabrics or bandages can be an attractive solution for constructing a real-time skin monitoring system that patients can wear in everyday life 3,26 . Additionally, exploiting mature remote communication technologies, such as Bluetooth or ZigBee, can allow sensing systems to continuously monitor any tiny abnormal signal variations of skin indicators 7,21,22 . ...
For multifunctional wearable sensing systems, problems related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues should be solved for precise physiological signal detection. To measure the critical transitions of pressure, temperature, and skin impedance when continuous pressure is applied on skin and tissue, we developed a sensor for decubitus ulcers using conventional analog circuitry for wireless and continuous communication in a disposable, breathable fabric-based multifunctional sensing system capable of conformal contact. By integrating the designed wireless communication module into a multifunctional sensor, we obtained sensing data that were sent sequentially and continuously to a customized mobile phone app. With a small-sized and lightweight module, our sensing system operated over 24 h with a coin-cell battery consuming minimum energy for intermittent sensing and transmission. We conducted a pilot test on healthy subjects to evaluate the adequate wireless operation of the multifunctional sensing system when applied to the body. By solving the aforementioned practical problems, including those related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues, our fabric-based multifunctional decubitus ulcer sensor successfully measured applied pressure, skin temperature, and electrical skin impedance.
... The evaporation of the ammonia solution changed the color of the phenolphthalein droplets at the mouth of the bottle from transparent to dark red, while the phenolphthalein droplet of control group did not change color, which indicated that the sensor had good air permeability. At the same time, the trichloromethane treated paper has good hydrophobicity and does not cause biological hazards 63 . In order to verify the water resistance, we placed the hydrophobic paper of the sensor with a drop of water on the top of pH test paper for 12 hours, and the pH test paper did not change color because of no water penetration ( Supplementary Fig. 13b). ...
Paper-based electronics have attracted much attention due to their softness, degradability, and low cost. However, paper-based sensors are difficult to apply to high-humidity environments or even underwater. Here, we report a fully paper-integrated piezoresistive sensing system that exhibits flexibility, waterproofing, air permeability, and biocompatibility. This system consists of hydrophobic paper as the substrate and encapsulation layer, conductive paper with a double ‘zig-zag’ and dotted surface structure as the sensing layer, and silver paste films as the interconnects. The structural design of the sensing layer helps to increase the contact area in adjacent layers under pressure and further improves the pressure sensitivity. The piezoresistive system can be worn on human skin in the ambient environment, wet environment, and water for real-time monitoring of physiological signals with air permeability and waterproofing due to its hydrophobic fiber structure. Such a device provides a reliable, economical, and eco-friendly solution to wearable technologies.
... A connected potentiostat quantifies the current output of the sensor, stores the data, and transmits signals to a connected smartphone. A similar system was also developed by Pal et al. (2018) wherein they developed a sub-bandage that monitors wound parameters and electrochemically quantifies the levels of wound pH and uric acid. The uric acid-based biosensors demonstrated sensitivity to detect samples with low volumes of uric acid, however, the potential of these sensors is limited due to interference from exudate constituents, such as lactate, electrolytes, proteins, and glucose. ...
... A connected potentiostat quantifies the current output of the sensor, stores the data, and transmits signals to a connected smartphone. A similar system was also developed by Pal et al. (2018) wherein they developed a sub-bandage that monitors wound parameters and electrochemically quantifies the levels of wound pH and uric acid. The uric acid-based biosensors demonstrated sensitivity to detect samples with low volumes of uric acid, however, the potential of these sensors is limited due to interference from exudate constituents, such as lactate, electrolytes, proteins, and glucose. ...
... LMP91000 IC is an I2C-capable low-power electrochemical sensing programmable analog front end suitable for portable and wearable applications. In another work, LMP91000 and AD5933 ICs together with a microcontroller and a bluetooth module were used in a battery-powered wearable potentiostat for electrochemical measurements in chronic wound monitoring (Pal et al., 2018). KickStat a high-resolution coin-sized potentiostat, was also built around the LMP91000 IC (Hoilett et al., 2020). ...
Since the inception of the first electrochemical devices on paper substrates, many different reports of microfluidic paper-based electroanalytical devices (μPEDs), innovative hydrophobic barriers and electrode fabrication processes have allowed the incorporation of diverse materials, resulting in different applications and a boost in performance. These advancements have led to the creation of paper-based devices with comparable performance to many standard conventional devices, with the added benefits of pumpless fluidic transport, component separation and reagent storage that can be exploited to automate and handle sample preprocessing. Herein, we review μPEDs, summarize the characteristics and functionalities of μPEDs, such as separation, fluid flow control and storage, and outline the conventional and emerging fabrication and modification approaches for μPEDs. We also examine the recent application of μPEDs in biomedicine, the environment, and food and water safety, as well as some limitations and challenges that must be addressed.
... A connected potentiostat quantifies the current output of the sensor, stores the data, and transmits signals to a connected smartphone. A similar system was also developed by Pal et al. (2018) wherein they developed a sub-bandage that monitors wound parameters and electrochemically quantifies the levels of wound pH and uric acid. The uric acid-based biosensors demonstrated sensitivity to detect samples with low volumes of uric acid, however, the potential of these sensors is limited due to interference from exudate constituents, such as lactate, electrolytes, proteins, and glucose. ...
Traditionally, wound management aims to control the underlying cause while allowing the wound to heal naturally. Over the decades, extensive investigations have been carried out to enhance the potential of conventionally available wound dressings. Although conventional dressings, such as bandages and hydrogels, assist with the healing process, they lack efficiency as they do not possess the ability to respond to the wound microenvironment. In this direction, a class of “SMART” dressings, has been proposed that can accelerate the healing process by interacting with the wound environment and reacting according to the built-in sensors, that is, stimuli-responsive materials. This chapter highlights the progress being made around the globe to develop “next-generation bandages,” including bandages integrated with drug delivery systems to control the precise release of drugs at the wound site.
... Wearable electronics have allured a significant amount of interest of the past few years, focusing on gathering various set of information such as temperatures, [190] strain (mainly bending strain) [190,191], pressure [192][193][194][195], light [196,197], biopotential [190,198], pH [190], gas [199][200][201][202][203], humidity and respiration [204,205], biochemical compositions [206,207], fitness tracking, medical diagnostics, and human-machine interface [208][209][210][211][212][213]. Even though flexible and bendable batteries to power them are fast growing, supplying adequate energy to power wearables is difficult [108]. ...
The increased demand for energy due to industrialisation and a steadily growing population has placed greater strain on the development of eco-friendly energy storage devices in recent years. Current methods with high efficiency are limited by high costs and waste. As a result, greater importance has been placed on the development of low-cost, lightweight, flexible, and biodegradable energy storage systems developed from paper and paper-like substrates. This study reviews recent advances in paper-based battery and supercapacitor research, with a focus on materials used to improve their electrochemical performance. Special mention is made of energy-storage configurations ranging from metal-air and metal-ion batteries to supercapacitors. Furthermore, methods of fabrication, functional materials, and efficiency are reviewed to offer prospects for future research into the field of paper-based Na-ion batteries. The review provides an updated discussion of recent research conducted in the field of paper-based energy systems published over the last five years and highlights the challenges for their commercial integration prospects.
... Obviously, it is the core task for ion and biomolecule sensors to find the proper material for the working electrode to achieve high selectivity. Meanwhile, benefiting from the high selectivity, the capacity of wearable sweat sensors has gradually developed from focusing on a single analyte (e.g., pH [163], Na + [164], Cl − [165], NH4 + [166] or glucose [167]) to simultaneously measuring multiple targets. Wei Gao's group has reported a fully integrated wearable sensor array for simultaneously and selectively analyzing four different parameters in sweat, including glucose, lactate, Na + and K + (Figure 16a) [35]. ...
As an important branch of wearable electronics, highly flexible and wearable sensors are gaining huge attention due to their emerging applications. In recent years, the participation of wearable devices in sports has revolutionized the way to capture the kinematical and physiological status of athletes. This review focuses on the rapid development of flexible and wearable sensor technologies for sports. We identify and discuss the indicators that reveal the performance and physical condition of players. The kinematical indicators are mentioned according to the relevant body parts, and the physiological indicators are classified into vital signs and metabolisms. Additionally, the available wearable devices and their significant applications in monitoring these kinematical and physiological parameters are described with emphasis. The potential challenges and prospects for the future developments of wearable sensors in sports are discussed comprehensively. This review paper will assist both athletic individuals and researchers to have a comprehensive glimpse of the wearable techniques applied in different sports.
... Porous silicon resonant microcavity structure based optical biosensor that is modified with fluorogenic peptide substrate is an efficient biomarker for the detection of bacterial infection caused by Staphylococcus aureus. The biomarker can detect the presence of a bacterial enzyme known as Sortase A (SrtA) found in the cell membrane of S. aureus [177]. Omniphobic paper-based smart bandages (OPSBs) proposed by Pal et al., 2018 are commercialized bandages made by incorporating low-cost impedance and electrochemical sensors. ...
Smart textiles with advanced functionalities are the new research area that attracts researchers to contribute to the wellness of human beings and provide comfort in a daily lifestyle. Smart textiles have the potential to perform multiple tasks and have significant applications in healthcare sectors including real-time monitoring of the physiological needs and health status of the wearer through sensors and integration of nanotechnology for better performance. The integration of sensors and nanomaterials in the fabrics has led the textile industries to deal with technological and physiological challenges such as the basic requirement of a textile to maintain the actual comfort, washability, perspiration, reusability and longevity. The objective of this review is to provide descriptive information to an expanding and challenging domain of smart textiles with a focus on their applications to human health and welfare. The study also highlights the role of nanomaterials in the development of antimicrobial smart textiles and discusses the challenges faced by smart textiles for their acceptance in society.
Early diagnosis of chronic kidney disease (CKD) and constant monitoring to guide optimal intervention is critical to prevent renal failure and other critical diseases. However, the conventional blood tests in hospital are time-consuming and have poor patient compliance. Herein, we demonstrate a real-time, minimally invasive, and self-administrable approach to detect kidney biomarkers in the skin interstitial fluid (ISF) using a polymeric microneedle coupled electrochemical sensor array (MNESA). Microneedles can readily penetrate stratum corneum and quickly extract ISF onto the sensors. Four biomarkers are simultaneously detected to avoid false positive and provide an accurate assessment of kidney functions. Using an artificial skin model, it is shown that MNSEA gives specific and sensitive responses to these kidney biomarkers in physiologically relevant ranges (phosphate: 0.3-1.8 mM, 3.62 μA/mM; uric acid: 50-550 μM, 4.19 nA/μM; creatinine: 50-550 μM, 12.58 nA/μM; urea: 1-16 mM, 44.6 mV/decade). Using a mouse model, we demonstrate that this approach is as reliable as the commercial assays and is feasible to readily monitor the progression of CDK.
Timely and accurate assessment of wounds during the wound healing process is key for correct diagnosis and treatment decisions for wound repair. However, traditional wound management strategies often fail to provide timely and accurate information on wound status, thereby delaying or misleading treatments. Smart wound dressings that enable the in situ real-time monitoring of wound-related biomarkers, early diagnosis and on-demand treatment of adverse wound healing events, such as bacterial infection and inflammation, by integrating wearable sensors, advanced drug delivery systems and wireless communication technology have recently been developed and could improve wound management. In this review, we provided an overview of biomarkers, including temperature, pH, uric acid, glucose, reactive oxygen (ROS), oxygen and enzymes, related to adverse wound healing events and exiting sensors for detecting these biomarkers based on colorimetric, fluorimetric and electrochemical approaches. Examples of smart wound dressings that integrate controllable drug delivery functions triggered by both endogenous and exogenous stimuli, the all-in-one wound dressing systems capable of real-time monitoring and on-demand treatment, and the major challenges and exciting opportunities of such smart wound dressings in wound management are presented and comprehensively discussed.
The number of patients with non-healing wounds is generally increasing globally, placing a huge social and economic burden on every country. The complexity of the wound-healing process remains a major health challenge despite the numerous studies that have been reported on conventional wound dressings. Therefore, a therapeutic system that combines diagnostic and therapeutic modalities is essential to monitor wound-related biomarkers and facilitate wound healing in real time. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. Their advantages are mainly reflected in painless transdermal drug delivery, good biocompatibility, and ease of self-administration. In this work, we review recent advances in the use of microneedle patches for wound healing and monitoring. The paper first provides a brief overview of the skin structure and the wound healing process, and then discusses the current state of research and prospects for the development of wound-related biomarkers and their real-time monitoring based on microneedle sensors. It summarizes the current state of research based on the unique design of microneedle patches, including biomimetic, conductive, and environmentally responsive, to achieve wound healing. It further summarizes the prospects for the application of different microneedle-based drug delivery modalities and drug delivery substances for wound healing, due to their superior transdermal drug delivery advantages. It concludes with challenges and expectations for the use of smart microneedle patches for wound healing and management.
Personalized point-of-care testing (POCT) devices, such as wearable sensors, enable quick access to health monitoring without the use of complex instruments. Wearable sensors are gaining popularity owing to their ability to offer regular and continuous monitoring of physiological data by dynamic, non-invasive assessments of biomarkers in biofluids such as tear, sweat, interstitial fluid and saliva. Current advancements have concentrated on the development of optical and electrochemical wearable sensors as well as advances in non-invasive measurements of biomarkers such as metabolites, hormones and microbes. For enhanced wearability and ease of operation, microfluidic sampling, multiple sensing, and portable systems have been incorporated with materials that are flexible. Although wearable sensors show promise and improved dependability, they still require more knowledge about interaction between the target sample concentrations in blood and non-invasive biofluids. In this review, we have described the importance of wearable sensors for POCT, their design and types of these devices. Following which, we emphasize on the current breakthroughs in the application of wearable sensors in the realm of wearable integrated POCT devices. Lastly, we discuss the present obstacles and forthcoming potentials including the use of Internet of Things (IoT) for offering self-healthcare using wearable POCT.
With the rapid emergence of mobile devices and telemedicine, electrochemical wearable devices capable of detecting and monitoring specific biomarkers in a noninvasively and timely manner have attracted huge attention across various applications. They offer distinctive possibilities for a personalized healthcare monitoring system by detecting and keeping track of target molecules in different biofluids with high specificity and sensitivity via versatile sensing platforms. This entry in the Encyclopedia of Electrochemistry reviews recent advances and developments of the electrochemical wearable device and provides a survey of basic sensing principles and target sampling methodologies. Major and minor obstacles that still exist in the commercialization of this sensing platform will also be covered at the end of this article. With continued tactical innovation and attention to critical challenges, such electrochemical wearable devices are expected to pave the way for the realization of distributed on-body sensors in a variety of application areas.
Introduction:
Wound microflora in hard-to-heal wounds is invariably complex and diverse. Determining the interfering organisms(s) is therefore challenging. Tissue sampling, particularly in large wounds, is subjective and, when performed, might involve swabbing or biopsy of several locations. Fluorescence (FL) imaging of bacterial loads is a rapid, non-invasive method to objectively locate microbial hotspots (loads >104 CFU/gr). When sampling is deemed clinically necessary, imaging may indicate an optimal site for tissue biopsy. This study aimed to investigate the microbiology of wound tissue incisional biopsies taken from sites identified by FL imaging compared with sites selected by clinical judgment.
Methods:
A post hoc analysis of the 350-patient FLAAG wound trial was conducted; 78 wounds were included in the present study. All 78 wounds were biopsied at two sites: one at the center of the wound per standard of care (SoC) and one site guided by FL-imaging findings, allowing for comparison of total bacterial load (TBL) and species present.
Results:
The comparison between the two biopsy sites revealed that clinical uncertainty was higher as wound surface area increased. The sensitivity of a FL-informed biopsy was 98.7% for accurately finding any bacterial loads >104 CFU/g, compared to 87.2% for SoC (p=0.0059; McNemar test). Regarding species detected, FL-informed biopsies detected an average of 3 bacterial species per biopsy versus 2.2 species with SoC (p < 0.001; t-test). Microbial hotspots with a higher number of pathogens also included the CDC's pathogens of interest.
Conclusions & perspective:
FL imaging provides a more accurate and relevant microbiological profile that guides optimal wound sampling compared to clinical judgment. This is particularly interesting in large, complex wounds, as evidenced in the wounds studied in this post hoc analysis. In addition, fluorescence imaging enables earlier bacterial detection and intervention, guiding early and appropriate wound hygiene and potentially reducing the need for antibiotic use. When indicated, this diagnostic partnership with antibiotic stewardship initiatives is key to ameliorating the continuing threat of antibiotic resistance.
Une plaie chronique désigne une plaie n’ayant pas cicatrisé en temps voulu pour reproduire une intégrité fonctionnelle et anatomique. L’escarre est un cas particulier de plaie chronique causée principalement par la présence d’une pression continue supérieure à la pression capillaire. Ces travaux de thèse s’inscrivent dans ce contexte en s’articulant autour de la prévention, de la détection et du traitement des escarres. Une première partie concerne le développement d’une matrice flexible et conformable de capteurs de pression piezorésistifs et de son électronique associée. Le but d’un tel dispositif est d’alerter le personnel hospitalier en cas d’exposition prolongée à une pression pouvant entraîner le développement d’une escarre chez un patient alité. Une deuxième partie concerne la détection d’escarres et le suivi de leur évolution par spectroscopie d’impédance. Un premier modèle électrique basé sur l’association de plusieurs systèmes Cole a été étudié, basé sur les résultats in vitro sur peau d’oreille de cochon excisée. Des expérimentations in vivo sur souris ont également été effectuées. L’analyse des paramètres physiques du modèle de Cole ont montré que cette méthode, non invasive, est particulièrement prometteuse en matière de résolution et de robustesse de suivi de cicatrisation. Enfin, une dernière partie traite de la mise en place d’une iontophorèse à visée thérapeutique pour le traitement de l’escarre à l’aide de vasodilatateurs. Des études préliminaires, in vitro et in vivo, ont permis de mettre en évidence l’influence de différents paramètres sur l’efficacité du passage transdermique des molécules de tolazoline et tréprostinil, respectivement.
The recent COVID-19 infection outbreak has raised the demand for rapid, highly sensitive POC biosensing technology for intelligent health and wellness. In this direction, efforts are being made to explore high-performance nano-systems for developing novel sensing technologies capable of functioning at point-of-care (POC) applications for quick diagnosis, data acquisition, and disease management. A combination of nanostructures [i.e., 0D (nanoparticles & quantum dots), 1D (nanorods, nanofibers, nanopillars, & nanowires), 2D (nanosheets, nanoplates, nanopores) & 3D nanomaterials (nanocomposites and complex hierarchical structures)], biosensing prototype, and micro-electronics makes biosensing suitable for early diagnosis, detection & prevention of life-threatening diseases. However, a knowledge gap associated with the potential of 0D, 1D, 2D, and 3D nanostructures for the design and development of efficient POC sensing is yet to be explored carefully and critically. With this focus, this review highlights the latest engineered 0D, 1D, 2D, and 3D nanomaterials for developing next-generation miniaturized, portable POC biosensors development to achieve high sensitivity with potential integration with the internet of medical things (IoMT, for miniaturization and data collection, security, and sharing), artificial intelligence (AI, for desired analytics), etc. for better diagnosis and disease management at the personalized level.
Bacterial infections have long been a serious global health issue. Biofilm formation complicates matters even more. The biofilm's extracellular polymeric substances (EPSs) matrix protects bacteria from the host's immune responses, yielding strong adhesion and drug resistance as the biofilm matures. Early bacterial biofilm detection and bacterial biofilm growth monitoring are crucial to treating biofilm-associated infections. Current detection methods are highly sensitive but not portable, are time-consuming, and require expensive equipment and complex operating procedures, limiting their use at the point of care. Therefore, there is an urgent need to develop affordable, on-body, and non-invasive biomedical sensors to continuously monitor and detect early biofilm growth at the point of care through personalized telemedicine. Herein, recent advances in developing non-invasive biomedical sensors for early detection and monitoring bacterial biofilm growth are comprehensively reviewed. First, biofilm's life cycle and its impact on the human body, such as biofilm-associated disease and infected medical devices, are introduced together with the challenges of biofilm treatment. Then, the current methods used in clinical and laboratory settings for biofilm detection and their challenges are discussed. Next, the current state of non-invasive sensors for direct and indirect detection of bacterial biofilms are summarized and highlighted with the detection parameters and their design details. Finally, commercially available products, challenges of current devices, and the further trend in biofilm detection sensors are discussed.
The demand for high-quality healthcare and well-being services is remarkably increasing due to the ageing global population and modern lifestyles. Recently, the integration of wearables and artificial intelligence (AI) has attracted extensive academic and technological attention for its powerful high-dimensional data processing of wearable biosensing networks. This work reviews the recent developments in AI-assisted wearable biosensing devices in disease diagnostics and fatigue monitoring demonstrating the trend towards personalised medicine with highly efficient, cost-effective, and accurate point-of-care diagnosis by finding hidden patterns in biosensing data and detecting abnormalities. The reliability of adaptive learning and synthetic data and data privacy still need further investigation to realise personalised medicine in the next decade. Due to the worldwide popularity of smartphones, they have been utilised for sensor readout, wireless data transfer, data processing and storage, result display, and cloud server communication leading to the development of smartphone-based biosensing systems. The recent advances have demonstrated a promising future for the healthcare system because of the increasing data processing power, transfer efficiency and storage capacity and diversifying functionalities.
Physiologic pH is vital for the normal functioning of tissues and varies in different parts of the body. The varying pH of the body has been exploited to design pH-sensitive smart oral, transdermal and vaginal drug delivery systems (DDS). The DDS demonstrated promising results in hard-to-treat diseases such as cancer and Helicobacter pylori infection. In some cases, a change in pH of tissues or body fluids has also been employed as a useful diagnostic biomarker. This paper aims to comprehensively review the development and applications of pH-sensitive DDS as well as recent advances in the field.
Recent advances in miniaturized nano-based devices are rapidly extending the boundaries of biomedical technologies, particularly biosensors. Highly selective biosensors with the ability to simultaneously detect multiple targets were developed in recent years. The most eye-catching classifications of such biosensors coupled with the emergence of stimuli-responsive and CRISPR/Cas-sensitive systems. Furthermore, attractive features of wearable and implantable biosensors have led to the design of portable, remote controllable diagnostic systems for tackling healthcare challenges in every part of the world, especially in places with limited access to clinical resources. Nevertheless, there are still some barriers to widespread applications of biosensors due mainly to their high costs and the lack of a single biosensing device for highly selective targeting of multiple analytes. Herein, we review the latest developments in biomedical technologies with a focus on biosensors including smart stimuli-responsive, CRISPR/Cas-sensitive, wearable, and implantable biosensors to spark innovations in this field.
Monitoring biosignals at the skin interface is necessary to suppress the potential for decubitus ulcers in immobile patients confined to bed. We develop conformally contacted, disposable, and breathable fabric-based electronic devices to detect skin impedance, applied pressure, and temperature, simultaneously. Based on the experimental evaluation of the multifunctional sensors, a combination of robust AgNW electrodes, soft ionogel capacitive pressure sensor, and resistive temperature sensor on fabric provides alarmed the initiation of early-stage decubitus ulcers without signal distortion under the external stimulus. For clinical verification, an animal model is established with a pair of magnets to mimic a human decubitus ulcers model in murine in vivo. The evidence of pressure-induced ischemic injury is confirmed with the naked eye and histological and molecular biomarker analyses. Our multifunctional integrated sensor detects the critical time for early-stage decubitus ulcer, establishing a robust correlation with the biophysical parameters of skin ischemia and integrity, including temperature and impedance.
Pressure injury (PI) is a hard-to-heal wound to patients with the limited mobility, especially paralyzed or elderly persons. These patients also commonly suffer from sensation loss or dementia that is unable to indicate symptoms in time, resulting in missing the “golden period” for treatment. Therefore, it is highly required to domestic long-term real-time monitoring as well as promoting wound healing of PI. However, no existing device has realized these functions for PI. Herein, we prepare a zwitterionic skin sensor that enables pro-healing as well as domestic real-time monitoring the multi-indicators of PI. To apply for a PI dressing that requires to tolerate patient body weight, organosilicon nanoparticles (OSNPs) are designed as crosslinks in the zwitterionic conductive hydrogel (CH-OSNP) that exhibits pressure-resistant properties (99.81% compression to recovery) as well as anti-bacterial adhesion. The CH-OSNP-based skin sensor is developed, and the resultant sensor can be sensitive to stress stimuli even under a long-term constant heavy load, which stimulates the pressure of a PI person lying down. In vivo results show that this sensor can not only promote PI healing, but also continuously monitor and distinguish multiple information, such as exudate, swelling, and infection, preventing PI from being worsen. This work provides a domestic feasible device to cure and monitor the PI of patients.
The number of hyperuricemia patients has been increasing. It is important that keep normal uric acid (UA) levels to prevent complicating disease of hyperuricemia. The current standard of UA tests uses a blood sample. However, it is not suitable for self-monitoring of UA level because it involves the burden of puncture and the risk of infection by taking a blood sample. Personal UA sensor is expected to monitor diurnal variation without invasiveness in a casual manner. In this study, we fabricated and evaluated a uricase-based biosensor toward the non-invasive continuous measurement of salivary UA concentration in the oral cavity. Uricase catalyzed UA and produced H2O2 in an enzyme-immobilized membrane on a Pt electrode. Then, generated H2O2 concentration which is correlated to the UA concentration was measured by the chronoamperometry technique. As a result, not only a wide dynamic range (0.1–10 μmol/L) but also high selectivity for UA was observed. In the future, the developed UA biosensor would allow monitoring UA levels non-invasively and continuously.
Wearable biochemical sensors have received substantial attention in recent years due to their great potential to provide insights into the physical condition of individuals. Based on the innovative biochemical sensing mechanisms and the recent advances in material science, the integrated biosensors are moving toward soft and small on-body electronic systems that can smartly and persistently monitor tiny changes in biochemical markers. They are beginning to transform almost every aspect of healthcare. This review looks into the state-of-the-art advances in this rising field by connecting the noninvasive biochemical sensing principles, materials science, advanced integration methods and the most representative cases of health monitoring wearable biosensors. Specifically, starting with a brief overview of the trends in wearable healthcare devices, we introduce the fundamental of chemistry for bio-sensing. The subsequent content highlights the contributions of nanomaterials and nanotechnologies in integrating and achieving on-body bio-sensing systems. We also discuss the key issues emerging in this area from a biocompatibility and material perspective. In the end, the review concludes with a summary of opportunities where advances in biochemistry and nanotechnology will be significant for future progress.
Keratin is a natural protein with a high content of cysteine residues (7–13%) and is widely found in hair, wool, horns, hooves, and nails. Keratin possesses abundant cell-binding motifs such as leucine-aspartate-valine (LDV), glutamate-aspartate-serine (EDS), and arginine-glycine-aspartate (RGD), which benefit cell attachment and proliferation. It has been confirmed that keratin plays important roles in every stage of wound healing, including hemostasis, inflammation, proliferation, and remodeling, making keratin-based materials good candidates for wound dressings. In combination with synthetic and natural polymers, keratin-based wound dressings in the forms of films, hydrogels, and nanofibers can be achieved with improved mechanical properties. This review focuses on the recent development of keratin-based wound dressings. Firstly, the physicochemical and biological properties of keratin, are systematically discussed. Secondly, the role of keratin in wound healing is proposed. Thirdly, the applications of keratin-based wound dressings are summarized, in terms of the forms and functionalization. Finally, the current challenges and future development of keratin-based wound dressings are presented.
In recent years, paper has become an essential substrate material for developing different types of sensors, from wearable devices to single‐use test strips and biosensors. In parallel, a polymer‐based toolbox has emerged in order to add additional functions to these paper‐based analytical devices. In this article, examples are compiled from the recent literature showing microfluidic systems based on printing impermeable polymer barriers with different methods as well as the implementation of electrochemical, fluorescent, and colorimetric polymer‐based transducers in paper‐based analytical platforms. Externally actuated or dissolvable polymer valves and reservoirs, analyte concentrators, and separation devices, as well as polymer‐based recognition elements (molecularly imprinted polymers) printed on paper substrates are also reviewed. The search has revealed a plethora of possibilities for developing complex lab‐on‐chip devices implementing different polymer‐based components in them. The ability of patterning these polymers with common printing methods that do not require specialized facilities paves the way for mass producing this kind of advanced paper‐based analytical device. Approaches for implementing polymer‐based microfluidic systems, transducers, valves, reservoirs, concentrators, and recognition elements in analytical platforms supported on paper are reviewed.
The flexible photodetector plays an important role in improving human medical health status. However, the narrow spectral detection range, poor stress stability, and non‐degradation of traditional flexible photodetectors greatly hinder the further development of wearable medical devices. In this paper, a novel flexible infrared photodetector is proposed for intelligent healthcare monitoring using high purity lead sulfide (PbS) nanoparticles on paper‐based flexible substrate synthesized by hydrothermal method and physical friction. The excellent performance of the detector is attributed to the 1.01 eV band gap and six‐arm stellate dendritic structure of PdS, a good combination between PbS and paper substrate via physical friction. As a result, our photodetector demonstrates wide‐spectrum detection capabilities from 365 to 1550 nm. The photodetector at 980 nm (50.4 μW cm−2) shows responsivity of 6.45 mA W−1, detectivity of 6.4 × 1010 Jones, response recovery time of 0.36 s/0.41 s, with good mechanical stability. By comparison, our detector has a wider detection range, better weak signal detection performance, and shorter response time than the performance of the former paper‐based detector. Furthermore, the paper‐based PbS photodetector as a dual‐wavelength photoplethysmography sensor is applied to analyze the oxygen saturation and develop an intelligent bandage to monitor wound healing. This paper‐based PbS photodetector has tremendous potential in the field of wearable medical devices and intelligent medical applications are expected. A flexible, broadband, and biodegradable paper‐based six‐arm stellate dendritic (SASD) PbS infrared photodetector is developed. The excellent performance is attributed to the SASD structure of PdS and good combination between PbS and paper substrate via physical friction. Simultaneously, this photodetector is applied to measure the oxygen saturation and monitor the wound healing.
Physical, chemical, or biological information is currently required in places that are different to those traditional, where bulky and complex instrumentation provide signals that are converted into understandable results. When one of those places is us, devices become wearable. Equipment for obtaining analytical signals has been miniaturized and sensors have been fabricated using materials with outstanding properties. Even being adaptable and small, a complete analytical process with detection as the main step can be performed on these tiny devices. Two detection principles are mainly employed: electrical/electrochemical and optical. Electrochemical techniques fit perfectly because in most of the cases an interfacial measurement is required, and the equipment is easy-to-miniaturize and inexpensive. Electrical measurements (without chemical contribution) are also very appropriate for designing simple physical sensors. On the other hand, optical detection, although not so common, includes naked-eye detection and takes advantage of components of reduced size. In all the cases, mobile platforms, mainly ubiquitous smartphones, are demonstrating to be excellent platforms for combination with wearable devices adding important advantages. In this chapter, an overview of these principles of detection with the most common modes: colorimetry and fluorescence together with photoplethysmography in optical detection; potentiometry, amperometry/voltammetry in electrochemical methodologies, as well as the main approaches employed in electrical detection, considering electrodes and equipment, are presented. Illustrative examples are included as well as some possibilities for multimodal detection, i.e., employing more than one signal transduction method.
Wearable Physical, Chemical and Biological Sensors introduces readers of all backgrounds—chemistry, electronics, photonics, biology, microfluidics, materials, and more—to the fundamental principles needed to develop wearable sensors for a host of different applications. The capability to continuously monitor organ-related biomarkers, environmental exposure, movement disorders, and other health conditions using miniaturized devices that operate in real time provides numerous benefits, such as avoiding or delaying the onset of disease, saving resources allocated to public health, and making better decisions on medical diagnostics or treatment. Worn like glasses, masks, wristwatches, fitness bands, tattoo-like devices, or patches, wearables are being boosted by the Internet of Things in combination with smart mobile devices. Besides, wearables for smart agriculture are also covered. Written by experts in their respective fields, Wearable Physical, Chemical and Biological Sensors provides insights on how to design, fabricate, and operate these sensors.
The increasing demand for point-of-care (POC) testing has leveraged the wearable sensor technology to a whole new level. Wearable systems aim at mimicking several properties of the human body by the employment of noninvasive methods, which enables such systems to obtain vital information on human health. Recent advances in material science, microfabrication, and Internet-of-things (IoT) have allowed for the development of fully wearable sensing systems. These integrated devices can store physiological information and transmitting gathered data to clinics in real time. In face of such great changes seen in the personalized medicine field and in POC tests, we have summarized the novel approaches employed in the manufacturing of wearable sensors applied for physiological and hybrid analyses. This chapter introduces the importance of the properties of substrates for the manufacturing of wearable sensors and the integration of such materials with the IoT technology for the monitoring of several hybrid human health–related signals (such as biochemical and physiological, etc.). At the end, the chapter draws a summary of challenges arising from the integration between electronic materials and flexible substrates upon skin.
Chronic wound remains a significant challenge in clinical care due to the long treatment process and the poor quality of tissue regeneration affected by bacterial infection, calling timely and effective wound management approach to achieve real-time intelligent wound monitoring and promote wound healing. In this work, a multifunctional hydrogel is employed as wound dressing for intelligent wound monitoring, which not only have the functions of antibacterial, hemostatic and adhesive properties for effectively promoting wound healing, but also can realize real-time wound status monitoring (e.g., pH). The whole intelligent wound monitoring process mainly includes three parts: wound recognition, real-time status monitoring and personalized wound management. Among them, the customized hydrogel wound dressing can accurately match the contour of the wound for precise treatment. Moreover, the personalized wound management model with high accuracy (94.47%) based on the convolutional neural network (CNN) machine learning algorithm can analyze and evaluate the wound healing and infection status through the colorimetric signal of the hydrogel dressing. This multifunctional hydrogel wound dressing, which integrates precise treatment, real-time monitoring and personalized management for intelligent wound monitoring, provides an advanced solution to accelerate wound healing and reduce bacterial infections and plays an inestimable step for future intelligent wound management.
We present a multi-modal sensor system for wound assessment and pressure ulcer care. Multiple imaging modalities including RGB, 3D depth, thermal, multi-spectral, and chemical sensing are integrated into a portable hand-held probe for realtime wound assessment. Analytic and quantitative algorithms for various assessments including tissue composition, wound measurement in 3D, temperature profiling, spectral, and chemical vapor analysis are developed. After each assessment scan, 3D models of the wound are generated on the fly for geometric measurement, while multi-modal observations are analyzed to estimate healing progress. Collaboration between developers and clinical practitioners was conducted at the Charlie Norwood VA Medical Center for in-field data collection and experimental evaluation. A total of 133 assessment sessions from 23 enrolled subjects were collected, on which the multi-modal data were analyzed and validated with respect to clinical notes associated with each subject. The system can be operated by non-technical caregivers on a regular basis to aid wound assessment and care. A web portal front-end was developed for clinical decision and telehealth support, where all historical patient data including wound measurements and analysis can be organized online.
This work describes the fabrication of self-powered, paper-based electrochemical devices (SPEDs) designed for sensitive diagnostics in low-resource settings and at the point of care. SPEDs are inexpensive, lightweight, mechanically flexible, easy to use, and disposable by burning. The top layer of the SPED is fabricated using cellulose paper with patterned hydrophobic domains that delineate hydrophilic, wicking-based microfluidic channels for accurate colorimetric assays, and self-pipetting test zones for electrochemical detection. The bottom layer of the SPED is a triboelectric generator (TEG) fabricated on hydrophobic paper and capable of harvesting electric energy from the user's interaction with the SPED. An inexpensive and rechargeable handheld potentiostat is fabricated to interface with the SPED, enabling the accurate quantitative electrochemical detection of glucose, uric acid, and l-lactate. The battery powering the potentiostat can be recharged by the user, using the sequential discharge of a capacitor previously charged with the TEG built into the SPED. A machine-vision diagnostic application is created to automatically identify and quantify each of the colorimetric tests from a digital image of the SPED, taken under a wide range of ambient light conditions, in order to provide fast diagnostic results to the user as well as to facilitate remote expert consultation.
Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.
The pH level in a chronic wound bed is a key indicative parameter for assessment of the healing progress. Due to their fragility and inability to measure multiple wound regions simultaneously, commercial glass microelectrodes are not well-suited for spatial mapping of the wound pH. To address this issue, we present an inexpensive flexible array of pH sensors fabricated on a polymer-coated commercial paper (palette paper). Each sensor consists of two screen-printed electrodes, an Ag/AgCl reference electrode and a carbon electrode coated with a conductive proton-selective polymeric (polyaniline, PANI) membrane. Laser-machining is used to create a self-aligned passivation layer with access holes that is bonded over the sensing and reference electrodes by lamination technology. Characterization of the pH sensors reveal a linear (r2 = 0.9734) relationship between the output voltage and pH in the 4–10 pH range with an average sensitivity of −50 mV/pH. The sensors feature a rise and fall time of 12 and 36 s for a pH swing of 8-6-8. The sensor biocompatibility is confirmed with HaCaT immortal human kertinocyte cells.
When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive 'smart bandage' for early detection of pressure ulcers.
Infection control is a key aspect of wound management strategies. Infection results in chemical imbalances and inflammation in the wound and may lead to prolonged healing times and degradation of the wound surface. Frequent changing of wound dressings may result in damage to healing tissues and an increased risk of infection. This paper presents the first results from a monitoring system that is being developed to detect presence and growth of bacteria in real time. It is based on impedance sensors that could be placed at the wound-dressing interface and potentially monitor bacterial growth in real time. As wounds can produce large volumes of exudate, the initial system reported here was developed to test for the presence of bacteria in suspension. Impedance was measured using disposable silver-silver chloride electrodes. The bacteria Staphylococcus aureus were chosen for the study as a species commonly isolated from wounds. The growth of bacteria was confirmed by plate counting methods and the impedance data were analysed for discernible differences in the impedance profiles to distinguish the absence and/or presence of bacteria. The main findings were that the impedance profiles obtained by silver-silver chloride sensors in bacterial suspensions could detect the presence of high cell densities. However, the presence of the silver-silver chloride electrodes tended to inhibit the growth of bacteria. These results indicate that there is potential to create a real time infection monitor for wounds based upon impedance sensing.
Pressure ulcers (PUs) can occur in any situations where people are subjected to non-uniform distribution of pressure over a prolonged period. They can have devastating effects on the patients' well-being and in extreme conditions can prove fatal. In addition to traditional wisdom implicating mechanically induced ischaemia, there is strong evidence that other mechanisms play a role in the cascade of events which can initiate the PU damage process at the cellular level. Some of these refer to a metabolic imbalance with compromised delivery of nutrients and accumulation of waste products in the local environment of the cells. The approach of much research has focused on the measure of oxygen in compressed tissues as a means of predicting early damage. However, the present review adopting a hierarchical approach, using length scales ranging from cells through to human models, has revealed compelling evidence which highlights the importance of carbon dioxide levels and associated concentration of other metabolites, such as lactate and purines. The temporal profiles of these metabolites have been monitored in the various models subjected to periods of mechanical-induced loading where the localized cells have converted to anaerobic metabolism. They reveal threshold levels of carbon dioxide which might be indicative of early tissue damage during both mechanical-induced ischaemia and subsequent reperfusion and an appropriate sensor could be used in a similar manner to the long-standing "canary in a cage" method to detect toxic gasses in enclosed mines.
Significance: Injury to the skin provides a unique challenge, as wound healing is a complex and intricate process. Acute wounds have the potential to move from the acute wound to chronic wounds, requiring the physician to have a thorough understanding of outside interventions to bring these wounds back into the healing cascade. Recent Advances: The development of new and effective interventions in wound care remains an area of intense research. Negative pressure wound therapy has undoubtedly changed wound care from this point forward and has proven beneficial for a variety of wounds. Hydroconductive dressings are another category that is emerging with studies underway. Other modalities such as hyperbaric oxygen, growth factors, biologic dressings, skin substitutes, and regenerative materials have also proven efficacious in advancing the wound-healing process through a variety of mechanisms. Critical Issues: There is an overwhelming amount of wound dressings available in the market. This implies the lack of full understanding of wound care and management. The point of using advanced dressings is to improve upon specific wound characteristics to bring it as close to "ideal" as possible. It is only after properly assessing the wound characteristics and obtaining knowledge about available products that the "ideal" dressing may be chosen. Future Directions: The future of wound healing at this point remains unknown. Few high-quality, randomized controlled trials evaluating wound dressings exist and do not clearly demonstrate superiority of many materials or categories. Comparative effectiveness research can be used as a tool to evaluate topical therapy for wound care moving into the future. Until further data emerge, education on the available products and logical clinical thought must prevail.
Significance
The ability to perform electrochemical testing in the field, and in resource-limited environments, and to transmit data automatically to “the cloud” can enable a broad spectrum of analyses useful for personal and public health, clinical analysis, food safety, and environmental monitoring. Although the developed world has many options for analysis and web connection, the developing world does not have broad access to either the expensive equipment necessary to perform these tests or the advanced technologies required for network connectivity. To overcome these limitations, we have developed a simple, affordable, handheld device that can perform all the most common electrochemical analyses, and transmit the results of testing to the cloud from any phone, over any network, anywhere in the world.
Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.
This paper describes the fabrication of pressure-driven, open-channel microfluidic systems with lateral dimensions of 45-300 microns carved in omniphobic paper using a craft-cutting tool. Vapor phase silanization with a fluorinated alkyltrichlorosilane renders paper omniphobic, but preserves its high gas permeability and mechanical properties. When sealed with tape, the carved channels form conduits capable of guiding liquid transport in the low-Reynolds number regime (i.e. laminar flow). These devices are compatible with complex fluids such as droplets of water in oil. The combination of omniphobic paper and a craft cutter enables the development of new types of valves and switches, such as "fold valves" and "porous switches," which provide new methods to control fluid flow.
Wound healing involves a complex series of biochemical events and has traditionally been managed with 'low tech' dressings and bandages. The concept that diagnostic and theranostic sensors can complement wound management is rapidly growing in popularity as there is tremendous potential to apply this technology to both acute and chronic wounds. Benefits in sensing the wound environment include reduction of hospitalization time, prevention of amputations and better understanding of the processes which impair healing. This review discusses the state-of-the-art in detection of markers associated with wound healing and infection, utilizing devices imbedded within dressings or as point-of-care techniques to allow for continual or rapid wound assessment and monitoring. Approaches include using biological or chemical sensors of wound exudates and volatiles to directly or indirectly detect bacteria, monitor pH, temperature, oxygen and enzymes. Spectroscopic and imaging techniques are also reviewed as advanced wound monitoring techniques. The review concludes with a discussion of the limitations of and future directions for this field.
The applicability of employing a carbon fibre mesh as the sensing element within a ''smart bandage" for assessing urate transforma-tions within wound exudates is evaluated and a novel strategy for the detection of bacterial contamination presented. Prototype sensor assemblies have been designed and their response characteristics towards the periodic monitoring of uric acid within whole blood, serum, blister fluid and microbial culture has been evaluated. The rapid and selective metabolism of urate by Pseudomonas aeruginosa, the bac-teria responsible for most adventitious wound infections, has been investigated. A preliminary evaluation of the efficacy of utilizing the microbial response to endogenous wound urate as means of detecting the onset of infection is presented.
Novel applications of online pH determinations at temperatures from -35 °C to 130 °C in technical and biological media, which are all but ideal aqueous solutions, require new approaches to pH monitoring. The glass electrode, introduced nearly hundred years ago, and chemical sensors based on field effect transistors (ISFET) show specific drawbacks with respect to handling and long-time stability. Proton sensitive metal oxides seem to be a promising and alternative to the state-of-the-art measuring methods, and might overcome some problems of classical hydrogen electrodes and reference electrodes.
With our aging population, chronic diseases that compromise skin integrity such as diabetes, peripheral vascular disease (venous hypertension, arterial insufficiency) are becoming increasingly common. Skin breakdown with ulcer and chronic wound formation is a frequent consequence of these diseases. Types of ulcers include pressure ulcers, vascular ulcers (arterial and venous hypertension), and neuropathic ulcers. Treatment of these ulcers involves recognizing the four stages of healing: coagulation, inflammation, proliferation, and maturation. Chronic wounds are frequently stalled in the inflammatory stage. Moving past the inflammation stage requires considering the bacterial burden, necrotic tissue, and moisture balance of the wound being treated. Bacterial overgrowth or infection needs to be treated with topical or systemic agents. In most cases, necrotic tissue needs to be debrided and moisture balance needs to be addressed by wetting dry tissue and drying wet tissue. Special dressings have been developed to accomplish these tasks. They include films, hydrocolloids, hydrogel dressings, foams, hydrofibers, composite and alginate dressings.
Wound healing is a complex regeneration process, which is characterised by intercalating degradation and re-assembly of connective tissue and epidermal layer. The pH value within the wound-milieu influences indirectly and directly all biochemical reactions taking place in this process of healing. Interestingly it is so far a neglected parameter for the overall outcome. For more than three decades the common assumption amongst physicians was that a low pH value, such as it is found on normal skin, is favourable for wound healing. However, investigations have shown that in fact some healing processes such as the take-rate of skin-grafts require an alkaline milieu. The matter is thus much more complicated than it was assumed. This review article summarises the existing literature dealing with the topic of pH value within the wound-milieu, its influence on wound healing and critically discusses the currently existing data in this field. The conclusion to be drawn at present is that the wound pH indeed proves to be a potent influential factor for the healing process and that different pH ranges are required for certain distinct phases of wound healing. Further systematic data needs to be collected for a better understanding of the pH requirements under specific circumstances. This is important as it will help to develop new pH targeted therapeutic strategies.
This article discusses the costs of chronic wound management and the impact on patients and the healthcare system.
Introduction:
In studies with experimental models of pressure ulcer, until date, there is no validated instrument to assess the various visual aspects of the healing process. Measure of wound area is the most used method for this purpose. Thus, we aimed to develop and validate a visual assessment tool for the evaluation of healing in experimental models of pressure ulcer.
Methods:
The Experimental Wound Assessment Tool (EWAT) was developed based on tools used in clinical practice. The tool was validated using 50 photographs of wound induced by a noninvasive pressure ulcer model in Swiss mice. Five judges performed the Content Validity and 3 raters evaluated the photos by EWAT. Items with the Content Validity Index score lower than 0.8 were modified in accordance to the suggestions of the judges.
Results:
The EWAT showed moderate to high reliability, whilst the Concurrent Validity Test obtained good to high results, demonstrating a significantly strong positive correlation between the analyses of the raters. Moreover, it was shown to have high correlation with the clinical Photographic Wound Assessment Tool.
Discussion:
EWAT showed good/excellent results in all the validation tests, showing it to be a good tool to evaluate wound healing process in animal models of pressure ulcer and being recommended for assessment of wound healing in small experimental animals.
Skin is the largest organ of the human body, and it offers a diagnostic interface rich with vital biological signals from the inner organs, blood vessels, muscles, and dermis/epidermis. Soft, flexible, and stretchable electronic devices provide a novel platform to interface with soft tissues for robotic feedback and control, regenerative medicine, and continuous health monitoring. Here, we introduce the term “lab-on-skin” to describe a set of electronic devices that have physical properties, such as thickness, thermal mass, elastic modulus, and water-vapor permeability, which resemble those of the skin. These devices can conformally laminate on the epidermis to mitigate motion artifacts and mismatches in mechanical properties created by conventional, rigid electronics while simultaneously providing accurate, non-invasive, long-term, and continuous health monitoring. Recent advances in the design and fabrication of soft sensors with more advanced capabilities and enhanced reliability suggest an impending translation of these devices from the research lab to clinical environments. Regarding these advances, the first part of this manuscript reviews materials, design strategies, and powering systems used in soft electronics. Next, the paper provides an overview of applications of these devices in cardiology, dermatology, electrophysiology, and sweat diagnostics, with an emphasis on how these systems may replace conventional clinical tools. The review concludes with an outlook on current challenges and opportunities for future research directions in wearable health monitoring.
Chronic wounds are highly heterogeneous with the complications of tissue remodelling and issues such as infection generating a multitude of molecular and cellular species. It could be anticipated that were information regarding the dynamics of key wound biomarkers available to the clinician, more informed decisions could be implemented to encourage the reinstatement of normal healing processes. There are few diagnostic options available at the time of consultation and the aim of this review has been to assess the capability of electrochemical sensing strategies to provide detailed point of care information on the wound condition. Advances in functional materials and the greater accessibility of disposable printed systems are beginning to provide a solid foundation through which low cost devices could be realised and whose deployment could lead to more informed decision making and positive outcomes.
Development of stretchable sensors has recently attracted considerable attention. These sensors have been used in wearable and robotics applications such as personalized health-monitoring, motion detection, and human-machine interfaces. Herein, we report on a highly stretchable electrochemical pH sensor for wearable point-of-care applications that consists of a pH sensitive working and a liquid-junction-free reference electrode, in which the stretchable conductive interconnections are fabricated by laser carbonizing and micromachining of a polyimide sheet bonded to an Ecoflex substrate. This method produces highly porous carbonized 2D serpentine traces that are subsequently permeated with polyaniline (PANI) as the conductive filler, binding material, and pH sensitive membrane. The experimental and simulation results demonstrate that the stretchable serpentine PANI/C-PI interconnections with the optimal trace widths of 0.3 mm can withstand elongations of up to 135 % and are robust to more than 12000 stretch-and-release cycles at 20% strain without noticeable change in the resistance. The pH sensor displays a linear sensitivity of -53 mV/pH (r2 = 0.976) with stable performance in the physiological range of pH 4-10. The sensor shows excellent stability to applied longitudinal and transverse strains up to 100% in different pH buffer solutions with a minimal deviation of less than ±4 mV. The material biocompatibility is confirmed with NIH 3T3 fibroblast cells via PrestoBlue assays.
The direct integration of sensors within the bandage to form a smart dressing has been proposed as a possible means of tackling some of the present challenges in the treatment of chronic wounds. The development of a “connected health” model through which the wound is remotely monitored within the community and assessed by a clinician or autonomously by an appropriate smart app algorithm has many advantages, but it is very much an “ideal.” Although there are many diagnostic assays and sensing techniques that can be translated from the lab bench to the clinic, the subsequent adaptation for continuous/periodic monitoring that would be required for outpatient monitoring faces numerous hurdles. The transition of the sensing technology from the lab bench to the clinic or to a patient’s home requires the integration of the biological, chemical, and materials elements with modern communication. The advent of the smartphone and tablet promises to revolutionize healthcare offering personalized medicine and greater patient awareness and management of their condition. This chapter explores the technological requirements necessary to process the signal from the sensor that is in contact with the wound, the mechanisms through which the signal can be transmitted and the wider implications of emerging eHealth and mHealth models.
Paper microfluidics and printed electronics have developed independently, and are incompatible in many aspects. This work demonstrates monolithic integration of microfluidics and electronics on paper. This integration makes it possible to print two- and 3D fluidic, electrofluidic, and electrical components on paper, and to fabricate devices using them.
The pH of wound fluid has long been recognized as an important diagnostic for assessing wound condition, but as yet there are few technological options available to the clinician. The availability of sensors that can measure wound pH, either in the clinic or at home could significantly improve clinical outcome – particularly in the early identification of complications such as infection. New material designs and electrochemical research strategies that are being targeted at wound diagnostics are identified and a critical overview of emerging research that could be pivotal in setting the direction for future devices is provided.
Current methods in treating chronic wounds have had limited success in large part due to the open loop nature of the treatment. We have created a localized 3D-printed smart wound dressing platform that will allow for real-time data acquisition of oxygen concentration, which is an important indicator of wound healing. This will serve as the first leg of a feedback loop for a fully optimized treatment mechanism tailored to the individual patient. A flexible oxygen sensor was designed and fabricated with high sensitivity and linear current output. With a series of off-the-shelf electronic components including a programmable-gain analog front-end, a microcontroller and wireless radio, an integrated electronic system with data readout and wireless transmission capabilities was assembled in a compact package. Using an elastomeric material, a bandage with exceptional flexibility and tensile strength was 3D-printed. The bandage contains cavities for both the oxygen sensor and the electronic systems, with contacts interfacing the two systems. Our integrated, flexible platform is the first step toward providing a self-operating, highly optimized remote therapy for chronic wounds.
This work describes the adaptive use of conventional stainless steel pins-used in unmodified form or coated with carbon paste-as working, counter, and quasi-reference electrodes in electrochemical devices fabricated using cotton thread or embossed omniphobic R(F) paper to contain the electrolyte and sample. For some applications, these pin electrodes may be easier to modify and use than printed electrodes, and their position and orientation can be changed as needed. Electroanalytical devices capable of multiplex analysis (thread-based arrays or 96-well plates) were easily fabricated using pins as electrodes in either thread or omniphobic R(F) paper.
Oxygen plays an important role in wound healing, as it is essential to biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of chronic ischemic wounds, which affect more than 6 million people each year in the United States alone at an estimated cost of $25 billion. Knowledge of oxygenation status is also important in the management of burns and skin grafts, as well as in a wide range of skin conditions. Despite the importance of the clinical determination of tissue oxygenation, there is a lack of rapid, user-friendly and quantitative diagnostic tools that allow for non-disruptive, continuous monitoring of oxygen content across large areas of skin and wounds to guide care and therapeutic decisions. In this work, we describe a sensitive, colorimetric, oxygen-sensing paint-on bandage for two-dimensional mapping of tissue oxygenation in skin, burns, and skin grafts. By embedding both an oxygen-sensing porphyrin-dendrimer phosphor and a reference dye in a liquid bandage matrix, we have created a liquid bandage that can be painted onto the skin surface and dries into a thin film that adheres tightly to the skin or wound topology. When captured by a camera-based imaging device, the oxygen-dependent phosphorescence emission of the bandage can be used to quantify and map both the pO2 and oxygen consumption of the underlying tissue. In this proof-of-principle study, we first demonstrate our system on a rat ischemic limb model to show its capabilities in sensing tissue ischemia. It is then tested on both ex vivo and in vivo porcine burn models to monitor the progression of burn injuries. Lastly, the bandage is applied to an in vivo porcine graft model for monitoring the integration of full- and partial-thickness skin grafts.
Chronic nonhealing wounds are a major source of morbidity and mortality in bed-ridden and diabetic patients. Monitoring of physical and chemical parameters important in wound healing and remodeling process can be of immense benefit for optimum management of such lesions. Low-cost flexible polymeric and paper-based substrates are attractive platforms for fabrication of such sensors. In this review, we discuss recent advances in flexible physiochemical sensors for chronic wound monitoring. After a brief introduction to wound healing process and commercial wound dressings, we describe various flexible biocompatible substrates that can be used as the base platform for integration of wound monitoring sensors. We will then discuss several fabrication methods that can be utilized to integrate physical and chemical sensors onto such substrates. Finally, we will present physical and chemical sensors developed for monitoring wound microenvironment and outline future development venues.
Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.
