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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.
... Paper-based Sensor Applications. The evolution of substrate materials for sensors has seen rapid development in recent years, with researchers working on materials asides from silicon and glass to improve the properties of sensors, such as flexibility, biocompatibility, stretchability, and easy disposal (Green disposal) (Aniket et al., 2018). This has given rise to paper-based sensors and their multiple uses Shagle et al. (2021). ...
... This sensor can be utilized for human health monitoring, such as breathing and coughing. Aniket et al. (2018) also proposed a smart bandage sensor made of a flexible paper-based substrate to track wound biomarkers to decrease the frequency of dressing changes and lessen the patient's stress and agony. This study applied omniphobic paper-based smart bandages (OPSBs) that are single-use, low-cost, flexible, breathable, lightweight, burnable, and designed to easily monitor the condition of open chronic wounds. ...
... There are several materials for measuring the wound pH. Hydrogel-based passive wireless sensor (Sridhar & Takahata, 2009), pH and reference electrodes fabricated on a paper substrate (Rahimi et al., 2016), cotton swabs (Schaude et al., 2017), bandages (Kassal et al., 2017;Mariani et al., 2021;Pal et al., 2018), pH sensor with near-field communication (Rahimi et al., 2018), and composite dressing (Nischwitz et al., 2019) are only some recently developed solutions. Although effective, these materials are expensive, need the intricate development of the instrument (tool/gadget), use synthetic dyes, do not have antimicrobial properties, require a prolonged time to measure the pH value of the wound, and can detect pH value only by taking a sample from the wound without being put directly on the wound. ...
... Even promising, synthetic dye-containing wound dressings show serious drawbacks because they could be allergenic and cytotoxic (Yadav et al., 2023b). The modern pH-indicating wound dressing has to be made of natural, bio-sourced, non-allergenic, and non-cytotoxic chemistry that detects a change in pH in seconds (Pal et al., 2018). In recent years, there has been a growing interest in utilizing biopolymers such as chitosan (Yadav et al., 2023a), alginate (Singh et al., 2021), pectin (Sutar et al., 2021), gelatin (Karydis-Messinis et al., 2023), arginine and curcumin (Jian et al., 2023), and quercetin (Li et al., 2022), for the development of biomaterial-based anti-infecting wound dressings. ...
Environmentally benign pH-indicating wound dressing comprised of carbohydrates chitosan (CH) and pectin (P), and anthocyanin grape (AG) dye is created via layer-by-layer assembly. Cotton fabric coated with eight bilayers of (CH-AG)4/(P-AG)4 deposited 1.97 % AG-dye. It exhibited a visible and immediate color change from pink to violet-blue while increasing its pH value from 6 to pH 7, matching the turning pH point of healing into an infected wound. Color transition of AG-dye in water-based buffers, tested by VIS-spectroscopy, shows the same color change when the pH value increased from 6 to 7. This coating imparts excellent antimicrobial activity against Gram-positive bacteria Staphylococcus aureus and yeast Candida albicans, moderate antibacterial activity against Gram-negative Escherichia coli bacteria, and no cytotoxicity on human fibroblast cells (MRC-5). This research proposes a sustainable, low-cost, and simple method for obtaining smart wound dressing that provides real-time monitoring of the wound pH.
... Recently, it has been demonstrated the use of fluoroalkylated trichlorosilanes (RFSiCl 3 ) to alter the surface chemistry of cellulose fibers, rendering paper omniphobic resistant to wetting by aqueous solutions and organic liquids with surface tensions as low as 25 mN m −1 while preserving the mechanical flexibility, strength, and breathability of untreated paper. [28] Omniphobic RF paper has been used to fabricate a variety of lowcost electronics [29] and microfluidic devices for environmental monitoring, [30] point-of-care diagnostics, [31] and biomedical fluid handling. [32] Unfortunately, because of its limited stretchability and lack of adherence to skin, RF paper has never been considered suitable for the development of skin-mountable devices. ...
The emergence of paper‐based electronic devices marks a significant leap forward in the design of flexible, lightweight, and eco‐friendly electronics. Paper‐based electronic sensors represent a transformative approach to creating flexible, lightweight, and environmentally friendly electronics. This review will discuss recent applications of paper‐based electronics, mainly in exploring emergent technologies employed in developing innovative sensors for chemical analysis. Furthermore, the role of paper‐based electronics in electrochemical, and physical sensing, specifically addressing relative humidity, temperature, pressure, and strain sensors will be commented. In addition, the integration of paper electronics in energy harvesting and storage is discussed, covering solar cells, tribogenerators, antennas, and supercapacitors. These advancements underscore the versatility and potential of paper‐based electronics in diverse applications, from wearable health monitors to sustainable energy solutions, paving the way for the future of recyclable and biodegradable electronic devices.
... Wearable sensors, integrated analytical devices for analyzing biological fluids, have garnered significant interest in recent years due to their unique capability for real-time and continuous monitoring of biomarkers in a noninvasive or minimally invasive manner 1,2 . These sensing devices have been developed in diverse forms, such as temporary tattoos 3,4 , wristbands 5,6 , bandages 7,8 , textiles 9,10 , face masks 11,12 , eyeglasses 13,14 , contact lenses 15,16 , mouthguard 17,18 and microneedles 19 , enabling access to biofluids for on-body analysis. In addition, recent advances in wearable sensors have demonstrated the effectiveness of real-time wireless monitoring 20 . ...
Wearable enzyme-based biosensors enable advanced healthcare diagnostics through the monitoring of biomarkers and physiological states. The integration of materials engineering and enzyme conjugation has established the groundwork for advancements in modern analytical chemistry, poised to extend the frontiers of wearable biosensing further. Recent advancements in enzymatic biofuel cells have also enhanced devices by harnessing biofuels, such as glucose and lactate in biofluids. Importantly, biofuel cells offer the potential for self-powered biosensors. Here, we present an overview of the principles and considerations associated with engineering materials and integrating enzymes with electrodes to achieve effective wearable biosensing and self-sustaining biofuel cell-based energy systems. Furthermore, we discuss challenges encountered by enzymatic sensors and biofuel cells. Representative applications of wearable devices in healthcare settings are highlighted, along with a summary of real sample analyses, emphasizing the concentration ranges of analytes present in actual sweat samples to underscore their relevance in real-world scenarios. Finally, the discussion explores the anticipated impact of future material innovations and integrations on the development of next-generation wearable biodevices.
... Wearable devices utilizing these biosensors offer the real-time monitoring of conditions such as diabetes, cardiovascular diseases, and infectious diseases, fostering a proactive approach to healthcare. Such wearable health monitors could measure parameters like biophysical features (body temperature, blood pressure, heart rate, and biopotential), sweat biochemicals (pH, uric acid, glucose, cholesterol, cortisol, etc.), lactate, or specific proteins, offering valuable data for individuals managing chronic conditions or athletes optimizing their performance [15,[166][167][168][169][170]. For example, Yang et al. [171] designed a paper-based sandwich-structured wearable pH sensor with in situ sebum filtering for reduced interference (Figure 6a). ...
This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper’s unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.
... Most of them, however, are still at the level of sensor integration, which do not address the issues and difficulties encountered in real-world applications, such as the lack of a multi-task detection system on the dressings or the requirement for additional external batteries or power supplies for detection 186 . Smart bandages with an embedded flexible multipurpose sensor that can diagnose the wound status by accurately detecting various wound parameters (uric acid (UA), pH, and temperature) simultaneously has the potential to revolutionise the concept of wound management and significantly impact the outcomes of therapy 30,186,197 . In order to detect UA, pH, and temperature at the wound site, Sharifuzzaman et al. created a smart, stretchable, and flexible multifunctional sensor-integrated wound bandage based on MXene-functionalized porous graphene scaffold 30 . ...
The objective of this review is to provide an up-to-date and all-encompassing primal account and recent advancements in the domain of interactive wound dressings. Appreciating the gap between obtained and...
... Wearable devices utilizing these biosensors offer real-time monitoring of conditions such as diabetes, cardiovascular diseases, and infectious diseases, fostering a proactive approach to healthcare. Such wearable health monitors could measure parameters like biophysical (body temperature, blood pressure, heart rate, biopotential), sweat biochemicals (pH, uric acid, glucose, cholesterol, cortisol, etc.), lactate, or specific proteins, offering valuable data for individuals managing chronic conditions or athletes optimizing their performance [15,[163][164][165][166][167]. For example, Yang et al. [168] designed a paper-based sandwich-structured wearable pH sensor with in-situ sebum filtering for reduced interference (Figure 6a). ...
This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper’s unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. The review discusses fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.
... [3] Recent advancements in wearable technology have spurred the development of electronically active wound dressings, mainly relying on integrated miniaturized electrochemical sensors (granting robust analyte sensing) on flexible polymeric substrates (granting skin conformability). [3,[12][13][14] Notable examples include dressings capable of tissue pH [10,[15][16][17][18] and oxygen [19][20][21][22] monitoring. Electrochemical sensors are appealing analytical tools owing to their fast response times, low limits of detection, wide sensing range, sensitivity, easy integration on wearable and flexible substrates, and cost-effectiveness. ...
Recent advancements in wearable technology have led to a new era of intelligent wound dressings capable of monitoring vital healing biomarkers. While a significant leap from traditional gauze dressings, these innovations still necessitate periodic removal and disposal. Bioresorbable electrochemical sensors have emerged as a promising and sustainable solution, offering continuous monitoring of critical wound healing biomarkers in real‐time and in situ, followed by their full physiological resorption. The current challenge lies in the susceptibility of metallic electrodes to harsh electrolytic biofluids, hindering the development of viable transient electrochemical sensors. This study pioneers a bioresorbable electrochemical material and unique architecture comprising engineered sputtered tungsten (W) plus tungsten oxide (WOx) thin films, taking advantage of their high catalytic activity and uniquely gradual biodissolution. While a bare W film electrode detached from the wafer substrate within 5 hours of soaking, an annealed W‐WOx electrode showcases a notable electrochemical stability at body temperature, for up to several days. The latter reliably senses multiple analytes during 24‐hour room‐temperature tests. These findings underscore the potential of annealed W plus WOx electrodes in future bioresorbable wound management systems.
... Consequently, this dynamic fluctuation in UA levels serves as an indicative pattern, reflecting either the severity of the wound or the presence of bacterial infection. Although enzymatic UA biosensors are available, offering good selectivity for detecting UA under relatively stable physiological pH conditions, such as in serum, previously reported amperometric UA biosensors have overlooked the fluctuating pH levels in real wound exudates 7,8 . This omission is inadequate for dynamic wound monitoring, potentially resulting in inaccurate UA concentration estimation due to variations in enzyme activity under different pH conditions. ...
Effective individual wound management, particularly in cases of prolonged healing and increased infection vulnerability, has prompted the development of wound theranostics, combining real-time diagnostic assessment and on-demand treatment. Here, we present a multifunctional conducting polymer-based smart theranostic bandage that integrates pH sensing, pH-compensated uric acid (UA) biosensing, and on-demand antibiotic release using different conducting polymers, each leveraging their advantageous intrinsic properties. Specifically, the polyaniline-based pH sensor operates reversibly across a pH range of 4–10, while the functionalized poly(3,4-ethylenedioxythiophene)-based UA biosensor exhibits a linear response up to 0.9 mM UA. Simultaneous detection of pH and UA allows accurate UA determination via pH compensation. Upon detecting abnormal pH/UA levels, the polypyrrole-based drug carrier releases ciprofloxacin via 0.6 V electrical stimulation, successfully inhibiting bacterial growth in vitro. The array is assembled as a 3D patch, connected to a flexible printed circuit board, and embedded in a wound bandage, offering potential for remote wound monitoring, targeted treatment, and wireless wound management.
... 11 These systems consist of a wearable device that is placed directly on the wound and is equipped with sensors and bioelectronic components. 13 The sensors are used to monitor wound conditions such as temperature, pH, and moisture levels. 14 The bioelectronic components are then used to deliver appropriate treatments, such as electrical stimulation or drug delivery, to promote healing. ...
... Accelerating the advancement of smart bandages in clinical applications demands intensive research and development in materials science, sensor technology, and biomedical engineering to bolster their functionality and reliability [83]. It is crucial to subject these bandages to extensive clinical trials, ensuring collaboration between researchers and regulatory bodies while adhering strictly to stringent safety and effectiveness standards [84]. ...
The management of wounds is a critical aspect of healthcare as it affects patients' quality of life and puts a financial burden on the healthcare industry. The development of smart bandages has shown great potential in wound monitoring and targeted treatment. This review paper gives information on the latest updates in smart bandage technology that can monitor various biomarkers such as temperature, moisture, oxygen, blood flow, external pressure, pH, and infection status in real time. Additionally, this review discusses targeted treatment by integrating drug delivery systems that can release drugs on-demand based on the wound condition. Furthermore, this paper gives a summary of information on the current improvements in smart bandages, including their design, fabrication, and clinical applications. This paper also discussed the current challenges and future opportunities with smart bandages and their potential to transform the field of wound care. With the ability to noninvasively diagnose wound parameters, reduce pain, and accelerate wound healing, smart bandages are expected to play a significant role in future wound care.
... Point-of-Care devices is an example of low-cost potentiostat being widely used under current health scenarios. Nevertheless, most of the development of point-of-care devices focuses on chemical compounds [18]- [22]. ...
... Chronic wounds significantly impact on the QoL of patients and impose a substantial financial burden owing to the recurring need for wound dressing replacement and prolonged hospital stays. Consequently, innovative wound care technologies, that offer simple monitoring, affordability, and wearability, with body-attachable sensors to fulfill these requirements are in high demand [10][11][12]. Therefore, a discernible call exists for the advancement of wound site treatment technologies at more affordable prices. ...
A wearable biosensor was specifically engineered to measure uric acid, a biomarker present at wound sites. This biosensor, fabricated as a disposable and wearable device, was seamlessly integrated onto a polyethylene terephthalate (PET) substrate by utilizing carbon and silver conductive paste as the electrodes. The enzyme uricase was immobilized onto the working electrode by utilizing chitosan, a biocompatible material, to create this biosensor. Notably, the uric acid biosensor fabricated with chitosan showcased exceptional performance metrics, including remarkable output current values and impeccable stability. These findings suggest the prospective utilization of chitosan-based uric acid biosensors for the accurate measurement of uric acid on human skin in future applications.
... 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.
... 55 Associated with oxidative stress and bacterial infection in the wound area, uric acid levels rise in unhealed chronic wounds and fall as the wound heals. 42,56,57 Wound moisture is a key parameter in ensuring optimal healing conditions in wound care. 47,58 However, moisture-induced infection might increase the exuding of tissue fluid, rendering wounds to be too wet and thus aggravating wound infection. ...
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.
... 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.
In the last decade, the chemistry research community has witnessed an explosive growth of microfluidic devices made of paper (paper-based microfluidics). Use of paper as a substrate material brings several attractive features including extremely low cost and auxiliary pump-free liquid transportation, among others, and application of paper-based microfluidics to on-site medical diagnosis has been actively pursued. To meet the demand for medical diagnostic devices operable by end-users without expert knowledge in resource-limited settings, recent studies on paper-based microfluidics pay particular attention to simplification of user operations prior to an assay (e.g. achieving multistep enzymatic assays by single pipetting) and resulting signal readout (e.g. achieving naked eye-based analog thermometer-style result interpretation). One of the objectives of this chapter is to overview state-of-the-art research progresses in simplification of user operational procedures and development of equipment-free signal readout approaches. Moreover, advanced technologies that show the potential to become the next generation of paper-based microfluidics for point-of-care applications are also discussed in this chapter. In addition, the basics of paper-based microfluidics including a short history of paper-based microfluidics, a comparison of paper-based and conventional plastic- or glass-based microfluidic devices and general requirements for ideal point-of-care testing devices are described. The authors believe this chapter helps researchers new to the field and researchers with different backgrounds to learn about analytical applications exclusively achieved by paper-based microfluidics and future challenges in developing “truly” practical medical diagnostic devices.
The physics of the moving contact line of an impacting droplet is widely applied in a variety of domains in rapidly advancing healthcare technology and medicine. The behavior of the dynamic contact line after impact of a biologically active droplet on a complex material surface involves complicated solid–liquid and liquid–gas interfacial interactions. Therefore, a deep understanding of such complex droplet contact line dynamics by applying the current physical models and state-of-the-art nanotechnology and artificial neural networks can be one of the ongoing promising interests in the field of interfacial physics. This review provides an overview of several scientific aspects of contact line dynamics of an impacting droplet and its influence on the current developed healthcare technology and medicine. Firstly, the potential applications in modern healthcare and personalized medicine are listed and discussed. Secondly, the theory of the moving contact line and the fundamental physical parameters related to the motion of impacting droplets are introduced. Afterwards, the current physical models of moving contact line dynamics are critically explained by emphasizing their limitations. Finally, current concerns and obstacles are summarized, and future perspectives and research directions are outlined to address poorly understood and conflicting issues.
Digital biosensors facilitate real-time, remote, precise disease detection and biochemical analysis. Recent trends in biosensing methods have focused on miniaturization, automation, and multiplexing. The miniaturization of biosensors has led to the development of portable, flexible, and wearable devices that can be used for point-of-care diagnostics and continuous health monitoring. Furthermore, digital automation has enabled the high-throughput screening of samples, reducing the time and cost of analysis, while integrated multiplexing allows for the simultaneous detection of multiple analytes, increasing the efficiency and accuracy of analysis. This article examines recent scientific advances in developing miniaturized biosensing procedures for digital healthcare. Advancements in digital devices have also contributed to the development of integrated biosensing. The use of smartphones, smartwatches, and other digital devices as readout platforms for biosensors has made biosensing more accessible and user-friendly. The development of artificial intelligence and machine learning algorithms has allowed for the interpretation and analysis of complex biosensor data. This review compares biosensing with current state-of-the-art diagnostic technology. After incorporating biosensors with artificial intelligence in an internet of things platform, they will have enormous potential and market value in the future for personalized healthcare. Based on various device performances and impacts, sensing methods, designs, compatibilities, functionalities, technology integrations, and developments are systematically discussed in this article. The primary objective of this review was to present a comprehensive discussion from the point of view of both technological advancements and translational wisdom. It is essential to have intelligent point-of-care devices with digital technologies for real-time healthcare management. The vision of the future healthcare industry encompasses a range of biosensing methods that offer a glimpse into new possibilities for the market.
Chronic wound monitoring can provide personalized pathophysiological information for wound management and treatment. Continuously monitoring the wound milieu via the holographic pH sensor can reflect the wound healing processes. However, the integration with wearable devices is hindered by its inherently restricted interrogation angle dependency within 5°. Herein, a ball bearing‐based double photopolymerization method is developed to fabricate holographic pH sensors with a broader interrogation angle range of 15°–60° in wound exudates. The fabricated holographic pH sensor is then integrated with the flexible ultrathin polyurethane substrate, which replays a total Bragg peak shift of approximately 150 nm with physiological pH changes from 7.00 to 8.75. The conformable holographic pH sensing bandages demonstrate the ability to quantify the pH value under various bending manipulations, simulating the mounting on the body surface. The reversibility in artificial wound exudate demonstrates the durability and capability of real‐time pH monitoring in the wound milieu with minimal effect on the replay wavelength. The addition of electrolytes, albumin, urea, uric acid, lactate, and glucose does not interfere with the readout over the physiological pH range of wound exudates. The obtained conformable holographic sensing bandage benefits the wound healing process monitoring through colorimetric interrogation at point‐of‐care (POC) settings.
Chronic wounds arising from accidents, surgeries, or diseases impose a significant clinical and economic burden, underscoring the need for effective solutions to prevent severe complications. Recent advancements in materials science and electrochemical technology have facilitated the development of conformable electrochemical platforms for detection and management, incorporating monitoring, diagnosis, and treatment. Nevertheless, current wound detection and therapy systems face challenges related to the stability and specificity of sensor monitoring, as well as the need for on-site and comprehensive evaluation criteria to offer timely treatment guidance and follow-up care. This review provides a comprehensive overview of the closed-loop management system, emphasizing wound biomarker detection, wound assessment, and on-demand treatment, ultimately culminating in an integrated wound management approach by conformable electrochemical devices. Additionally, we explore the challenges, opportunities, and future prospects of soft and stretchable electrochemical biosensors, with the aim of enhancing the efficiency and timeliness of wound management.
Effective individual wound management, particularly in cases of prolonged healing and increased infection vulnerability, has prompted the development of wound theranostics, combining real-time diagnostic assessment and on-demand treatment. We present a multifunctional conducting polymer-based smart theranostic bandage platform that integrates pH sensing, pH-compensated uric acid (UA) biosensing, and on-demand antibiotic release using different conducting polymers, each leveraging their advantageous intrinsic properties. Specifically, the polyaniline-based pH sensor operates reversibly across a broad pH range (4–10), while the functionalized poly(3,4-ethylenedioxythiophene)-based UA biosensor exhibits a linear response up to 0.9 mM UA. Simultaneous detection of pH and UA allows accurate UA determination via pH compensation. Upon detecting abnormal pH/UA levels, the polypyrrole-based drug carrier releases ciprofloxacin via an electrical stimulation (0.6 V), successfully inhibiting bacterial growth in vitro . The array is assembled as a 3D patch, connected to a flexible printed circuit board, and embedded in a wound bandage, offering potentials for remote wound monitoring, targeted treatment, and wireless wound management.
Wound diagnosis and treatment have become massive challenges in health care all
over the world due to multiple causes extending from an aging population, increasing
costs of wound treatments, bacterial resistance to antimicrobials to the growing
occurrence of lifestyle disease like obesity, diabetes, heart diseases, and hyper and
hypo pressure. In addition, the lack of facilities for onsite wound diagnosis and time
delayed biopsy lab tests adds further to the complexities in wound diagnosis and
treatments. In recent times, the innovations and developments in the field of
materials and process engineering enables a paradigm shift in wearable electronics
and computing from a hospital based health care system to a miniaturised wearable
health patch enabling self-health monitoring.
This PhD thesis addresses the development of a flexible and wearable smart wound
dressing utilising the emerging innovative materials formulated into functional inks
and applying printing methods to deposit it on the skin compatible substrates. The
fabrication route is generally identified with low integration density and low response
time of the devices in comparison to clean room based microfabrication, however, the
process viability to fabricate mass volume in ambient room conditions, low cost and
the feasibility to a large variety of substrates and functional materials enabled the
technology ideal for specific health care applications. This Ph.D. thesis is exclusively
dedicated on the fabrication of multiparametric wearable sensor systems for wound
monitoring through different sensing entities such as wound temperature, pH,
exudate and via wound imaging the size and shape. Along with wound monitoring,
optimisation of the healing conditions is highly significant and hence the study has
been extended to wound dressing strain and moisture balance monitoring
functionalities. This work discusses in detail the development of different printed
sensor concepts; the bioimpedance sensor for wearable tomographic imaging;
printed, wearable and highly stretchable dual parameter temperature-strain sensor,
biofluid monitoring sensor on textiles applying thermal and impedance principles and
a wearable textile pH sensor.
Wearable biosensors have attracted considerable attention because of their potential use in real-time monitoring and personalized disease diagnosis. The good deformability and stretchability of flexible electronics enable the elimination of expensive and bulky detection instruments, combination of diagnosis and treatment strategies, modification of traditional clinical practice involving invasive detection methods, and creation of a new platform for personalized wearable medical devices. Using a combination of flexible devices, new sensing mechanisms, and structural design methodologies, continuous physiological health checks can be realized under the premise of noninvasivess; moreover, physiological information obtained from the human body can be transformed into intuitive data and medical staff can realize predictive and objective disease diagnosis. Most of the present reviews have focused on introducing the material composition of flexible sensors. In this study, we initially focus on electronic sensing and subsequently focus on the electronic technology itself. Then, the latest developments associated with flexible and wearable sensing devices are discussed and the sensing of continuous monitoring Is summarized. The mechanism, system structure, typical applications, current challenges, and possible future development associated with the usage of biosensors are presented.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A new wearable electrochemical sensor for monitoring the pH of wounds is introduced. The device is based on the judicious incorporation of a screen-printed pH potentiometric sensor into bandages. The fabrication of this sensor, which uses an electropolymerized polyaniline (PANi) conducting polymer for pH sensing, combines the screen-printing fabrication methodology with all-solid-state potentiometry for implementation of both the reference and the working electrodes. The pH bandage sensor displays a Nernstian response over a physiologically relevant pH range (5.5–8), with a noteworthy selectivity in the presence of physiological levels of most common ions. The bandage-embedded sensor can track pH fluctuations with no apparent carry-over effect. The sensor displays good resiliency against mechanical stress, along with superior repeatability and reproducibility. The in vitro performance of the device was successfully evaluated using buffer solutions emulating the composition of a wound. The novel pH-sensitive bandages facilitate new avenues towards the realization of telemedicine.
Chronic wounds are an important health problem because they are difficult to heal and treatment is often complicated, lengthy and expensive. For a majority of sufferers the most common outcomes are long-term immobility, infection and prolonged hospitalisation. There is therefore an urgent need for effective therapeutics that will enhance ulcer healing and patient quality of life, and will reduce healthcare costs. Studies in our laboratory have revealed elevated levels of purine catabolites in wound fluid from patients with venous leg ulcers. In particular, we have discovered that uric acid is elevated in wound fluid, with higher concentrations correlating with increased wound severity. We have also revealed a corresponding depletion in uric acid precursors, including adenosine. Further, we have revealed that xanthine oxidoreductase, the enzyme that catalyses the production of uric acid, is present at elevated levels in wound fluid. Taken together, these findings provide evidence that xanthine oxidoreductase may have a function in the formation or persistence of chronic wounds. Here we describe the potential function of xanthine oxidoreductase and uric acid accumulation in the wound site, and the effect of xanthine oxidoreductase in potentiating the inflammatory response.
Thin film Carbon Nanotube (CNT) networks are used as a conductive, transparent and flexible electrode for electrochemically depositing a conducting polymer on it, polypyrrole or polyaniline in the present work. We analyse the properties of the device as an electrochemical sensor, measuring his pH dependence by recording the open circuit potential in various buffer solutions, ranging from pH 1 to 13. The results show a good sensitivity, linearity and stability in both cases. In the case of CNT/polyaniline, it can be used simply as an optical sensor, as the colour of polyaniline changes with pH. The CNT/polypyrrole and CNT/polyaniline devices could have applications as solid state gas sensor or biosensor deposited on any shape of surface that can be transparent and flexible. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Carbon loaded polyethylene films were selected as the base substrate for a mechanically flexible and conductive sensing material for use wound monitoring technologies. The films were processed using laser ablation of the surface to increase the effective surface area of the electrode and then subject to an oxidative electrochemical etch to improve the electron transfer kinetics. The surface morphology of the resulting films was analysed and the electrode performance in relation to monitoring uric acid, a key wound biomarker, was optimized. A prototype smart bandage was designed, based on interfacing the mesh to a portable potentiostat, and the response to urate and potential interferences assessed.
The management of chronic wounds has emerged as a major health care challenge during the 21st century consuming, significant portions of health care budgets. Chronic wounds such as diabetic foot ulcers, leg ulcers, and pressure sores have a significant negative impact on the quality of life of affected individuals. Covering wounds with suitable dressings facilitates the healing process and is common practice in wound management plans. However, standard dressings do not provide insights into the status of the wound underneath. Parameters such as moisture, pressure, temperature and pH inside the dressings are indicative of the healing rate, infection, and wound healing phase. But owing to the lack of information available from within the dressings, these are often changed to inspect the wound, disturbing the normal healing process of wounds in addition to causing pain to the patient. Sensors embedded in the dressing would provide clinicians and nurses with important information that would aid in wound care decision making, improve patient comfort, and reduce the frequency of dressing changes. The potential benefits of this enabling technology would be seen in terms of a reduction in hospitalization time and health care cost. Modern sensing technology along with wireless radio frequency communication technology is poised to make significant advances in wound management. This review discusses issues related to the design and implementation of sensor technology and telemetry systems both incorporated in wound dressings to devise an automated wound monitoring technology, and also surveys the literature available on current sensor and wireless telemetry systems. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2013.
