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Pusta, A.; Tertiş, M.; Mirel, S. Wearable Sensors for Wound Infection Biomarkers Detection. Encyclopedia. Available online: https://encyclopedia.pub/entry/17964 (accessed on 17 May 2024).
Pusta A, Tertiş M, Mirel S. Wearable Sensors for Wound Infection Biomarkers Detection. Encyclopedia. Available at: https://encyclopedia.pub/entry/17964. Accessed May 17, 2024.
Pusta, Alexandra, Mihaela Tertiş, Simona Mirel. "Wearable Sensors for Wound Infection Biomarkers Detection" Encyclopedia, https://encyclopedia.pub/entry/17964 (accessed May 17, 2024).
Pusta, A., Tertiş, M., & Mirel, S. (2022, January 10). Wearable Sensors for Wound Infection Biomarkers Detection. In Encyclopedia. https://encyclopedia.pub/entry/17964
Pusta, Alexandra, et al. "Wearable Sensors for Wound Infection Biomarkers Detection." Encyclopedia. Web. 10 January, 2022.
Wearable Sensors for Wound Infection Biomarkers Detection
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This entry is adapted from the peer-reviewed paper 10.3390/bios12010001


Infection represents a major complication that can affect wound healing in any type of wound, especially in chronic ones. There are currently certain limitations to the methods that are used for establishing a clinical diagnosis of wound infection. Thus, new, rapid and easy-to-use strategies for wound infection diagnosis need to be developed. To this aim, wearable sensors for infection diagnosis have been recently developed. These sensors are incorporated into the wound dressings that are used to treat and protect the wound, and are able to detect certain biomarkers that can be correlated with the presence of wound infection. Among these biomarkers, the most commonly used ones are pH and uric acid, but a plethora of others (lactic acid, oxygenation, inflammatory mediators, bacteria metabolites or bacteria) have also been detected using wearable sensors.

wearable biosensors wearable sensors wound infection biomarker electrochemical colorimetric

1. Introduction

Infection represents a major complication of both acute and chronic wounds, with a negative impact on wound healing, patient quality of life and economic resources [1][2]. Although the overall impact of wound infection is difficult to assess, it is estimated that surgical site infections in the UK alone affect 3–4% of surgery patients, cost an average €5800 per patient and cause an average mortality rate of 5% [3]. A retrospective study from 2018 in the USA indicated that around 8.2 million people suffered from infected or non-infected wounds. The highest costs of treatment were associated with surgical wounds and chronic foot ulcers. Due to factors such as an aging population and the rising incidence of diabetes and obesity, chronic wounds represent an increasingly problematic aspect of wound management [2]. In this context, it is vital to diagnose wound infection as early as possible in order to ensure the best treatment course for the patient. Currently used diagnostic methods are represented by clinical inspection and microbiological assays [4][5][6]. Despite being routinely used, these methods present several disadvantages such as inaccuracy, need for traumatic bandage removal and reliance on the physician’s expertise in the case of clinical examination. A few limitations of microbiological assays are long analysis times, invasive techniques in the case of microbiological assays carried out on biopsy tissue and failure to identify bacteria invading deep tissues in the case of swab cultures [4].
An alternative infection diagnosis method is the detection of certain biomarkers in the wound environment. In order to increase patient comfort and eliminate the possibly traumatic bandage removal process for clinical inspection, an ideal way of biomarker monitoring is the inclusion of wearable sensors for infection biomarkers in wound dressings. Numerous proof-of-concept examples of such sensors have been recently published, although, to date, none of these approaches has been clinically implemented on a large scale due to certain limitations. The development of wearable devices is faced with numerous challenges in respect to the materials used, energy sources and data transmission [5]. The incorporated materials need to be biocompatible and tailored so that they can conform to the curvilinear surface of the skin [5][6]. Moreover, they need to be flexible and resistant in order to ensure the user’s free movement [7]. Energy sources such as batteries are difficult to miniaturize and incorporate into wearable devices [6], but are indispensable for their operation and proper functioning, so it is necessary to find a solution to solve this inconvenience. Numerous challenges are also posed by designing appropriate and safe ways of wireless communication between the sensor and devices such as laptops and smartphones [5][7]. Such technologies are currently represented by Bluetooth [5][8], Near-Field-Communication (NFC) [9][10][11] and radio-frequency identification (RFID) [9][11]. Despite all these challenges, the development of sensors for point-of-care (POC) applications is a promising direction for the field of analytical techniques. The advent of wearable commercial devices for biological parameters (heart rate, blood pressure, movement) foreshadows the vital role wearable devices will play in personalized medicine.

2. Sensors for Wound Infection Biomarkers

Electrochemical, colorimetric and fluorimetric wearable sensors for wound infection biomarker monitoring are presented comparatively in Table 1 and Table 2.

2.1. Electrochemical Sensors

Chemical sensors were defined by The International Union of Pure and Applied Chemistry (IUPAC) as devices that provide the transformation of chemical response such as the concentration of a specific sample component, into an analytically useful signal which can be observed or recorded and used to detect the presence of the analyte in unknown samples [12]. Two individual but interdependent functional units are contained in a typical chemical sensor: a receptor and a transducer [12]. The receptor consists of either biomimetic elements such as aptamers, nanozymes or molecularly imprinted polymers (MIPs) [13] or biocomponents such as enzymes and antibodies in which case we have a biosensor [14]. Regardless of its nature, the role of the receptor is to transform the analyte concentration into a chemical or physical signal with a well established sensitivity and to provide high selectivity towards the target molecule in the presence of potentially interfering compounds [12]. The second functional unit of a chemical sensor is the physio-chemical transducer. Depending on the type of transducer, sensors can be classified as optical, calorimetric, piezoelectric and electrochemical [15][16].
Electrochemical sensors have the advantage of sensitivity, an important feature of electroanalytical methods, that can be combined with the selectivity of the receptor. In the case of electrochemical biosensors, the biocomponent recognizes its complementary analyte resulting in a catalytic or binding event that ultimately produces an electrical signal that is proportional to the analyte concentration and that can be monitored by the transducer [17]. Numerous applications have been tested for electrochemical sensors and biosensors in biomedical [18][19][20], environmental [20][21][22], industrial [20], and agricultural [23] applications. The sensitivity of the electrochemical sensors and biosensors can be greatly improved by using different nanomaterials such as graphene [24], carbon nanotubes, MXenes and metal nanoparticles [25]. Since nanomaterials represent a key element in the development of electrochemical wearable sensors, a quick overview of the most important types of nanomaterials employed in their fabrication will be briefly presented. Numerous extensive reviews [26][27][28][29][30] exist on this topic, so only the essential aspects will be detailed herein. Graphene is a two-dimensional nanomaterial composed of sp2 bonded carbon atoms, which displays remarkable properties like high surface area and excellent electrical and thermal conductivity [31][32][33]. Due to these properties, graphene is a widely used nanomaterial in countless sensor applications [31][32], including in the development of wearable sensors for wound infection biomarker monitoring [34]. Single-walled carbon nanotubes (SWCNT) are another type of carbon-based nanomaterial employed for sensor applications. They are considered a one-dimensional form of carbon that is formed by ‘rolling’ graphene into a cylindrical structure [33][35]. They present good chemical stability, strength and electrochemical conductivity. SWCNT were employed for electrode modification for the detection of lactate in order to increase electrode surface area and thus to increase sensitivity [36]. MXenes are a novel class of two-dimensional conductive nanomaterials, comprised of carbides, nitrides or carbonitrides of early transition metals. They present several properties which make them attractive for the design of wearable sensors. They are highly flexible and combine the high electrical conductivity of transition metals with the hydrophilic properties of their outer layer [37][38].
The wide diversity of nanomaterials that can be employed in the fabrication of electrochemical sensors, as well as the inherent advantages of electrochemical sensors have qualified them for applications in numerous fields, including wound monitoring.
Table 1. Examples of electrochemical wearable and disposable sensors for wound infection biomarker monitoring.
Detection Analyte Method Linear Range LOD Matrix Wireless Data Transfer Ref
AMP UA C-SPE/PB/uricase/Chi on wound dressing 100–800 μM NS PBS RFID, NFC [9]
AMP UA Embroided ink coated/uricase thread (on gauze) 0–800 μM NS Simulated wound fluid - [37]
POT pH C/PANI on Ecoflex substrate 4–10 - Standard pH buffer solutions, emulated wounds - [39]
POT pH ITOE/PANI, can be attached to bandage + NFC probe 4–10 - Emulated wound and emulate infected wound NFC [10]
POT pH C-SPE/PANI on PET film, attached to commercial transparent tape 4–10 - Standard pH buffer solutions Bluetooth [8]
POT pH C electrode on commercial bandage 2–13 - Acidic and alkaline solutions Using 2.4 GHz ISM band [40]
EIS pH Screen-printed CuO NR on IDE 5–8.5 - Buffer solution, DMEM - [41]
SWV pH Riboflavin/LIG/polyimide 2–8 - Buffer solution - [42]
AMP UA Screen-printed carbon/uricase on omniphobic paper 0.22–0.75 mM 0.2 mM PBS Using 2.4 GHz ISM band [43]
EIS pH 5.5–8.5 - Standard pH buffer solutions
DPV pH LGG/MXene/PANI 4–9 - Artificial wound exudate - [44]
AMP UA LGG/MXene/uricase 50–1200 μM 50 μM Artificial wound exudate -
SWV UA CNT/PA 100–1000 μM NS Simulated wound fluid - [45]
Pyo 0.10–100 μM 0.1 μM Simulated wound fluid, bacteria culture media
SWV UA CUA 100–700 μM 1 ± 0.4 μM PBS, simulated wound fluid - [46]
Pyo 1–250 μM 1 ± 0.5 μM PBS, Simulated wound fluid, bacteria culture
Nitric oxide 1–100 μM 0.2 μM PBS, simulated wound fluid, eukaryotic cell culture
AMP Oxygen AuE/Nafion/PDMS on wound dressing 58.5–178 [O2]% NS PBS - [36]
AMP Lactate AuE/PB/SWCNT/Chi/LO/SWCNT/Chi on wound dressing 0.1–0.5 mM PBS -
SWV TNF-α AuE/AuNPs-GP/Apt-MB 0–2 ng/mL NS Spiked serum, mice wounds, wound exudate Bluetooth [34]
IL-6 0–30 ng/mL
IL-8 0–30 ng/mL
TGF-β1 0–150 pg/mL
Staph. aureus 0–1 × 109 CFU
pH PANI/AuE 4–9
AMP—amperometry; POT—potentiometric; UA—uric acid; C-SPE—carbon screen-printed electrodes; PB—prussian blue; Chi—chitosan; NS—not specified; PBS—phosphate buffer saline; RFID—radio frequency identification; NFC—Near-Field Communication; PANi-EB—polyaniline emeraldine base; PANI—polyaniline; ITOE—indium tin oxide electrode; PET—polyethyleneterephtalate; EIS—electrochemical impedance spectroscopy; NR—nanorods; IDE—interdigitated electrodes; DMEM—Dulbecco’s Modified Eagle Medium; SWV—squarewave voltammetry; LIG—laser-induced graphene; DPV—differential pulse voltammetry; LGG—laser guided graphene; Pyo—pyocyanin; CNT—carbon nanotube; PA—polyacrylamide; CUA—carbon ultramicroelectrode arrays; AuE—gold electrode; PDMS—polydimethylsiloxane; SWCNT—single-walled carbon nanotubes; LO—lactate oxidase; TNF-α—tumor necrosis factor α; IL-6—interleukin 6; IL-8—interleukin 8; TGF-β1—transforming growth factor-β1; AuNPs-GP—gold nanoparticles graphene nanocomposite; Apt—aptamer; MB—methylene blue; CFU—colony forming units.

 
 
 
Table 2. Examples of colorimetric and fluorimetric wearable and disposable sensors for wound infection biomarker monitoring.
Detection Analyte Method Linear Range LOD Matrix Wireless Data Transfer Ref
COL pH pH indicator dye embedded in hydrogel wound dressing + optoelectronic probe 6.4–8.4 - Standard pH buffer solutions RFID, NFC [11]
COL pH pH indicator dye embedded in alginate microfibers 6.2–8.2 - Agarose and standard pH solutions on pig skin Smartphone photo [47]
COL pH Curcumin embedded in PCL fibers 6–9 - Standard pH buffer solutions Smartphone photo [48]
COL + FL pH O-QDs on commercial medical cotton cloth 5–9 - PBS - [49]
COL Bacteria MB embedded in PVA/CMC NS NS Bacteria suspension - [50]
FL Bacteria Florescent dye vesicles embedded in GelMA NS NS Mice wounds - [51]
FL H2O2 Eu CP/PAN fiber mats 20–200 μM NS Standard solutions, animal wounds - [52]
FL O2 Ru(dpp)3Cl2/paper 5–26 ppm NS Oxygenated water, mice wounds - [53]
COL—colorimetric; RFID—radiofrequency identification; NFC—Near-Field Communication; PCL—polycaprolactone; FL—fluorimetric; O-QD—orange-emitting quantum dots; MB—methylene blue; PVA—polyvinyl alcohol; CMC—carboxymethylcelulose; NS—not specified; GelMA—methacrylated gelatin; Eu CP—Europium coordination polymers; PAN—polyacrylonitrile; Ru(dpp)3Cl2—Tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride.
 

 

3. Perspectives and Conclusions

In the last years, technology and smart devices have rapidly become an integrated part of our everyday lives. Sensors for biological parameters such as gait, pulse or blood pressure have already been incorporated into smartphones and commercial wearable devices. In this context, it is natural to expect that wearable and smart sensors will start playing a crucial role in the future of personalized medicine. The field of wound infection diagnosis and monitoring makes no exception to this general trend. By measuring the changes in different biomarkers present in the wound milieu, wearable sensors for wound infection represent the next generation of devices that could be used in the future for a more rapid and accurate diagnosis of infected wounds.
The development of wearable sensors for wound infection biomarker monitoring can provide numerous advantages both for the patient and for healthcare personnel. Constant monitoring of wound environment changes can increase patient comfort and compliance by reducing the need for traumatic bandage removal for wound inspection. By reducing disruption to the wound healing process, this will also facilitate a quicker healing of the wound.
In order to successfully implement wearable sensors for wound monitoring, it is vital to ensure certain characteristics of the sensors, such as high sensitivity, biocompatibility, stability, as well as autonomous functioning and wireless data transmission. The integration of nanomaterials such as carbon-based or metal-based nanoparticles can help increase sensor surface and sensitivity but their use is still controversial, since no relevant information about their long term toxicity and biocompatibility exist for the moment. In the future, research needs to focus on the development of fully autonomous sensors, that ensure wireless data transfer and can function without the need for non-portable devices. This will ensure increased compliance and feasibility of the developed devices. There are currently several limitations regarding the miniaturization of potentiostats, optic probes or batteries that are required for sensor functioning, but consistent effort is being made in order to overcome these challenges. There are already promising examples of autonomous sensors in the literature as well as examples of sensors that can be improved to reach these desired goals.
In order for wearable sensors to be used on a large scale, they need to be intuitive to use and to offer results that are easy to read and interpret. In this context, the integration of smartphones with specially designed applications in sensor use is of great interest. Examples of devices that can yield a result by simply taking a photograph of the sensor or that can offer a naked-eye estimation of different parameters are especially promising for the field of wound infection biomarker monitoring.
Another direction that needs to be taken into consideration in the future is the combination between diagnostic and treatment strategies into the same ‘smart dressing’. Wound dressings that release medicine depending on the concentration of biomarkers present in the wound milieu are of great interest due to their capacity of delivering the substance at exactly the right time.
In conclusion, this contribution presents the latest advances in the field of wearable and disposable sensors for wound infection biomarker monitoring. Some recent examples of wearable and disposable sensors from the literature have been discussed comparatively in Tables 1 and Table 2. 

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Subjects: Electrochemistry
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Alexandra Pusta
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Mihaela Tertiş
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Simona Mirel
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Entry Collection: Biopharmaceuticals Technology
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Update Date: 10 Jan 2022
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