Smart Bandage for Wound Status

Overview

• A smart bandage uses wireless connectivity for uric acid (UA) biosensing to indicate wound status

Introduction

• Approximately 2% of individuals in the developed world experience a chronic wound in their lives
• A chronic venous leg ulcer affects 15% of individuals over 70 years old worldwide
• The United States spends $25 billion annually on chronic wound care
• Wound management creates social and financial strain, with outpatient services heavily burdened due to treatment costs
• Cost reduction strategies focus on reducing dressing change frequency
• Advanced technologies and smart bandages are needed to monitor wound status parameters and communicate effectively
• Smart bandages aid in shifting chronic wound care to personalized and knowledge-based treatments

Sensor Research

• Sensor research in wound monitoring focuses on indicators like temperature, moisture, pH, oxygen levels and bacterial presence
• The concentration of uric acid (UA) in wound exudate correlates with wound severity and bacterial infection
• Uric acid is highly specific to wound status and is a key biomarker of research
• Electrochemical UA detection has been described previously using square wave voltammetry on a carbon fiber mesh electrode
• Effective data communication through wireless or non-contact methods is essential for smart bandage adoption and usability

Development

• The novel amperometric bandage-based UA biosensing system described uses non-contact wireless connectivity
• Fabrication involves screen-printing a Prussian blue (PB) modified carbon electrodes with immobilized uricase on a commercial bandage
• Uricase oxidizes uric acid and the PB-carbon electrode reduces the hydrogen peroxide product and enables UA detection
• A novel potentiostat was developed specifically for mobile and wearable biosensors with integral wireless capability
• The potentiostat measures and stores the biosensor current output in proportion to UA concentration and wirelessly transfers data via radio frequency identification (RFID) or near-field communication (NFC)

Materials and Methods

• Uricase from Candida, bovine serum albumin (BSA), glutaraldehyde solution (8%), and chitosan are used in sensor fabrication.
• Uric acid, creatinine, D-(+)-glucose, L-(+)-lactic acid, L-ascorbic acid, and 0.1 M phosphate-buffered saline, pH7 (PBS), prepared from K2HPO4 and KH2PO4, are used in characterization experiments.
• Electrochemical characterization is performed with CH Instruments (Austin, TX) 440 electrochemical analyzer and the wearable potentiostat.

Smart Bandage Fabrication

• Smart bandage biosensors are fabricated by screen printing.
• First, a transparent insulator layer is printed on bandages and cured at 120 °C for 20 min.
• Subsequent printing steps fabricate an Ag/AgCl pseudo-reference electrode and PB-carbon working and counter electrodes.
• A final insulator layer is printed and cured to coat conductive tracks and define the working electrode area.
• The working electrode is functionalized by drop casting a solution of BSA, glutaraldehyde, and uricase in PBS before being coated with chitosan solution.

Sensor Characterization Experiments

• In vitro experiments were performed by dispensing 200 μL of phosphate-buffered saline onto the sensing area of the bandage.
• Smart bandages were connected to the electrochemical analyzer or wearable potentiostat with microclip connectors.
• Chronoamperometric measurements were made at −0.3 V vs. Ag/AgCl, based on cyclic voltammetry of the PB-carbon transducer.
• The wearable potentiostat collected data at a sample rate of 0.80 s−1
• Redox current values were digitized, stored and transmitted to a computer fitted with a desktop RFID reader.
• Chronoamperograms were plotted on the computer in MS-Excel, with steady-state current taken as the average of 10 data points recorded around t = 60s.

Smart Bandage Design

• The new UA biosensor was fabricated by screen printing directly onto the fabric of a bandage, followed by functionalization of the working electrode

Results

• The biosensor exhibits excellent linearity, sensitivity, selectivity, operational stability, and robustness evaluated through in vitro experiments in PBS

Response to Uric Acid

• The current response of the smart bandage biosensor to 100–800 μM UA was determined using the CHI 440 electrochemical analyzer and the wearable potentiostat
• Uric acid concentration in wound fluid varies between approximately 220 and 750 μM
• The sensitivity coefficient (SC) of the biosensor was -2.4 nA/μM UA with both instruments
• The UA biosensor exhibits excellent linearity over the full physiological concentration range independent of the instrument and excellent agreement between the two instruments
• The repeatability of the smart bandage when performing repeat serial calibrations on the same sensor was −2.39 ± 0.04 ηΑ/μΜ (1.85% RSD, n = 3)

Selectivity

• The UA sensor operates at a very low negative working potential (Ewrk = − 0.3 V), virtually eliminating interference from other easily oxidized species found in wound fluid.
• Urate oxidase makes the biosensor highly specific to UA and the PB-carbon electrode has a catalytic action on the hydrogen peroxide product of the uric acid oxidation.
• The sensor was tested in the presence of common electroactive species at physiological concentrations and the interferents had no significant effect on the UA current signal, less than 3% compared to a 400 μM UA standard.

Stability

• The stability of the smart bandage sensor was assessed by measuring the response to a 400 μM UA standard repeatedly every 15 min over a period of 8 hours.
• Measurements with the wireless potentiostat were taken at 15 min intervals, and the UA solution was replenished 1 min prior to each measurement to simulate a dynamic wound environment.
• Insignificant variation of the current signal was observed over the repeated measurements (ranging between 95% and 102% of the original response and the stability is attributed to tight glutar-aldehyde cross-linking of the enzyme with the BSA stabilizer and the protective chitosan layer

Impact of Mechanical Deformation

• The impact of mechanical deformation on current response of the UA biosensor was tested by folding/releasing the bandage 80 times through 180°
• Repeated bending stress was not found to have a significant affect on the electrochemical response of the smart bandage biosensor (RSD = 5.60%)

Conclusion

• A wireless smart bandage biosensor for uric acid (UA) was developed
• This electrochemical UA biosensor shows analytical performance in terms of sensitivity, selectivity, operational stability, and robustness
• The low-cost screen-printing process developed to fabricate PB-carbon electrodes directly is combined with the custom designed wearable potentiostat and wireless electronics for determining UA status
• This is an important step for smart bandage technology in chronic wound care and will be deployed in outpatient and homecare settings to inform wound status
• The biosensor for UA can provide status data to inform clinical intervention
• Transferring data to a healthcare service provider would empower the patient and lead to informed treatment decisions, and potentially reduce the number of unnecessary dressing changes and improve patient care quality