With a surface area of 1.5–2 m2, the skin is the largest organ in the human body, making it more accessible as a diagnostic organ. As a result, it has been used as a matrix for multiple wearable sensing technologies to date. The stratum corneum (SC) is the epidermis’ outer layer, which has a diverse variety of biomarkers as well as a high metabolic activity.
Image Credit: Geinz Angelina/Shutterstock.com
Quantifying the quantities of various biomarkers found in skin fluid matrices, including interstitial fluid (ISF) and perspiration, can reveal important information about a person’s health.
ISF, for example, is being evaluated as a viable alternative to blood for obtaining disease-related systemic biomarkers. ISF contains small chemicals, such as lactate, glucose, cortisol, and urea, and examining their concentrations and flow patterns can reveal details about individual disorders.
Microneedles (MNs) were created recently to extract and collect ISF from the skin. However, since the studies were only conducted on mice, and human participant testing is still needed, this strategy is far from being therapeutically viable.
Sweat is a more easily accessible skin matrix that can be sampled without intrusive procedures. It can provide information about human health in a similar way to ISF by analyzing the biomarkers it carries. The SWEATCH wearable platform, which was built to gather and evaluate salt concentration in sweat in real-time, is a great example of this.
New research expands on the previous study by looking into the wearable sensor’s capacity to reliably detect skin surface pH, as well as the numerous elements that influence the measurement, such as gender, body site, measurement time, and topical skin therapy.
A previously reported methodology was used to make the colorimetric sol-gel solution.
Before usage, 0.5 μL of BCG sol-gel solution were dropped as a single spot onto a 10% acetate cellulose thin-layer chromatography (TLC) plate (3 × 2 cm) and dried in a vacuum desiccator.
The RGB values of the individual spots were measured using ImageJ after the colorimetric sensor was built, scanned, and the RGB values of the individual spots were evaluated. The sensor was glued to the lid of a plastic petri dish (0.04 L) with Blu-Tack to evaluate the reaction of the sensor spots to ammonia.
The wearable platform was composed of a stainless steel woven wire mesh that defined the headspace (4 × 3 cm) and a cellulose substrate with six replicate BCG sensor locations on top.
As illustrated in Figure 1a, the sensor locations were coated with a polyethylene terephthalate (PET) film (5 × 4 cm) and the entire platform was sealed.
Figure 1. (a) Schematic of the different layers comprising the wearable platform applied to the skin surface; (b) image of wearable platform worn on palm; and (c) on the forearm. Image Credit: Shetewi, et al. 2021
This study enlisted ten healthy participants (five females and five males, ages 20–45). On the days of sample collection, volunteers were not allowed to use scents or beauty products on their bodies.
The study’s goal and objective were explained to participants, and they were requested to provide informed written consent.
Scheme 1. Consort diagram showing the flowchart for the different aspects of the participant study. Image Credit: Finnegan, et al., 2022
Results and Discussion
The reaction behavior of sensor spots containing an integrated pH-sensitive dye as sensor spots worn just above the surface of the skin aiming for skin volatile emission, with the purpose of employing it to detect skin surface pH, was explored in this study.
To evaluate the dyes sensitivity to variations in pH over the necessary range, a test of the colorimetric response of produced BCG sol-gel solutions was carried out, as shown in Figure 2a.
Figure 2. (a) Image of BCG sol-gel solutions across the pH range 2.5–6.9, and (b) graph showing average ED response as a function of mass of ammonia (mg) added to the HS that the sensor was exposed to. Error bars represent standard deviation in ED response from n = 6 sensor spots on a single substrate. Image Credit: Finnegan, et al., 2022
As illustrated in Figure 2b, a quantitative ammonia calibration plot was created based on sensor ED response, in connection with ED response detected up to a mass of approximately 2.5 mg ammonia.
Figure 3a illustrates the average color of the BCG sensor spots after being worn on the skin by five different female and five different male subjects with various skin surface pHs.
Figure 3. (a) Reproduced average ED color response from wearable platform (6 replicate BCG sensor spots) after being worn on 5 females and 5 males (left palm, 5 h); the corresponding skin surface pHs as measured by a calibrated ISE (bold text) and estimated ammonia flux in mg h−1 cm−2 (italicised text in parenthesis) also given. (b) ED value from (a) plotted as a function of skin surface pH. Error bars represent standard deviation in ED response from n = 6 sensor spots within a single wearable platform. Note: See SI Table 1 for tabulated data. Image Credit: Finnegan, et al., 2022
Single participant information was analyzed on numerous days to evaluate the impact of inter-person variation on sensor response. Figure 4 shows that ED interacts with pH as predicted and that the connection between ED response and skin surface pH for a single participant is substantially higher than in Figure 3, which plotted data from numerous individuals against skin surface pH.
Figure 4. Average ED response from wearable platform (6 replicate BCG sensor spots) after being worn on Female 1 and Female 2 for 5 hours (left palm used for sampling) plotted against skin surface pH (measured using a calibrated ISE). Error bars represent standard deviation in ED response from n = 6 sensor spots within a single wearable platform. Image Credit: Finnegan, et al., 2022
The pH of the skin surface did not change during the measuring period (Figure 5 a-d), showing that the ammonia emission flow from the skin stayed stable over the time period studied.
Figure 5. Average ED color response from wearable platform (6 replicate BCG sensor spots) over time on one female and one male participant and corresponding skin surface pH values for (a) palm, (b) foot, (c) abdomen and (d) forehead. Error bars represent standard deviation in ED response from n = 6 sensor spots within a single wearable platform. Image Credit: Finnegan, et al., 2022
The wearable platform was worn constantly on the palm for different set lengths of time up to 270 minutes to explore sensor spot response over time for periods of constant wear, and the sensor spots were scanned in the normal manner, as shown in Figure 6.
Figure 6. Average ED color response from wearable platform (6 replicate BCG sensor spots) worn for different periods of time by a single participant, (female; left palm; average skin surface pH = 4.82 ± 0.05). Error bars represent standard deviation in ED response from n = 6 sensor spots within a single wearable platform. Image Credit: Finnegan, et al., 2022
To understand the sensitivity and connection of sensor in response to skin surface pH values, a larger number of sensors were worn by a single person over numerous days for varying wear times to help comprehend the time dependence on the sensor spot ED response.
Table 1. 1-D linear regression parameters for regression lines fitted to ED color response as a function of skin surface pH for wearable platforms (6 replicate BCG sensor spots) worn by a single participant collected for continuous sampling times between 30 and 270 minutes. Source: Finnegan, et al., 2022
|Skin surface pH range
||No. of measurements
||Average ED response
Note: see SI Fig. 5 for ED data and 1-D linear regression analysis of data.
Figure 7 depicts the sensor spots’ color changes after every treatment, as well as the ED response shown as a function of skin surface pH after treatment.
Figure 7. Average ED color response from wearable platform (6 replicate BCG sensor spots) worn for different periods of time by a single participant, (female; left palm; average skin surface pH = 4.82 ± 0.05). Error bars represent standard deviation in ED response from n = 6 sensor spots within a single wearable platform. Image Credit: Finnegan, et al., 2022
In a healthy participant investigation, the use of a simple wearable platform with pH-responsive sensor spots for measuring skin surface pH via volatile ammonia emission from the skin was described.
The findings show that wearable colorimetric sensor platforms may be utilized to precisely monitor target elements of skin volatile emission, and that they are a reasonable alternative to skin fluid collection and examination.
This investigation also highlights problems connected with the technique, such as inter-person heterogeneity in the sensor ED response. Also, the effects of wearables obstructing the skin must be considered, as this might cause the skin to sweat, possibly interfering with sensor response.
In the future, the advancement of simple color-based wearable sensing techniques could be useful in individualized general medical screening as well as self-management of chronic diseases linked with volatile biomarkers.
Finnegan, M., Duffy, E., Morrin, A. (2022) The determination of skin surface pH via the skin volatile emission using wearable colorimetric sensors. Sensing and Bio-Sensing Research, p. 100473. Available Online: https://www.sciencedirect.com/science/article/pii/S2214180422000022.
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