An epidermal serine sensing system for skin healthcare

Abstract

Portable biosensors mainly focus on detecting biomarkers in biofluids but neglect the abundant skin biomarkers on the stratum corneum, which are associated with the functionality and integrity of the skin barrier. Here, we propose a sensing patch designed for direct sampling and in situ quantification of epidermal serine, an important biomarker for skin healthcare. The patch consists of a porous hydrogel for serine diffusion and ion conduction, and a molecular imprinted polymer-based electrochemical serine sensor. By integrating with a customized handheld serine tester, the serine sensing system enables in situ measurement of epidermal serine levels. We demonstrate the application of this serine sensing system in assessing the moisturizing effect of a skincare product and tracking the recovery progress of skin barrier function in a patient with atopic dermatitis. Our work opens up a potential application scenario for portable biosensors in personalized skin healthcare.

Fig. 1. Design and operation of the epidermal serine sensing system.

a Schematic of the wearable serine sensing patch. b Dissolution and diffusion process of epidermal serine after the patch attachment to the skin. The inset shows the serine leaving keratinocytes by passive transport. c Schematic diagram of serine measurement by the serine sensor in the hydrogel matrix, the left illustration shows the concentration distribution of serine in the stratum corneum and hydrogel. d Comparison of serine levels in the lesion area and normal area of an AD patient before and after three weeks of topical medication treatment. e Operation steps of the serine sensing system for epidermal serine detection and construction of the customized handheld serine tester consisting of an internal main control board, a display screen, a patch port, a rechargeable lithium battery, and buttons. f Comparison between the serine sensing system proposed in this article and traditional methods for skin biomarkers evaluation.

Fig. 2. Characterization of MIP-Based Serine Sensors.

a Synthesis and detection mechanism of the MIP-based serine sensor. b Optimization of the incubation time prior to serine sensing in 0.1 M KCl. 5 minutes of incubation was determined to be the most efficient and accurate incubation time for the serine to interact with the MIP electrode. c Electrochemical response of the MIP sensor to different serine concentrations in 0.1 M KCl and the corresponding calibration plot. The line represents the fitted trendline. Data are presented as mean values ± standard deviation (SD) from three electrodes. d Responses of the MIP serine sensor to different epidermal analytes (including phenylalanine, tyrosine, glycine, histidine, uric acid, lactic acid, glucose, and urea). The serine sensor shows insignificant response to these analytes, while it shows a clear response after the addition of serine. e EIS responses of a MIP-based electrode before and after binding with serine. f Electrochemical responses of the serine sensing patch to different serine concentrations in the porous PVA hydrogel containing 0.1 M KCl, and the corresponding calibration plot. The line represents the fitted trendline. Data are presented as mean values ± SD from three electrodes. g Responses of the serine sensing patch to different serine concentrations at different temperatures (25 °C and 37 °C) in porous PVA hydrogel containing 0.1 M KCl.

Fig. 3. Serine sensing system for assessing moisturizing effect of skincare products.

a Sensor-measured serine levels versus corresponding standard readouts in their hydrogels by a commercial serine colorimetric assay kit (n = 8 subjects). Pearson correlation coefficient, r = 0.82, Coefficient of determination, R² = 0.67. b Serine levels, SCHs, and TEWLs of the forearm skin of a subject moisturized with and without essence application (Blank skin and Moisturized skin). Six measurements were conducted using the serine sensing system and GPSkin Barrier® for repeatability verification. SCH and TEWL units are ‘%’ and ‘g/m²/h’, respectively. Data are presented as mean values ± SD. c Photographs of a subject wearing the serine sensing patch on the left inner forearm. Detection results display on the handheld serine tester screen before and after essence application. d Changes in epidermal serine levels in 7 subjects after applying the essence. e Corresponding box-and-whisker plot of epidermal serine levels before and after essence application (n = 7). The difference is statistically significant (**P < 0.01, P = 0.003). The box ends represent the 25th and 75th percentiles. The horizontal line represents the median. The upper and lower whiskers represent the maxima and minima, respectively. f Correlation of sensor-measured serine levels and TEWLs obtained by the commercial instrument. r = −0.72. R² = 0.52. g Sensor-measured serine levels across different body parts (n = 6 subjects). The differences in epidermal serine levels are statistically significant between the forearm and forehead (**P < 0.01, P = 0.002), and between the forearm and back of hand (*P < 0.05, P = 0.033), but not statistically significant (ns) between the back of hand and forehead (P > 0.05, P = 0.682). Data are presented as mean values ± SD. h Sensor-measured serine levels versus corresponding standard readouts in the tape-stripping samples by the commercial serine colorimetric assay kit (n = 8 locations). r = 0.71. R² = 0.50. Inset: the schematic diagram of the tape-stripping method. All statistical analyses were performed using two-tailed paired t-tests. Lines in a, f, and h represent fitted trendlines.

Fig. 4. Serine sensing System for tracking treatment of a patient with AD.

a Filaggrin gene mutation in the pathogenesis of AD. b Photographs of the AD patient using the system to measure the epidermal serine level after his lesion skin area recovered. c Optical images and corresponding magnified photographs of lesion areas in the AD patient at different stages of treatment. Erythema and flakes are highlighted in these images. d Sensor-measured response currents in the lesion and normal areas. e Histogram of epidermal serine levels in the lesion and normal areas at different medication timepoints. f Epidermal serine levels measured by the system versus AAs obtained by a commercial colorimetric assay kit. The line represents the linear-fitted trendline.