Remote analysis and management of sweat biomarkers using a wearable microfluidic sticker in adult cystic fibrosis patients

Abstract

Sweat parameters such as volume and chloride concentration may offer invaluable clinical insights for people with CF (PwCF). Pilocarpine-induced sweat collection for chloridometry measurement is the gold standard for a CF diagnosis, but this technique is cumbersome and not suitable for remote settings or repeat measurements. We have previously reported the utility of a skin-interfaced microfluidic device (CF Patch) in conjunction with a smartphone image processing platform that enables real-time measurement of sweating rates and sodium chloride loss in laboratory and remote settings. Here, we conducted clinical studies assessing the accuracy of the CF Patch compared to chloridometry when using pilocarpine to induce sweat. We also tested the feasibility and accuracy of exercise-induced sweat chloride measurements in PwCF and healthy volunteers (HV). In the laboratory, using either pilocarpine or exercise to induce sweat, the CF Patch demonstrated strong correlations with sweat chloride measured by pilocarpine-induced chloridometry. In remote settings, exercise-induced sweat chlorides measured using the CF patch were strongly correlated with in-laboratory exercise-induced CF patch sweat chlorides in HV but had a weaker correlation in PwCF. For PwCF on CFTR modulators, there was greater day-to-day variability in sweat chloride compared to HV, which highlights the limitations of assessing CFTR modulator efficacy and pharmacodynamics based on a single in-laboratory chloridometry measurement. Moreover, these findings demonstrate that the CF Patch is suitable as a remote management device capable of measuring serial sweat chloride concentrations and offers the potential of monitoring the efficacy of CF medication regimens but should not replace pilocarpine-based chloridometry for making a CF diagnosis.

Keywords: CFTR modulator pharmacodynamics; cystic fibrosis remote monitoring; exercise-induced sweat chloride; sweat patch colorimetric analysis; wearable microfluidic biosensors.

Fig. 1.

CF Patch. Schematic drawing of the CF patient exercising on treadmill and wearing sweat sensor (CF Patch) on their volar forearm. The CF Patch contains two fluidic channels for i) measuring regional and whole-body sweat loss (orange colored channel) and ii) chloride concentrations (purple colored channel). Color reference markers printed on the CF Patch enable image analysis in different lighting conditions.

Fig. 2.

Flow diagram of the study protocol.

Fig. 3.

Pilocarpine-induced CF Patch sweat chloride correlation versus MSCS chloridometry. People with CF and HV had resting paired pilocarpine-induced sweat chlorides collected, one via a Macroduct for chloridometry and the other via a CF sweat patch. A regression line is shown for the paired sweat chloride concentration measurements for the combined CF and HV cohort (A). The Bland–Altman plot for assessing agreement between the CF sweat patch and chloridometry shows good agreement with limited bias. The dashed line represents the mean difference (bias), and the gray shaded area represents the limits of agreement (mean difference ±1.96 standard deviations). The shaded area denotes the 95% confidence interval for the limits of agreement (B).

Fig. 4.

Exercise-induced CF Patch sweat chloride correlation versus pilocarpine-induced CF Patch sweat chloride. People with CF and HV had sweat collected with the CF patch during constant work exercise, and it was compared to pilocarpine-induced sweat chloride measured by CF patch. The regression line indicates a comparison of sweat chloride concentrations between pilocarpine and exercise for the combined CF and HV cohort (A). The Bland–Altman plot for assessing agreement between the CF sweat patch and chloridometry shows good agreement and almost no bias. The dashed line shows the mean difference (bias), and the gray shaded area represents the limits of agreement (mean difference ±1.96 standard deviations). The shaded area denotes the 95% confidence interval for the limits of agreement (B).

Fig. 5.

Exercise-induced CF Patch sweat chloride correlation versus pilocarpine-induced chloridometry sweat chloride. People with CF and HV had sweat collected with the CF patch during constant work exercise, and it was compared to pilocarpine-induced sweat chloride measured by MSCS chloridometry. Shown is the regression line for the comparison of sweat chlorides between pilocarpine and exercise for the combined CF and HV cohort (A). The Bland–Altman plot for assessing agreement between the CF Patch and chloridometry shows agreement and a small bias. The dashed line shows the mean difference (bias), and the gray area represents the limits of agreement (mean difference ± 1.96 standard deviations) (B).

Fig. 6.

Remote exercise-induced CF Patch sweat chlorides have stronger correlation with exercise laboratory CF sweat chloride in HV than in PwCF. PwCF (Mod = on modulator, No mod = not on a modulator) and HV had sweat chloride assessed sweat during remote exercise sessions, and the mean of these values (A) for each individual was compared to the exercise laboratory sweat chloride collected during constant work exercise. Shown is the regression line for the comparison of sweat chlorides between remote and laboratory exercise for the combined CF and HV cohort (B), and correlation was lower than the laboratory-only comparisons. When examined as separate cohorts, HV had a much stronger correlation than PwCF (C and D).

Fig. 7.

PwCF have greater variability in serial sweat chloride concentrations compared to HV by CF Patch. Each point represents the mean remote exercise sweat chlorides measured by CF Patch for HV and PwCF. We also calculated standard deviations within individuals for remote exercise sweat chlorides and compared HV and PwCF. PwCF had higher mean sweat chlorides and greater standard deviations (*P = 0.005, ^@P = 0.03).