Proteomic Characterization of Dermal Interstitial Fluid Extracted Using a Novel Microneedle-Assisted Technique

As wearable fitness devices have gained commercial acceptance, interest in real-time monitoring of an individual’s physiological status using noninvasive techniques has grown. Microneedles have been proposed as a minimally invasive technique for sampling the dermal interstitial fluid (ISF) for clinical monitoring and diagnosis, but little is known about its composition. In this study, a novel microneedle array was used to collect dermal ISF from three healthy human donors and compared with matching serum and plasma samples. Using a shotgun quantitative proteomic approach, 407 proteins were quantified with at least one unique peptide, and of those, 135 proteins were differently expressed at least 2-fold. Collectively, these proteins tended to originate from the cytoplasm, membrane bound vesicles, and extracellular vesicular exosomes. Proteomic analysis confirmed previously published work that indicates that ISF is highly similar to both plasma and serum. In this study, less than one percent of proteins were uniquely identified in ISF. Taken together, ISF could serve as a minimally invasive alternative for blood-derived fluids with potential for real-time monitoring applications

Estimated proportions of Vietnamese people meeting WHO recommendations, and average time spent on physical activity (MET-hours/week) by all persons, and mean time sitting (hours/day).

<p>Mean (standard errors, SE) estimated with a shifted Box-Cox power transformation.</p><p>Estimated proportions of Vietnamese people meeting WHO recommendations, and average time spent on physical activity (MET-hours/week) by all persons, and mean time sitting (hours/day).</p

Frequency of errors (item non-response and implausible or improbable responses) in reporting physical activity with the WHO GPAQ questionnaire (N = 14706).

<p>* Number of item non-responses.</p><p>† Cumulative number of different respondents.</p><p>‡ Reported physical activity ˃112 hours per week (7 days × 16 hours/day), in near accordance with Global Physical Activity Questionnaire Analysis Guide.</p><p>§ Number of item non-responses and implausible values.</p><p>¶ Number of item non-responses, implausible values and improbable values.</p><p>**Energy expenditure from reported activity > average energy intake per day of Vietnamese people (2100 kcal).</p><p>Frequency of errors (item non-response and implausible or improbable responses) in reporting physical activity with the WHO GPAQ questionnaire (N = 14706).</p

Characteristics of subjects^*.

<p>* The data presented are mean (standard error, SE) estimated with a shifted Box-Cox power transformation, or weighted percentage (unweighted number in this category/unweighted total number).</p><p>† Monthly household income (per adult member).</p><p>Characteristics of subjects<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140941#t001fn001" target="_blank">^*</a>.</p

Estimates of self-reported time spent on physical activity (MET-hours/week) made with alternative approaches to reducing the influence of improbably and/or implausibly large values.

<p>* Mean (standard error, SE) estimated by the Hansen-Hurwitz estimator for cluster survey designs with clusters sampled with unequal probabilities and with replacement.</p><p>† Median (interquartile range).</p><p>‡ Summary values estimated with a shifted Box-Cox transformation.</p><p>§ Top 5% and bottom 5% distribution set to missing, and non-missing data reweighted.</p><p>¶ Top 5% and bottom 5% of distribution reset to 95^th and 5^th percentiles respectively.</p><p>** Total hours per week reset to 7×16 hours if in excess of 7×16 hours (this allows a person to work more than 16 hours per day on some days of the week) with proportional allocation across sub-domains.</p><p>†† Total transport, total moderate–intensity activity (work and leisure) and total vigorous-intensity activity (work and leisure) per week each reset to 7×3 hours if in excess of 7×3 hours, with proportionate reductions across work and leisure domains.</p><p>‡‡ Reported values set to the level of physical activity requiring energy expenditure of 2100 kcal/day.</p><p>Estimates of self-reported time spent on physical activity (MET-hours/week) made with alternative approaches to reducing the influence of improbably and/or implausibly large values.</p

Characteristics of survey participants.

<p>Characteristics of survey participants.</p

Estimated proportions of the Vietnamese population meeting the WHO recommendation of achieving at least 600 MET-minutes of activity per week (low), at least 600 MET-minutes but not 3000 MET-minutes per week (moderate), or at least 3000 MET-minutes per week (high level of activity).

<p>Estimated proportions of the Vietnamese population meeting the WHO recommendation of achieving at least 600 MET-minutes of activity per week (low), at least 600 MET-minutes but not 3000 MET-minutes per week (moderate), or at least 3000 MET-minutes per week (high level of activity).</p

Mean values of systolic BP, diastolic BP, glucose and total cholesterol cross-classified in categories of BMI and WC.

<p>Mean values of systolic BP, diastolic BP, glucose and total cholesterol cross-classified in categories of BMI and WC.</p

AUC for discrimination of hypertension, elevated glucose and raised total cholesterol by anthropometric indices.

<p>AUC for discrimination of hypertension, elevated glucose and raised total cholesterol by anthropometric indices.</p

Coefficients from the regression of standardised values of systolic and diastolic blood pressure, logarithm of glucose, and total cholesterol on standardised values of the anthropometric indices^*.

<p>Coefficients from the regression of standardised values of systolic and diastolic blood pressure, logarithm of glucose, and total cholesterol on standardised values of the anthropometric indices^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198202#t002fn001" target="_blank">*</a>}.</p