Extraction and biomolecular analysis of dermal interstitial fluid collected with hollow microneedles

Philip R Miller,Kunal Poorey,Trevor Glaros,Robert M Taylor,Raga Krishnakumar,Victor H Chavez,Bao Quoc Tran,Justin T Baca,Anupama Sinha,Ronen Polsky,Kelly P Williams,Steven S Branda,Gabrielle Boyd

doi:10.1038/s42003-018-0170-z

Abstract

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize. Here, we present a facile microneedle approach for dermal ISF extraction with minimal pain and no blistering for human subjects and rats. Extracted ISF volumes were sufficient for determining transcriptome, and proteome signatures. We noted similar profiles in ISF, serum, and plasma samples, suggesting that ISF can be a proxy for direct blood sampling. Dynamic changes in RNA-seq were recorded in ISF from induced hypoxia conditions. Finally, we report the first isolation and characterization, to our knowledge, of exosomes from dermal ISF. The ISF exosome concentration is 12–13 times more enriched when compared to plasma and serum and represents a previously unexplored biofluid for exosome isolation. This minimally invasive extraction approach can enable mechanistic studies of ISF and demonstrates the potential of ISF for real-time health monitoring applications.

Highlights

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize
Microneedle insertion and ISF extraction is complicated by the dynamic properties and elasticity of skin
We present a needle substrate that minimize dermal compaction at insertion site(s), allowing extraction of higher ISF volumes

Summary

Introduction

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize. The ISF exosome concentration is 12–13 times more enriched when compared to plasma and serum and represents a previously unexplored biofluid for exosome isolation This minimally invasive extraction approach can enable mechanistic studies of ISF and demonstrates the potential of ISF for real-time health monitoring applications. We report a facile method that uses an array of hollow microneedles to extract large quantities (up to 20 μl and 60 microliters from humans and rats, respectively) of dermal ISF, with no need for blistering of the skin and uses widely available materials for easy construction. ISF could constitute an informative proxy for blood in health monitoring, and microneedle-enabled sampling could advance wearable, real-time sensing devices

Methods

Results

Conclusion