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

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.

Microneedles: a potential strategy in transdermal delivery and application in the management of psoriasis

“…Once the microneedle array was attached to the skin surface with the aid of a xative, a preset syringe pump began delivering liquid compounds stored in the needle space in a continuous manner. The use of HMNs is suggested for sample extraction, 19 because of their special design and structure.…”

Parametric study of 3D printed microneedle (MN) holders for interstitial fluid (ISF) extraction

“…With this technique, drug delivery can be achieved with minimal pain and minimal damage to skin and veins. This technique has also been experimentally verified to assist in extraction of ISF from the dermis layer (Miller et al 2018;Taylor et al 2018;Tran et al 2018;Wang et al 2005). MNs have also been used for drug and vaccine delivery (He et al 2019;Kim et al 2012).…”

“…Thus, ISF has been inadequately characterized for biomedical or clinical applications. We recently devised MN arrays (MAs, which includes microneedles extending from a 3D-printed holder) that are able to extract upwards of 20 lL and 60 lL of ISF in 1 h from both humans and rats, respectively (Miller et al 2018;Taylor et al 2018;Tran et al 2018). These volumes of ISF are adequate for downstream analysis such as transcriptomics (Miller et al 2018), proteomics (Tran et al 2018), and metabolomics (Miller et al 2018;Taylor et al 2018).…”

“…It is important to note that fluid extraction from the deep dermis layer not only depends on the MNs but also on the MN holders used to house the MNs and to apply them to the tissue. One of the important observations when using different types of MAs is that extraction may also be influenced by the pressure exerted by the holder during the fluid extraction process (Miller et al 2018;Samant and Prausnitz 2018). It would be of interest to users to enable extraction of ISF with a reduced amount of pressure.…”

Porous microneedles on a paper for screening test of prediabetes

“…Moreover, unlike conventional hypodermic injection, MNs do not require users with medical training (Donnelly et al, 2012; Lee, Park, & Prausnitz, 2008; Mcallister, Allen, & Prausnitz, 2000). In the field of bio‐sensors, MNs have been applied to collect interstitial fluid (ISF) from the epidermis to analyse biomolecules for health monitoring (Kolluru, Williams, Chae, & Prausnitz, 2019; Miller et al, 2018). ISF is a bio‐fluid that surrounds cells and shuttles various biomaterials such as glucose between cells and blood vessels.…”