The dermis consists of two sublayers (the papillary dermis, about 15 μm thick and highly vascularized 18, which supplies nutrients to the epidermis and the 1–4-mm-thick gel-like reticular dermis) and has low cellular content, consisting mainly of fibroblasts and immune cells. The epidermis is approximately 100 μm thick at common ISF-access sites such as the arm or the abdomen, and is composed of four to five layers of different thicknesses and compositions, including the stratum corneum-a cornified outer layer that acts as a barrier to the transport of many compounds and prevents excessive water loss. 1a), the epidermis is avascular and has the lowest ISF content (15–35% by mass) of the three main skin layers-epidermis, dermis and hypodermis 16, 17. We argue that when designed with a deep understanding of the properties of ISF, diagnostic applications based on biomarkers in it may prove advantageous for a wide range of biomarkers and diseases beyond glucose and diabetes.Īs the outermost barrier of the skin (Fig. We refer to previous review articles for a detailed discussion on the flow of analytes into ISF 11, on microneedle devices for ISF sensing 12, 13, 14 and on specific applications such as therapeutic-drug monitoring 15. We provide cautionary insights, rooted in the incomplete understanding of how analytes partition into ISF. In this Perspective, we overview the utility of ISF for diagnostic applications by exploring the opportunities and challenges of the use of dermal ISF as a biofluid that is potentially rich in diagnostic value. Because of the successes in the monitoring of glucose via ISF, increasing attention and research-and-development efforts have been directed towards exploring the utility of ISF for diagnostic assays (either ex situ or in situ via wearable or implantable sensors). This contrasts with more accessible biofluids (in particular, saliva, tears and sweat) which are associated with inconsistencies in sample collection arising from variable sample dilutions and compositions, and from other complications 10. Also, continuous glucose metres relying on ISF are similarly accurate (even when not requiring blood-based calibration 9) to finger-prick glucose metres using blood (typical mean absolute relative differences are less than 10%). Microsensors within the dermis can continuously measure changing glucose levels in ISF with high accuracy and fast temporal resolution over several weeks. The most notable diagnostic application of ISF is in glucose monitoring for the management of diabetes. The diagnostic utility of ISF has been increasingly explored. More generally, the physiological concentrations of analytes in ISF relative to their concentrations in blood remain poorly characterized. This makes it exceedingly difficult to quantify the actual concentrations of large protein biomarkers such as cytokines, peptide hormones and immunoglobulins within extracted ISF samples. When fast sampling of large ISF volumes is attempted, in most cases the mesh-like ECM acts as a filter that hinders the extraction of large solutes 8 (but not of small molecules, such as glucose). Extracted ISF can provide valuable information, but the design of ISF-collection methods that produce accurate samples remains challenging. Components of the extracellular matrix (ECM) within the interstitial space (in particular, collagen and glycosaminoglycans (GAGs)) can bind water, conferring ISF a hydrogel-like consistency 7. Beyond circulating proteins, ISF is also host to a small portion of proteins that are not present in blood 5.ĭespite its apparent ease of access, ISF can be challenging to collect. Virtually every analyte present in blood can be assumed to be present in ISF, including more than 92% of RNA species and over 90% of circulating proteins, with multiple studies stating that 99% of the proteins in blood are also present in ISF 4, 5, 6. ![]() ![]() Dermal ISF-that is, ISF within the skin-is commonly thought to be roughly equivalent to blood in terms of biomarker composition hence, because it is present near the skin’s surface, it could enable easier access to biomarkers without the pain or clotting associated with blood draws 2, 3. By volume, the human body contains at least three times more ISF than blood 1. It is the medium through which cells receive nutrients, secrete waste and communicate through molecular signals. Interstitial fluid (ISF) surrounds cells within tissue.
0 Comments
Leave a Reply. |