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</ref> ISF surrounds cells and tissues, serving as an interface between blood and cells. It may be a source of biomarkers in addition to blood biomarkers, as research shows that 83% of proteins found in blood serum are also present in ISF, but 50% of proteins in ISF are not found in serum. <ref name = "Ref25">Samant, Pradnya P, and Mark R Prausnitz. “Mechanisms of Sampling Interstitial Fluid from Skin Using a Microneedle Patch.” Proceedings of the National Academy of Sciences of the United States of America, 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939066/
</ref> Due to its accessibility and similarity in composition to serum, ISF is a suitable candidate for continuous monitoring <ref name = "Ref23">Friedel, M., Thompson, I. a. P., Kasting, G. B., Polsky, R., Cunningham, D., Soh, H. T., & Heikenfeld, J. (2023b). Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-022-00998-9</ref> and is currently used in clinical settings for continuous glucose monitoring (CGM).
Worldwide research is ongoing on the development of continuous ISF biosensors for analytes such as glucose, urea, and cortisol, with urea being the most relevant to kidney failure. <ref name = "Ref26">Chen, Q., Zhao, Y., & Liu, Y. (2021b). Current development in wearable glucose meters. Chinese Chemical Letters, 32(12), 3705–3717. https://doi.org/10.1016/j.cclet.2021.05.043</ref> <ref name = "Ref27">Venugopal, M., Arya, S. K., Chornokur, G., & Bhansali, S. (2011b). A realtime and continuous assessment of cortisol in ISF using electrochemical impedance spectroscopy. Sensors and Actuators A: Physical, 172(1), 154–160. https://doi.org/10.1016/j.sna.2011.04.028
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=== Continuous glucose monitoring ===
Glucose sensors are commercially available for continuous monitoring, primarily used in diabetes management [28]. Most of the CGM biosensors with ISF as a matrix are catalytic biosensors, using glucose oxidase (GOD) as the recognition molecule to bind with glucose [28]. Microneedle array electrodes have been used for CGM, e.g. by functionalizing them through entrapment of GOD in an electropolymerized film [30], or by non-enzymatic amperometric readout [31]. Other examples of CGM biosensors in ISF include an enzymatic open circuit potential biosensor using GOD [32] and an electrochemical glucose sensor composed of electroplated nanoporous platinum [33].
