Abstract
Dermal interstitial fluid (ISF) is a novel source of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment. Nevertheless, in vivo extraction and analysis of ISF are challenging. On the other hand, microneedle (MN) technology can address most of the challenges associated with dermal ISF extraction and is well suited for long-term, continuous ISF monitoring as well as in situ detection. In this review, we first briefly summarise the different dermal ISF collection methods and compare them with MN methods. Next, we elaborate on the design considerations and biocompatibility of MNs. Subsequently, the fabrication technologies of various MNs used for dermal ISF extraction, including solid MNs, hollow MNs, porous MNs, and hydrogel MNs, are thoroughly explained. In addition, different sensing mechanisms of ISF detection are discussed in detail. Subsequently, we identify the challenges and propose the possible solutions associated with ISF extraction. A detailed investigation is provided for the transport and sampling mechanism of ISF in vivo. Also, the current in vitro skin model integrated with the MN arrays is discussed. Finally, future directions to develop a point-of-care (POC) device to sample ISF are proposed.
Highlights
Accepted: 15 April 2021Interstitial fluid (ISF) is a novel source of biomarkers
The synergistic combination of interstitial fluid (ISF) detection and microfluidic technology can address most of these challenges, leading to enormous progress in this field
We first discussed the ISF collection mechanism and briefly investigated the pros and cons of conventional ISF collection methods compared to the MN ISF sampling approach
Summary
Interstitial fluid (ISF) is a novel source of biomarkers. The ISF flows through the extracellular matrix of tissue between the blood and lymphatic vessels [1]. The second application, i.e., using MNs for both ISF collection and sensing, has been mainly investigated for continuous glucose monitoring as a part of wearable POC devices for diabetes. The applications of MNs for sampling ISF and measuring the unique biomarkers for disease diagnosis, prognosis, and treatment monitoring have attracted a great deal of attention [33]. The surface of the MNs can act as a biosensor when functionalised with biorecognition elements, such as peptides, antibodies, and antigens, to directly interact with the target of interest in the ISF This can be considered as a paradigm shift for POC, in situ disease detection, and longitudinal monitoring [34]. There is still a lack of a comprehensive review paper that systematically investigates the design consideration, fabrication, and sensing applications of MNs for ISF extraction and monitoring. Future direction to develop a POC device to sample ISF is proposed
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