Interstitial Fluid Biomarkers’ Minimally Invasive Monitoring Using Microneedle Sensor Arrays

Abstract

Skin interstitial fluid (ISF) is a biofluid with information-rich biomarkers for disease diagnosis and prognosis. Microneedle (MN) integration of sampling and instant biomarker readout hold great potential in health status monitoring and point-of-care testing (POCT). The present work describes an attractive MN sensor array for minimally invasive monitoring of ISF microRNA (miRNA) and Cu2+. The MN array is made of methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (MeHA), and a further divisionally encapsulated miRNA and Cu2+ detection system, and is cross-linked through blue-light irradiation. The MN patch displays good mechanical properties that enable withstanding more than 0.4 N per needle, and exhibits a high swelling ratio of 700% that facilitates timely extraction of sufficient ISF for biomarker analysis. For proof-of-concept, it realizes detection of miRNAs and Cu2+ efficiently and quantitatively in an agarose skin and fresh porcine cadaver skin model. Given the good sampling and in situ monitoring ability, the MN array holds great promise for skin ISF-based applications.

Microneedle-based transdermal detection and sensing devices

“…So far, targets of integrated microneedle-integrated detection systems have covered ions, 50,118 small molecules (glucose, 119–122,124 lactate, 30,123 cholesterol 125 and ROS 126,127 ), and nucleic acids. 49,100,116,128,129 In this section, we summarize recently reported integrated microneedle sensing devices, highlighting distinct sensing principles including colorimetric, fluorometric and electronic systems (Fig. 1).…”

The most promising microneedle device: present and future of hyaluronic acid microneedle patch

“…MNP technology is a new device with high drug delivery efficiency, easy administration, painless, low risk of infection, and has strong potential for clinical application, which is expected to become an effective drug delivery route for an insulin treatment of diabetes (Li et al., 2022 ). HA MNP has become an excellent choice for diabetes treatment because it facilitates wound healing, including micropores from injections and chronic wounds from diabetes.…”

“…The natural water absorption of HA makes it an ideal candidate for rapid ISF extraction. Extraction of ISF with HA MNP is becoming an emerging method for the diagnosis and prognosis of diseases (Li et al., 2022 ).…”

Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial Fluid

“…2 Therefore, the composition similarity of ISF to blood enables ISF to be a promising candidate for point-of-care testing (POCT) diagnosis. 4,5 Microneedles (MNs) are known as powerful tools to pass through the skin epidermis to reach the dermis, where MNs can make contact with ISF for collecting and detecting analytes. 6−8 The small tip size (1−100 μm) and appropriate needle length (50−2000 μm) without touching the nerve enable MNs minimally invasive and painless puncture.…”

“…For proteins with a higher molecular weight, the concentration ratio between the ISF and blood has been investigated to vary in an inverse logarithmic relationship . Therefore, the composition similarity of ISF to blood enables ISF to be a promising candidate for point-of-care testing (POCT) diagnosis. , …”