Development of a high-performance sliding microneedle-lateral flow immunoassay strip device for ultra-rapid point-of-care diagnosis

Abstract

Interstitial fluid (ISF) is a promising biofluid for non-invasive diagnostics, but its clinical application is limited by slow extraction rates and small sample volumes. To address these challenges, we developed the high-performance sliding microneedle-lateral flow immunoassay (HP-SML) device, an improved microneedle (MN)-based platform for rapid ISF extraction and on-site biomarker detection. The device incorporates extended MNs (1400 μm), a 3D-printed insertion case, and a lateral flow assay (LFA), enabling efficient ISF collection and immediate visual confirmation of test results. The HP-SML device demonstrated a 5-fold increase in ISF extraction speed compared to conventional SML devices, achieving 1.5 μL min⁻¹ extraction rates with minimal tissue disruption and rapid skin recovery within 15 minutes. The device successfully detected C-reactive protein (CRP) at a clinically relevant limit of 10⁴ ng mL⁻¹, confirming its applicability for Hodgkin lymphoma (HL) prognosis monitoring. It also exhibited high specificity for CRP, with no cross-reactivity observed against other inflammatory biomarkers such as IL-6, TNF-α, MMP-9, and MMP-2. Furthermore, ISF-derived CRP levels strongly correlated with serum CRP concentrations, validating ISF as a viable alternative for HL management. Given its high efficiency, ease of use, and on-site detection capabilities, the HP-SML device presents a significant advancement in point-of-care diagnostics and continuous disease monitoring.