Micro-vibration assisted dual-layer spiral microneedles to rapidly extract dermal interstitial fluid for minimally invasive detection of glucose.

Abstract

Various hydrogels have been explored to create minimally invasive microneedles (MNs) to extract interstitial fluid (ISF). However, current methods are time-consuming and typically require 10-15 min to extract 3-5 mg of ISF. This study introduces two spiral-shaped swellable MN arrays: one made of gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA), and the other incorporating a combination of PVA, polyvinylpyrrolidone (PVP), and hyaluronic acid (HA) for fast ISF extraction. These MN arrays demonstrated a rapid swelling ratio of 560 ± 79.6% and 370 ± 34.1% in artificial ISF within 10 min, respectively. Additionally, this study proposes a novel method that combines MNs with a custom-designed Arduino-based applicator vibrating at frequency ranges (50-100 Hz) to improve skin penetration efficiency, thereby enhancing the uptake of ISF in ex vivo. This dynamic combination enables GelMA/PVA MNs to rapidly uptake 6.41 ± 1.01 mg of ISF in just 5 min, while PVA/PVP/HA MNs extract 5.38 ± 0.77 mg of ISF within the same timeframe. To validate the capability of the MNs to recover glucose as the target biomarker, a mild heating procedure is used, followed by determining glucose concentration using a D-glucose content assay kit. The efficient extraction of ISF and glucose detection capabilities of the spiral MNs suggest their potential for rapid and minimally invasive biomarker sensing.