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

Khaled Mohammed Saifullah; Asim Mushtaq; Pouria Azarikhah; Philip D Prewett; Graham J Davies; Zahra Faraji Rad

doi:10.1038/s41378-024-00850-x

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

Microsyst Nanoeng. 2025 Jan 8;11(1):3. doi: 10.1038/s41378-024-00850-x.

Authors

Khaled Mohammed Saifullah^{1

2}, Asim Mushtaq², Pouria Azarikhah^{1

2}, Philip D Prewett^{3

4}, Graham J Davies^{5

6}, Zahra Faraji Rad^{7

8}

Affiliations

¹ School of Engineering, University of Southern Queensland, Springfield, QLD, 4300, Australia.
² Centre for Future Materials, Institute for Advanced Engineering and Space Sciences, University of Southern Queensland, Springfield, QLD, Australia.
³ School of Engineering, University of Birmingham, Birmingham, B15 2TT, UK.
⁴ Oxacus Ltd, Dorchester-on-Thames, OX10 7HN, UK.
⁵ Faculty of Engineering, UNSW Australia, Sydney, NSW, 2052, Australia.
⁶ College of Engineering & Physical Sciences, School of Engineering, University of Birmingham, Birmingham, B15 2TT, UK.
⁷ School of Engineering, University of Southern Queensland, Springfield, QLD, 4300, Australia. [email protected].
⁸ Centre for Future Materials, Institute for Advanced Engineering and Space Sciences, University of Southern Queensland, Springfield, QLD, Australia. [email protected].

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.