Enhanced extraction of skin interstitial fluid using a 3D printed device enabling tilted microneedle penetration

Sanha Kim,Jae Hwan Jung,Hee Seok Yang,Min Suk Lee

doi:10.1038/s41598-021-93235-3

Abstract

Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed. To address the issues, we developed the tilted microneedle ISF collecting system (TMICS) fabricated by 3D printing. In this system, the microneedle (MN) was inserted at 66° to the skin by TMICS so that the MN length could be extended within a safe range of skin penetration. Moreover, TMICS incorporating three MN patches created reliable ISF collecting conditions by penetrating the skin at consistent angle and force, 4.9 N. Due to the MN length increase and the patch number expansion, the surface area of the penetrated tissue was increased, thereby confirming that ISF extraction efficiency was improved. Skin ISF was collected into the paper reservoir on the patch, and the absorbed area was converted into a volume. ISF extraction from the rat skin in vivo by TMICS was well tolerated, and the 2.9 μL of ISF was obtained within 30 s. Therefore, TMICS is promising to apply in the diagnosis of multiple biomarkers in ISF with high speed and stability.

Highlights

Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed
The MN length combined in tilted microneedle ISF collecting system (TMICS) was calculated to 820 μm considering the previous MN length of 750 μm used in the previous studies[1,18] and the MN insertion angle (66°) so that to obtain the same skin penetration depth between the 820 and 750 μm MNs (Fig. 1a)
We studied a method for uniformly extracting large amounts of ISF using a MN patch

Summary

Introduction

Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed. We developed the tilted microneedle ISF collecting system (TMICS) fabricated by 3D printing In this system, the microneedle (MN) was inserted at 66° to the skin by TMICS so that the MN length could be extended within a safe range of skin penetration. TMICS incorporating three MN patches created reliable ISF collecting conditions by penetrating the skin at consistent angle and force, 4.9 N. Of all, metal MNs including the paper reservoir, were reported to extract ISF at a rate of 2–4 μL per minute under in vivo conditions, which is faster than that of hydrogel M N3,13–16. MN devices for biomarker diagnosis should have the ability to obtain enough amount of ISF within a safe range with rapid extraction speed. When the width of MN increases, the patient’s pain increases, and the skin permeability decreases, while increasing the length allows the needle to penetrate the capillaries of the upper dermal layer and increases the patient’s p ain[25,26]

Results

Discussion

Conclusion