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. 2017 Oct 9:3:17034.
doi: 10.1038/micronano.2017.34. eCollection 2017.

High-fidelity replication of thermoplastic microneedles with open microfluidic channels

Zahra Faraji Rad  1   2   3 , Robert E Nordon  1 , Carl J Anthony  2 , Lynne Bilston  4 , Philip D Prewett  2 , Ji-Youn Arns  5 , Christoph H Arns  5 , Liangchi Zhang  3 , Graham J Davies  1
Affiliations

High-fidelity replication of thermoplastic microneedles with open microfluidic channels

Zahra Faraji Rad et al. Microsyst Nanoeng. .

Abstract

Development of microneedles for unskilled and painless collection of blood or drug delivery addresses the quality of healthcare through early intervention at point-of-care. Microneedles with submicron to millimeter features have been fabricated from materials such as metals, silicon, and polymers by subtractive machining or etching. However, to date, large-scale manufacture of hollow microneedles has been limited by the cost and complexity of microfabrication techniques. This paper reports a novel manufacturing method that may overcome the complexity of hollow microneedle fabrication. Prototype microneedles with open microfluidic channels are fabricated by laser stereolithography. Thermoplastic replicas are manufactured from these templates by soft-embossing with high fidelity at submicron resolution. The manufacturing advantages are (a) direct printing from computer-aided design (CAD) drawing without the constraints imposed by subtractive machining or etching processes, (b) high-fidelity replication of prototype geometries with multiple reuses of elastomeric molds, (c) shorter manufacturing time compared to three-dimensional stereolithography, and (d) integration of microneedles with open-channel microfluidics. Future work will address development of open-channel microfluidics for drug delivery, fluid sampling and analysis.

Keywords: drug delivery; laser lithography; microneedles; point-of-care diagnostics; soft embossing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Microneedles geometries used for FEA.
Figure 2
Figure 2
(a) SEM of fabricated single open-channel microneedle connected to a reservoir by 3D laser lithography. (b) A 16 microneedle array (2.17 mm×2.17 mm) with side channels connected to reservoirs fabricated by 3D laser lithography, microneedles have 700 μm total height, 150 μm tip height, 150 μm flange height. (c) A 16 microneedle array (2.17 mm×2.17 mm) with side channels connected to reservoirs fabricated by 3D laser lithography, microneedles have 700 μm total height, 350 μm tip height, 150 μm flange height. (d) Microneedles in the middle rows having two side-opened channels connected to different reservoirs. (e) Ultra-sharp microneedle tip. (f) Stitching of two adjacent blocks.
Figure 3
Figure 3
(a) Single side-opened microneedle replica with a fluid reservoir. (b) Precise replication of microneedle tip. (c) Microneedle array replica with straight projections. (d) Precise replication of features.
Figure 4
Figure 4
Micro-CT of (a) master microneedle array. (b) Microneedle array replica. (c) PDMS negative mold. (d) Cross sectional view of master microneedle array.
Figure 5
Figure 5
COMSOL FEM simulation of microneedle bending and stress concentration when a 20 mN lateral load (along x-direction) is applied to the needle tip taper region. Color map shows surface stress (a) no flange at base of the microneedle. (b) Flange at base of the microneedle.
Figure 6
Figure 6
(a) Schematic setup of compression test on microneedles performed by rheometer. (b) Force (N) versus displacement (mm) curves of compression tests with speeds of 35, 45, and 55 μm s−1, on three separate microneedles connected to a reservoir. (c) Force (N) versus displacement (mm) graph of a compression test on an array of 16 microneedles by applying 35 μm s−1 speed. (d) SEM image of the microneedle array with tip heights of 150 μm after compression test.
Figure 7
Figure 7
Multiphoton microscopy image of (a) topical application of fluorescein solution on tissue surface. (b) Fluorescein solution diffusion underneath the skin surface of rabbit ear. (c) Confocal microscopy image showing the diffusion of fluorescein solution underneath the skin surface of rabbit ear over four time intervals. (d) SEM image of the array of microneedles after removal from rabbit ear.
Figure 8
Figure 8
A 15 μL of DI water droplet on Zeonor 1060R film (a) with no surface modification. (b) With surface modification measured at day 1. (c) Contact angle measurement for evaluation of hydrophobicity recovery 10–18 days after surface modification.
See this image and copyright information in PMC

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