Polymeric Microneedle Array Fabrication by Photolithography

Summary

Here, we present a protocol describing a mold-free fabrication process of the polymeric microneedles by photolithography.

Abstract

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a photomask consisting of embedded micro-lenses. Embedded micro-lenses were found to influence MN geometry (sharpness). Robust MN arrays with tip diameters ranging between 41.5 µm ± 8.4 µm and 71.6 µm ± 13.7 µm, with two different lengths (1,336 µm ± 193 µm and 957 µm ± 171 µm) were fabricated. These MN arrays may provide potential applications in delivery of low molecular and macromolecular therapeutic agents through skin.

Introduction

Transdermal drug delivery offers an attractive alternative approach for drug administration, especially for biomolecules, which are almost exclusively administered by hypodermic injections. However, skin, especially the top layer (the stratum corneum), is a formidable barrier preventing exogenous molecules from entering the human body. Recently, MN devices have emerged as enabling tools to deliver drugs through skin. The MN devices create temporary pores inside the stratum corneum to allow the passage of drug molecules to achieve the desired physiological activity with improved patient compliance and convenience^1-3.

Various fabri....

Protocol

1. Photomask Fabrication

1. Clean a 4” glass wafer with piranha solution (H₂SO₄/H₂O₂ in 2:1 ratio) for 20 min at 120 °C by immersion in a quartz tank.
2. Deposit a layer of Chromium/Gold (30 nm of Cr/1 µm of Au) layer on the glass wafer using an e-beam evaporator⁷ (Figure 1A).
   1. Place the wafers in an e-beam evaporator. Once the vacuum reaches 5 x 10^-6 Torr, turn on the high voltage source (10 kV). Control the thickness by the monitor control panel.
   2. Pre-clean each material for 30 sec using the e-beam gun, keeping the shutter “OF....

Results

The geometry of the MNs can be significantly affected by the photomask characteristics and embedded microlens. The degree of refraction affects the transmission path of the UV rays, which influenced the MN geometry (Figure 2A). Each microlens was found to have a 350 µm diameter, a 130 µm flattened convex surface, and a 62.3 µm depth (Figure 2B-D). Using the Pythagoras theorem, the radius of curvature of the first surface was found to be 272.89 µm. The focal length was calculated to be 50.......

Discussion

The protocol described above for fabrication of the MNs array has been presented to fabricate the MNs array of ~1 cm². The arrays can be scaled up by creating a large size cavity and by using a larger photomask. The increased cavity size can be created by increasing the width between the spacers on either side. Though each step to fabricate the MN arrays in the protocol was important, the most crucial steps were: the photomask positioning, the filling of prepolymer solution, and irradiation of the setup. Posit.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Poly(ethylene glycol) diacrylate (PEGDA Mn=258)	SIGMA	475629-500ML
2-hydroxy-2-methyl-propiophenone (HMP)	SIGMA	405655-50ML
Bovine collagen type 1, FITC conjugate	SIGMA	C4361
UV curing station	EXFO Photonic Solutions Inc., Canada	OmniCure S2000-XL
Collimating Adaptor	EXFO Photonic Solutions Inc., Canada	EXFO 810-00042
24-well plate	Thermo Fisher Scientific, USA
Nikon SMZ 1500 stereomicroscope	Nikon, Japan
Dillon GL-500 digital force gauge	Dillon, USA
A-1R confocal microscope	Nikon, Japan