Photolithography Technology for Microneedles Preparation

Photolithography is a simple microneedle preparation process that allows precise control of the microneedle size, shape and preparation material. The steps for the preparation of soluble microneedles by soft photolithography: first, the polymer film is paired with a microneedle mold, which is filled by a heated roller, then the filled mold is placed on a flexible substrate, and again the mold is separated by a heated roller, and the microneedles are retained on the backing material to make a microneedle patch. In addition, heated roller curing can be used instead of light curing. Soft lithography preparation of microneedles is similar to the stereoscopic plate stretching method, with the advantages of high efficiency and low cost and good scalability.

Fig.1 Brightfield macroscopic images of a microneedle patch. (Moga et al., 2013)

Photolithography Preparation Procedure

1. A thick layer of negative photoresist is applied to the wafer by spin coating, a mask with square and certain spacing (base to base) is placed on the resist, and the complex is exposed to UV light. Both the mask size and the angle of incidence of UV light determine the depth of the die and ultimately the length of the microneedle. The wafer is then rotated 90° around the surface normal and exposed again; a total of four exposures result in a master master template with square conical cavities. These templates were imaged by environmental scanning electron microscopy (ESEM) to determine the length and tip radius of curvature achieved by replication. Template length lengths were chosen based on the desire to reach the viable epidermis after puncturing the cuticle.
2. A positive replica of the master template is made as an intermediate. The replica shows significant reproducibility of the master template by ESEM with comparable needle length and tip radius of curvature. The elastomer is cast onto the replica and cured under UV light to create a mold for microneedle fabrication.
3. The raw material is filled with the mold, placed on a flexible backing, and the mold is separated by a heated roller, with the microneedles retained on the backing material to make the microneedle patch.

Evaluation of Microneedles Prepared by Photolithography Technology

• Penetration performance

For this evaluation, all patches left behind were left in the skin for 10 seconds, then removed and a green tissue marking dye was immediately applied to the skin and subsequently wiped off so that the location of skin penetration could be identified macroscopically. Drug substitutes can be visually perceived within the microneedle insertion site and cannot be wiped off from the surface.

• Puncture experiments

Further studies were conducted to assess the complete dissolution of the microneedle patch and the release of the drug substitute. For these studies, all patches were left in the skin for 10 minutes, followed by a few drops of water on the back of the microneedle patch.

• Analysis of skin penetration studies

The tested skin samples were then embedded in optimal cutting temperature media and frozen sections . Half of the sections were set aside for imaging using fluorescence microscopy. These sections were fixed briefly in the cancer diagnostic for 10 seconds prior to capping. The remaining sections were stained for bright-field microscopic imaging, using Cancer Diagnostics' procedures prior to coverslip.

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