High density cleanroom-free microneedle arrays for pain-free drug delivery

Abstract

The purpose of this work is to demonstrate the fabrication process of cleanroom-free solid metal microneedles and quantify their insertion profiles. Metal microneedles were created using a modified wire-bonding process and inserted into porcine tissue to determine the design efficacy. The microneedle arrays were analyzed using optical imaging and SEM. The insertion forces were measured using a combined uniaxial load cell and resistance measurement data. Microneedle arrays were successfully inserted into porcine tissues with high repeatability and reliability. These arrays demonstrate lower or equivalent insertion forces (less than 3 N) to other forms of microneedles in the literature, without the need for complex cleanroom fabrication processes. The microneedle fabrication method presented here rapidly produces mass-manufacturable, high-quality microneedle arrays with minimal insertion forces that can reliably penetrate tissue samples. The manufacturing method presented here achieved array densities as high as 3200 needles per square centimeter. These microneedle arrays demonstrate the simple fabrication of a reliable, high-density, pain-free drug delivery system with potential applications in biosensing and electric-field-modulated drug delivery.

A method for the rapid fabrication of solid metal microneedles

“…To overcome the limitations of existing microneedle fabrication methods, our group previously developed a method of fabricating solid metal microneedles using a modified wire bonding process shown in Figure 2 9,10 . Wire bonding is typically used in the semiconductor industry to connect chips and packages by bonding fine metal wires (<0.1mm diameter) between electrical contact points.…”

“…Furthermore, since the microneedles are conductive, they can be used to electrically stimulate the target tissue which can increase skin permeability to improve drug uptake (electroporation), or to assist in electrokinetically driving drug compounds deeper into tissue (iontophoresis) 11 . Additionally, electrical resistance measurements of the target tissue can be obtained during insertion, which makes it easier to identify when the needles have punctured through the stratum corneum 9 . This is because the stratum corneum has a much higher resistance than the underlying tissue, and a large drop in electrical resistance is expected upon puncturing through this layer.…”

“…An ENIG surface finish was chosen for the flexible PCBs because it was the only option available from the supplier. It is known that ENEPIG is more suited for wire bonding but is more costly, while ENIG is cheaper and more widely available 9 . Rigid substrates were 42 mm by 12 mm with a 10 mm by 11 mm bonding pad area and were designed to have a plated through hole to allow for electrical resistance measurements to be obtained from the microneedle array, as shown in Figure 3a.…”

“…Microneedles were fabricated to have a target height of 300 μm on all samples to remain consistent with prior work for comparative purposes 9 . Arrays were imaged after fabrication using an optical microscope and a Phenom XL desktop scanning electron microscope (SEM) (Thermo Fisher Scientific Inc., MA, USA) to characterize tip shape and measure microneedle height.…”

“…A Tinius Olsen H1kT universal testing machine (UTM) with a 100N load cell was used to insert each microneedle array perpendicularly into the tissue samples at a constant rate and a force vs. position plot was recorded. The insertion rate was set to 100 μm/s based on literature and prior testing results 9 . Six samples of the 2500 needles/cm 2 arrays were reserved to test the effect of faster insertion rates on insertion forces, where half were inserted at 400 μm/s and half at 800 μm/s.…”