Metallic Microneedle Manufacturing

A metallic microneedle manufacturer faces challenges ensuring its shipped product meets customer requirements for biocompatibility and corrosion resistance, as poor material quality can cause adverse reactions. Precision in microfabrication is critical, since slight dimensional errors affect penetration and drug delivery. Surface finish and coating uniformity must be controlled to avoid tissue damage. Consistency in sterilization, mechanical strength, and sharpness across batches is difficult but essential. Meeting regulatory standards, maintaining cleanroom conditions, and preventing contamination add further complexity.

During production, changes in the viscosity of the raw materials, wear of the molds, and control of the drying temperature can all affect the final needle shape. Therefore, strict quality control and inspection are key to helping to ensure the effectiveness and safety of the final patch.

The Importance of Metals Used in Microneedle Patches

Microneedle (MN) patches are an innovative drug delivery technology featuring tiny needles that penetrate the outer layer of the skin without reaching pain receptors, making them virtually painless.  They come in various forms, including solid, coated, dissolving, and hollow needles, and are used for applications such as vaccinations, diabetes management, transdermal drug delivery, and cosmetic treatments. Their advantages over traditional methods include reduced pain, improved patient compliance, enhanced drug efficacy, and a lower risk of infection, positioning them as a promising advancement in modern healthcare.

Microneedles for drug delivery are typically made from a variety of materials, including metals. Other materials such as silicon, polymers, and ceramics are also used depending on the specific application and design requirements, but we will address metal microneedles in this article.

The publication, Metallic Microneedles for Transdermal Drug Delivery: Applications, Fabrication Techniques and the Effect of Geometrical Characteristics, notes that stainless steel and titanium are the most commonly used metals for MN arrays due to their high strength, biocompatibility, and ability to penetrate the skin without fracturing. Titanium offers lower corrosion rates and higher mechanical properties compared to stainless steel, making it suitable for both solid and hollow applications. Nickel poses biocompatibility issues, such as toxicity and allergic reactions, while palladium and platinum had not been adequately studied for MN manufacture when the publication was written.

Fabrication Concerns

Technological advancements in the microelectronics industry have enabled the development of various microfabrication tools for producing microneedles (MNs) from metals. The fabrication of metallic MNs focuses on optimizing geometry, shape, size, and tip sharpness to enhance mechanical strength and ease of skin penetration. Techniques used include 3D printing, laser cutting, laser ablation, etching, electroplating, hot embossing, and metal injection molding, with 3D printing offering notable advantages in versatility, customizability, and precision.

As noted, the manufacturing of microneedles involves precise control over their geometric shape, base and tip diameter, length, and spacing. These factors are crucial for the penetrative ability of the microneedles. During production, changes in the viscosity of the raw materials, wear of the molds, and control of the drying temperature can all affect the final needle shape. Therefore, strict quality control and inspection are key to helping to ensure the effectiveness and safety of the final patch.

Testing with Scanning Electron Microscopy Technology Aids in Strict Quality Control

Scanning Electron Microscopy (SEM) is a powerful tool for analyzing the surface morphology of microneedle patches. It provides high-resolution images that reveal detailed structural features, including the shape, size, and sharpness of the needles. These characteristics are crucial for helping to ensure that the patches can effectively penetrate the skin and deliver the intended dose of medication.

SEM operates by directing a focused beam of electrons onto the sample surface, causing the emission of secondary electrons, backscattered electrons, and characteristic X-rays. These emissions are detected and used to construct detailed images, revealing the sample’s topography and elemental composition.

SEM is known for its ability to produce images with magnifications ranging from tens to hundreds of thousands of times, allowing researchers to observe fine structural details that are not visible with conventional light microscopy. The versatility, efficiency, and high resolution of SEM make it an essential tool in quality testing for several reasons:

1. Needle Integrity: SEM images help in assessing the integrity of the microneedles. Any deformation or damage to the needles can affect their performance. SEM allows researchers to identify manufacturing defects and optimize production processes.
2. Surface Morphology: The detailed images from SEM reveal the surface texture and any potential irregularities. This information is essential for understanding how the needles interact with the skin and help ensure consistent drug delivery.
3. Material Composition: SEM can be combined with other techniques like Energy Dispersive X-ray Spectroscopy (EDS) to analyze the material composition of the needles. This helps in determining the suitability of different materials for microneedle fabrication.

Summary

Using scanning electron microscopes for inspection helps metallic microneedle manufacturers ensure quality by providing extremely high-resolution imaging to detect surface defects such as cracks, burrs, or irregularities that optical methods might miss. SEM also allows precise measurement of tip sharpness, geometry, and dimensional uniformity, which are vital for reliable skin penetration. In addition, it enables assessment of coating thickness, adhesion, and surface integrity, ensuring biocompatibility and effective drug delivery.

By identifying defects like voids, corrosion, or wear, SEM supports failure analysis, process optimization, and regulatory compliance, making it a powerful tool for maintaining consistent product quality and meeting customer requirements.

For more details, including an indepth look at high-resolution imaging of microneedles, read the Application Note: Scanning electron microscopy in microneedle patch testing

Additional Resources and References

• Application Note: Scanning electron microscopy in microneedle patch testing
• Desktop scanning electron microscopes

References

• Metallic Microneedles for Transdermal Drug Delivery: Applications, Fabrication Techniques and the Effect of Geometrical Characteristics – https://www.mdpi.com/2306-5354/10/1/24: Sargioti, N.; Levingstone, T.J.; O’Cearbhaill, E.D.; McCarthy, H.O.; Dunne, N.J. Metallic Microneedles for Transdermal Drug Delivery: Applications, Fabrication Techniques and the Effect of Geometrical Characteristics. Bioengineering 2023, 10, 24. https://doi.org/10.3390/bioengineering10010024