Fabrication of High-Density Out-of-Plane Microneedle Arrays with Various Heights and Diverse Cross-Sectional Shapes

Out-of-plane microneedle structures are widely used in various applications such as transcutaneous drug delivery and neural signal recording for brain machine interface. This work presents a novel but simple method to fabricate high-density silicon (Si) microneedle arrays with various heights and diverse cross-sectional shapes depending on photomask pattern designs. The proposed fabrication method is composed of a single photolithography and two subsequent deep reactive ion etching (DRIE) steps. First, a photoresist layer was patterned on a Si substrate to define areas to be etched, which will eventually determine the final location and shape of each individual microneedle. Then, the 1st DRIE step created deep trenches with a highly anisotropic etching of the Si substrate. Subsequently, the photoresist was removed for more isotropic etching; the 2nd DRIE isolated and sharpened microneedles from the predefined trench structures. Depending on diverse photomask designs, the 2nd DRIE formed arrays of microneedles that have various height distributions, as well as diverse cross-sectional shapes across the substrate. With these simple steps, high-aspect ratio microneedles were created in the high density of up to 625 microneedles mm−2 on a Si wafer. Insertion tests showed a small force as low as ~ 172 µN/microneedle is required for microneedle arrays to penetrate the dura mater of a mouse brain. To demonstrate a feasibility of drug delivery application, we also implemented silk microneedle arrays using molding processes. The fabrication method of the present study is expected to be broadly applicable to create microneedle structures for drug delivery, neuroprosthetic devices, and so on.

Optimization of Printing Parameters for Digital Light Processing 3D Printing of Hollow Microneedle Arrays

3D printing is an emerging technology aiming towards personalized drug delivery, among many other applications. Microneedles (MN) are a viable method for transdermal drug delivery that is becoming more popular for delivery through the skin. However, there is a need for a faster fabrication process with potential for easily exploring different geometries of MNs. In the current study, a digital light processing (DLP) method of 3D printing for fabrication of hollow MN arrays using commercial UV curable resin was proposed. Print quality was optimised by assessing the effect of print angle on needle geometries. Mechanical testing of MN arrays was conducted using a texture analyser. Angled prints were found to produce prints with geometries closer to the CAD designs. Curing times were found to affect the mechanical strength of MNs, with arrays not breaking when subjected to 300 N of force but were bent. Overall, DLP process produced hollow MNs with good mechanical strength and depicts a viable, quick, and efficient method for the fabrication of hollow MN arrays.

Photo-Responsive Hydrogel Mns with Interlocking Control for Easy Extraction in Sustained Ocular Drug Delivery

Microneedle arrays provide a minimally invasive platform for ocular drug delivery. Self-adhesive microneedle arrays, which incorporate barb-like locking features, have been developed secure the array in place without using any adhesive. However, these locking features present a challenge on removing the microneedle array when the drug delivery is completed. In this study, we demonstrated a photo-responsive hydrogel microneedle array that can self-adhere to the application site upon swelling and can deswell for easy removal when illuminated with light. The photo-responsive hydrogel microneedle arrays were made by a mixture of polyvinyl alcohol and spiropyran-conjugated N-isopropylacrylamide (NIPPAM). Experimental results show a significant decrease in extraction force after the microneedle of 20% spiropyran-conjugated NIPPAM was illuminated with light for 15 minutes. At the same time, the width of the interlocking feature also deswelled by 20% due to the photo-responsive behavior. However, the addition of the spiropyran-conjugated NIPPAM also weakens the mechanical properties of the microneedle and thus an increase in insertion force.

High-resolution two-photon polymerization: the most versatile technique for the fabrication of microneedle arrays

Microneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring purposes. Microneedles are manufactured using a variety of additive and subtractive micromanufacturing techniques. In the last decade, much attention has been paid to using additive manufacturing techniques in both research and industry, such as 3D printing, fused deposition modeling, inkjet printing, and two-photon polymerization (2PP), with 2PP being the most flexible method for the fabrication of microneedle arrays. 2PP is one of the most versatile and precise additive manufacturing processes, which enables the fabrication of arbitrary three-dimensional (3D) prototypes directly from computer-aided-design (CAD) models with a resolution down to 100 nm. Due to its unprecedented flexibility and high spatial resolution, the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic devices. This is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding, photolithography, and etching. Thus, microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching processes. This article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures, which may overcome the shortcomings of conventional manufacturing processes.

Evaluation of Ball End Micromilling for Ti6Al4V ELI Microneedles Using a Nanoadditive Under MQL Condition

The use of nanoadditives in lubricants has gained much attention to the research community due to the enhancement of tribological properties and cooling capabilities. This paper studies the advantages of using a MQL (Minimum Quantity of Lubrication) system and nanoadditive in the manufacture of microneedle arrays in Ti6Al4V ELI alloy. Tungsten carbide ball nose tools with a cutting diameter of 200 µm were used in experimental tests. Surface and dimensional characterization was performed to evaluate the impact of a nanoadditive to a vegetable-based oil. Additionally, cutting forces and cutting edge radius (CER) were measured while needles were machined. Experimental tests confirmed that micro end milling with nanoadditives provide slightly better dimensional features and low cutting forces compared to oil. The performance of nanoadditives resulted in a reduction of surface roughness (~ 0.3 μm). Qualitative study of microneedles illustrated burr formation on needle surface manufactured without a nanoadditive solution. Results reveal an increment of CER using low feed rate values (2.0 µm/flute) while a reduction of CER was observed with feed rates up to 2.5 µm/flute. Our results indicated that the addition of nanoadditives to vegetable oil promotes a better product surface topography and cutting tool performance.