Microinjection protocols that involve using a hollow, high-aspect-ratio microneedle to deliver foreign material (e.g., cells, DNA, viruses, and micro/nanoparticles) into biological targets (e.g., embryos, tissues, and organisms) are essential to diverse biomedical applications in both research and clinical settings. A key deficit of such protocols, however, is that standard microneedle architectures are inherently susceptible to clogging-induced failure modes, which can diminish experimental rigor and lead to failed microinjections. Additive manufacturing (or “three-dimensional (3D) printing”) strategies based on “Two-Photon Direct Laser Writing (DLW)” offer a promising route to address clogging failure phenomena by rearchitecting the needle tip, yet achieving 3D-printed microneedles with the mechanical strength necessary to penetrate into biological targets (e.g., embryos) has remained a critical barrier to efficacy. To overcome this barrier, here we harness a recently reported polyhedral oligomeric silsequioxane (POSS) photomaterial to DLW-print fused silica glass high-aspect-ratio microinjection needles with enhanced mechanical strength. Experimental results for POSS-based 3D-nanoprinted microneedles with inner and outer diameters of 10 μm and 15 μm, respectively, and heights ranging from 500–750 μm revealed that the needles not only enabled successful puncture and penetration into early-stage zebrafish embryos, but also significantly reduced the magnitude of undesired deformations to the embryos during needle puncture and penetration from 61.0±12.1 μm for standard glass-pulled control microneedles to 42.4±11.5 μm for the POSS-enabled 3D microneedles (p < 0.01). In combination, these results suggest that wide-ranging biomedical fields could benefit from the presented 3D microinjection needles.
more »
« less
Direct Printing of High-Resolution Metallic Three-Dimensional Microneedle Arrays Via Electrohydrodynamic Jet Printing
Abstract Three-dimensional (3D) microneedle arrays (MAs) have shown remarkable performances for a wide range of biomedical applications. Achieving advanced customizable 3D MAs for personalized research and treatment remain a formidable challenge. In this paper, we have developed a high-resolution electrohydrodynamic (EHD) 3D printing process for fabricating customizable 3D MAs with economical and biocompatible molten alloy. The critical printing parameters (i.e., voltage and pressure) on the printing process for both two-dimensional (2D) and 3D features are characterized, and an optimal set of printing parameters was obtained for printing 3D MAs. We have also studied the effect of the tip-nozzle separation speed on the final tip dimension, which will directly influence MAs' insertion performance and functions. With the optimal process parameters, we successfully EHD printed customizable 3D MAs with varying spacing distances and shank heights. A 3 × 3 customized 3D MAs configuration with various heights ranging from 0.8 mm to 1 mm and a spacing distance as small as 350 μm were successfully fabricated, in which the diameter of each individual microneedle was as small as 100 μm. A series of tests were conducted to evaluate the printed 3D MAs. The experimental results demonstrated that the printed 3D MAs exhibit good mechanical strength for implanting and good electrical properties for electrophysiological sensing and stimulation. All results show the potential applications of the EHD printing technique in fabricating cost-effective, customizable, high-performance MAs for biomedical applications.
more »
« less
- Award ID(s):
- 2200200
- PAR ID:
- 10583100
- Publisher / Repository:
- American Society of Mechanical Engineers (ASME)
- Date Published:
- Journal Name:
- Journal of Micro and Nano Science and Engineering
- Volume:
- 12
- Issue:
- 2
- ISSN:
- 2994-7316
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Electrohydrodynamic (EHD) printing has become a promising and cost-effective technique for producing high-resolution and large-scale features. One widely recognized obstacle in EHD printing is nozzle clogging due to solvent evaporation or ink polymerization. Moreover, printing highly viscous materials often requires pressure or other external force to assist the ink flow during the printing, which increases the complexity of process control and the required energy. In this work, we developed a novel ultrasonic vibration-assisted EHD printhead and associated process to effectively eliminate the nozzle clogging for the printing of high-viscosity and high-evaporation-rate inks. A series of experimental tests were conducted to characterize the printhead design and process parameters (i.e., vibration frequency, vibration amplitude, and printing voltage). The results demonstrated that superimposing ultrasonic vibration on the EHD printing nozzle can effectively enhance current EHD printing capabilities, such as reducing required pressure, eliminating nozzle clogging, and providing stable and continuous printing for high viscosity and high solvent evaporation rate material. With the optimal parameters, a filament with a diameter of around 1 µm can be continuously printed. In the paper, we successfully applied this developed ultrasonic-assisted EHD process to print high-resolution 2D patterns.more » « less
-
Abstract Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein‐based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field‐assisted 3D printing (MF‐3DP). Micro‐bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D‐printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long‐term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.more » « less
-
Abstract Though 3D printing shows potential in fabricating complex optical components rapidly, its poor surface quality and dimensional accuracy render it unqualified for industrial optics applications. The layer steps in the building direction and the pixelated steps on each layer's contour result in inevitable microscale defects on the 3D‐printed surface, far away from the nanoscale roughness required for optics. This paper reports a customized vat photopolymerization‐based lens printing process, integrating unfocused image projection and precision spin coating to solve lateral and vertical stair‐stepping defects. A precision aspherical lens with less than 1 nm surface roughness and 1 µm profile accuracy is demonstrated. The 3D‐printed convex lens achieves a maximum MTF resolution of 347.7 lp mm−1. A mathematical model is established to predict and control the spin coating process on 3D‐printed surfaces precisely. Leveraging this low‐cost yet highly robust and repeatable 3D printing process, the precision fabrication of multi‐scale spherical, aspherical, and axicon lenses are showcased with sizes ranging from 3 to 70 mm using high clear photocuring resins. Additionally, molds are also printed to form multi‐scale PDMS‐based lenses.more » « less
-
Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that offers many advantages including but not limited to a painless experience, being time-effective, and real-time sensing. This research implements additive manufacturing (AM) technology to fabricate MN arrays for advanced therapeutic applications. Stereolithography (SLA) was used to fabricate six MN designs with three aspect ratios. The MN array included conical-shaped 100 needles (10 × 10 needle) in each array. The microneedles were characterized using optical and scanning electron microscopy to evaluate the dimensional accuracy. Further, mechanical and insertion tests were performed to analyze the mechanical strength and skin penetration capabilities of the polymeric MN. MNs with higher aspect ratios had higher deformation characteristics suitable for penetration to deeper levels beyond the stratum corneum. MNs with both 0.3 mm and 0.4 mm base diameters displayed consistent force–displacement behavior during a skin-equivalent penetration test. This research establishes guidelines for fabricating polymeric MN for high-accuracy and low-cost 3D printing.more » « less
An official website of the United States government

