Appl. Mater. Today: Aerosol Jet Printing Revolutionizes Microneedle Fabrication, Preserving the Activity of Biologics
Product Introduction
Equipment Parameters
I. Research Background
Biologics—such as proteins, antibodies, and vaccines—are steadily increasing their share in the pharmaceutical sector. However, conventional injectable formulations suffer from poor patient compliance, making dissolvable microneedles an ideal transdermal delivery platform. Traditional microneedle fabrication relies on mold‑casting, photolithography, and stereolithographic 3D printing, which are plagued by complex processes, thermal or UV‑induced drug deactivation, limited structural precision, and insufficient mechanical strength. In contrast, aerosol jet printing, with its advantages of low temperature, non‑contact operation, broad material compatibility, and high precision, has emerged as a key technology for the green and efficient manufacturing of dissolvable microneedles.
II. Working Principle and Advantages
Working principle
Centered on aerosol jet printing, an aqueous formulation of PVP, trehalose, and glycerol is ultrasonically atomized into a stable aerosol. The aerosol is then precisely deposited onto a silicon substrate via gas‑assisted pneumatic focusing, with carrier and sheath gases. Layer‑by‑layer stacking, guided by CAD programming, yields a conical microneedle array—entirely carried out at low temperatures and without intense light exposure, thereby ensuring optimal preservation of bioactive components.
Core Advantages
- Manufactured throughout the process at mild, low temperatures, without compromising the activity of proteins, vaccines, and other biopharmaceuticals.
- Non-contact pneumatic focusing enables precise micro-needle formation with high straightness and sharpness.
- The ink is widely compatible and enables direct, integrated printing of biopharmaceuticals.
- Digitally programmable, enabling rapid customization of arrays in various sizes without the need for molds.
III. Core Pain Points and Breakthroughs
Core pain points
1. Conventional microneedle fabrication requires high temperatures, ultraviolet irradiation, and organic solvents, which can easily lead to the degradation and loss of activity of biopharmaceuticals.
2. Mold manufacturing involves complex processes, long lead times, and high customization costs, making personalized production challenging.
3. Conventional 3D printing suffers from insufficient resolution and poor needle sharpness, making it difficult to penetrate the skin.
4. The mechanical strength and solubility of microneedles are difficult to balance, leading to easy fracture or excessively slow dissolution.
5. During printing, nozzle clogging and excessive material drooling are common, resulting in poor build consistency.
Core Breakthrough
1. Pioneered aerosol jet printing for the fabrication of dissolvable microneedles, operating under mild conditions throughout the process and compatible with biopharmaceuticals.
2. Mold-free digital direct writing enables rapid customization of 4×4 arrays, significantly shortening the fabrication cycle.
3. Precise control of the focus ratio and printing parameters yields micro‑needles with high sharpness, enabling successful skin penetration.
4. Optimized the PVP–trehalose formulation to balance mechanical strength with rapid dissolution properties.
5. The system optimizes atomization flow rate, temperature, and velocity to enhance molding uniformity and stability.
IV. Innovative Highlights
1. For the first time internationally, aerosol jet printing has been applied to the fabrication of dissolvable microneedle arrays, paving the way for a completely new technological approach.
2. Enables mild preparation under low-temperature conditions, free of ultraviolet radiation and organic solvents, with perfect compatibility for biopharmaceuticals.
3. Digital layer-by-layer printing allows for precise control over microneedle height, taper, sharpness, and array density.
4. The microneedles exhibit both sufficient mechanical strength and rapid dissolution, successfully achieving penetration of ex vivo skin.
V. Scope of Application
1. Painless transdermal delivery of protein-, peptide- and antibody-based biologics;
2. Non-invasive transcutaneous vaccination enhances adherence;
3. Personalized, custom-designed microneedle patches tailored to different body sites and dosing regimens;
4. A portable transdermal formulation for self-administration at home.
Image and Text Guide
Figure 1. Representative scanning electron microscopy (SEM) images of microneedles fabricated via the AJP technique, illustrating their morphological evolution.
(A) Filling patterns of each layer. (D) Spherical tip. (E) Rough needle structure. (F) Needle body enveloped by overspray.
Figure 2. SEM images of representative printed lines fabricated from the dissolution formulation at different flow rates, with material deposition progressing from left to right; magnification: 50×.
(A) 20, (B) 22, (C) 24, (D) 26, (E) 28, (F) 30, (G) 32, (H) 34, and (I) 36 cubic centimeters. The fixed printing conditions are as follows: working distance of 4 mm, nozzle diameter of 300 µm, printing speed of 0.25 mm/s, platen temperature of 40°C, focus ratio of 1, and a layer count of 1 when printing an 11.11 wt% dissolvable microneedle formulation (3:1 PVP : trehalose).
Figure 3. SEM images of printed dissolving microneedle formulations at different atomizer flow rates.
(A) 26, (B) 28, (C) 30, (D) 32, (E) 34, and (F) 36 ccm. The fixed printing conditions were as follows: working distance of 4 mm, nozzle diameter of 300 µm, printing speed of 0.25 mm/s, platen temperature of 40 °C, focus ratio of 1, needle diameter set to 90 µm according to the CAD design, and 60 repetitions. When fabricating a 11.11 wt% dissolved microneedle formulation (3:1 PVP:trehalose), the fabrication time was approximately 30 minutes.
Figure 4. (A) Effect of atomizer flow rate on line width for n = 6. (B) Effect of atomizer flow rate on circle diameter for n = 8. Error bars represent ± standard deviation.
Figure 5. SEM images of printed dissolving microneedle formulations at different temperatures.
(A) 25°C, (B) 30°C, (C) 35°C, (D) 40°C, (E) 55°C, and (F) 70°C. Printing was performed using fixed parameters: a working distance of 4 mm, a nozzle diameter of 300 µm, a focusing ratio of 1, an atomizer flow rate of 32 cc/min, a sheath flow rate of 32 cc/min, a needle body diameter of 90 µm as designed in the CAD model, and 60 repetitions. When printing a 11.11 wt% dissolved microneedle formulation (3:1 PVP:trehalose), the process took approximately 30 minutes.
Figure 6. SEM images of printed dissolvable microneedle formulations at different printing speeds.
(A) 0.25 mm/s, (B) 0.75 mm/s, and (C) 1.25 mm/s. The fixed printing conditions were as follows: working distance of 4 mm, nozzle diameter of 300 µm, focusing ratio of 1, atomizer flow rate of 32 ccm, sheath flow of 32 ccm, needle diameter of 90 µm as designed in the CAD model, 60 repetitions, and a fabrication time of ≤30 minutes when printing an 11.11 wt% soluble microneedle formulation (3:1 PVP : trehalose).
Figure 7. (A) Effect of the focus ratio on measured line width and (B) effect of the focus ratio on measured line height. Average cross-sectional profiles of microneedle formulations printed at different focus ratios: (C) 0.03, (D) 0.5, (E) 1. n = 6. Error bars represent ± standard deviation.
Figure 8. SEM images of printed dissolving microneedles at different focusing ratios.
(A) CAD design, (B) 0.03, (C) 0.5, and (D) 1. The fixed printing conditions are as follows: working distance of 4 mm, nozzle diameter of 300 µm, printing speed of 0.25 mm/s, platen temperature of 40 °C, atomizer flow rate of 32 ccm, 60 repetitions, and a fabrication time of approximately 24 minutes when printing an 11.11 wt% dissolving microneedle formulation (3:1 PVP : trehalose).
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