Precisely Constructing Micro Worlds: How Micro-Nano 3D Printing Can Help Microfluidic Chips Achieve Manufacturing Breakthroughs?

2025-10-24

Microfluidic chips, as an integrated micro-scale fluid manipulation platform, have demonstrated remarkable technical potential in fields such as life sciences, drug screening, disease diagnosis, and environmental analysis in recent years. Their basic principle is to construct micro-meter-sized closed channels and reaction units within the chip. Through external control systems, they drive the liquid to flow within the micro-chambers, achieving high-throughput, low-loss, and multi-parameter coupling experimental functions. They are known as "lab-on-a-chip".
The core of microfluidic chips lies in their ability to spatially construct complex fluid paths. The current main manufacturing methods include soft lithography, micro-milling, and molding, etc. Although they have been applied in some scenarios, they still face manufacturing challenges in terms of complex structures, high-precision molding, and functional integration.
In response to the increasing complexity of microfluidic chip manufacturing, micro-nano 3D printing technology, as an emerging precise construction technology, is becoming the key path to break through the current manufacturing bottlenecks and is emerging as an ideal solution for fabricating highly precise and complex microfluidic chip structures.
Application Case 1: Multi-functional integrated microfluidic chip
The microfluidic chip with multi-functional integration and suitable for micro-sample processing can significantly improve the analysis efficiency by integrating the sample introduction unit and the pre-treatment module. The research group led by Professor Hu Bin from Wuhan University reported a microfluidic chip constructed by 3D printing technology, which integrates functions such as cell lysis, overall column micro-extraction, micro-valve control unit and full-flow type high-efficiency atomizer. This chip was applied to the analysis of trace rare earths in cells.
The research team used the integrated sample introduction system fabricated by the MoFen Precision Surface Projection Micro Stereolithography (PμSL) 3D printing technology. This system mainly consists of a multi-functional array integrated column micro-extraction chip and a detachable microfluidic all-consuming high-efficiency atomizer (MTHEN). The 3D-printed (3DP) array integrated micro-extraction chip is composed of a cell lysis unit and an array integrated micro-extraction unit, and integrates a micro-valve control unit to achieve automatic switching between sample loading and desorption. It is connected to ICP-MS online through the 3DP-MTHEN with a customized structure and interface. Combined with ICP-MS detection, the system evaluated the extraction performance of the 3DP overall column for trace rare earth elements (REEs) and the atomization performance of the 3DP-MTHEN, and applied it to the analysis of trace REEs in a small amount of MCF-7 cells.

Schematic diagram of the 3D printing ICP-MS sample introduction system

The above structure was 3D fabricated using the MoFang Precision Micro-Nano 3D Printing System: microArch? S130 (with an accuracy of 2 μm). The 3DP array integrated column micro-extraction chip consists of two parallel micro-extraction units, which are integrated together through a micro-valve control unit. Each micro-extraction unit is designed with three inlets, which are used to introduce cell solutions, lysis solutions, and desorption solutions into the chip.
The microfluidic device fabricated by the Mofang Precision Micro-Nano 3D Printing System has a structural feature where the separation unit is an elliptical channel with an inner diameter of 150 μm, and the micro-extraction unit is composed of repetitive lattice structures, with the rod diameter being 20 μm.
The study constructed a multi-functional integrated sample introduction system composed of an array overall column micro-extraction chip, micro-valves, and micro-flow atomizer using 3DP technology. It was then combined with ICP-MS for the analysis of ultra-trace REEs in cells. The multi-functional array overall column micro-extraction chip integrates a cell lysis unit, an overall column micro-extraction unit, and a micro-valve control unit, featuring a simple structure, long service life, small dead volume, low cost, and ease of matching with ICP-MS detection. The highly integrated 3DP integrated sample introduction system was used as the sample introduction unit of ICP-MS. The online analytical method constructed based on this has a low cell consumption and is suitable for analyzing small-volume complex samples, providing strong technical support for the subsequent study on the cytotoxicity of REEs.
Paper link: https://doi.org/10.1021/acs.analchem.4c05810
Application Case 2: Utilizing the Porous Structure of the Pyramid for Liquid Separation
Currently, when dealing with the separation of water-in-oil emulsions, scholars usually employ super-hydrophilic underwater super-oil-repellent filtration membranes. However, many existing materials, such as sponges and metal foams, can become contaminated over time, thereby reducing the separation efficiency. Therefore, developing separation materials with anti-fouling properties has become the key to achieving long-lasting and efficient oil-water separation.
A research team from Northwest A&F University and Dalian University of Technology used high-precision 3D printing technology to design and fabricate an ultra-hydrophilic pyramid-shaped porous material, and achieved efficient separation of oil-in-water emulsions. The unique pyramid structure enhanced the ability to intercept droplets. When water droplets were dropped into the emulsion (oil-in-water), water could pass through the porous structure, while oil would be blocked within the porous structure, significantly improving the separation efficiency. The surface of this material was modified with self-polymerized dopamine (DA) and polyethyleneimine (PEI) coatings to give it super hydrophilic and underwater super oleophobic properties. The separation flux of this porous material reached 3098 L/m2h, and the separation purity reached 99.3%. Computational fluid dynamics (CFD) simulation technology was used to visualize the emulsion separation mechanism, thereby gaining a deeper understanding of the dynamic process of droplet behavior within the funnel structure.

Structural Design and Manufacturing Process of Pyramid-Shaped Porous Materials

The required structure for the experiment was first fabricated using the Mofang Precision PμSL technology with a pyramid-shaped porous structure base. Then, through coating treatment (polydopamine/polyethyleneimine copolymer), a hydrophilic and underwater superhydrophobic porous structure was obtained. This study shows that by using high-precision 3D printing technology, polyacrylic acid resin was layer-by-layer printed, and then coated with PDA/PEI polymer to form an ultra-hydrophilic pyramid-shaped porous material, which will enhance the droplet interception effect and significantly improve the emulsion separation efficiency. It is expected to be applied in the fields of environmental remediation and industrial wastewater treatment.
Original link: https://doi.org/10.1016/j.cej.2024.156808
Application Case 3: Microfluidic Chips for the Construction of Pancreatic Islet Microbiological System
The microphysiological system, including the organ-on-a-chip system, can achieve in vitro biomimicry of tissues and organs using microfluidic three-dimensional cell culture devices. These technologies can make up for the shortcomings of animal models in basic disease research and, in some cases, even replace them. For example, they show significant advantages and potential in the evaluation and screening of diabetes drugs.
Based on this, the research team from Shanghai University developed a pancreatic islet microphysiological system based on fibrous materials and microfluidic spinning. This system includes pancreatic islet-loaded microfibers prepared by combining controllable pneumatic valves with microfluidic rotation technology, as well as a microfluidic system composed of microfibers assembled with vascular endothelial cells. The results show that the prepared microfibers are loaded with a large number of monodisperse pancreatic islet clusters with good cell activity and function. The microfibers are assembled with vascular endothelial cells in the microfluidic system, providing a 3D environment that simulates natural blood vessels and supports high-throughput cell loading. The microfibers are vascularized by endothelial cells growing on their surface. The microfluidic system simulates capillary blood flow and nutrient exchange, thereby enhancing the physiological relevance of the model. The ability of this system to simulate physiological conditions through the synergistic action of biophysical and biochemical factors makes it a powerful tool for biomedical research.

Schematic diagram of pancreatic islet-loaded microfibers prepared by microfluidic spinning technology combined with pneumatic valves

The research team used the MoFang Precision Micro-Nano 3D Printing System: nanoArch S140 (with an accuracy of 10 micrometers) to fabricate two types of templates: microfluidic rotating chip template and assembly chip template. They combined PDMS mold-making technology to complete the required structures for the experiment. They produced insulin-secreting microfibers to construct an insulin micro-physiological system, which can be used for in vitro evaluation of anti-diabetic drugs and will promote the transformation of microfluidic technology to pre-clinical drug development.
Original link: https://doi.org/10.1016/j.biomaterials.2025.123480
The value of microfluidic chips lies not only in their ability to perform precise testing or miniaturize chips, but they are also becoming the underlying hardware for dissecting life, diagnosing diseases, simulating environments, and evaluating drug efficacy. Of course, their manufacturing methods must also undergo innovation.
Micro-nano 3D printing, by precisely controlling the structural scale, providing diverse support for material systems, and systematically reconfiguring functional integration, is becoming the breakthrough solution for the innovation in microfluidic chip manufacturing. The integrated platform of "equipment + materials + terminal applications" constructed by Mofang Precision offers unprecedented design freedom and manufacturing capabilities to research institutions, medical enterprises, and biomanufacturing companies, and will further promote the implementation of high-throughput chip manufacturing capabilities and industrial applications.

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