Additive manufacturing (AM) is an emerging technology for building complex geometries by depositing or photo-curing materials. It includes fused deposition molding (FDM), inkjet printing, two-photon polymerization (TPP), and vat photopolymerization (VPP).
In 3D microstructure fabrication, 3D printing technologies based on photopolymerization have emerged as effective methods for realizing structures with micrometer or submicrometer resolution, especially stereolithography (SLA) and digital light processing (DLP) technologies.
DLP's projected microstereolithography (PμSL) offers significant advantages in fabricating microfluidic chips, such as rapid preparation, flexibility in building complex 3D structures, and the ability to print complex curved surfaces and integrated chip interfaces that cannot be fabricated by traditional MEMS processes without the need for clean rooms and specialized personnel.
1. How PμSL technology works
The printing system for PμSL technology consists of four subsystems: the light engine, the projection objective, the motorized table and the resin tank.
The technology adopts a layer-by-layer processing method to fabricate complex three-dimensional structures. By initiating the photopolymerization reaction of the photosensitive material with ultraviolet light, the liquid photosensitive material is transformed into a solid state, and the curing layer is constructed with a single face exposure using a computer-generated dynamic mask image.
After each completed layer of photopolymerization, the molding platform moves one layer thickness interval until 3D printing is complete. Photopolymerization resin formulations generally consist of monomers, photoinitiators, and light absorbers.
In the PμSL technique, the light engine consists of a light source and a device that dynamically generates a mask image, usually using a digital micromirror device (DMD) or a liquid crystal display (LCD).
Compared to LCD, DMD has advantages in contrast and switching response speed, and is especially suitable for UV processing. Currently, almost all of the high-precision PμSL printing systems on the market use DMDs to generate mask images.
2. Development of microfluidic chips prepared by PμSL technology
There are two main ways to fabricate microfluidic chips using PμSL technology: indirect fabrication and direct fabrication.
The indirect fabrication method starts with the creation of a mold by 3D printing, followed by mold turning. This method requires special treatment of the light-cured mold to avoid adhesion of the PDMS to the mold, as well as a subsequent bonding process.
The direct fabrication methods are divided into two categories: the first is to print an open pipe structure first, and then combine with other materials to form a closed pipe through methods such as gluing; the second is to integrate the printing of closed pipes to achieve a single-step rapid prototyping of microfluidic devices.
1) High Precision Printing
In PμSL technology, the microchannel printing accuracy can be improved in two directions: the Z-axis and the XY-plane. the XY-plane accuracy mainly depends on the performance of the optical system, which is related to the DMD resolution and the optical magnification system. In addition to optimizing the optical system, image recognition-based methods can also effectively improve the XY plane accuracy.
Z-axis resolution, on the other hand, is mainly determined by the depth of light penetration of the material, a value that can be measured by a logarithmic fitting experiment of the curing depth and the corresponding exposure time. Improving Z-axis accuracy can be achieved in three main ways: optimizing the light path and resin formulation, optimizing different printing methods for different layers, and optimizing the image.
Adjusting the optical system and adding light absorbers to the resin material are common optimization methods. Adding a light absorber reduces the light penetration depth of the liquid resin, making the printing process more controllable, which improves Z-axis printing accuracy and XY-plane feature size.
2) Multi-material printing
Unlike single-material 3D printing, multi-material printing technology enables the same chip to exhibit diverse performance characteristics in different structures, enhancing the functionality of microfluidic devices and broadening their potential applications.
Currently, the main challenges of integrated multi-material printing technology are to realize rapid material switching and to effectively remove residual resin from the printed structure to prevent mutual contamination between different materials.
3. Application of PμSL technology in microfluidic chips
1) Microfluidic Functional Devices
The PμSL technology offers new possibilities for fabricating highly integrated chips, making multiple liquid manipulations and reactions on microfluidic chips a reality. Studies have been conducted to reduce the diameter of thin-film valves from 300 μm to 46 μm, and extruded valves with dimensions of 15 μm × 15 μm have been successfully fabricated.
As chip size decreases, connecting to external fluids or pneumatic devices becomes more difficult, making high-density interfaces an important requirement for microfluidics.
Some academics have used 3D printing technology to print valves with a diameter of 300 μm inside a microfluidic chip, containing two pneumatic drive channels and two fluid channels, creating the smallest 3D-printed valve at the time.
In addition, microdroplet generation chips and Micromixer chips are also important applications of 3D printing in recent years.
Single-emulsion and double-emulsion microdroplet-generating chips fabricated based on PμSL technology are capable of simultaneously realizing single-emulsion generation in five parallel channels, advancing the development of high-throughput microfluidic technology.
The technology allows different types of emulsions to be generated on the same equipment and reused several times after cleaning, with significant advantages, especially in droplet formation, without surface treatment.
With the growing importance of cell sorting in the medical field, the use of 3D printing technology to create inertial microfluidic chips for cell separation has received a lot of attention. The research team designed a modular microfluidic system containing two micromixers, a spiral microfluidic separator and a microfluidic concentrator.
2) organ chip
Human organs form three-dimensional transportation mechanisms through a complex network of biophysical and biochemical blood vessels that provide cells with an external environment, but these mechanisms have been difficult to study.
With the development of PμSL printing technology, complex multivessel topologies can be fabricated, which have a wide range of biomaterial and tissue engineering applications.
Using a food dye additive with good biocompatibility as a photoabsorbent, the researchers constructed a three-dimensional mathematical algorithm-based three-dimensional structure of an entangled vascular network using the PμSL technique and perfused human erythrocytes and oxygen into two adjacent channels to evaluate the efficiency of interstitial transport between blood vessels, thus demonstrating the feasibility of oxygen transport in a 3D entangled network.
Organ chips require high biocompatibility of printing materials, and the choice of materials is limited. Photosensitive resin materials may lead to greater cytotoxicity, while biocompatible hydrogel materials may not be able to meet the mechanical property requirements of organ chips.
Transparency, cytocompatibility, and print resolution requirements can be met by adapting the printing hardware (e.g., printing platform), resin formulations (e.g., photoinitiators and photoabsorbents), and employing specialized post-treatments (e.g., UV irradiation, solvent extraction).
Three different resin materials were utilized to fabricate organoids, and all of them successfully achieved cell culture. Among them, acrylate-PDMS showed good biocompatibility and was able to support the growth of lung and skin epithelial cells without genotoxic effects, while avoiding the problem of small molecule adsorption of PDMS.
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