An automated 3D visible light stereolithography platform for hydrogel-based micron-sized structures

In recent years, many studies has focused on the fabrication of micron-sized biomaterial structure for drug delivery as their tiny volume and multifunction are necessary for work in vivo environment.^1,2 However, conventional manufacturing methods still have limitations in producing specific structure of micron-sized biomaterial structure. The manufacturing methods like mask lithography and machining could limit the development of functional but complicated designs of micron-sized structure.³ Three-dimensional (3D) printing which builds an object layer by layer. With the development of 3D printing, it could provide those drug delivery carriers with complex bio-inspired 3D structure.⁴ 

Although DLP 3D printing was investigated widely in recent years and reached high precision.^5,6 But most of those 3D printing manufacturing methods based micron-sized structure were rigid and non-degradable in human body. Different form other 3D printing materials, micron-sized structure based on hydrogel could improve biocompatibility significantly, and have easy controllable swollen ratio and great mechanical performance. However, one of the limitation of hydrogel-based 3D printing was that we can only produce the hydrogel based micron-sized structure at a relative low accuracy comparing to photosensitive resin.⁷ 

The requirement of UV light also limited the application area, and only few of them focused on the printing of biomaterials.⁸ Recently reported works had limitations such as a compromised balance between precision, printing area, speed and cost. In this paper, an automated visible light stereolithography platform is presented. High-precision micro structures for biomaterials could be quickly printed with bio-functional printing area in low cost. The visible light source also provide a wide application for bio-applications. Details of the whole automated DLP system for researchers as a reference in areas such as biomaterials, drug delivery, biomedical engineering and instruments. The schematic of the printing platform based on Digital light processing (DLP) is shown in Fig. 1. A micro-manipulator controlled the printing platform on the z-axis, and a projector-convex lens system was assembled to the platform to print precise patterned light on the x-axis and y-axis. Instead of UV, visible light is chosen as light source. Damage to the lens system is reduced so that the service life of the system would increase. A Personal computer (PC) controlled the whole system and controlling software was programmed. The Digital micromirror device (DMD) chip received Video graphics array (VGA) signal from PC and reflected diffusing surface light source to specific pattern according to the signal. Precision motorized stage on z-axis also received orders from PC in serial port. Undering the coordinate work of the projector-lens system and motorized stage, the platform would allow us to build 3D micron-sized structure precisely and automatically.

In the projector-lens system, point light source was provided by a blue Light-emitter diode (LED) chip, while a thermistor and cooling system work together control the temperature of LED. The whole structure of light engine is illustrated in Fig. 2. By using the collimating lens, the point light source was converted to non-uniform area source. Then the fly-eye lens formed a uniform illumination distribution with respect to a reflector. Diffusing surface light source was illuminated on the DMD chip, and the patterned light was obtained. The light engine was refitted from a commercial projector. The commercial DLP projector was opened and the semi-transparent mirrors for red LED and yellow LED which weaken blue-light LED light intensity were dismantled. The blue LED was driven by current source, while heavy current cause stronger light than light current. The light intensity at different value of current were measured by a photometer at working distance, the relationship between light intensity and current was made to a line chart and shown in Fig. 3. The linear fit equation of the relationship was expressed as

while I, E represent current value and light intensity respectively. In Eq. (1), α is the slope and equals 92.73 W$•$A^-1$•$cm^-2 and β is the y-intercept and equals minus 3.6 W$•$cm^-2. With this equation, the light intensity of LED can be controlled by adjusting the value of current.

The automated 3D visible light stereolithography platform made by ourselves is displayed in Fig. 4. The platform are made up of three main parts. The first part is ink bathing pool, the pool was placed upon a height adjustable holder which was fastened to an optical table. Adjusting the height of the holder could adjust the relative location of the sample holder to ink level. Light engine is the second part which project visible light image to the sample holder. A commercial projector refitted earlier was linked to computer and a camera convex lens was used to concentrate the light with pattern. This lens could project high resolution image with ideal parameters. Projector and convex lens were hang on a support bar on the optical table at different altitude when projector projects from top down to the lens, and finally to the sample holder. The last part is moving kit, which were consisted of sample holder, precision motorized stage and its control cabinet. Sample holder was fixed to the motorized stage, while the motorized stage move vertically to alter the altitude of the sample holder. Precise z-axis positioning could be achieved by combing second part and third part. At the same time, we used a microscope to observe the image projected during focusing process. And printing operation steps are as follows:

1. Connect projector and precision motorized stage to computer, then turn on the DLP based platform operating software based on labview.

2. Set the Cluster communication (COM) port number and printing parameters such as thickness, exposure time and dark time.

3. Run the software and establish communication with DLP projector and precision motorized stage.

4. Project the test image into the film, and adjust the height of the sample holder to the focus of the convex lens.

5. Pour ink into bathing pool and put a glass slice on the sample holder. Then twist the base of bathing pool to make the glass slice just immersed in the ink.

6. Press start button on operating software and the platform would work automatically.

Since the platform started to work automatically, a slice image prepared earlier would be projected from commercial projector to interface between ink and glass slice as long as preset exposure time and then stopped projecting as long as preset dark time. During dark time the precision motorized stage would carry the glass slice on sample holder downward for thickness of a single layer. The thickness was calculated by preset parameters and height of model. Displacement occurred after precision stage received certain numbers of impulse given by PC. Printing process above would be repeated until all the images were projected. The program run in labview environment and flow chart in details are displayed in Fig. 5.

Printing samples observed with microscope are shown in Fig. 6, the top left picture was pattern of school bandage of Anhui medical university which is a two-dimensional model. This pattern was used to demonstrate the precision of planar structure built by the platform. Three-dimensional helix with high accuracy in the top right picture were printed from bio-inspired structure which may have well propelling performance in nature. The helix was used to qualify the precision of building three-dimensional complex structure. Many micron-sized structure reported have spiral structure as it can provide sufficient propulsion to move while it keep rotating.⁹ The bottom left picture was cage structure designed in solidworks and the bottom right picture was printed from the model. It was also used to test the printing precision and stability of the platform. As cage structure were used to transport cells and drug.⁴ The interval and details of cage structure were restored well under the observation with industry camera. The scale bar are attached to the bottom right corner in every picture respectively. Obviously, the precision of those samples printed by the low cost DLP based platform reach micro meter and have well details. The relationship between precision and printing area is that precision times resolution equals the printing area. The highest resolution of DMD chip is 1280^*720 and the printing precision of the platform could reach 10 μm.

Among micron-sized biomaterial structure manufacturing methods, 3D printing is an efficient method. But using hydrogel as material to build high-precision structure was a problem. We achieved 3D printing high accuracy structure based on hydrogel in micro scale successfully at low cost with the automatic high-precision 3D printing platform. As the light engine was refitted from a commercial projector, the cost of core part in this platform was significantly reduced. Thus, the threshold of high-precision 3D printing of hydrogel is lower. This platform provides a low-cost and fast micron-sized structure manufacturing method which bring much convenience in producing micron-sized biomaterial structure. Besides, details are provided. What’s more, this kind of platform would be necessary for high-precision printing of micron-sized structure based on different types of hydrogel in future and have potential for multi-solution 3D printing for micro structure. The technique which may enable formation of multi-functional high-precision micron-sized structure in future.

This work was supported by the National Natural Science Foundation of China (Project No. 61603002).