A new concept of micro nano processing has promoted the scalability and continuous manufacturing and assembly of particles in microfluidic systems. Scientists from RWTH Aachen University in Germany have developed and demonstrated a new flow, channel integration, and continuous production process using Nanoscribe's 2PP 3D printing technology for manufacturing ultra small, arbitrarily shaped 3D particles. The printing process demonstrated the continuous production of 150000 particles within 72 hours. 2PP technology (two)-photon polymerization,TPP)The high design freedom, high shape accuracy, and flexibility of materials enable the manufacture of particles with different shapes, micrometer sizes, submicron features, and various materials. The study aims to apply this particle assembly method to cellular tissue engineering applications and expand the scope of manufacturing self regulating, responsive, and permeable 3D scaffolds.

Millimeter and micrometer sized particles can be flexibly applied to the supports required for chemical and biochemical reactors. Bioreactors are used to immobilize and analyze enzymes, cells, or microorganisms on the surface of the internal structure of the reactor. The key to their performance is the ability to adjust the properties of particles that affect the characteristics of biological reactions. In order to expand this application, scientists from RWTH Aachen University and the DWI Leibniz Institute for Interactive Materials in Aachen, Germany, proposed a novel micro nano processing concept of two-photon continuous vertical flow lithography, which enables high-throughput micro nano processing of particles with complex shapes, micrometer sizes, and submicron features, allowing particles with a size of about 20 μ m to self assemble 3D scaffolds under surface interactions. In the study, scientists also analyzed the permeability resistance and bulk density of 3D components using various particle shapes, sizes, and materials.

The key lies in the two-photon polymerization (2PP) technology of Nanoscribe printing equipment. Two photons scan on the xy plane while the fluid resin flow continuously transmits the printed xy slices along the z direction. Once one particle is completed, the next particle will be produced in the same way during the continuous printing process. By using Nanoscribe's DeScribe software and phyton scripts to adjust the output file, various designs with complex geometric shapes can be sliced and prepared for fluid printing. The fluid printing process is continuous, so thousands of particles can be produced within a few hours, achieving printing up to 150000 particles within 72 hours. Based on the great design freedom of 2PP 3D printing, particles of any shape can be produced. Compared with substrate printing, particle flow printing has obvious advantages, but it can achieve continuous manufacturing of one particle after another without any waiting time between two particles. When printing layer by layer, the flow printing method also bypasses the z-movement of the stage, as it is the flow that transports xy slices in the z-direction. Therefore, flow printing represents an increase in the speed of manufacturing small and complex shaped particles.

Particle assembly applied to 3D biological mixed tissues

Particles smaller than 100 μ m can form complex cell scaffolds after self-assembly, and the reaction characteristics of the scaffolds can be adjusted accordingly when adjusting the particle shape, size, porosity, and material properties. This high degree of flexibility is highly suitable for creating scaffolds for cell culture and tissue engineering. Adjusting the particle geometry will affect the surface volume ratio, thereby customizing the fluid dynamics passing through and around the structure. However, there are still challenges in controlling the particle organization process when using flow self-assembly to produce scaffolds.

In order to study 3D bio hybrid tissues, scientists investigated the interaction between mouse fibroblast cultures and particles printed using Nanoscribe's non-toxic IP Visio photoresist, which has low fluorescence and better cell analysis under a microscope. After four days of cultivation, the cells continuously proliferate, adhere, and infiltrate the printed scaffold through interaction, and connect the particles to form a new tissue morphology.

Reference:

Fabrication, Flow Assembly, and Permeation of Microscopic Any-Shape Particles