Complex three-dimensional (3D)-shaped particles could play unique roles in biotechnology, structural mechanics and self-assembly. Current methods of fabricating 3D-shaped particles such as 3D printing, injection moulding or photolithography are limited because of low-resolution, low-throughput or complicated/expensive procedures. Here, we present a novel method called optofluidic fabrication for the generation of complex 3D-shaped polymer particles based on two coupled processes: inertial flow shaping and ultraviolet (UV) light polymerization. Pillars within fluidic platforms are used to deterministically deform photosensitive precursor fluid streams. The channels are then illuminated with patterned UV light to polymerize the photosensitive fluid, creating particles with multi-scale 3D geometries. The fundamental advantages of optofluidic fabrication include high-resolution, multi-scalability, dynamic tunability, simple operation and great potential for bulk fabrication with full automation. Through different combinations of pillar configurations, flow rates and UV light patterns, an infinite set of 3D-shaped particles is available, and a variety are demonstrated.

Mechanical biomarkers associated with cytoskeletal structures have been reported as powerful label-free cell state identifiers. In order to measure cell mechanical properties, traditional biophysical (e.g., atomic force microscopy, micropipette aspiration, optical stretchers) and microfluidic approaches were mainly employed; however, they critically suffer from low-throughput, low-sensitivity, and/or time-consuming and labor-intensive processes, not allowing techniques to be practically used for cell biology research applications. Here, a novel inertial microfluidic cell stretcher (iMCS) capable of characterizing large populations of single-cell deformability near real-time is presented. The platform inertially controls cell positions in microchannels and deforms cells upon collision at a T-junction with large strain. The cell elongation motions are recorded, and thousands of cell deformability information is visualized near real-time similar to traditional flow cytometry. With a full automation, the entire cell mechanotyping process runs without any human intervention, realizing a user friendly and robust operation. Through iMCS, distinct cell stiffness changes in breast cancer progression and epithelial mesenchymal transition are reported, and the use of the platform for rapid cancer drug discovery is shown as well. The platform returns large populations of single-cell quantitative mechanical properties (e.g., shear modulus) on-the-fly with high statistical significances, enabling actual usages in clinical and biophysical studies.

Complex‐shaped microparticles can enhance applications in drug delivery, tissue engineering, and structural materials, although techniques to fabricate these particles remain limited. A microfluidics‐based process called optofluidic fabrication that utilizes inertial flows and ultraviolet polymerization has shown great potential for creating highly 3D‐shaped particles in a high‐throughput manner, but the particle dimensions are mainly at the millimeter scale. Here, a next generation optofluidic fabrication process is presented that utilizes on‐the‐fly fabricated multiscale fluidic channels producing customized sub‐100 µm 3D‐shaped microparticles. This flexible design scheme offers a user‐friendly platform for rapid prototyping of new 3D particle shapes, providing greater potential for creating impactful engineered microparticles.

Particles with non-spherical shapes can exhibit properties which are not available from spherical shaped particles. Complex shaped particles can provide unique benefits for areas such as drug delivery, tissue engineering, structural materials, and self-assembly building blocks. Current methods of creating complex shaped particles such as 3D printing, photolithography, and imprint lithography are limited by either slow speeds, shape limitations, or expensive processes. Previously, we presented a novel microfluidic flow lithography fabrication scheme combined with fluid inertia called optofluidic fabrication for the creation of complex shaped three-dimensional (3D) particles. This process was able to address the aforementioned limits and overcome two-dimensional shape limitations faced by traditional flow lithography methods; however, all of the created 3D particle shapes displayed top-down symmetry. Here, by introducing the time dimension into our existing optofluidic fabrication process, we break this top-down symmetry, generating fully asymmetric 3D particles where we termed the process: four-dimensional (4D) optofluidic fabrication. This 4D optofluidic fabrication is comprised of three sequential procedures. First, density mismatched precursor fluids flow past pillars within fluidic channels to manipulate the flow cross sections via fluid inertia. Next, the time dimension is incorporated by stopping the flow and allowing the denser fluids to settle by gravity to create asymmetric flow cross sections. Finally, the fluids are exposed to patterned ultraviolet (UV) light in order to polymerize fully asymmetric 3D-shaped particles. By varying inertial flow shaping, gravity-induced flow shaping, and UV light patterns, 4D optofluidic fabrication can create an infinite set of complex shaped asymmetric particles.