Aram J. Chung

Optofluidic fabrication for 3D-shaped particles

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.

Pulsed laser activated cell sorting with three dimensional sheathless inertial focusing.

We present a Pulsed Laser Activated Cell Sorter (PLACS) integrated with 3D sheathless inertial focusing that is capable to sort at 10,000 particles sec-1 with >90% sort purity and 6,000 cells sec-1 with >80% sort purity. It is realized by exciting laser induced cavitation bubbles in a single layer PDMS microfluidic channel to create high speed liquid jets to deflect detected fluorescent samples. Fluid inertia and secondary flows induced by stepped microchannels are used to focus samples in 3 dimensions. After focusing, samples go through an expansion chamber whose function is to enlarge the separation distance between two closely positioned particles by particle-particle interaction in inertial flows and reduce the coincident events within the switching window (16 μsec in time or 32 μm in distance). This sorter uses 10 times lower initial concentration cell samples than that in sheath-based PLACS in order to avoid severe dilution effects from high volume sheath flows at the same throughput.

Inertial Microfluidic Cell Stretcher (iMCS): Fully Automated, High‐Throughput, and Near Real‐Time Cell Mechanotyping

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.

DIY 3D Microparticle Generation from Next Generation Optofluidic Fabrication

Abstract 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.

Non-special particle generation from 4D optofluidic fabrication

To create asymmetric three-dimensional shaped particles, density mismatched precursor streams are first shaped by fluid inertia, and then further shaped by gravity. Finally, patterned TJV light polymerizes complex shaped asymmetric 3D particles.

Pulsed laser activated cell sorting with three dimensional sheathless inertial focusing

We present a Pulsed Laser Activated Cell Sorter (PLACS) integrated with 3D sheathless inertial focusing that is capable to sort at 10,000 particles sec -1 with >90% sort purity and 6,000 cells sec -1 with >80% sort purity. It is realized by exciting laser induced cavitation bubbles in a single layer PDMS microfluidic channel to create high speed liquid jets to deflect detected fluorescent samples. Fluid inertia and secondary flows induced by stepped microchannels are used to focus samples in 3 dimensions. After focusing, samples go through an expansion chamber whose function is to enlarge the separation distance between two closely positioned particles by particle-particle interaction in inertial flows and reduce the coincident events within the switching window (16 μsec in time or 32 μm in distance). This sorter uses 10 times lower initial concentration cell samples than that in sheath-based PLACS in order to avoid severe dilution effects from high volume sheath flows at the same throughput.

Pulsed laser activated cell sorter (PLACS) for high-throughput fluorescent mammalian cell sorting

We present a Pulsed Laser Activated Cell Sorter (PLACS) realized by exciting laser induced cavitation bubbles in a PDMS microfluidic channel to create high speed liquid jets to deflect detected fluorescent samples for high speed sorting. Pulse laser triggered cavitation bubbles can expand in few microseconds and provide a pressure higher than tens of MPa for fluid perturbation near the focused spot. This ultrafast switching mechanism has a complete on-off cycle less than 20 μsec. Two approaches have been utilized to achieve 3D sample focusing in PLACS. One is relying on multilayer PDMS channels to provide 3D hydrodynamic sheath flows. It offers accurate timing control of fast (2 m sec-1) passing particles so that synchronization with laser bubble excitation is possible, an critically important factor for high purity and high throughput sorting. PLACS with 3D hydrodynamic focusing is capable of sorting at 11,000 cells/sec with >95% purity, and 45,000 cells/sec with 45% purity using a single channel in a single step. We have also demonstrated 3D focusing using inertial flows in PLACS. This sheathless focusing approach requires 10 times lower initial cell concentration than that in sheath-based focusing and avoids severe sample dilution from high volume sheath flows. Inertia PLACS is capable of sorting at 10,000 particles sec-1 with >90% sort purity.