Gene therapy shows promise for treating everything from cancer to some viral infections and inherited disorders. The demand for next-generation manufacturing of synthetic constructs and gene-targeted therapy drugs has grown significantly, reaching $19 billion USD around the world in 2020.
To stay competitive and meet this increasing demand, biotech and biopharma companies can look to modeling. At any stage of the design process, companies can use modeling to explore multiple design options in the manufacturing processes (Kosuri, 2014; Palomo, 2014)
Many of these processes involve synthesis performed within a solvent and require complex methodologies to route reagents to spatially localized supports. For example, biopharmaceutical companies may utilize submerged electronic microchips, which can be used as identifiable supports for synthesis, to accelerate the manufacturing of synthetic products. Simulation can help engineers understand the motion of the microchips in the microchannels in order to optimize the throughput.
With Rocky DEM coupled with Ansys Fluent, engineers can evaluate orientations and trajectories of particles within fluids, including during microfluidic device sorting.
University of California, Riverside’s Simulation
Recently, scientists at the Bioengineering Department at the University of California, Riverside were interested in increasing the sorting rate for microchips. This complex particulate flow system required two-way coupled Ansys Fluent and Rocky Dem simulations to model the behavior of the flowing microchips.
The researchers sought to quickly optimize the geometric design and operating flow parameters of a high-throughput microfluidic sorter. These microchips have a flat plate shape and non-neutral buoyancy, and they are sorted through a microfluidic manifold. UC Riverside researchers chose Rocky DEM because it can accurately model nonspherical particles and particle-particle and particle-wall interactions.
By coupling Ansys Fluent’s CFD power and Rocky DEM’s unique capabilities, researchers evaluated the orientations and trajectories of the nonspherical particles and gained insight into the microfluidic device’s sorting efficiency.
To do so, researchers used the Two-Way Fluent Semi-Resolved Method in Rocky DEM. Unlike the standard Two-Way Fluent method, which relies on standard correlations for fluid forces based on the centroid fluid velocity and velocity gradients, the Two-Way Fluent Semi-Resolved Method computs the trajectories of the particles following integration of fluid forces at the particle’s surface. This alternative method is critical for accurately modeling the system of microchips flowing in microchannels where particles are larger than the fluid mesh cells, and wall effects are expected to significantly affect trajectory of the microchips.
ROCKY DEM has continued to improve their two-way coupling methods to accommodate different particulate flow applications.
Raymond Yeung, Ph.D. Candidatefor Biotransport & Bioreaction Kinetics (B2K) – GroupDepartment of Bioengineering, University of California, Riverside.
Coupling CFD and Rocky DEM allowed researchers to evaluate the orientations and trajectories of non-spherical particles and the sorting efficiency of the microfluidic device, resolving boundary-layer effects with a fine Fluent mesh.
Rocky DEM and Ansys Fluent Two-Way Coupling simulation gave researchers insight they needed. Computation time was reduced compared with continuum models that use moving meshes. Simulation helped bypass the need for time-consuming experimental studies. The modeling results can be used to optimize the equipment to maximize the sorting and increase the production rate of electronic microchips.
1 Kosuri, S., and Church, G.M. (2014). Large-scale de novo DNA synthesis: technologies and applications. Nature methods, 11(5), 85-107.
2 Palomo, J.M. (2014). Solid-phase peptide synthesis: an overview focused on the preparation of biologically relevant peptides. Rsc Advances, 4(62), 32658-32672.
PhD Candidate at UC Riverside
Raymond Yeung is a Ph.D. graduate student researcher in the Biotransport and Bioreaction Kinetics (B2K) Group in the Department of Bioengineering at the University of California, Riverside, where he also obtained his M.S. degree in bioengineering. His current research focus is on developing models and experiments of nonspherical particles in microchannel flow towards optimizing the design and operation of a microfluidic sorting device for high-throughput combinatorial synthesis. His prior roles at the University of California, Berkeley, the University of California, San Francisco, and his current institution included characterization and modeling of transport phenomena through membranes for biomedical and energy applications.