Needle to needle robot-assisted manufacture of cell therapy products

Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapies for untreatable diseases, generating the need for large volumes of high-quality, clinically-compliant GMP cells to replace costly, high-risk and limited scale manual expansion processes. We present the design of a fully automated, robot-assisted platform incorporating the use of multiliter stirred tank bioreactors for scalable production of adherent human stem cells. The design addresses a needle-to-needle closed process incorporating automated bone marrow collection, cell isolation, expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular, adaptable, fully closed system ensures no direct operator interaction with biological material; all commands are performed through a graphic interface. Seeding of source material, process monitoring, feeding, sampling, harvesting and cryopreservation are automated within the closed platform, comprising two clean room levels enabling both open and closed processes. A bioprocess based on human MSCs expanded on microcarriers was used for proof of concept. Utilizing equivalent culture parameters, the AUTOSTEM robot-assisted platform successfully performed cell expansion at the liter scale, generating results comparable to manual production, while maintaining cell quality postprocessing

Sensitivity of crossflow surfacetransitionroughnessto free-stream conditions and

The present work is an experimental investigation of stationary crossflow (CF) instability-induced transition of the boundary layer over a 45°swept wing, under varying free-stream turbulence, surface roughness, angle of attack and Reynolds number. Key topological features of the transition front, such as the mean transition location and the jaggedness of the front, are retrieved via IR thermography. Linear Stability Theory (LST) is used to extract the N-factor of the most amplified stationary crossflow mode at the transition location, identified experimentally. Results show clear causality between free-stream turbulence, surface roughness, Reynolds number, angle of attack and transition. Large losses of laminarity and a consistent decrease in the transition N-factor are observed with rising turbulence and roughness. Remarkably, N-factor sensitivity to free-stream turbulence is found to vary significantly and non-linearly with angle of attack for the modest levels of turbulence explored in this campaign, whereas the N-factors scale linearly with the log of the surface roughness level, which is consistent with a receptivity mechanism, which is independent of the angle of attack.Aerodynamic

Simulation of Swept-Wing Receptivity to Distributed Roughness

Simulations were carried out to model the receptivity and growth of stationary crossflow vortices from Distributed Roughness Elements (DRE) on a swept wing. A highly resolved Large Eddy Simulation (LES) numerical method was used for the study, the aim of the results were to achieve validation of the code to relevant experimental data and to gain a better understanding of the flow behaviour. The base flow for the simulations were based upon the experiment run by Hunt and Saric. The LES replicated the experimental setup using a WALE sub grid model and a streamline extraction process to only simulate the upper surface and reduce the overall computational expense. The WALE model is more suitable to modelling of transitional flows as it allows the sub-grid scale viscosity to vanish in laminar regions and in the inner regions of the boundary layer. Simulations were carried out for two spanwise wavelengths (λ = 6mm, 12mm) and for roughness heights ranging from 12 μm to 42 μm. The critical wavelength results showed, when comparing the stationary crossflow mode shapes, that the simulations at the larger roughness element sizes compare well with the experimental data. The control wavelength equally showed a good agreement to the experimental data at the larger roughness element sizes however the simulations over predict the amplitude of the smallest roughness element size. This can be attributed to either the simulation requiring a further refinement around the cylinder for the smallest roughness element size or to differences in the experimental and simulation roughness element shape. Overall the simulations successfully predict the receptivity from arrays of distributed roughness elements