Optimized personnel flow with minimal contamination: development and validation of an air-barrier cleanroom for cell...

Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants-plain opening, wing walls, push-pull ventilation, and a conventional swing door-to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR-corridor interface.

Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm² opening, supplied at 23 m³/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100-500 mm wing-wall panels, push-pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.

CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push-pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push-pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.

The SO cleanroom concept suppresses fluctuations in particle content at the CPR-corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push-pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.