Bulk Mixing in a Milligram-Scale Solid Phase Batch Reactor

Adequate mixing is essential during reactions, especially in heterogeneous systems such as Solid Phase Synthesis (SPS), where the reagents transit from the fluid phase into the solid support. Despite the importance of mixing, a quantitative analysis within a theoretical framework is missing for SPS reactors. We analyze mechanical stirring (100–1300 rpm) and argon bubbling (1–30 cm3/min; 0.02–0.70 cm/s) as mixing methods in a milligram-scale batch reactor. Digital Image Analysis (DIA) was used to characterize the liquid mixing and particle dispersion. Typical solvents for SPS of biomolecules─acetonitrile (ACN), dichloromethane (DCM), and dimethylformamide (DMF)─were studied. The dispersion model represented the mixing process. Both mixing methods homogenize the liquid in times as short as 1s. Particle dispersion is accomplished in DCM and DMF but is limited in ACN, where the Archimedes number (Ar) was larger. The synthesis of various glycan probes through Automated Glycan Assembly (AGA) suggests that adequate mixing and thermal conditions are indispensable for process optimization.