Aluminum adjuvants have been used for almost a century due to their good record of safety and efficacy. However, their preparation is rather traditional and usually exhibits batch-to-batch variations. To achieve optimal adjuvanticity, the controllable and consistent preparation of aluminum adjuvants is desired, but remains a great challenge to date. Here, the preparation of aluminum phosphate (AP) adjuvant through a microfluidic approach is investigated. A chaotic micromixer is applied to enhance the mixing between the reactants. In addition, the effects of magnetic stirring and continuous-flow shearing during the settling of the AP precipitate are compared. The influences of the concentration of reactants, flow rate, residence time, as well as the heating temperature and shear intensity in the stabilizing stage are analyzed. Results show that the current method provides better control over the particle size distribution. The median particle size Dv(50) is tunable in the range of 1.6–3.4 µm, and the uniformity index varies from 0.24 to 0.45. The isoelectric point (IEP) and the adsorption capacity are also examined. Relevant findings provide useful references for the development and optimization of AP-adjuvanted vaccines.

由于其良好的安全性和有效性记录，铝佐剂已经使用了近一个世纪。然而，它们的制备方法相当传统，并且通常会出现批次间的差异。为了实现最佳佐剂性，需要可控且一致地制备铝佐剂，但迄今为止仍然是一个巨大的挑战。在这里，研究了通过微流体方法制备磷酸铝（AP）佐剂。应用混沌微混合器来增强反应物之间的混合。此外，还比较了磁力搅拌和连续流剪切在 AP 沉淀沉降过程中的效果。分析了稳定阶段反应物浓度、流量、停留时间以及加热温度和剪切强度的影响。结果表明，当前方法可以更好地控制粒度分布。中值粒径Dv(50)在 1.6–3.4 µm 范围内可调，均匀性指数在 0.24 到 0.45 之间变化。还检查了等电点 (IEP) 和吸附能力。相关研究结果为AP佐剂疫苗的研发和优化提供了有益的参考。