Protein solubility is a critical attribute in the development and production of monoclonal antibodies. Available solubility data refer to pure solutes which do not consider solvents and impurities which have a significant effect on solubility. Thus, solubility curves need to be determined experimentally. Previously established methods to determine the apparent solubility of proteins are based on manual assays which are time-consuming and labor-intensive. We present the design of simple and adaptable millidevices for fast solubility curve determination. Such a device in the form of a tubular reactor was manufactured from polymethylmethacrylate by laser cutting. The reactors had multiple injection points for the precipitant that allowed a controlled and precise addition of the precipitating agent at different concentrations. Hence, antibodies could be directly harvested at different concentrations of precipitating agents. The simple and flexible design allowed the number of pumps required to be reduced to only one for each solution and the distribution of the precipitating agent at different concentrations without valves. To demonstrate the wide applicability of the prototype in determining solubility curves, we used 2 industrially relevant precipitating agents, PEG6000 and ZnCl₂, to measure the apparent solubilities of 4 antibodies and CaCl₂ to measure the apparent solubility curves for dsDNA. In all cases, the data obtained were consistent between the device and manual assays with good reproducibility. This millidevice can be used for fast characterization of protein solutions such as solubility, degradation or stability of the antibodies under different conditions.

中文翻译：

---

设计毫装置以加快表观溶解度测量

蛋白质溶解度是单克隆抗体开发和生产的关键属性。可用的溶解度数据是指不考虑对溶解度有显着影响的溶剂和杂质的纯溶质。因此，溶解度曲线需要通过实验确定。以前建立的确定蛋白质表观溶解度的方法是基于人工测定，这既费时又费力。我们介绍了用于快速确定溶解度曲线的简单且适应性强的毫器件的设计。这种管式反应器形式的装置是由聚甲基丙烯酸甲酯通过激光切割制造的。反应器有多个沉淀剂注入点，可以控制和精确地添加不同浓度的沉淀剂。因此，可以在不同浓度的沉淀剂下直接收获抗体。简单而灵活的设计使得每种溶液所需的泵数量减少到只有一个，并且无需阀门即可分配不同浓度的沉淀剂。为了证明原型在确定溶解度曲线中的广泛适用性，我们使用了 2 种工业相关的沉淀剂，PEG6000 和 ZnCl₂，测量4种抗体的表观溶解度和CaCl ₂以测量dsDNA的表观溶解度曲线。在所有情况下，获得的数据在设备和手动测定之间是一致的，具有良好的重现性。这种毫装置可用于快速表征蛋白质溶液，例如不同条件下抗体的溶解度、降解或稳定性。