Issue 9, 2022

Design of millidevices to expedite apparent solubility measurements


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.

Graphical abstract: Design of millidevices to expedite apparent solubility measurements

Article information

Article type
21 Jan 2022
23 Apr 2022
First published
17 Jun 2022
This article is Open Access
Creative Commons BY license

React. Chem. Eng., 2022,7, 2045-2053

Design of millidevices to expedite apparent solubility measurements

M. D. C. Pons Royo, J. Beulay, E. Valery, A. Jungbauer and P. Satzer, React. Chem. Eng., 2022, 7, 2045 DOI: 10.1039/D2RE00022A

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