A regenerable microfluidic device with integrated valves and thin-film photodiodes for rapid optimization of chromatography conditions

• Published in: Sensors and actuators. B, Chemical Chemical, 2018-02, Vol.255, p.3636-3646
• Main Authors: Pinto, I.F., Santos, D.R., Soares, R.R.G., Aires-Barros, M.R., Chu, V., Azevedo, A.M., Conde, J.P.
• Format: Article
• Language: English
• Subjects: Chromatography; Complex media; Elution; Fluorescence; Ligands; Medical screening; Microfabricated photodiodes; Microfluidics; Monoclonal antibodies; Multimodal chromatography; Optimization; Photodiodes; Pneumatic valves; Pneumatics; Reagents; Regeneration; Screening; Thin films; Valves
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2017.09.167

[Display omitted] •A regenerable microfluidic platform for on-chip chromatography was developed.•The device integrates pneumatically-actuated valves and thin-film photosensors.•Binding of mAbs from a real supernatant was monitored using fluorescence detection.•Robust and reproducible results were obtained in each chromatography cycle.•A set of adsorption/elution conditions was screened within a few minutes. The optimization of chromatography operating conditions is a lengthy and demanding task that typically requires large volumes of reagents and costly dedicated equipment. In particular, the use of multimodal chromatography, in which multiple interaction groups co-exist in the same ligand, can make the optimization process even more challenging. Nevertheless, the interest in using this emerging type of ligands has been increasing due to the enhanced selectivity and stability demonstrated by multimodal ligands in the purification of several biopharmaceuticals and their lower cost compared to biological affinity ligands. In this work, we report the development of an integrated, regenerable and portable microfluidic platform for performing a rapid screening of chromatography conditions. This platform was tested for the capture of fluorophore-labeled monoclonal antibodies directly from a cell culture supernatant using a multimodal ligand (Capto MMC). Liquid insertion in the microfluidic device was controlled by pneumatically actuated embedded valves and chromatography cycles were monitored via fluorescence measurements using thin-film a-Si:H photodiodes aligned beneath the device. The regeneration of the chromatography micro-column (70nL) was performed in the end of each cycle, providing repeatable results over several consecutive cycles. Different buffers were successively evaluated in cycles, each cycle having duration of about 3min, and the different adsorption and elution kinetics were compared, allowing the rapid optimization of conditions to address the capture of the monoclonal antibody from complex media. Overall, a versatile, rapid and relatively inexpensive platform to perform screening studies was developed, providing a high degree of scalability.