Development and validation of an automated microfluidic perfusion platform for parallelized screening of compounds in vitro.

Autor: Brugnoli FR; Elvesys - Microfluidic Innovation Center, Paris, France.; Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria., Holy M; Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria., Niello M; Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria., Maier J; Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria., Hanreich M; Höhere Technische Bundeslehr- und Versuchsanstalt Mödling (HTL Mödling), Mödling, Austria., Menzel M; Höhere Technische Bundeslehr- und Versuchsanstalt Mödling (HTL Mödling), Mödling, Austria., Haberler M; Höhere Technische Bundeslehr- und Versuchsanstalt Mödling (HTL Mödling), Mödling, Austria., Zulus N; Höhere Technische Bundeslehr- und Versuchsanstalt Mödling (HTL Mödling), Mödling, Austria., Pickl T; Höhere Technische Bundeslehr- und Versuchsanstalt Mödling (HTL Mödling), Mödling, Austria., Ivanova C; Elvesys - Microfluidic Innovation Center, Paris, France., Muiznieks LD; Elvesys - Microfluidic Innovation Center, Paris, France., Garlan B; Elvesys - Microfluidic Innovation Center, Paris, France., Sitte HH; Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.; Center for Addiction Research and Science - AddRess, Medical University Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2023 Nov; Vol. 133 (5), pp. 535-547. Date of Electronic Publication: 2023 Sep 17.
DOI: 10.1111/bcpt.13940
Abstrakt: Monoamine transporters are of great interest for their role in the physiological activity of the body and their link to mental and behavioural disorders. Currently, static well-plate assays or manual perfusion systems are used to characterize the interaction of psychostimulants, antidepressants and drugs of abuse with the transporters but still suffer from significant drawbacks caused by lack of automation, for example, low reproducibility, non-comparability of results. An automated microfluidic platform was developed to address the need for more standardized procedures for cell-based assays. An automated system was used to control and drive the simultaneous perfusion of 12 channels on a microfluidic chip, establishing a more standardized protocol to perform release assays to study monoamine transporter-mediated substrate efflux. D-Amphetamine, GBR12909 (norepinephrine transporter) and p-chloroamphetamine, paroxetine (serotonin transporter) were used as control compounds to validate the system. The platform was able to produce the expected releasing (D-Amphetamine, p-chloroamphetamine) or inhibiting (GBR12909, paroxetine) profiles for the two transporters. The reduction of manual operation and introduction of automated flow control enabled the implementation of stronger standardized protocols and the possibility of obtaining higher throughput by increasing parallelization.
(© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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