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

Abstract

Monoamine transporters are of great interest for their role in physiological activity of the body and their link to mental and behavioral 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, e.g., 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. Reduction of manual operation and introduction of automated flow control enabled the implementation of stronger standardized protocols and the possibility to obtain higher throughput by increasing parallelization.

Transmembrane transporter proteins: Capturing transport in motion

“…The molecular mechanism underlying this reverse transport mode is not fully understood, primarily due to the intricate experimental setups required to investigate this phenomenon. Brugnoli et al 9 have developed an automated microfluidic platform to study the efflux mechanism, reducing manual interventions and introducing automated flow control. This technological innovation enables the implementation of standardized protocols and enhances the throughput for future efflux studies.…”

Welcome to Basic & Clinical Pharmacology & Toxicology 2024

“…As we embark on the new year, we invite you to explore the wealth of knowledge and exciting content our journal offers. In 2023, we published three Special Collections from focused conferences supported by the Nordic Association for the Publication of Basic and Clinical Pharmacology and Toxicology, including Adhesion G‐Protein‐coupled Receptors, 1–10 Transmembrane Transporter Proteins: Catching Transport in Motion 11–19 and Advancing Deprescribing: Learnings from the first International Conference on Deprescribing 20–31 . The second part of the latter Special Collection will appear in the January 2024 issue.…”