A Microfluidic System for Investigating Anticipatory Medication Effects on Dopamine Homeostasis in Dopaminergic Cells

Dopamine (DA) homeostasis influences emotions, neural circuit development, cognition, and the reward system. Dysfunctions in DA regulation can lead to neurological disorders, including depression, developmental disorders, and addiction. DA homeostasis disruption is a primary cause of Parkinson's Disease (PD). Therefore, understanding the relationship between DA homeostasis and PD progression may clarify the mechanisms for pharmacologically treating PD. This study developed a novel in vitro DA homeostasis platform which consists of three main parts: (1) a microfluidic device for culturing DAergic neurons, (2) an optical detection system for reading DA levels, and (3) an automatic closed-loop control system that establishes when and how much medication to infuse; this uses a microfluidic device that can cultivate DAergic neurons, perfuse solutions, perform in vitro PD modeling, and continuously monitor DA concentrations. The automatically controlled closed-loop control system simultaneously monitors pharmacological PD treatment to support long-term monitoring of DA homeostasis. SH-SY5Y neuroblastoma cells were chosen as DAergic neurons. They were cultivated in the microfluidic device, and real-time cellular DA level measurements successfully achieved long-term monitoring and modulation of DA homeostasis. When applied in combination with multiday cell culture, this advanced system can be used for drug screening and fundamental biological studies.

Automated summary

Dopamine (DA) homeostasis plays a crucial role in regulating emotions, neural circuit development, cognition, and the reward system. Dysregulation of DA can lead to neurological disorders such as depression, developmental disorders, and addiction, and is a primary cause of Parkinson's Disease (PD). This study developed an innovative in vitro DA homeostasis platform consisting of a microfluidic device for culturing DAergic neurons, an optical detection system for measuring DA levels, and an automatic closed-loop control system for precise medication infusion. The platform successfully achieved long-term monitoring and modulation of DA homeostasis, providing a valuable tool for drug screening and biological studies.