Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module.

Area of Science:

• Biophysics
• Pharmacology
• Neuroscience

Background:

• High-throughput screening is crucial for ion channel drug discovery.
• Existing methods face limitations in throughput and efficiency.

Purpose of the Study:

• To develop and validate an automated patch clamp module for high-throughput ion channel screening.
• To assess the module's performance with various cell lines and ion channels.

Main Methods:

• Integration of a 384-channel pipettor robot with a digital amplifier for parallel recordings.
• Simultaneous recording from 384 cells using automated cell and compound application.
• Implementation of rapid external solution exchange (<50 ms) and short ligand exposure times.

Main Results:

• Achieved >85% success rates for concentration-response curves in HEK, CHO, and RBL cell lines expressing ion channels like hNa_V1.7, hERG, Kir2.1, GABA, and glutamate receptors.
• Demonstrated fast solution exchange (<50 ms) with Kir2.1.
• Successfully recorded from stem cell-derived cardiomyocytes with a 52% success rate for cells exhibiting >200 MΩ seal resistance.

Conclusions:

• The automated patch clamp module significantly enhances throughput for ion channel screening.
• The system demonstrates broad applicability across diverse cell types and ion channel targets.
• This technology accelerates the pace of ion channel research and therapeutic development.