High-Throughput Screening Platform
High-Throughput Screening (HTS) platform is a cutting-edge technique that has revolutionized the field of neuropharmacology research. Creative Biolabs has developed a high-throughput screening platform which combines cutting-edge robotics and automation with advanced imaging and data analysis tools to provide researchers with a fast, reliable, and cost-effective way to screen large libraries of compounds. Our HTS platform is highly flexible and can be customized to meet the specific needs of our clients. We offer a range of assays, including electrophysiology assays, calcium imaging assays, and cell-based assays, enabling researchers to screen compounds for a wide range of biological activities.
Establishment of Reporter iPSC Lines
Reporter iPSC lines are essential for monitoring the activity of specific cell types in culture. To establish these reporter iPSC lines, patient-derived iPSCs are first generated, then we applied CRISPR technology to integrate reporter Nluc or GFP into the disease related gene, followed by differentiation into neurons using a standard protocol. The resulting reporter iPSC lines allow researchers to study the effects of neuropharmacological drugs on patient-derived neurons in real-time.
Fig. 1 Reporter Construction. (A) NFL-Nluc and (B) SMN2-Nluc reporter lines by CRISPR.
Neuron Differentiation and Characterization
Creative Biolabs has developed a robust and efficient protocol for motor neuron differentiation from human iPSCs. The protocol involves the use of small molecules that promote the differentiation of iPSCs into neural progenitor cells (NPCs) and subsequently into neurons. The resulting neurons are functionally mature and charaterized by typical neuronal morphology and electrophysiological properties.
Fig.2 Neuron Production and Characterization.
MEA analysis is a high-throughput method for recording the electrical activity of neurons in vitro. MEA records extracellular action potentials (spikes) from numerous neurons at the same time, allowing networks and synchronized signaling to be studied. Creative Biolabs has developed a high-throughput MEA analysis platform that can record the activity of up to 96-well plates simultaneously. The platform also includes automated data analysis software that can quickly and accurately analyze large amounts of data.
The high-throughput screening platform combines reporter iPSC lines, differentiated neurons, and MEA assays to rapidly screen potential neuropharmacological drugs. These assays are tuned to meet HTS requirements including: high volume, 1536-well format, minimal well-to-well variation, short-term culture, auto-dispenser plating, and low reagent volumes. Applying a quantitative HTS approach, we dose-dependently screened >6,000 compounds against two motor neuron lines with approximately 0.5% hit rate. This work demonstrates the feasibility of running HTS activity using human neurons, which provides a more physiologically relevant drug discovery platform.
Fig.3 Example Screening Data.
The High-Throughput Screening Platform is a powerful tool that has revolutionized drug discovery and neuropharmacology research. Its ability to quickly and efficiently screen large numbers of compounds has enabled researchers to identify new drug targets, chemical probes, and potential off-target effects. At Creative Biolabs, we are committed to providing our clients with the most advanced. contact us to learn more about how we can advance your neuroscience research and improve our understanding of the brain.