Monitoring intracellular calcium in response to GPCR activation using thin-film silicon photodiodes with integrated fluorescence filters

• Amorphous silicon photodiodes with integrated fluorescence filters were fabricated.
• The selectivity of filters was tuned for fluorophore-based Ca2+ detection.
• Photodiodes were used to capture intracellular Ca2+ dynamics in HEK293 cells.
• Ca2+ fluxes were evoked by the addition of ionophores or M1 GPCR agonists
• Devices were used to accurately measure potency of test molecules.

G-protein coupled receptor (GPCRs) drug discovery is a thriving strategy in the pharmaceutical industry. The standard approach uses living cells to test millions of compounds in a high-throughput format. Typically, changes in the intracellular levels of key elements in the signaling cascade are monitored using fluorescence or luminescence read-out systems, which require external equipment for signal acquisition. In this work, thin-film amorphous silicon photodiodes with an integrated fluorescence filter were developed to capture the intracellular calcium dynamics in response to the activation of the endogenous muscarinic M1 GPCR of HEK 293T cells. Using the new device it was possible to characterize the potency of carbachol (EC50=10.5 µM) and pirenzepine (IC50=4.2 μM), with the same accuracy as standard microscopy optical systems. The smaller foot-print provided by the detection system makes it an ideal candidate for the future integration in microfluidic devices for drug discovery.