Large molecules and automated patch clamp: A case study of Scorpion toxin block of BK channels on Qube 384

Currently, more than 90% of approved drugs are small molecules, but large molecules (>1.000 Da, also known as biologics) are rapidly rising in prominence and importance in drug discovery and already constitute the lion’s share of the top 10 selling drugs worldwide. Large molecules have gained attention due to their mode of action, often achieving greater target specificity and potency than small molecule drugs.

While automated patch clamp systems have been used for small molecule drug discovery and characterization for the past 20 years, the use of APC systems for large molecule characterization have been scarcer. However, our systems are fully capable of characterizing large molecules such as peptides, toxins, knotbodies and antibodies.

In this new application report, we show that Qube 384 is fully capable of performing pharmacology measure­ments with large molecules, but also that the low volume microfluidic application ensures that expensive and scarce molecules like antibodies and toxins can be effi­ciently tested.

The effect of ChTx was evaluated on Qube to show affinity in accordance with that found in the literature. Also, the time course of block was concentration-dependent, which could be monitored due to the microfluidic architecture of QChip. The same principle allows for testing of such scarcely available or expensive compounds because the quantity needed is as little as 18 µL per concentration. Read more here.