Label-free cardiac contractility monitoring for drug screening applications based on compact high-speed lens-free imaging

Cardiotoxicity is the major cause of drug withdrawal from the market, despite rigorous toxicity testing during the drug development process. Existing safety screening techniques, some of which are based on simplified cellular assays, others on electrical (impedance) or optical (fluorescent microscopy) measurements, are either too limited in throughput or offer too poor predictability of toxicity to be applied on large numbers of compounds in the early stage of drug development. We present a compact optical system for direct (label-free) monitoring of fast cellular movements that enable low cost and high throughput drug screening. Our system is based on a high-speed lens-free in-line holographic microscope. When compared to a conventional microscope, the system can combine adequate imaging resolution (5.5 μm pixel pitch) with a large field-of-view (63.4 mm 2 ) and high speed (170 fps) to capture physical cell motion in real-time. This combination enables registration of cardiac contractility parameters such as cell contraction frequency, total duration, and rate and duration of both contraction and relaxation. The system also quantifies conduction velocity, which is challenging in existing techniques. Additionally, to complement the imaging hardware we have developed image processing software that extracts all the contractility parameters directly from the raw interference images. The system was tested with varying concentration of the drug verapamil and at 100 nM, showed a decrease in: contraction frequency (-23.3% ± 13%), total duration (-21% ± 5%), contraction duration (-19% ± 6%) and relaxation duration (-21% ± 8%). Moreover, contraction displacement ceased at higher concentrations.