ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysis.

Autonomous migration is essential for the function of immune cells such as neutrophils and plays an important role in numerous diseases. The ability to routinely measure or target it would offer a wealth of clinical applications. Video microscopy of live cells is ideal for migration analysis, but cannot be performed at sufficiently high-throughput (HT). Here we introduce ComplexEye, an array microscope with 16 independent aberration-corrected glass lenses spaced at the pitch of a 96-well plate to produce high-resolution movies of migrating cells. With the system, we enable HT migration analysis of immune cells in 96- and 384-well plates with very energy-efficient performance. We demonstrate that the system can measure multiple clinical samples simultaneously. Furthermore, we screen 1000 compounds and identify 17 modifiers of migration in human neutrophils in just 4 days, a task that requires 60-times longer with a conventional video microscope. ComplexEye thus opens the field of phenotypic HT migration screens and enables routine migration analysis for the clinical setting.

Analytical Evaluation of Signal-to-Noise Ratios for Avalanche- and Single-Photon Avalanche Diodes.

Performance of systems for optical detection depends on the choice of the right detector for the right application. Designers of optical systems for ranging applications can choose from a variety of highly sensitive photodetectors, of which the two most prominent ones are linear mode avalanche photodiodes (LM-APDs or APDs) and Geiger-mode APDs or single-photon avalanche diodes (SPADs). Both achieve high responsivity and fast optical response, while maintaining low noise characteristics, which is crucial in low-light applications such as fluorescence lifetime measurements or high intensity measurements, for example, Light Detection and Ranging (LiDAR), in outdoor scenarios. The signal-to-noise ratio (SNR) of detectors is used as an analytical, scenario-dependent tool to simplify detector choice for optical system designers depending on technologically achievable photodiode parameters. In this article, analytical methods are used to obtain a universal SNR comparison of APDs and SPADs for the first time. Different signal and ambient light power levels are evaluated. The low noise characteristic of a typical SPAD leads to high SNR in scenarios with overall low signal power, but high background illumination can saturate the detector. LM-APDs achieve higher SNR in systems with higher signal and noise power but compromise signals with low power because of the noise characteristic of the diode and its readout electronics. Besides pure differentiation of signal levels without time information, ranging performance in LiDAR with time-dependent signals is discussed for a reference distance of 100 m. This evaluation should support LiDAR system designers in choosing a matching photodiode and allows for further discussion regarding future technological development and multi pixel detector designs in a common framework.