Dual-mode multichannel imaging system for high-throughput live-cell monitoring across large fields of view

High-throughput live-cell imaging is crucial for biological applications, including organ-on-a-chip (OoaC) platforms, yet conventional optical systems face a fundamental trade-off between magnification and field of view (FOV). This limitation hinders the ability to capture large-scale biological dynamics while maintaining single-cell resolution. We address this gap by introducing a scalable, high-resolution imaging solution specifically tailored for OoaC platforms and other microfluidic-based systems.

We aim to develop a dual-mode multichannel optical imaging system capable of achieving single-cell resolution over an extended FOV while maintaining a working distance suitable for integration with microfluidic devices.

The system employs microlens arrays in conjunction with laser-fabricated micro-aperture arrays to optically isolate imaging channels, minimizing crosstalk. Two operational modes are implemented: (1) rapid sampling mode for instantaneous, partial-area imaging and (2) full-field imaging mode, utilizing micro-scanning and computational stitching to generate a seamless high-resolution composite. The system's performance was validated through experimental imaging and theoretical modeling.

The system achieves an FOV of $8.4\times 6m{m}^2$ at 4× magnification with single-cell resolution while preserving a 14 mm working distance. Experimental results closely align with theoretical expectations, confirming high-fidelity imaging without requiring a large sensor. Dual-mode functionality enables both rapid assessments and detailed, large-area imaging, enhancing its applicability in biological research.

This compact and scalable imaging system overcomes the traditional magnification-FOV trade-off, offering a powerful tool for drug screening, cellular dynamics studies, and microfluidic-based biological analyses. Its high-resolution capability and adaptability make it a valuable asset for advancing OoaC technologies.