A 3D Printed Modular Microscope for In-Incubator Time-Lapse Fluorescence Imaging

Long-term fluorescence imaging of live cells enables visualization of dynamic cellular processes but often requires expensive, specialized instrumentation for operation within cell-culture incubators. We developed a low-cost, modular fluorescence microscope based on the open-source UC2 framework for automated time-lapse imaging under incubator conditions. The system uses standardized UC2 modules for motorized objective positioning and camera mounting, alongside custom 3D-printed modules for laser illumination, beam expansion, neutral-density filtering, dichroic beam splitting, tube-lens imaging, and sample mounting. An infinity-optics configuration allows optical components to be readily added or rearranged to accommodate different imaging modalities and incubator constraints. A Raspberry Pi controls objective positioning and laser illumination through custom Python software, enabling automated time-lapse acquisition. This work demonstrates a reconfigurable, low-cost fluorescence microscope potentially capable of automated long-term imaging of cell behavior responses and provides an adaptable platform for live-cell imaging applications in constrained laboratory environments.