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Large-scale imaging of biological dynamics with high spatiotemporal resolution is indispensable to system biology studies. However, conventional microscopes have an inherent compromise between the achievable field of view and spatial resolution due to the space–bandwidth product theorem. In addition, a further challenge is the ability to handle the enormous amount of data generated by a large-scale imaging platform. Here, we break these bottlenecks by proposing the use of a flat–curved–flat imaging strategy, in which the sample plane is magnified onto a large spherical image surface and then seamlessly conjugated to multiple planar sensors. Our real-time, ultra-large-scale, high-resolution (RUSH) imaging platform operates with a 10 × 12 mm² field of view, a uniform resolution of ~1.20 μm after deconvolution and a data throughput of 5.1 gigapixels per second. We use the RUSH platform to perform …