Fluorescence live-cell imaging allows for continuous interrogation of cellular behaviors, and the recent development of portable live-cell imaging platforms has rapidly transformed conventional schemes with high adaptability, cost-effective functionalities and easy accessibility to cell-based assays. However, broader applications remain restrictive due to compatibility with conventional cell culture workflow and biochemical sensors, accessibility to up-right physiological imaging, or parallelization of data acquisition. Here, we introduce miniaturized modular-array fluorescence microscopy (MAM) for compact live-cell imaging in flexible formats. We advance the current miniscopy technology to devise an up-right modular architecture, each combining a gradient-index (GRIN) objective and individually-addressed illumination and acquisition components. Parallelization of an array of such modular devices allows for multi-site data acquisition in situ using conventional off-the-shelf cell chambers. Compared with existing methods, the device offers a high fluorescence sensitivity and efficiency, exquisite spatiotemporal resolution (∼3 µm and up to 60 Hz), a configuration compatible with conventional cell culture assays and physiological imaging, and an effective parallelization of data acquisition. The system has been demonstrated using various calibration and biological samples and experimental conditions, representing a promising solution to time-lapse in situ single-cell imaging and analysis.

中文翻译：

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小型化模块化阵列荧光显微镜

荧光活细胞成像可连续询问细胞行为，便携式活细胞成像平台的最新发展已迅速转变了常规方案，具有高适应性，具有成本效益的功能以及对基于细胞的测定法的便捷访问性。但是，由于与常规细胞培养工作流程和生化传感器的兼容性，直立式生理成像的可访问性或数据采集的并行性，更广泛的应用仍然受到限制。在这里，我们介绍了小型化的模块化阵列荧光显微镜（MAM），用于灵活格式的紧凑型活细胞成像。我们改进了当前的微型镜技术，以设计出一种直立的模块化体系结构，每个体系结构都将梯度折射率（GRIN）物镜与单独寻址的照明和采集组件结合在一起。使用常规的现成细胞室原位 与现有方法相比，该设备具有较高的荧光灵敏度和效率，出色的时空分辨率（约3 µm，最高60 Hz），与常规细胞培养测定和生理成像兼容的配置以及有效的数据采集并行化。该系统已使用各种校准和生物学样品以及实验条件进行了演示，代表了一种有前途的原位单细胞成像和分析解决方案。