With advancements in human induced pluripotent stem cell (hiPSC) technology, there is an increasing demand for quality control techniques to manage the long-term process of target cell production effectively. While monitoring systems designed for use within incubators are promising for assessing culture quality, existing systems still face challenges in terms of compactness, throughput, and available metrics. To address these limitations, we have developed a compact and high-throughput lens-free imaging device named INSPCTOR. The device is as small as a standard culture plate, which allows for the installation of multiple units within an incubator. INSPCTOR utilises a large thin-film transistor image sensor, enabling simultaneous observation of six independent culture environments, each approximately 1 cm². With this device, we successfully monitored the confluency of hiPSC cultures and identified the onset timing of epithelial-to-mesenchymal transition during mesodermal induction. Additionally, we quantified the beating frequency and conduction of hiPSC-derived cardiomyocytes by using high-speed imaging modes. This enabled us to identify the onset of spontaneous beating during differentiation and assess chronotropic responses in drug evaluations. Moreover, by tracking beating frequency over 10 days of cardiomyocyte maturation, we identified week-scale and daily-scale fluctuations, the latter of which correlated with cellular metabolic activity. The metrics derived from this device would enhance the reproducibility and quality of target cell production.

中文翻译：

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使用薄膜晶体管的紧凑型无镜头成像仪，用于干细胞培养和心肌细胞产生的长期定量监测


随着人诱导多能干细胞 （hiPSC） 技术的进步，对质量控制技术的需求越来越大，以有效管理靶细胞生产的长期过程。虽然设计用于培养箱的监控系统在评估培养质量方面很有希望，但现有系统在紧凑性、通量和可用指标方面仍面临挑战。为了解决这些限制，我们开发了一种名为 INSPCTOR 的紧凑且高通量的无晶状体成像设备。该设备与标准培养板一样小，允许在培养箱内安装多个单元。INSPCTOR 利用大型薄膜晶体管图像传感器，可以同时观察六个独立的培养环境，每个环境约为 1 cm²。使用该设备，我们成功监测了 hiPSC 培养物的汇合度，并确定了中胚层诱导过程中上皮到间充质转化的开始时间。此外，我们使用高速成像模式量化了 hiPSC 衍生的心肌细胞的跳动频率和传导。这使我们能够识别分化过程中自发跳动的发生，并评估药物评估中的变时性反应。此外，通过跟踪心肌细胞成熟 10 天内的跳动频率，我们确定了周尺度和日尺度的波动，其中后者与细胞代谢活动相关。从该设备得出的指标将提高靶细胞生产的可重复性和质量。