论文标题

用于图像扫描显微镜的基于SPAD的异步阅读阵列探测器

SPAD-based asynchronous-readout array detectors for image-scanning microscopy

论文作者

Buttafava, Mauro, Villa, Federica, Castello, Marco, Tortarolo, Giorgio, Conca, Enrico, Sanzaro, Mirko, Piazza, Simonluca, Bianchini, Paolo, Diaspro, Alberto, Zappa, Franco, Vicidomini, Giuseppe, Tosi, Alberto

论文摘要

荧光显微镜和衍生技术一直在寻找能够确保提高灵敏度,高空间和时间分辨率以及易于整合到现代显微镜体系结构中的光电检测器。用行业标准的微电源过程制造的单个光子雪崩二极管(SPAD)的最新进展允许开发量身定制的新检测系统,以满足高级成像技术的要求(例如图像扫描显微镜)。为此,我们介绍了两个双二维SPAD阵列的完整设计和表征,由25个完全独立和异步的像素组成,均具有约50%的填充因子,并专门设计用于整合到现有的激光扫描显微镜中。我们使用两种不同的微电子技术来制造我们的探测器:第一种技术表现出非常低的噪声(在室温下每秒大约200个黑暗计数),第二种技术显示出提高的检测效率(在500 nm的波长下超过60%)。从硅水平的设备结构开始,然后朝着以像素和读取电子描述向移动,我们提出了两个检测器之间的性能评估和比较。将生物样品集成到我们的自定义图像扫描显微镜中后获得的生物样品的图像最终证明了它们在空间分辨率和对比度增强方面的精致场上性能。我们设想这项工作可以触发一类新的基于SPAD的检测器阵列的开发,以替代荧光激光扫描显微镜中使用的典型单元素传感器。

Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution and ease of integration into modern microscopy architectures. Recent advances in single photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays composed of 25 fully independent and asynchronously-operated pixels, both having fill-factor of about 50% and specifically designed for being integrated into existing laser scanning microscopes. We used two different microelectronics technologies to fabricate our detectors: the first technology exhibiting very low noise (roughly 200 dark counts per second at room temperature), and the second one showing enhanced detection efficiency (more than 60% at a wavelength of 500 nm). Starting from the silicon-level device structures and moving towards the in pixel and readout electronics description, we present performance assessments and comparisons between the two detectors. Images of a biological sample acquired after their integration into our custom image-scanning microscope finally demonstrate their exquisite on-field performance in terms of spatial resolution and contrast enhancement. We envisage that this work can trigger the development of a new class of SPAD-based detector arrays able to substitute the typical single-element sensor used in fluorescence laser scanning microscopy.

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