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基于生物发光报告基因的活体基因表达分析用超小型紧凑型 CMOS 成像系统。

Ultrasmall compact CMOS imaging system for bioluminescence reporter-based live gene expression analysis.

机构信息

Nara Institute of Science and Technology, Photonics Device Science Laboratory, Division of Materials, Japan.

Nara Institute of Science and Technology, Gene Regulation Research Laboratory, Division of Biologica, Japan.

出版信息

J Biomed Opt. 2021 Nov;26(11). doi: 10.1117/1.JBO.26.11.116002.

Abstract

SIGNIFICANCE

Gene expression analysis is an important fundamental area of biomedical research. However, live gene expression imaging has proven challenging due to constraints in conventional optical devices and fluorescent reporters.

AIM

Our aim is to develop smaller, more cost-effective, and versatile imaging capabilities compared with conventional devices. Bioluminescence reporter-based gene expression analysis was targeted due to its advantages over fluorescence-based imaging.

APPROACH

We created a small compact imaging system using micro-CMOS image sensors (μCIS). The μCIS model had an improved pixel design and a patterned absorption filter array to detect the low light intensity of bioluminescence.

RESULTS

The device demonstrated lower dark current, lower temporal noise, and higher sensitivity compared with previous designs. The filter array enabled us to subtract dark current drift and attain a clearer light signal. These improvements allowed us to measure bioluminescence reporter-based gene expression in living mammalian cells.

CONCLUSION

Using our μCIS system for bioluminescence imaging in the future, the device can be implanted in vivo for simultaneous gene expression imaging, behavioral analysis, and optogenetic modulation.

摘要

意义

基因表达分析是生物医学研究的一个重要基础领域。然而,由于传统光学设备和荧光报告器的限制,活体基因表达成像一直具有挑战性。

目的

我们的目标是与传统设备相比,开发更小、更具成本效益和多功能的成像能力。由于其优于荧光成像的优势,我们将基于生物发光报告器的基因表达分析作为目标。

方法

我们使用微 CMOS 图像传感器 (μ CIS) 创建了一个小型紧凑的成像系统。μ CIS 模型具有改进的像素设计和图案吸收滤光片阵列,可检测生物发光的低光强度。

结果

与以前的设计相比,该设备显示出更低的暗电流、更低的时间噪声和更高的灵敏度。滤光片阵列使我们能够减去暗电流漂移并获得更清晰的光信号。这些改进使我们能够测量活哺乳动物细胞中的基于生物发光报告器的基因表达。

结论

将来使用我们的 μ CIS 系统进行生物发光成像,该设备可以植入体内进行同时的基因表达成像、行为分析和光遗传学调节。

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