首页|深度学习图像识别辅助原子力显微镜单细胞力学特性精准高效探测

深度学习图像识别辅助原子力显微镜单细胞力学特性精准高效探测

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目的 原子力显微镜(AFM)的出现为生命科学研究提供了强大工具,特别是AFM压痕实验技术已成为细胞力学特性探测的重要方法,从单细胞尺度为生理病理活动过程带来了大量新的认识,是对传统生化集群平均研究方法的有力补充。然而现有AFM压痕实验技术存在着依赖人工、效率低下等不足,严重制约了其在生命科学领域的实际应用。本文通过将光学显微成像自动目标识别技术与AFM压痕技术结合,建立了单个游离态细胞及聚团生长细胞的力学特性精准高效测量方法。方法 利用YOLO深度学习算法识别出光学图像中细胞的中心部位,并通过嵌入视觉转换器(ViT)模块的双UNet神经网络模型对细胞边缘部位进行精确分割,同时采用模板匹配算法对光学图像中AFM微球探针进行定位,在此基础上自动确定AFM探针上的微球针尖与细胞不同部位之间的空间位置关系,进而对细胞中心部位和边缘部位的力学特性进行快速测量。选取HEK293(人胚胎肾细胞)和HGC-27(人未分化胃癌细胞)两种细胞进行验证实验,并利用Hertz模型对获取的力曲线进行分析以得到细胞杨氏模量。结果 在深度学习光学图像自动识别导引下可将AFM探针准确移动至细胞不同部位(中心和边缘)进行力学特性测量,同时实验结果表明,本文提出的方法不仅可对单个游离态细胞进行可靠测量,也适用于聚团生长的细胞。结论 深度学习图像识别在辅助AFM单细胞力学特性精准高效探测方面具有巨大潜力,将深度学习图像识别与AFM结合有助于发展面向生物医学应用的高通量单细胞力学特性测量方法。
Deep Learning Image Recognition-assisted Atomic Force Microscopy for Precise and Efficient Detection of Single-cell Mechanical Properties
Objective The advent of atomic force microscope(AFM)provides a powerful tool for the studies of life sciences.Particularly,AFM-based indentation assay has become an important method for the detection of cellular mechanics,yielding numerous novel insights into the physiological and pathological activities from the single-cell level and considerably complementing traditional biochemical ensemble-averaged assays.However,current AFM indentation technology is mainly dependent on manual operation with low efficiency,seriously restricting its practical applications in the field of life sciences.Here,a method based on the combination of deep learning image recognition and AFM is developed for precisely and efficiently detecting the mechanical properties of single isolated cells and clustered cells.Methods The YOLO deep learning algorithm was used to recognize the central region of the cell in the optical image,the dual UNet neural network with an embedded vision transformer(ViT)module was used to recognize the peripheral regions of cell,and the template matching algorithm was used to recognize the tip of spherical probe.Based on the automatic determination of the positional relationships between the microsphere tip and the different parts of cell,the AFM tip was accurately moved to the central and peripheral regions of the target cell for rapid measurements of cell mechanical properties.Two types of cells,including HEK 293 cell(human embryonic kidney cell)and HGC-27 cell(human undifferentiated gastric cancer cell),were used for the experiments.The Hertz model was applied to analyze the force curves obtained on cells to obtain cellular Young's modulus.Results AFM probe can be precisely moved to the different parts(central areas and peripheral areas)of cells to perform mechanical measurements under the guidance of deep learning-based optical image automatic recognition.The experimental results show that the proposed method is not only suitable for single isolated cells,but also suitable for clustered cells.Conclusion The research demonstrates the great potential of deep learning image recognition to aid AFM in the precise and efficient detection of cellular mechanical properties mechanics,and combining deep learning-based image recognition with AFM will benefit the development of high-throughput AFM-based methodology to measure the mechanical properties of cells.

atomic force microscopycell mechanical propertyoptical imagedeep learningYoung's modulusspherical probe

吕晓龙、李密

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中国科学院沈阳自动化研究所,机器人学国家重点实验室,沈阳 110016

中国科学院机器人与智能制造创新研究院,沈阳 110169

沈阳工业大学人工智能学院,沈阳 110870

原子力显微镜 细胞力学特性 光学图像 深度学习 杨氏模量 微球探针

国家自然科学基金国家自然科学基金中国科学院前沿科学重点研究计划

6227333061922081ZDBS-LY-JSC043

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(2)
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