Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Department of Chemical and Biomolecular Engineering (BK21 Plus Program), KAIST, Daejeon 34141, Republic of Korea.
Sci Adv. 2017 Aug 4;3(8):e1700606. doi: 10.1126/sciadv.1700606. eCollection 2017 Aug.
Establishing early warning systems for anthrax attacks is crucial in biodefense. Despite numerous studies for decades, the limited sensitivity of conventional biochemical methods essentially requires preprocessing steps and thus has limitations to be used in realistic settings of biological warfare. We present an optical method for rapid and label-free screening of spores through the synergistic application of holographic microscopy and deep learning. A deep convolutional neural network is designed to classify holographic images of unlabeled living cells. After training, the network outperforms previous techniques in all accuracy measures, achieving single-spore sensitivity and subgenus specificity. The unique "representation learning" capability of deep learning enables direct training from raw images instead of manually extracted features. The method automatically recognizes key biological traits encoded in the images and exploits them as fingerprints. This remarkable learning ability makes the proposed method readily applicable to classifying various single cells in addition to , as demonstrated for the diagnosis of , without any modification. We believe that our strategy will make holographic microscopy more accessible to medical doctors and biomedical scientists for easy, rapid, and accurate point-of-care diagnosis of pathogens.
建立炭疽攻击的预警系统在生物防御中至关重要。尽管数十年来进行了大量研究,但传统生化方法的灵敏度有限,实质上需要预处理步骤,因此在生物战的实际环境中存在局限性。我们提出了一种通过全息显微镜和深度学习的协同应用来快速、无标记筛选孢子的光学方法。设计了一个深度卷积神经网络来对未标记的活细胞的全息图像进行分类。经过训练,该网络在所有准确度测量方面均优于以前的技术,实现了单孢子灵敏度和亚属特异性。深度学习的独特“表示学习”能力使得可以直接从原始图像进行训练,而无需手动提取特征。该方法自动识别图像中编码的关键生物特征,并将其用作指纹。这种出色的学习能力使得该方法除了炭疽以外,还可以很容易地应用于分类各种单细胞,无需任何修改即可实现诊断。我们相信,我们的策略将使全息显微镜更容易被医生和生物医学科学家用于病原体的便捷、快速和准确的即时诊断。