Lee Haneol, Moon Youngil, Lee Donghyun, Kim Jinwoo, Lee Gyuseok, Han Haewook
Pohang University of Science and Technology (POSTECH), Department of Electrical Engineering, Pohang, Republic of Korea.
University of Arkansas, Department of Biological and Agricultural Engineering and Institute for Nanoscience and Engineering, Fayetteville, Arkansas, United States.
J Biomed Opt. 2025 Sep;30(9):096006. doi: 10.1117/1.JBO.30.9.096006. Epub 2025 Sep 27.
Terahertz (THz) waves have gained significant attention as an imaging technology due to their ability to provide physical and chemical information in a label-free, noninvasive, and nonionizing manner. Notably, their low energy enables nondestructive inspection of internal structures without damaging samples, making them well-suited for biomedical applications. However, the use of THz imaging has been constrained by limited spatial resolution due to the diffraction limit.
This study introduces an approach using THz scattering-type scanning near-field optical microscopy, an advanced technique capable of overcoming these limitations and enabling single-cell scale measurements to image and distinguish individual bacterial cells, specifically and , representing Gram-negative and Gram-positive bacteria, respectively.
We utilized tungsten vertical nanoprobes in an apertureless setup to achieve high-resolution imaging.
In our experiments, bacteria were measured on a hydrophilic gold substrate with a spatial resolution of 50 nm, demonstrating excellent resolution and image contrast. In addition, quantitative analysis using the line dipole image method allowed calculation of the complex refractive indices, revealing clear differences between the two bacterial species.
This technique offers a nonlabel, noninvasive method for bacterial identification, with promising implications for advanced biomedical applications.
太赫兹（THz）波作为一种成像技术已受到广泛关注，因为它能够以无标记、非侵入性和非电离的方式提供物理和化学信息。值得注意的是，其低能量使得能够在不损坏样品的情况下对内部结构进行无损检测，这使其非常适合生物医学应用。然而，由于衍射极限，太赫兹成像的空间分辨率有限，限制了其应用。
本研究介绍了一种使用太赫兹散射型扫描近场光学显微镜的方法，这是一种先进技术，能够克服这些限制，并实现单细胞尺度测量，以对单个细菌细胞进行成像和区分，具体来说，分别是代表革兰氏阴性菌和革兰氏阳性菌的 和 。
我们在无孔径设置中使用钨垂直纳米探针来实现高分辨率成像。
在我们的实验中，在亲水性金基底上对细菌进行测量，空间分辨率达到50纳米，显示出优异的分辨率和图像对比度。此外，使用线偶极子图像法进行定量分析能够计算复折射率，揭示了两种细菌之间的明显差异。
该技术为细菌鉴定提供了一种无标记、非侵入性的方法，对先进的生物医学应用具有广阔的前景。
