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在衍射极限下对亚细胞生物学进行实时同时折射率和厚度测绘。

Real-time simultaneous refractive index and thickness mapping of sub-cellular biology at the diffraction limit.

机构信息

PRIMALIGHT, Computer, Electrical and Mathematical Sciences and Engineering (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.

Physik-Institut, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.

出版信息

Commun Biol. 2024 Feb 6;7(1):154. doi: 10.1038/s42003-024-05839-w.

DOI:10.1038/s42003-024-05839-w
PMID:38321111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10847501/
Abstract

Mapping the cellular refractive index (RI) is a central task for research involving the composition of microorganisms and the development of models providing automated medical screenings with accuracy beyond 95%. These models require significantly enhancing the state-of-the-art RI mapping capabilities to provide large amounts of accurate RI data at high throughput. Here, we present a machine-learning-based technique that obtains a biological specimen's real-time RI and thickness maps from a single image acquired with a conventional color camera. This technology leverages a suitably engineered nanostructured membrane that stretches a biological analyte over its surface and absorbs transmitted light, generating complex reflection spectra from each sample point. The technique does not need pre-existing sample knowledge. It achieves 10 RI sensitivity and sub-nanometer thickness resolution on diffraction-limited spatial areas. We illustrate practical application by performing sub-cellular segmentation of HCT-116 colorectal cancer cells, obtaining complete three-dimensional reconstruction of the cellular regions with a characteristic length of 30 μm. These results can facilitate the development of real-time label-free technologies for biomedical studies on microscopic multicellular dynamics.

摘要

绘制细胞折射率(RI)图谱是涉及微生物组成和开发模型的核心任务,这些模型提供了超过 95%准确率的自动化医学筛查。这些模型需要显著提高现有的 RI 映射能力,以便以高通量提供大量准确的 RI 数据。在这里,我们提出了一种基于机器学习的技术,该技术可以从常规彩色相机获取的单个图像中实时获得生物样本的 RI 和厚度图谱。该技术利用了经过适当设计的纳米结构膜,该膜在其表面拉伸生物分析物并吸收透射光,从而从每个样本点产生复杂的反射光谱。该技术不需要预先存在的样本知识。它在衍射极限的空间区域上实现了 10 RI 的灵敏度和亚纳米厚度分辨率。我们通过对 HCT-116 结直肠癌细胞进行亚细胞分割来说明实际应用,获得了具有 30 μm 特征长度的细胞区域的完整三维重建。这些结果可以促进实时无标记技术的发展,用于对微观多细胞动力学的生物医学研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/ec39b7c1670d/42003_2024_5839_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/946dadc1cc34/42003_2024_5839_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/d649d5dd04a9/42003_2024_5839_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/709d693f668e/42003_2024_5839_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/b2c825fea456/42003_2024_5839_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/08ad438ba7ad/42003_2024_5839_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/ec39b7c1670d/42003_2024_5839_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/946dadc1cc34/42003_2024_5839_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/d649d5dd04a9/42003_2024_5839_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/709d693f668e/42003_2024_5839_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/b2c825fea456/42003_2024_5839_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/08ad438ba7ad/42003_2024_5839_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdf/10847501/ec39b7c1670d/42003_2024_5839_Fig6_HTML.jpg

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