Label-free digital cytopathology using deep-ultraviolet coded ptychography with intrinsic molecular contrast

使用具有内在分子对比的深紫外编码叠层描记术进行无标记数字细胞病理学

• 批准号: 10718442
• 负责人: Guoan Zheng
• 金额: $ 36.3万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718442
• 关键词: Address; Adjuvant Therapy; Amino Acids; Anatomy; Area; Biopsy; Brain Neoplasms; Brightfield Microscopy; Cell Nucleus; Cells; Chemicals; Code; Critical Care; Cytology; Cytopathology; Cytoplasm; Data; Devices; Diagnosis; Disease; Dyes; Elements; Engineering; Evaluation; Excision; Fine needle aspiration biopsy; Fluorescence; Glass; Health; Histologic; Histology; Histopathology; Hospitals; Hour; Image; Imaging Device; Individual; Intervention; Label; Laboratories; Lighting; Lung; Maps; Measurement; Measures; Medicine; Methods; Microscope; Modeling; Modern Medicine; Molecular; Morphology; Mus; Nucleic Acids; Operative Surgical Procedures; Optics; Pathologist; Pathology; Patients; Performance; Phase; Preparation; Process; Proteins; Quartz; Research Personnel; Resolution; Sampling; Signal Transduction; Site; Skin Neoplasms; Slide; Specificity; Specimen; Spectrum Analysis; Stains; Surgical Oncology; Surgical margins; System; Thick; Time; Tissue Sample; Tissues; Ultraviolet Rays; Validation; Variant; Visible Radiation; Work; absorption; biological research; cancer imaging; code development; cost; data acquisition; deep neural network; diffraction of light; digital; fluorescence microscope; histopathological examination; immunopathology; lens; meter; prototype; sensor; success; tool; tool development; transmission process; tumor; ultraviolet; virtual

Project Summary / Abstract Histopathological examination of tissue is a pillar of modern medicine and biological research. Commonly used bright-field microscopy requires prior preparation of micrometer-thick tissue sections mounted on glass slides and stained with dyes, a process that takes hours or days, delaying access to critical information for interventions. This project aims to develop a new type of high-throughput digital cytopathology tool with intrinsic molecular contrast for label-free and slide-free histology. This tool will be built based on lensless high-throughput coded ptychography operated at the 260-nm and 280-nm deep ultraviolet (DUV) wavelengths. DUV light directly interacts with and is absorbed by biomolecules of nucleic acids (nucleus) and amino acids (protein) of cells. Absorption spectra are different for these two types of biomolecules. By measuring the specimen profiles at the 260-nm and 280-nm DUV wavelengths, we can recover the quantitative mass maps of cell nucleus and protein without any dye labeling. In contrast, there is no absorption for these biomolecules in the visible light regime. In the proposed DUV coded ptychography tool, we do not use any optical lens as in a conventional microscope platform. Instead, we fabricate a disorder-engineered coded layer on top of an image sensor. This coded layer serves as a large-scale scattering ‘lens’ for imaging specimens placed on top of it. When light diffracts from the tissue samples at a large angle, the coded layer redirects the diffracted light into smaller angles that are detectable by sensor pixels. As such, the otherwise inaccessible high-resolution object details can be acquired using the pixel array underneath the coded layer. Our preliminary data show that the image throughput is greater than the fastest whole slide scanner in the world: resolving 308-nm linewidth over a 240-mm2 effective field of view in 15 seconds. By using the dual wavelength DUV LEDs for sample illumination, the proposed tool will provide both phase-based quantitative morphology measurement and amplitude-based intrinsic chemical specificities for different biomolecules. It can be used for rapid onsite evaluation of cytology smear obtained from fine-needle aspirate. It can also reduce sample preparation time and provides intraoperative pathology guidance on surgical margins. The cost of the entire device will be similar to that of an iPad, making it a handheld, high-throughput ‘personal’ whole slide scanner for most individual pathologists and researchers worldwide.

项目摘要 /摘要 组织病理学检查是现代医学和生物学研究的支柱。通常 使用的明亮场显微镜需要事先准备安装在玻璃上的微米厚的组织切片 幻灯片并用染料染色，这一过程需要数小时或几天，延迟访问关键信息 干预措施。该项目旨在开发一种新型的高通量数字细胞病理学工具 无标签和无幻灯片组织学的固有分子对比度。该工具将基于无镜头构建 高通量编码的Ptychography在260 nm和280 nm深紫外线（DUV）运行 波长。 DUV光与核酸（核）的生物分子（核）和 细胞的氨基酸（蛋白质）。对于这两种类型的生物分子，吸收光谱是不同的。经过 在260 nm和280 nm的DUV波长下测量样品曲线，我们可以恢复 细胞核和蛋白质的定量质量图，没有任何染料标记。相反，没有 这些生物分子在可见光状态下的抽象。 在拟议的DUV编码的Ptychography工具中，我们不像常规的那样使用任何光学镜头 显微镜平台。取而代之的是，我们在图像传感器的顶部制造了一个无序工程的编码层。 该编码层用作大型散射“镜头”，用于成像标本放在其顶部。什么时候 从组织样品中衍射的光衍射以较大的角度，编码层将衍射光重定向到 通过传感器像素可检测的较小角度。因此，原本无法访问的高分辨率 可以使用编码层下面的像素数组来获取对象详细信息。我们的初步数据显示 图像吞吐量大于世界上最快的整个幻灯片扫描仪：解决308 nm 在15秒内的240 mm2有效视野上的线宽。通过使用双波长DUV LED 样品照明，所提出的工具将提供基于阶段的定量形态测量 和基于振幅的不同生物分子的内在化学规范。它可用于快速现场 从细子抽吸物获得的细胞学涂片评估。它还可以减少样品准备时间 并提供有关手术边缘的术中病理指南。整个设备的成本将是 与iPad相似，使其成为大多数手持式高通量的“个人”全幻灯片扫描仪 全球个体病理学家和研究人员。