EFRI-BioFlex: Miniature, low-cost fiber-optics technology for measurement of tissue structure at sub-diffractional length scales: a platform for cancer screening

EFRI-BioFlex：用于在亚衍射长度尺度上测量组织结构的微型、低成本光纤技术：癌症筛查平台

• 批准号: 1240416
• 负责人: Vadim Backman
• 金额: $ 200万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1240416&HistoricalAwards=false
• 关键词: EFRI; BioFlex; Miniature; low; cost

This project is at the interface of biophotonics, electronics and computational electrodynamics with applications to medicine. The main thrust is the development of a principally new disposable, low-cost, miniature fiber-optics probe technology that would enable minimally or non-invasive population screening for major cancers while being comfortable to patients, enabling a major improvement in diagnostic accuracy, and reducing health care costs. Intellectual Merit: From the engineering perspective, the key areas of innovation are biophotonics and computational electromagnetics. The underlying biophotonics technology is Low-coherence Enhanced Backscattering Spectroscopy. The major technological advantages are miniaturization and the ability to depth-selectively quantify sub-diffractional (down to a few tens of nanometers) structure of live tissue, which is impossible with existing endoscopic or fiber-optic tools. In its application to cancer screening, the proposed approach takes advantage of the concept of field carcinogenesis, the notion that, initially, molecular/nanostructural alterations develop diffusely throughout an affected organ while further stochastic mutations lead to focal tumors. Thus, a cancer risk can be assessed by non-invasive analysis of tissue ultrastructure from an easily accessible surrogate site, such as the rectum for colon cancer, cheek mucosa for lung cancer, duodenal mucosa for pancreatic cancer, endocervix for ovarian cancer, etc. The project has three aims: (1) Development of a new paradigm for linking the ultrastructural and optical properties of tissue based on the Finite-Difference Time-Domain modeling of light-tissue interactions with nanoscale detail. Stochastic Finite-Difference Time-Domain simulation, a principally new approach to numerically solving Maxwell?s equations and modeling light transport in tissue of arbitrary complexity, will be developed. (2) Development of the miniature Low-coherence Enhanced Backscattering Spectroscopy probe. The design is a radical departure from other fiber-optics probes currently under development for biomedical applications, leveraging micro- and nano-fabrication technology and new sub-millimeter image sensors to produce an integrated device with unprecedented compactness capable of fully resolving the enhanced backscattering peak, and in turn, quantifying nanostructural changes in tissue. (3) Pilot human studies to demonstrate the potential clinical impact of the technology. Broader Impact:Although it is well accepted that cancer screening can dramatically decrease cancer mortality, no population screening exists for the majority of cancers. This is because existing techniques require examination of already formed cancerous or pre-cancerous lesions through interventional procedures (colonoscopy, endoscopy, bronchoscopy, etc.) and suffer from some of the following drawbacks: invasiveness, expense, low patient tolerance, or low sensitivity to curable lesions. The proposed technology may lead to a new paradigm in cancer screening that would be applicable to essentially any major cancer type and, due to its low-cost and high patient tolerance, can actually be used in the entire population. Furthermore, the implementation of the technology has the potential to dramatically reduce health care costs by identifying early preventable neoplastic lesions or early, readily treatable cancers. The project will also help increase the exposure of middle and high school students from underrepresented minority groups and inner-city schools to engineering, science and technology.

该项目处于生物光子学、电子学和计算电动力学与医学应用的交叉领域。主要目标是开发一种新型一次性、低成本、微型光纤探头技术，该技术将能够对主要癌症进行微创或无创人群筛查，同时让患者感到舒适，从而大幅提高诊断准确性，以及减少医疗保健费用。智力优势：从工程角度来看，创新的关键领域是生物光子学和计算电磁学。基本的生物光子技术是低相干增强背散射光谱。主要技术优势是小型化以及能够深度选择性地量化活体组织的亚衍射（低至几十纳米）结构，这是现有内窥镜或光纤工具不可能实现的。在癌症筛查的应用中，所提出的方法利用了现场致癌的概念，即最初分子/纳米结构改变在整个受影响的器官中广泛发展，而进一步的随机突变导致局灶性肿瘤。因此，可以通过对易于接近的替代部位的组织超微结构进行非侵入性分析来评估癌症风险，例如结肠癌的直肠、肺癌的脸颊粘膜、胰腺癌的十二指肠粘膜、卵巢癌的宫颈内膜等。该项目有三个目标：（1）开发一种新的范式，基于光组织相互作用与纳米级细节的有限差分时域模型，将组织的超微结构和光学特性联系起来。将开发随机有限差分时域模拟，这是一种对麦克斯韦方程进行数值求解和对任意复杂性组织中的光传输进行建模的主要新方法。 (2)微型低相干增强背散射光谱探头的研制。该设计与目前正在开发的用于生物医学应用的其他光纤探头截然不同，它利用微米和纳米制造技术以及新型亚毫米图像传感器来生产具有前所未有的紧凑性的集成设备，能够完全解决增强的反向散射峰值，进而量化组织中的纳米结构变化。 (3) 试点人体研究以证明该技术的潜在临床影响。更广泛的影响：尽管人们普遍认为癌症筛查可以显着降低癌症死亡率，但大多数癌症都没有进行人群筛查。这是因为现有技术需要通过介入手术（结肠镜检查、内窥镜检查、支气管镜检查等）检查已经形成的癌性或癌前病变，并且存在以下一些缺点：侵入性、费用高、患者耐受性低或对癌症的敏感度低。可治愈的病变。所提出的技术可能会带来癌症筛查的新范例，该范例基本上适用于任何主要癌症类型，并且由于其低成本和患者耐受性高，实际上可以用于整个人群。此外，该技术的实施有可能通过识别早期可预防的肿瘤病变或早期易于治疗的癌症来显着降低医疗保健成本。该项目还将帮助增加代表性不足的少数群体和市中心学校的初中和高中学生接触工程、科学和技术的机会。