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

该项目是生物光子学、电子学和计算电动力学与医学应用的交汇点。主要的推动力是开发一种主要是一次性的、低成本的微型光纤探头技术，该技术将能够在患者舒适的同时，对主要癌症进行最小限度或非侵入性的人群筛查，从而大幅提高诊断准确性，并降低医疗保健成本。智力优势：从工程学的角度来看，创新的关键领域是生物光子学和计算电磁学。生物光子学的基本技术是低相干增强后向散射光谱。主要的技术优势是小型化和深度选择性地量化活组织的亚衍射(低至几十纳米)结构的能力，这是现有的内窥镜或光纤工具无法做到的。在癌症筛查中，所提出的方法利用了现场致癌的概念，即最初，分子/纳米结构的变化在整个受影响的器官中扩散发展，而进一步的随机突变导致局灶性肿瘤。因此，可以通过对容易到达的替代部位的组织超微结构的非侵入性分析来评估癌症风险，例如直肠癌的直肠、肺癌的颊粘膜、胰腺癌的十二指肠粘膜、卵巢癌的子宫内膜等。该项目有三个目标：(1)开发一种新的范例，用于基于光-组织相互作用的纳米级细节的有限差分时间域建模，将组织的超微结构和光学特性联系起来。随机时域有限差分模拟是数值求解麦克斯韦-S方程和模拟任意复杂组织中光传输的一种主要新方法。(2)小型化低相干增强背向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测器截然不同，利用微纳制造技术和新的亚毫米图像传感器来生产一种具有前所未有的紧凑性的集成设备，能够完全分辨增强的后向散射峰值，进而量化组织中的纳米结构变化。(3)试点人体试验，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著降低癌症死亡率，但大多数癌症都没有人群筛查。这是因为现有技术需要通过介入性程序(结肠镜检查、内窥镜检查、支气管镜检查等)检查已经形成的癌或癌前病变。并遭受以下一些缺点：侵袭性，费用，患者耐受性低，或对可治愈的皮损敏感性低。这项拟议的技术可能会带来一种新的癌症筛查模式，基本上适用于任何主要的癌症类型，并且由于其低成本和高患者耐受性，实际上可以在整个人群中使用。此外，这项技术的实施有可能通过识别早期可预防的肿瘤性病变或早期、容易治疗的癌症来显著降低医疗成本。该项目还将帮助来自代表性不足的少数民族群体和市中心学校的初中生和高中生更多地接触工程、科学和技术。

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.