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

本项目是生物光子学、电子学和计算电动力学与医学应用的结合。主要目标是开发一种全新的一次性、低成本、微型光纤探针技术，该技术将使主要癌症的人群筛查达到最低或无创程度，同时使患者感到舒适，从而大大提高诊断准确性，并降低医疗保健成本。智力优势：从工程的角度来看，创新的关键领域是生物光子学和计算电磁学。基础生物光子学技术是低相干增强后向散射光谱。主要的技术优势是微型化和深度选择性量化活组织亚衍射（低至几十纳米）结构的能力，这是现有内窥镜或光纤工具无法做到的。在应用于癌症筛查时，所提出的方法利用了场致癌的概念，即最初，分子/纳米结构改变在整个受影响器官中弥漫性发展，而进一步的随机突变导致局灶性肿瘤。因此，癌症风险可以通过对易接近的替代部位的组织超微结构进行无创分析来评估，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)基于光-组织相互作用的有限差分时域建模与纳米尺度细节，开发一种连接组织超微结构和光学特性的新范式。随机时域有限差分模拟，一个主要的新方法，以数值解决麦克斯韦？S方程和模拟任意复杂组织中的光输运，将被开发。(2)微型低相干增强后向散射光谱探针的研制。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针截然不同，利用微纳米制造技术和新型亚毫米图像传感器，生产出具有前所未有的紧凑性的集成设备，能够完全解决增强的后向散射峰，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：虽然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进行人群筛查。这是因为现有技术需要通过介入性手术（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、患者耐受性低或对可治愈病变的敏感性低。这项提议的技术可能会导致癌症筛查的新模式，基本上适用于任何主要的癌症类型，并且由于其成本低和患者耐受性高，实际上可以在整个人群中使用。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治疗的癌症来显著降低医疗保健成本。该项目还将有助于增加来自代表性不足的少数民族和市中心学校的初高中学生对工程、科学和技术的接触。

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.