PHOTON TUNNELING: SHEDDING NEW LIGHT ON BIOMEDICINE

描述 摘要： 大多数幼儿对世界的了解有80%到90%来自于视觉。的 当我们试图了解我们自己身体的内部运作时，同样的话就不能说了，因为光超越了 "表皮深度"由于多次散射而变得漫射。相反，研究者们采用了 诸如X射线、磁共振和超声波等深入人体的探测手段。到目前为止，大多数 光学成像的进展已经转向高分辨率的功能和分子成像 散射组织中的深度小于1mm。高空间分辨率的深部组织光学成像技术的研究 固有的光学扩散阻碍了分辨率的提高，这是自 生物医学光学。我们必须迎接这一挑战，充分发挥光的潜力，因为它是如此强大的 从物理和生物学的角度来看。从物理上讲，电磁波的一小部分 光所覆盖的光谱是直接探测分子结构的唯一部分;生物学上， 用于感测、反应和发射光的分子被编码在最基本的（即，基因）水平!在 此外，作为非电离辐射的光对生物体的安全性与空气和水一样。因此，光是 最自然的选择可视化生物结构和事件，询问和控制生物 过程，以及诊断和治疗疾病，只要我们能克服光学扩散-a 似乎牢不可破的屏障。尽管在传统的光散射技术中光的多次散射被视为一个问题 智慧，我相信它应该是解决方案的一部分。我们最近在时间反转超声上的工作 编码（TRUE）光学聚焦（Nature Photonics 2011）是该方向的第一个突破。真 聚焦可以非侵入性地将光传递到散射介质深处的动态限定的焦点。这 一项发明为一个更大的范式转换机会打开了大门--一个控制光子路径的机会 以最小化组织中的传输损失。在此，我提出一种新的技术，称为"光子隧穿"， 实现了如此大胆的目标。光子隧穿的目的是将光沿着 动态"钻孔"光隧道。前所未有的光线穿透深度，仅受吸收而非 数量级的更强散射。因为光吸收系数很低 当为0.1/cm时，1/e穿透深度可达10 cm（~4英寸）。如果研制成功，这样的突破性 科技将彻底改变生物医学。在生物医学的各个方面都有应用 光学器件，包括成像（例如，荧光断层成像和报告基因成像）、传感（血氧测定和 血糖测定法）、操作（光遗传学和神经刺激）和治疗（光动力学治疗和 光热疗法）。一个国家卫生研究院院长的先锋奖将给予我的知识自由和 资源来开发一个全新的领域，从字面上照亮生物医学研究的核心。

DESCRIPTION Abstract: Eighty to ninety percent of what most young children learn about the world comes through vision. The same cannot be said when we seek to learn about the inner workings of our own body, because light beyond “skin deep” becomes diffused due to multiple scattering. Instead, researchers have resorted to alternative means—such as X-ray, magnetic resonance, and ultrasound—to probe deep into the body. Until now, most advances in optical imaging have been geared towards high-resolution functional and molecular imaging at depths less than 1 mm in scattering tissue. The pursuit of deep-tissue optical imaging with high spatial resolution has been stymied by the inherent optical diffusion—the grand challenge since the inception of biomedical optics. We must meet this challenge to reach the full potential of light because it is such a powerful tool from both the physical and biological perspectives. Physically, the tiny fraction of the electromagnetic spectrum that light covers is the only part that probes molecular structures directly; biologically, the ability of molecules to sense, react to, and emit light is encoded on the most fundamental (i.e., genetic) level! In addition, light as nonionizing radiation is as safe to biological organisms as air and water. Therefore, light is the most natural choice for visualizing biological structures and events, interrogating and controlling biological processes, as well as diagnosing and treating diseases, if only we could overcome the optical diffusion—a seemingly unbreakable barrier. While multiple scattering of light is treated as a problem in conventional wisdom, I believe that it should be part of the solution. Our recent work on time-reversed ultrasonically encoded (TRUE) optical focusing (Nature Photonics 2011) is a first breakthrough in this direction. TRUE focusing can noninvasively deliver light to a dynamically defined focus deep in a scattering medium. This invention opens the door to an even greater paradigm-shifting opportunity—one that controls the photon paths to minimize transmission loss in tissue. Here I propose a novel technology, called “photon tunneling”, to achieve such an audacious goal. Photon tunneling aims to send light deep into biological tissue along dynamically “drilled” light tunnels. Unprecedented light penetration depth, limited by only absorption instead of orders-of-magnitude stronger scattering, can be reached. Because the optical absorption coefficient is as low as 0.1/cm, the 1/e penetration can be as deep as 10 cm (~4 inches). If successfully developed, such a groundbreaking technology would revolutionize biomedicine. Applications can be found in all aspects of biomedical optics, including imaging (e.g., fluorescence tomography and reporter gene imaging), sensing (oximetry and glucometry), manipulation (optogenetics and nerve stimulation), and therapy (photodynamic therapy and photothermal therapy). An NIH Director’s Pioneer Award would grant me the intellectual freedom and resources to develop a completely new field that will literally illuminate the core of biomedical research.