PHOTON TUNNELING: SHEDDING NEW LIGHT ON BIOMEDICINE

描述 摘要： 大多数儿童对世界的了解有80%到90%是通过视觉来实现的。这个 当我们试图了解我们自己身体的内部工作时就不能说同样的话了，因为光超越了 由于多次散射，“皮肤深度”变得弥散。取而代之的是，研究人员求助于替代方案 通过X光、磁共振和超声波等手段深入人体。到目前为止，大多数 光学成像的进展已经朝着高分辨率功能和分子成像方向发展， 散布组织的深度小于1毫米。追求高空间的深部组织光学成像 分辨率一直受到固有光学扩散的阻碍-这是自成立以来的重大挑战 生物医学光学。我们必须迎接这一挑战，以充分发挥光的潜力，因为它是如此强大 从物理和生物学的角度来看，这是一种有效的工具。从物理上讲，电磁场的一小部分 光覆盖的光谱是唯一直接探测分子结构的部分；从生物学上讲， 感知、反应和发射光的分子是在最基本的(即遗传的)水平上编码的！在……里面 此外，作为非电离辐射的光对生物有机体来说就像空气和水一样安全。因此，光是 可视化生物结构和事件、询问和控制生物的最自然选择 过程，以及诊断和治疗疾病，如果我们能克服光扩散-a 看似牢不可破的障碍。虽然光的多次散射在传统中被视为一个问题 智慧，我认为这应该是解决方案的一部分。我们最近关于时间反转的工作--超声波反转 编码(真实)光学聚焦(自然光子学2011)是在这一方向上的第一次突破。千真万确 聚焦可以非侵入性地将光传递到散射介质深处动态定义的焦点。这 这项发明开启了一个更大的范式转换机会--一个控制光子路径的机会 以将组织中的传输损失降至最低。在这里，我提出了一种新的技术，称为“光子隧道”，以 实现如此大胆的目标。光子隧道技术的目标是将光深入生物组织 动态“钻”出的光隧道。前所未有的透光深度，仅受吸收限制，而不是 数量级更强的散射，可以达到。因为光吸收系数很低 当为0.1/cm时，1/e的穿透深度可达10厘米(~4英寸)。如果开发成功，这样一种开创性的 技术将给生物医学带来革命性的变化。在生物医学的各个方面都有应用 光学，包括成像(例如，荧光断层扫描和报告基因成像)、传感(血氧仪和 血糖仪)、操作(光遗传学和神经刺激)和治疗(光动力疗法和 光热疗法)。NIH导演先锋奖将授予我知识自由和 资源，以开发一个全新的领域，将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.