Listening to the Micro-World

与观察微观世界相关的技术非常成熟，包括各种各样的显微镜。相比之下，将我们的听觉扩展到微观世界的工作却很少。这项拨款的目的是开发一种倾听微观世界的基本技术，就像微型耳朵一样。就像我们自己的耳朵一样，大多数声音探测器对压力的变化做出反应，产生小的声学力和相应的传感器位移。测量力的一种非常灵敏的方法是将力与光束的动量进行比较。紧密聚焦的激光束现在通常用于形成光学镊子，它可以捕获微米大小的珠子，克服热作用力和引力。这些镊子系统通常围绕显微镜构建，并操作悬浮在流体介质中的样品，因此该技术与生物系统高度兼容。使用显微镜观察头的位置可以测量皮牛顿力和相应的几纳米的位移。这些被光学捕获的珠子的细微运动将构成我们微型耳朵的基础。我们计划开发、演示和测试许多不同的微耳方法。所有基于聚焦的成像系统都被限制在一个波长左右的尺度上。即使在水中，声波波长也只有100毫米，这使得聚焦的概念与微观系统无关。然而，正如大多数管乐器或古董助听器所证明的那样，亚波长喇叭仍然有效。在这个提议中，我们计划使用微制造技术来制造结构，将流体从发射物体引导到传感器头，提供一种引导压力波的方法，并在必要时将其放大（例如在喇叭形通道中）。我们将使用光学捕获珠作为传感器来测量这些力（如上所述）。然而，重要的是要考虑到，在微观尺度上，由于声响应引起的珠子运动可能被布朗运动所掩盖，因此从这种热背景中区分真实信号将是一个重大挑战。克服布朗背景的关键将是使用高速摄像机同时测量许多珠子的位置。信号不是来自一个珠子，而是珠子的相关运动将传感器响应与不相关的背景区分开来。我们设想了两种基本结构。在第一种最简单的情况下，这些珠子将被放置在定义的喇叭微流体结构的末端，以测量由机械生物系统（分子马达）产生的分子相互作用。或者，我们将在测试对象周围创建一个圆形阵列，并测量环的径向呼吸。在后一种配置中，有可能在非接触模式下进行新的和令人兴奋的生物测量，在这种模式下，我们将确定细胞和表面之间的短程和长距离相互作用。

Technologies associated with looking at the microworld are extremely mature, and include a wide variety of microscopies. By contrast little work has been done to extend our sense of hearing into the micro-world. The purpose of this grant is to develop a basic technology for listening to the micro world, in as sense a micro ear.Just like our own ears, most sound detectors respond to changes in pressure, creating small acoustic forces and corresponding displacement of a sensor. One extremely sensitive way of measuring force is to compare it against the momentum of a light beam. Tightly focused laser beams are now routinely used to form optical tweezers, which can trap micron-sized beads, overcoming both the thermal and gravitation forces. These tweezers systems are typically built around a microscope and manipulate samples suspended in a fluid medium / such that the technology is highly compatible with biological systems. Using a microscope to observe the bead position allows the measurement of piconewton forces and the corresponding displacement of a few nanometres. The subtle movements of these optically trapped beads will form the basis of our micro-ear. We plan to develop, demonstrate and test a number of different micro-ear approaches. All imaging systems based upon focusing are restricted to scales of a wavelength or so. Even in water, acoustic wavelengths are 100s mm, making the concept of focussing irrelevant to microscopic systems. However, as evident by most wind instruments or antique hearing aids, sub wavelength horns still work. In this proposal we plan to use microfabrication techniques to produce structures that channel the fluid flow from the emitting object to the sensor bead, providing a method of guiding the pressure wave, and if necessary amplifying it (e.g. in a flared channel). We will use the optically trapped beads as sensors to measure these forces (as described above). However, it is important to consider that, at the microscale, the movements of the beads due to an acoustic response may be masked by Brownian motion / and hence distinguishing the real signal from this thermal background will be a major challenge challenge.The key to overcoming the Brownian background will be the use of high-speed cameras to measure the position of many beads simultaneously. Rather than the signal being derived from one bead, it is the correlated motion of the beads that distinguishes the sensor response from the uncorrelated background. We envisage two basic configurations. In the first, simplest case, the beads will be positioned at the ends of defined flared microfluidic structures to measure molecular interactions resulting from mechanical biological systems (molecular motors). Alternatively, we will create a circular array around the test object and measure the radial breathing of the ring. In this latter configuration there is the possibility of being able to make new and exciting biological measurements in a non-contact mode, where we will determine both short and long range interactions between cells and surfaces.