The noise is the signal: exploring physico-chemical fluctuations with multiscale experimental models

噪声是信号中明显的随机波动，就像未调谐的收音机上的静电一样，是实验科学的一个普遍方面。我们经常谈论寻找“噪音中的信号”;事实上，科学家通常会竭尽全力减少其发生率。然而，噪声来自系统内部的微观波动，其性质敏感地取决于该系统的基本特征。就像降噪耳机屏蔽了我们周围的环境一样，如果只看信号而不看噪音，我们可能会忽略关于实验系统如何真正工作的重要信息。事实上，正是对天线上残留噪声的仔细解释，为宇宙微波背景辐射提供了第一个实验证据--这是大爆炸的一个关键特征，也是获得诺贝尔物理学奖的一个观测结果。然而，噪声作为一种信息来源往往被忽视，因为很难解释实验数据中的波动。解开导致噪声的许多因素并了解它们各自的噪声产生特性是具有挑战性的，特别是在微观波动仍然知之甚少的非平衡系统中。此外，虽然分子系统中波动的重要性越来越被认识到，但获得理解这种噪声所需的详细定量实验数据在技术上是不允许的，因为这里的波动是复杂的，快速的，并且太小而无法通过常规显微镜观察到。我的研究旨在通过研究实验模型中的波动来揭示这种噪音的起源，这些模型显示出类似的物理化学行为，但这些行为是直接可观察的，高度可调的，易于操作的，关键是使每个单独的贡献因素能够被隔离，识别和理解。物理化学系统中波动的不同方面将通过三个研究目标来解决。第一个考虑通过通道移动的相互作用的粒子的电流。至关重要的是，这些粒子足够大，可以直接观察到电流的波动，使我们能够探索系统的不同特征如何产生特定的噪声特性。这在理解在自然现象中观察到的特定形式的噪声方面具有潜在的应用，例如潮汐模式或神经元的放电，这些都是目前知之甚少的。目标二考虑了柔性模型聚合物的波动如何通过狭窄的孔来控制其运输;这一过程对细胞膜运输和新兴的DNA测序技术都至关重要。第三个目标是解决由DNA构建的更复杂、更灵活的纳米结构所产生的噪音，这些结构的规模与细胞机器相似。这些结构可以被设计成具有已知的特征，但是由于它们的小尺寸，它们的波动不能被直接观察到。然而，我们可以看到这些涨落对流经系统的分子电流的影响。最重要的是，这些数据可以用我们在目标一中所学到的关于可观察电流的知识来解释，从而提供对这些纳米结构的性质和波动的见解。每个目标都阐明了导致物理化学系统中噪声的单个因素，并提供了测试和指导理论预测所需的详细实验数据。总的来说，我的综合结果相互迭代，形成了物理化学过程中噪音的全面图景，这些过程支撑着从技术到生物学的复杂系统。更广泛地说，我的工作将促进新的方法来分析噪声的发展，支持努力工程技术具有更好的噪声特性，并揭示围绕实验科学的这一普遍方面的基本问题。

Noise is the apparently random fluctuation in a signal, like static on an untuned radio, and is a universal aspect of experimental science. We often talk about finding 'the signal in the noise'; indeed, scientists typically go to great lengths to reduce its incidence. Yet noise arises from the microscopic fluctuations within a system, the nature of which depend sensitively upon that system's underlying features. Just as noise-cancelling headphones screen out our surroundings, by looking only at the signal and not at the noise we risk ignoring significant information about how an experimental system really works. In fact, it was careful interpretation of residual noise on an antenna that provided the first experimental evidence for cosmic microwave background radiation - a key signature of the Big Bang and an observation which resulted in the Nobel Prize in Physics.Noise is often overlooked as a source of information, however, because it is difficult to interpret fluctuations in experimental data. Disentangling the many factors that contribute to noise and understanding their individual noise-creating characteristics is challenging, especially in non-equilibrium systems where microscopic fluctuations remain poorly understood. Moreover, while the importance of fluctuations in molecular systems is increasingly recognised, obtaining the detailed quantitative experimental data needed to understand this noise is technically prohibitive, as here fluctuations are complex, rapid and too small to observe by conventional microscopy. My research aims to unravel the origins of this noise by studying fluctuations in experimental models that display analogous physico-chemical behaviour, but which are directly observable, highly tuneable and easily manipulable, crucially enabling each individual contributing factor to be isolated, identified and understood.Differing aspects of fluctuations in physico-chemical systems will be addressed via three research objectives. The first considers currents of interacting particles moving through channels. Crucially these particles are large enough for fluctuations in the current to be directly visualised, allowing us to explore how different features of a system give rise to particular noise characteristics. This has potential applications in understanding particular forms of noise observed in natural phenomena, e.g. tidal patterns or the firing of neurons, that are currently poorly understood. Objective two considers how the fluctuations of flexible model polymers govern their transport through narrow pores; a process of key importance both to cell membrane transport and emerging DNA-sequencing technologies. Objective three addresses noise arising from more complex, flexible nanoscale structures built from DNA and similar in scale to cellular machinery. These structures can be designed with known features, but their fluctuations cannot be directly observed due to their small size. We can, however, see the effect these fluctuations have on a molecular current running through the system. Crucially, this data can be interpreted using what we have learnt about observable currents in Objective one, thus providing insights into the properties and fluctuations of these nanostructures.Each objective elucidates an individual factor contributing to noise in physico-chemical systems and provides the detailed experimental data required to test and guide theoretical predictions. Taken together, my combined results feed iteratively into one another to forge a comprehensive picture of noise in the physico-chemical processes which underpin complex systems from technology to biology. More broadly, my work will facilitate the development of new approaches to analysing noise, support efforts to engineer technologies with better noise characteristics, and shed new light on fundamental questions surrounding this universal aspect of experimental science.