Lensfree On-Chip Near-field Microscopy based on Resonant Nano-Apertures

描述（由申请人提供）：为了实现高空间分辨率，大多数光学显微镜依赖于昂贵的组件，如高数值孔径物镜或其他镜头。由于这种自由空间组件，大多数高分辨率显微镜仍然体积庞大，使其难以与具有成本效益的小型化系统集成。然而，在医学/生物学中，存在一组应用程序，这些应用程序将非常受益于理想的芯片上的小型化高分辨率显微镜。为此，拟议的研究计划旨在开发一种新形式的无透镜，紧凑的数字显微镜，使用芯片上密集排列的纳米孔径阵列。通过适当地设计金属纳米孔阵列，即使不使用任何透镜或机械扫描，也将实现高空间分辨率。为此，所设计的纳米阵列将被制造到标准的光电传感器阵列上，并且感兴趣的对象将与孔径阵列直接接触。因此，所提出的片上显微镜可以以d500 nm的高空间分辨率对二维物体（>5 mm 2宽）进行成像，并且具有~150 mm 2/min的快速成像速度。总体而言，该应用旨在通过使用纳米光子学和等离子体激元学的关键概念来推进片上显微镜的当前状态。由于所提出的方法是无透镜的，因此它可以与微流体系统集成在紧凑的空间中，从而可以显着改善目前进行高通量筛选显微镜或即时诊断的方式。当今迫切需要可与一次性微流体装置集成的高分辨率和快速成像技术，特别是对于资源稀缺的发展中国家。所提出的成像模式在医疗保健中的另一个显著影响可能是在组织病理学领域。所提出的近场成像方案可以潜在地使得能够相当快速地捕获组织病理学样本的高分辨率图像，然后可以通过互联网将其传输给世界上的任何医生。这种被称为“远程病理学”的机会将意味着全球共享医疗资源。为此，该应用可以通过显著提高成像速度（>150 mm 2/min）来实现远程病理学的实际实施。这种快速的图像采集速度也可能对基于微阵列的基因组学或蛋白质组学产生重大影响，其中需要在短时间内收集大量的高分辨率数据。 公共卫生相关性：基于共振纳米结构的无透镜片上近场显微镜项目叙述我们提出开发一种新型的高分辨率和无透镜数字显微镜，该显微镜基于在光电传感器芯片上制造的专门设计的纳米孔阵列的光学共振特性。这种新的显微镜方法不需要任何机械扫描或物镜，因此为高分辨率近场成像提供了一种更简单，更紧凑的方法。此外，图像采集和计算时间相当短，使其成为一种非常快速的成像模式，可以显着改善目前进行高通量筛选显微镜或即时诊断的方式。

DESCRIPTION (provided by applicant): To achieve high spatial resolution, most optical microscopes rely on expensive components such as high numerical aperture objectives or other lenses. Due to such free-space components, most high resolution microscopes still remain bulky, making them harder to integrate with cost-effective and miniaturized systems. However, in medicine/biology there exists a set of applications that would highly benefit from miniaturized high resolution microscopes that are ideally on chip. For this purpose, the proposed research plan aims to develop a new form of lens-free, compact digital microscope using a densely packed array of on chip nano-apertures. By properly designing an array of metallic nano-apertures, a high spatial resolution will be achieved even without using any lens or mechanical scanning. For this end, the designed nano-array will be fabricated onto a standard opto-electronic sensor array, and the object of interest will be in direct contact with the aperture array. As a result, the proposed on chip microscope can image two dimensional objects (>5 mm2 wide) at a high spatial resolution of d500 nm, and with a fast imaging speed of ~150 mm2/min. Overall, this application aims to advance the current state of on chip microscopy by using the key concepts of nano-photonics and plasmonics. Because the proposed approach is lensfree, it can be integrated with microfluidic systems in a compact space, and thus can significantly improve the way that high-throughput screening microscopy or point-of-care diagnostics are currently done. High resolution and rapid imaging technologies that can be integrated with disposable microfluidic devices are urgently needed today, especially for the developing world, where the resources are scarce. Another significant impact of the proposed imaging modality in health care may be in the field of histopathology. The proposed near-field imaging scheme can potentially enable quite rapid capturing of high resolution images of histopathology samples, which can then be transmitted over the internet to any physician in the world. This opportunity, which is termed "telepathology", will imply the global sharing of medical resources. For this end, this application may enable practical implementations of telepathology by significantly improving the imaging speed (>150 mm2/min). This rapid image acquisition speed may also have a significant impact on micro-array based genomics or proteomics, where massive amounts of high resolution data need to be collected in a short amount of time. PUBLIC HEALTH RELEVANCE: Lensfree On-Chip Near-field Microscopy based on Resonant Nano-Apertures Project Narrative We propose to develop a novel high resolution and lens-free digital microscope that is based on optical resonance properties of a specially designed array of nano-apertures fabricated on an opto-electronic sensor chip. This new microscopy approach does not require any mechanical scanning or objective-lenses, and therefore offers a simpler and more compact approach for high resolution near-field imaging. Furthermore, the image acquisition and computation time is fairly short, making it a quite fast imaging modality that can significantly improve the way that high-throughput screening microscopy or point-of-care diagnostics are currently done.