Quantitative phase microscopy of thick objects

显微镜对厚标本的成像一直存在问题。问题是，当显微镜试图聚焦在这些物体深处的一个平面上时，图像会被样本其他部分产生的失焦背景淹没——而且要求的分辨率越高，这个问题就越严重。最简单的解决方法是将样品切得非常薄，但这既耗时又具有破坏性，会破坏样品的原始状态。本研究的目的是研究计算方法实现相同的切片效果，而不需要物理改变试样。我们假设这可以通过一种相对较新的技术来实现，这种技术被称为ptychography，结合断层扫描的样本旋转思想和算法。通过解开照明光源与厚样品之间复杂的多重散射相互作用，我们希望扩展这种混合方法的3D成像能力，超越这两种技术传统形式的限制。该研究的潜在应用范围横跨显微镜模式的光谱。在红外波长检测半导体晶圆中的小缺陷是一项令人兴奋的应用，目前超出了现有的基于光的检测设备的范围-最终结果将改善对光刻工艺的理解并提高产量。对于可见光，一个主要的例子是厚组织标本的成像，这是生物学家长期困扰的问题，他们将从以微米级分辨率进行无染色的体内成像的能力中受益匪浅。在光谱的x射线端，应用包括骨碎片的腔隙-管状网络成像和软x射线全细胞成像，如果可以超越当前成像方法固有的厚度限制，则精度和可实现的分辨率都将大大提高。对于电子，我们的研究可以改善半导体关键材料特性的成像，例如掺杂浓度和磁场，测量这些对未来电子设备的发展至关重要。

Microscopes have always had trouble imaging thick specimens. The problem is that when the microscopist tries to focus on a plane deep within such objects, the image is swamped by out-of-focus background generated by the rest of the sample - and the higher the resolution required the worse this problem gets. The simplest solution is to physically slice the specimen very thinly, but this is time consuming and disruptive, destroying the sample's native state. The aim of this research is to investigate computational methods for achieving the same slicing effect, without the need to physically alter the specimen. We hypothesise that this can be achieved using a relatively new technique called ptychography, in combination with the sample rotation idea and algorithms from tomography. By unravelling the complex, multiple-scattering interaction of an illumination source with a thick specimen, we hope to stretch the 3D imaging capabilities of this hybrid approach beyond the limits imposed upon the conventional forms of these two techniques. Potential applications for the research stretch across the spectrum of microscope modalities. At infrared wavelengths detecting small defects in semiconductor wafers is an exciting application, currently beyond the reach of existing light-based inspection devices - the end result would be improved understanding of the lithographic process and better yields. For visible light, a primary example is the imaging of thick tissue specimens, a long-standing bugbear for biologists, who would benefit greatly from the ability to perform stain-free in vivo imaging at micron-scale resolutions. At the X-ray end of the spectrum, applications include the imaging of the lacuna-canalicular network of bone fragments and soft X-ray whole cell imaging, where both accuracy and achievable resolution will be greatly improved if the thickness limit inherent to the current imaging methods can be surpassed. For electrons, our research could improve the imaging of key material properties of semiconductors, such as doping concentrations and magnetic fields, measurement of which is vital to the development of future electronic devices.