Toda Keiichiro, Tamamitsu Miu, Ideguchi Takuro
Department of Physics, The University of Tokyo, Tokyo, 113-0033, Japan.
Institute for Photon Science and Technology, The University of Tokyo, Tokyo, 113-0033, Japan.
Light Sci Appl. 2021 Jan 1;10(1):1. doi: 10.1038/s41377-020-00435-z.
Quantitative phase imaging (QPI) with its high-contrast images of optical phase delay (OPD) maps is often used for label-free single-cell analysis. Contrary to other imaging methods, sensitivity improvement has not been intensively explored because conventional QPI is sensitive enough to observe the surface roughness of a substrate that restricts the minimum measurable OPD. However, emerging QPI techniques that utilize, for example, differential image analysis of consecutive temporal frames, such as mid-infrared photothermal QPI, mitigate the minimum OPD limit by decoupling the static OPD contribution and allow measurement of much smaller OPDs. Here, we propose and demonstrate supersensitive QPI with an expanded dynamic range. It is enabled by adaptive dynamic range shift through a combination of wavefront shaping and dark-field QPI techniques. As a proof-of-concept demonstration, we show dynamic range expansion (sensitivity improvement) of QPI by a factor of 6.6 and its utility in improving the sensitivity of mid-infrared photothermal QPI. This technique can also be applied for wide-field scattering imaging of dynamically changing nanoscale objects inside and outside a biological cell without losing global cellular morphological image information.
具有光学相位延迟（OPD）图高对比度图像的定量相位成像（QPI）常用于无标记单细胞分析。与其他成像方法不同，灵敏度的提高尚未得到深入探索，因为传统的QPI足够灵敏，能够观察到限制最小可测量OPD的基底表面粗糙度。然而，新兴的QPI技术，例如利用连续时间帧的差分图像分析，如中红外光热QPI，通过解耦静态OPD贡献来减轻最小OPD限制，并允许测量小得多的OPD。在此，我们提出并展示了具有扩展动态范围的超灵敏QPI。它通过波前整形和暗场QPI技术的组合实现自适应动态范围偏移。作为概念验证演示，我们展示了QPI的动态范围扩展（灵敏度提高）6.6倍及其在提高中红外光热QPI灵敏度方面的效用。该技术还可应用于生物细胞内外动态变化的纳米级物体的宽场散射成像，而不会丢失全局细胞形态图像信息。
