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We report a novel lensless on-chip microscopy platform based on near-field blind ptychographic modulation. In this platform, we place a thin diffuser in between the object and the image sensor for light wave modulation. By blindly scanning the unknown diffuser to different x – y positions, we acquire a sequence of modulated intensity images for quantitative object recovery. Different from previous ptychographic implementations, we employ a unit magnification configuration with a Fresnel number of ∼50 000, which is orders of magnitude higher than those of previous ptychographic setups. The unit magnification configuration allows us to have the entire sensor area, 6.4 mm by 4.6 mm, as the imaging field of view. The ultra-high Fresnel number enables us to directly recover the positional shift of the diffuser in the phase retrieval process, addressing the positioning accuracy issue plaguing regular ptychographic experiments. In our implementation, we use a low-cost, DIY scanning stage to perform blind diffuser modulation. Precise mechanical scanning that is critical in conventional ptychography experiments is no longer needed in our setup. We further employ an up-sampling phase retrieval scheme to bypass the resolution limit set by the imager pixel size and demonstrate a half-pitch resolution of 0.78 μm. We validate the imaging performance via in vitro cell cultures, transparent and stained tissue sections, and a thick biological sample. We show that the recovered quantitative phase map can be used to perform effective cell segmentation of a dense yeast culture. We also demonstrate 3D digital refocusing of the thick biological sample based on the recovered wavefront. The reported platform provides a cost-effective and turnkey solution for large field-of-view, high-resolution, and quantitative on-chip microscopy. It is adaptable for a wide range of point-of-care-, global-health-, and telemedicine-related applications. 

Abstract Microtubule‐associated protein tau is an intrinsically disordered, highly soluble protein found primarily in neurons. Under normal conditions, tau regulates the stability of axonal microtubules and intracellular vesicle transport. However, in patients of neurodegeneration such as Alzheimer's disease (AD), tau forms neurofibrillary deposits, which correlates well with the disease progression. Identifying molecular signatures in tau, such as posttranslational modification, truncation, and conformational change has great potential to detect earliest signs of neurodegeneration and develop therapeutic strategies. Here, we show that full‐length human tau, including the longest isoform found in the adult brain, can be robustly displayed on the surface of yeastSaccharomyces cerevisiae. Yeast‐displayed tau binds to anti‐tau antibodies that cover epitopes ranging from the N‐terminus to the 4R repeat region. Unlike tau expressed in the yeast cytosol, surface‐displayed tau was not phosphorylated at sites found in AD patients (probed by antibodies AT8, AT270, AT180, and PHF‐1). However, yeast‐displayed tau showed clear binding to paired helical filament (PHF) tau conformation‐specific antibodies Alz‐50, MC‐1, and Tau‐2. Although the tau possessed a conformation found in PHFs, oligomerization or aggregation into larger filaments was undetected. Taken together, yeast‐displayed tau enables robust measurement of protein interactions and is of particular interest for characterizing conformational change.