RT Journal Article SR Electronic T1 Speckle illumination microscopy enables slide-free and non-destructive pathology of human lung adenocarcinoma JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.11.464016 DO 10.1101/2021.10.11.464016 A1 Yan Zhang A1 Lei Kang A1 Claudia T. K. Lo A1 Terence T. W. Wong YR 2021 UL http://biorxiv.org/content/early/2021/10/13/2021.10.11.464016.abstract AB Histopathology based on formalin-fixed and paraffin-embedded tissues remains the gold standard for surgical margin assessment (SMA). However, routine pathological practice is lengthy and laborious, failing to provide immediate feedback to surgeons and pathologists for intraoperative decision-making. In this report, we propose a cost-effective and easy-to-use histological imaging method with speckle illumination microscopy (i.e., HiLo). HiLo can achieve rapid and non-destructive imaging of large and fluorescently-labelled resection tissues at an acquisition speed of 5 cm2/min with 1.3-μm lateral resolution and 5.8-μm axial resolution, demonstrating a great potential as an intraoperative SMA tool that can be used by surgeons and pathologists to detect residual tumors at surgical margins. It is experimentally validated that HiLo enables rapid diagnosis of different subtypes of human lung adenocarcinoma and hepatocellular carcinoma, producing images with remarkably recognizable cellular features comparable to the gold-standard histology. This work will facilitate the clinical translations of HiLo microscopy to improve the current standard-of-care.Competing Interest StatementThe authors have declared no competing interest.