Abstract
Core needle biopsy is the gold standard procedure for sampling tissues for pathology-based diagnostics. However, it produces significant tissue damage and may lead to undue pain and risk of complications such as infections. Alternatives such as fine needle aspiration and liquid biopsy have not yet achieved the same widespread utility owing to the limited abundance of cells and relevant biomarkers in extracted samples. Here we introduce a shock-scattering micro-histotripsy-aided fine needle aspiration technology which uses cavitation to liquefy nano-liter to micro-liter volumes to produce tissue homogenates with both intact and lysed cells. It permits not only conventional cytopathology with high success but sufficient high-quality tissue homogenates to enable reliable ancillary testing such as genetic biomarker profiling and even whole genome sequencing with improved quality compared to formalin-fixed samples. Our approach represents an advance in tissue diagnostics with orders of magnitude less damage than core-needle biopsy procedures.
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Acknowledgements
We gratefully acknowledge funding from the Alberta Cancer Foundation (ACF JFMRP 27587, RJZ), the Mary Johnston Chair for Melanoma Research (ACF JFMRP 27587), an Alberta Cancer Research for Screening and Prevention Grant (CRSPPF 017061, R.J.Z.), and the Canadian Cancer Society (CCS 702032, R.J.Z.). P.K. (PGSD3-558531-2021), J.W. (CGSM 574839-2022) and E.A.M. (CGSM 596784-2024) acknowledge scholarship funding from NSERC.
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R.J.Z. is a founder and shareholder of 5Q Laser Inc., OptoBiomeDx Inc., CliniSonix Inc., and IllumiSonics Inc., which however did not support this work. R.J.Z. served on the Scientific Advisory Board of FUJIFILM Visualsonics, which, however, did not support this work. J.W., P.K., E.A.M., and F.R.W. are shareholders of OptoBiomeDx Inc., which however did not support this work. J.A.B. is a founder and shareholder of SoundBlade Medical Inc. and DaxSonics Inc., which, however, did not support this work. The histotripsy transducer and electronics are protected by a patent (Daxsonics Ultrasound Inc., Jeffrey Kyle Woodacre and Jeremy Brown, US11806553B2, active status). The remaining authors declare no competing interests.
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Wang, J., Kedarisetti, P., McAlister, E.A. et al. Shock-scattering micro-histotripsy-aided fine needle aspiration for enhanced biomarker profiling and cytopathology. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72488-4
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DOI: https://doi.org/10.1038/s41467-026-72488-4
