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MIT Microscope Combines Three-Photon and Acoustic Detection to Image Brain Cells Over a Millimeter Deep

Having validated the platform ex vivo at single-cell resolution without external labels, the team is reconfiguring its ultrasound detector for live-animal use with the goal of reaching two-millimeter depth.

A picture of MIT's new multiphoton, photoacoustic, label free microscope system. Image by Tatsuya Osaki.
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Overview

  • The ‘Multiphoton-In and Acoustic-Out’ system uses three-photon excitation to induce localized thermal expansion in cells and acoustic detection to avoid external labels.
  • Researchers detected NAD(P)H molecules through 1.1 mm-thick cerebral organoids and 0.7 mm mouse brain slices, exceeding previous depth limits by more than fivefold.
  • A sensitive ultrasound transducer captures the sound waves generated by molecular excitation and software converts them into high-resolution images.
  • To enable in vivo imaging, engineers are redesigning the detector placement so that both light source and microphone sit on the same side of living tissue.
  • The label-free approach could monitor biomarkers such as NAD(P)H and GCaMP in real time during neuroscience experiments or human brain surgeries.