A team of MIT researchers has developed a new microscope technology that can see deeper into brain tissue at a single-cell level than conventional microscopes can. The system employs a novel combination of light and sound to create high-resolution images without the need for external labels. The work is detailed in a paper published in the journal Light: Science and Applications.
The new “Multiphoton-In and Acoustic-Out” operates in two major stages. First, it uses an intense, ultra-short burst of long-wavelength light to penetrate deep and precisely into the brain tissue. The “three-photon light” excites the target molecule within a single cell.
For the second step, instead of trying to detect the faint fluorescent light the molecule gives off, it measures the sound. As the light energy is absorbed, it causes a thermal expansion within the cell, producing sound waves that travel through tissue. A very sensitive ultrasound microphone picks up the sound, the system then converts the sound signal into a detailed image.
Using the new system, the team successfully imaged NAD(P)H — a molecule associated with cellular metabolism and neuron activity — right through a 1.1 millimeter-thick human cerebral organoid. To put it into perspective, that number is 5 times higher than what other label-free microscope technologies are capable of.
Given that the new system requires no added chemicals or genetic engineering, the researchers project it could one day be used in clinical settings, such as the detection of biomarkers for diseases like Alzheimer’s during brain surgery. The tests conducted so far have been in vitro and ex vivo, but the team is now targeting a demonstration on a living animal.
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