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Inside the Lab Digital and computational pathology, Analytical science

An Imaging Revolution: from CERN to the Clinic

The evolution of physical-chemical analytical instruments has traditionally focused on the improvement of resolution, separation, sensitivity, and throughput. Here, resolution refers to different parameters such as spectral resolution, molecular resolution, structural resolution, spatial resolution, and several more. In pathology based clinical diagnosis, the speed of analysis is key. Optical scanning of immunostained slides can be performed in minutes, but limited possibilities for multiplexing exist. For example, imaging lanthanide-labeled antibodies with SIMS offers the multiplexing capabilities but lacks the speed. In imaging technologies in particular, the detail that can be observed is crucial and the “resolution revolution” is strongly based on advances in detector technology and image processing. But it usually comes at the expense of throughput. Make the pixel size 10 times smaller and the same analytical area requires 100 times longer data acquisition time.

But a new development in secondary ion mass spectrometry imaging changes that paradigm – based on an innovation in mass spectrometry that takes advantage of massively parallel detection of arrival time and position capabilities, combined with an innovative detector coming from CERN: the Timepix3 system. The detector offers nanosecond timing resolution and continuous time resolved image detection. M4i researchers have coupled it to a microscope-mode mass spectrometry imaging system that allows for the detection of more than a million pixels per second – that’s orders of magnitude faster than what is possible with conventional imaging experiments. It uniquely combines throughput and spatial resolution with single ion detection capabilities for large m/z ions.

We’ve applied this new system for ultrafast SIMS based molecular imaging of large areas at submicron spatial resolution. When applied to biomedical tissue analysis, a variety of molecules can be visualized at cellular detail in a matter of minutes. I believe this approach could revolutionize digital molecular pathology, as well as peri-operative diagnostics in a true clinical translational setting. In other words, bridging the translational gap between fundamental mass spec research and pathology – by making tissue diagnoses more precise and rapidly improving precision medicine through more individually tailored therapies.

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About the Author
Ron M. A. Heeren

Director, M4I, and Distinguished Professor, University of Maastricht, Netherlands

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