Miniaturisation session December 2, 2021
December 2, 11:15-13:00
From millimetre to molecule: microscopy across scales with light and electrons
Jacob P. Hoogenboom PhD
Dept of Imaging Physics, Delft University of Technology, Delft, the Netherlands
Microscopy has been and still is a key technology in science and industry, but each microscopy technique has its own strengths and limitations. Electron microscopy offers near-atomic resolution but images are in grayscale on fixed or specially treated materials and throughput is notoriously low. Light microscopy can be used for fast acquisitions over relatively large areas, as well as live and functional imaging, but resolution is limited by diffraction. We have been developing integrated light and electron microscopy, using illumination with precisely aligned beams of photons and electrons, to lift current barriers in microscopy. In this presentation, I will first show how this microscope allows us to correlate the signals from both microscopes in an automated fashion, with few nanometers spatial precision. Next, I will show how the integrated light microscope can solve the detection bottleneck in multi-beam electron microscopy, enabling 100x faster imaging on biological tissue. Finally, I will present the addition of temporal resolution to the electron microscope by using a laser pulse pump electron pulse probe detection scheme. Thus, these examples show how integrated microscopy allows to go beyond mere correlation of image data to crossing scales and barriers in spatial and temporal nanoscale imaging.
Jacob Hoogenboom is an associate professor at TU Delft who is fascinated by microscopes and molecules. Microscopes have catalyzed science ever since in the 17th century the first discoveries with simple light microscopes were made. Modern-day microscopes are incredibly powerful, but no microscope can cover all spatial and temporal scales needed to fully unravel how molecules function and how this functionality is influenced by or in turn influences itself the local structural environment. In the Hoogenboom group, we aim to invent, develop, and implement new techniques that cross the boundaries and limitations of existing microscopes in visualizing molecules, molecular functionality, and structural details. Most of our work centers around the combination of light and electron microscopy, physically integrated in a single instrument. An important aspect of our work is that we want our techniques and instruments to impact science, society, and economy. Therefore, we actively collaborate with industry and end users to pursue application of our techniques in the areas of life sciences, health, and materials. Already in the conceptual phase of new technology, we discuss with experts in, e.g., biomedical microscopy the efforts needed in probe development, sample preparation, and biological applications. Our work has been awarded with 8 valorization and implementation grants, 14 patents have been transferred to industry, and three commercial products spun out of or were co-developed with the lab. Jacob is also co-founder and supervisory board member of Delmic BV, established in 2010.