The science of microscopy is hundreds of years old. The first compound microscopes were made in Europe in the early 1600s – and, since then, the field has steadily evolved. Each advance has brought continuous improvement in quality, accuracy, and efficiency for life science research. In the past, the microscope was used purely for raw data acquisition – but, today, sophisticated algorithms support scientists in the interpretation of images, providing immediate insights. In the future, I anticipate that the microscope will likely be fully integrated and digitized, with intelligent solutions that allow scientists in a laboratory to more fully visualize what is happening throughout a biological sample. Although optics will always remain a key component in microscopy, the image itself is now only one part of the process. More important are the technological advances being made to provide scientists with visual information and interpretations to which they may otherwise have remained blind.
Key to the growth of modern microscopy is our evolving ability to clearly and accurately visualize samples in three dimensions – which comes mainly from advances in software and graphical processing that improve our ability to capture, store, and examine complex 3D data. Imaging beyond two dimensions remains difficult because of the need to properly prepare the sample and optimize the technology to acquire and transform the data – but imagers are being developed to address those challenges. Novel software removes unwanted signals from out-of-focus regions of the specimen to reveal the in-focus region of interest, automatically increasing the visibility of structures without any manual real-time modifications. Such processing minimizes modification of the raw sensor data from the region of interest, preserving the image structure and other parameters while minimizing user interaction. The resulting precision and reliability offer reproducible and statistically relevant results.
In a similar vein, manufacturers are developing solutions for extracting as much information as possible from samples. Confocal laser scanning microscopy is the standard for true 3D-resolved fluorescence imaging and, together with modern technologies, helps researchers extract as much information as possible from images. However, as with all imaging systems, physically caused diffraction can still lead to blur, reducing the effective resolution and causing misplaced imaging of the exact position of individual photons.
Additionally, biological sample background noise means that faint details of the raw data close to the noise level might be hard to extract. These effects can be displayed by the triangle of microscopy, whose three components – resolution, speed, and sensitivity – are incompatibly located at each corner of the triangle. Increasing one of the accessible areas decreases the others accordingly, so a system that aims to obtain true images must infiltrate these limits in near real time and “push the corners of the triangle.” Ideally, such a system would be automated for inexperienced users, but allow full control for those who wish to fine-tune each parameter individually.
In my view, the future of microscope imaging hinges on the development of systems that enable a user to precisely and confidently visualize samples in 3D. Future microscope systems will likely be fully integrated and digitized, with intelligent software solutions that give an unprecedented look into what is happening throughout a biological sample. The new information will be an asset when it comes to big data, because a larger sample base will allow researchers to combine results from different experiments and identify previously unknown rules. Such capabilities will not only spearhead a new age of scientific imaging and fundamentally change the way that researchers work when imaging model organisms, tissue sections, and 3D cell cultures like organoids; they will also optimize and further evolve what is already in place.
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