(a) Structure of the mesoscopic objective, (b) Aberration distribution of the mesoscopic objective, (c) Wide-field imaging system built with the mesoscopic objective, (d) Laser point-scanning imaging system built with the mesoscopic objective. Credit: Opto-Electronic Advances (2024). DOI: 10.29026/oea.2024.230212

Optical microscopes are indispensable research tools in fields such as life sciences, medical science, and materials science. The objective lens is the core component of the microscope, determining two key parameters of microscopic imaging: resolution and imaging field of view (FOV).

These two parameters are mutually constrained. Commercial microscope objectives with a numerical aperture (NA) of 0.5 offer submicron resolution; however, their imaging FOV is often limited to around 1 mm. The 2014 Nobel Prize in Chemistry was awarded for , a technology that greatly enhances imaging resolution.

However, achieving high resolution and a large FOV simultaneously remains a research challenge. In recent years, the demand for cross-scale high-throughput imaging has been increasing, but conventional microscope objectives cannot simultaneously achieve both a large FOV and high resolution.

This makes high-resolution imaging of large samples difficult. The usual method is to image the sample multiple times in small FOV and then stitch the images together to form the desired imaging field. However, this method produces artifacts at the stitching edges and has a slow imaging speed, making it impossible to observe dynamic changes of the sample in real-time.

To address these issues, mesoscopic objectives have been proposed. They have complex optical structures and excellent aberration optimization, enabling high NA and a super-large imaging FOV, significantly enhancing the imaging throughput of .

In 2016, the University of Strathclyde first developed a mesoscopic objective with a 0.47 NA, a 6 mm FOV, and a working wavelength range from 400 nm to 700 nm. That same year, Physics World magazine selected it as one of the top ten physics breakthroughs of the year. Subsequently, related research has been reported internationally.

However, optimizing chromatic aberration over a large FOV is extremely challenging. Current mesoscopic objectives are limited to a single imaging wavelength band, either visible or near-infrared, and cannot meet the requirements for diverse fluorescence imaging, such as or two-photon imaging. Additionally, the FOV of existing mesoscopic objectives is concentrated in the range of 3 mm to 6 mm. Increasingly, application scenarios demand further enhancement of the imaging FOV to achieve higher imaging throughput.

To overcome the current obstacles of narrow imaging wavelength band and insufficient imaging FOV in mesoscopic objectives, a research group led by Prof. Guohua Shi from the Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, designed a flat-field apochromatic objective structure for mesoscopic fields and developed the world's largest imaging field and broadest working wavelength mesoscopic objective with submicron resolution.

More information: Xin Xu et al, Large-field objective lens for multi-wavelength microscopy at mesoscale and submicron resolution, Opto-Electronic Advances (2024). DOI: 10.29026/oea.2024.230212

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