Recently, a team of researchers from the National University of Singapore has been working to develop an imaging technique for matter in the microsphere that is: “non-invasive, dynamic, real-time, and label-free”. This is known as remote-mode microsphere nano-imaging and is described by the team behind it, as opening new boundaries for optical microscopes.
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What is microsphere nano-imaging?
A microsphere is a spherical particle between one and one thousand micrometers (μm) and in diameter. 1,000 μm is the same size as one millimeter, while 1 μm is 1,000 nanometers (nm) or 10-6 meters (m). Microspheres are available commercially in a variety of materials, including glass and plastics.
Microsphere nano-imaging is a recent advance in microscopy that effectively breaks the constraints of the optical refraction limit barrier to higher resolutions in traditional confocal microscopes, that have been used since the time of Galileo Galilei and Isaac Newton.
The technique uses dielectric microspheres to generate resolutions up to five times smaller than confocal lenses can (50 nm compared to the 250 nm diffraction limit). This is because these tiny orbs can focus on evanescent light with much greater precision power than lenses. The result of this is a reduction in light wavelength in the medium that the specimen is suspended in, resulting in the above-mentioned resolution capability.
As well as the improved resolution for optical microscopy, microsphere nano-imaging may also prove useful due to their ability to place microspheres much closer to the specimen surface due to their size.
Also, unlike other forms of ultra-high-resolution microscopy, microsphere assisted optical microscopy does not require so-called labeling of the specimen to work. The dyes or tags used to label specimens have been a cause for concern among some researchers, with speculation as to how much of the specimen’s properties are affected by this labeling, growing.
The advances in microsphere nano-imaging
The first commercially available microsphere nano-imaging instrument (or nanoscope) was brought to the market in 2017 by the nanotechnology start-up company LIG Nanowise in Manchester, UK. The Nanopsis can achieve 400 times magnification, generating full color and can produce widefield scans of materials and life samples with resolution detail as low as 70 nm.
“Nanopsis nanoscopes,” said LIG Nanowise Chairman and Director of the Laser Processing Research Centre at the University of Manchester Professor Lin Li, “Can be used by anyone with basic undergraduate scientific training.” This could save valuable time and expense, as researchers looking for cancer cures and nanotechnology applications would no longer need to book time in a dedicated nano-imaging facility.
A recent advance in microsphere nano-imaging sought to eliminate the limitation caused by the direct deposit of microspheres on the specimen surface. This requirement prevented microsphere nano-imaging from being entirely non-invasive, as the microsphere material would necessarily interact with the specimen, producing occasionally unreliable results.
The Singapore team developed a remote-mode platform for microsphere nano-imaging to overcome this. By adjusting distances between the specimen surface, microsphere and microscope lens, a greatly enlarged image can be detected in the objective lens.
This new technique brings the benchmark for nanoscale optical observations down to only 23 nm. This is achieved without any need to control ambient atmosphere, prepare or label samples, and is non-invasive and dynamic (meaning real-time images can be generated).
The new frontier of optical microscopy: nanoscopy
As microsphere nano-imaging continues to advance, it enables a much greater understanding of critical biological and physical functions. In the last two centuries, the impact of conventional confocal microscopes has been dramatic, especially in the field of medicine. With the advent of optical nanoscopy, especially medical applications of such powerful real-time, non-invasive magnification techniques like microsphere nano-imaging will play an important role in the treatment and eradication of many diseases.
Chen, L.-W., Zhou, Y., Wu, M.-X. and Hong, M.-H. (2018). Remote-mode microsphere nano-imaging: new boundaries for optical microscopes. Opto-Electronic Advances, 1(1), pp.17000101–17000107.
Surat, P. (2019). Microsphere-Assisted Microscopy: Advantages and Limitations. [online] News Medical Life Sciences. Available at: https://www.news-medical.net/life-sciences/Microsphere-Assisted-Microscopy-Advantages-and-Limitations.aspx.