A better view with new mid-infrared nanoscopy

This illustration represents a bacteria being illuminated with mid-infrared in the top left, while visible light from a microscope underneath is used to help capture the image.
Credit: 2024 Ideguchi et al./ Nature Photonics

Chemical images taken of insides of bacteria 30 times clearer than those from conventional mid-infrared microscopes.

A team at the University of Tokyo have constructed an improved mid-infrared microscope, enabling them to see the structures inside living bacteria at the nanometer scale. Mid-infrared microscopy is typically limited by its low resolution, especially when compared to other microscopy techniques. This latest development produced images at 120 nanometers, which the researchers say is a thirtyfold improvement on the resolution of typical mid-infrared microscopes. Being able to view samples more clearly at this smaller scale can aid multiple fields of research, including into infectious diseases, and opens the way for developing even more accurate mid-infrared-based imaging in the future.

The microscopic realm is where viruses, proteins and molecules dwell. Thanks to modern microscopes, we can venture down to see the inner workings of our very own cells. But even these impressive tools have limitations. For example, super-resolution fluorescent microscopes require specimens to be labeled with fluorescence. This can sometimes be toxic to samples and extended light exposure while viewing can bleach samples, meaning they are no longer useful. Electron microscopes can also provide very impressive details, but samples must be placed in a vacuum, so live samples cannot be studied.

By comparison, mid-infrared microscopy can provide both chemical and structural information about live cells, without needing to color or damage them. However, its use has been limited in biological research because of its comparatively low resolution capability. While super-resolution fluorescent microscopy can narrow down images to tens of nanometers (1 nanometer being one-millionth of a millimeter), mid-infrared microscopy can typically only achieve around 3 microns (1 micron being one-thousandth of a millimeter).

However, in a new breakthrough, researchers at the University of Tokyo have attained a higher resolution of mid-infrared microscopy than ever before. “We achieved a spatial resolution of 120 nanometers, that is, 0.12 microns. This amazing resolution is roughly 30 times better than that of conventional mid-infrared microscopy,” explained Professor Takuro Ideguchi from the Institute for Photon Science and Technology at the University of Tokyo.

The team used a “synthetic aperture,” a technique combining several images taken from different illuminated angles to create a clearer overall picture. Typically, a sample is sandwiched between two lenses. The lenses, however, inadvertently absorb some of the mid-infrared light. They solved this issue by placing a sample, bacteria (E. coli and Rhodococcus jostii RHA1 were used), on a silicon plate which reflected visible light and transmitted infrared light. This allowed the researchers to use a single lens, enabling them to better illuminate the sample with the mid-infrared light and get a more detailed image.

“We were surprised at how clearly we could observe the intracellular structures of bacteria. The high spatial resolution of our microscope could allow us to study, for example, antimicrobial resistance, which is a worldwide issue,” said Ideguchi. “We believe we can continue to improve the technique in various directions. If we use a better lens and a shorter wavelength of visible light, the spatial resolution could even be below 100 nanometers. With superior clarity, we would like to study various cell samples to tackle fundamental and applied biomedical problems.”

Paper Title

Miu Tamamitsu, Keiichiro Toda, Masato Fukushima, Venkata Ramaiah Badarla, Hiroyuki Shimada, Sadao Ota, Kuniaki Konishi, and Takuro Ideguchi. Mid-infrared wide-field nanoscopy. Nature Photonics. April 17th 2024. DOI: 10.1038/s41566-024-01423-0

Useful Links

Department of Physics: https://www.phys.s.u-tokyo.ac.jp/en/

Graduate School of Science: https://www.s.u-tokyo.ac.jp/en/index.html

Ideguchi Group: https://takuroideguchi.jimdo.com/

[Press releases] See live cells with 7 times greater sensitivity using new microscopy technique

[Press releases] Giant leap for molecular measurements

[Press releases] Unprecedented 3D images of live cells plus details of molecules inside

[Press releases] A laser, a crystal and molecular structures

[Press releases] Researchers give standard light microscopes an upgrade to see inside cells



This research was supported by the Japan Society for the Promotion of Science (20H00125, 23H00273), JST PRESTO (JPMJPR17G2), Precise Measurement Technology Promotion Foundation, Research Foundation for Opto-Science and Technology, Nakatani Foundation, and UTEC-UTokyo FSI Research Grant. Fabrication of the custom-made resolution test chart was performed using the apparatus at the Takeda Clean Room of d.lab at The University of Tokyo.

Competing interests

M.T., K.T., and T.I. are inventors of patents related to MIP-QPI. [mid-infrared photothermal quantitative phase imaging]

Research Contact:

Professor Takuro Ideguchi
Institute for Photon Science and Technology,
The University of Tokyo, Tokyo 113-0033, Japan
Tel.: +81-3-5841-1026
Email: ideguchi@ipst.s.u-tokyo.ac.jp

Press contact:
Mrs. Nicola Burghall (she/her)
Public Relations Group, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan


About the University of Tokyo

The University of Tokyo is Japan’s leading university and one of the world’s top research universities. The vast research output of some 6,000 researchers is published in the world’s top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 4,000 international students. Find out more at www.u-tokyo.ac.jp/en/ or follow us on X at @UTokyo_News_en.

Journal: Nature Photonics
DOI: 10.1038/s41566-024-01423-0
Method of Research: Experimental study
Subject of Research: Cells
Article Title: Mid-infrared wide-field nanoscopy
Article Publication Date: 17-Apr-2024
COI Statement: M.T., K.T., and T.I. are inventors of patents related to MIP-QPI. [Mid-infrared photothermal quantitative phase imaging]

Media Contact

Nicola Burghall
University of Tokyo

Expert Contact

Professor Takuro Ideguchi
The University of Tokyo

Media Contact

Nicola Burghall
University of Tokyo

All latest news from the category: Physics and Astronomy

This area deals with the fundamental laws and building blocks of nature and how they interact, the properties and the behavior of matter, and research into space and time and their structures.

innovations-report provides in-depth reports and articles on subjects such as astrophysics, laser technologies, nuclear, quantum, particle and solid-state physics, nanotechnologies, planetary research and findings (Mars, Venus) and developments related to the Hubble Telescope.

Back to home

Comments (0)

Write a comment

Newest articles

Detector for continuously monitoring toxic gases

The material could be made as a thin coating to analyze air quality in industrial or home settings over time. Most systems used to detect toxic gases in industrial or…

On the way for an active agent against hepatitis E

In order to infect an organ, viruses need the help of the host cells. “An effective approach is therefore to identify targets in the host that can be manipulated by…

A second chance for new antibiotic agent

Significant attempts 20 years ago… The study focused on the protein peptide deformylase (PDF). Involved in protein maturation processes in cells, PDF is essential for the survival of bacteria. However,…

Partners & Sponsors