Quoting foreign media reports, the Chinese Academy of Sciences announced that the Chinese research team has developed an advanced imaging technology to achieve super-resolution microscopes at an unprecedented speed and with fewer images. The new method should be able to capture speeds previously unattainable in living cells.

Super-resolution technology (commonly called nanotechnology) achieves nanometer-level resolution by overcoming the diffraction limit of light. Although nanomicroscopes can capture images of individual molecules in cells, they are difficult to use with living cells because hundreds of thousands of images are required to reconstruct the image-the process is too slow to capture fast-changing dynamics.

On the Optica page of the “High Impact Research” journal published by the Optical Society (OSA), researchers from the Shanghai Institute of Optics and Fine Mechanics (SIOM) of the Chinese Academy of Sciences described how they used an unconventional imaging method called “ghost imaging” to improve The imaging speed of the nanomicroscope. Their new technology uses several orders of magnitude fewer images than traditional nanotechnology to produce nanometer resolution.

Wang Zhongyang, co-leader of the research team, said: “Our imaging method can potentially detect the dynamics that occur on the millisecond scale in subcellular structures, with a spatial resolution of tens of nanometers-the temporal and spatial resolution of biological processes that occur.”

Combining technology for faster imaging

The new method is based on stochastic optical reconstruction microscopy (STORM), one of three researchers who won the Nobel Prize in Chemistry in 2014. STORM, sometimes called light activated positioning microscope (PALM), is a label that uses a wide-area technique of fluorescence to switch between a light-emitting state (bright) and a dark state (off).

Hundreds or thousands of images are collected, and each image captures a subset of the fluorescent markers that are turned on at a given time. The position of each molecule can be determined and used to reconstruct the fluorescent image.

Researchers turned to ghost imaging to speed up the STORM imaging process. Ghost imaging forms a picture by associating a light pattern that interacts with an object with a reference pattern that does not interact with it.

Separately, the light pattern does not carry any meaningful information about the object. The researchers also used compressed imaging technology, which is a computational method that can reconstruct the image with less exposure because it uses an algorithm to fill in the missing information.

“Although STORM requires low-density fluorescent markers and many image frames, our method can use very few frames and high-density fluorophores to create high-resolution images,” said Han Shensheng, one of the other co-leaders of the research team. “It also does not require any complicated lighting, which helps reduce photobleaching and phototoxicity that can damage dynamic biological processes and living cells.”

Improve imaging efficiency

To implement this new technique, the researchers used an optical component called a random phase modulator to convert the fluorescence in the sample into a random spot pattern. Encoding the fluorescence in this way allows each pixel of a very fast CMOS camera to collect the light intensity from the entire object in a single frame.

In order to form an image through ghost imaging and compression imaging, it takes only one step to associate the light intensity with the reference light pattern. The result is more efficient image acquisition and a reduction in the number of frames required to form a high-resolution image.

The researchers tested the technology by using it to image the 60-nanometer ring. The new nanomicroscopy method uses only 10 images to solve the ring problem, while the traditional STORM method may require up to 4000 frames to achieve the same result. The new method also addresses a 40-nanometer ruler with 100 images.

“We hope that this method can be used for a variety of fluorescent samples, including those with weaker fluorescence intensity than the fluorescence used in this study.” Wang said.

The researchers also hope to make the technology faster to achieve video-rate imaging with a large field of view to obtain 3D and color images.

It has to be said that from the middle of the last century to the present, chip technology has been cutting-edge technology in the high-tech field. Nowadays, a smart phone uses dozens of chips. Not only that, the integration of chips is getting higher and higher. , The manufacturing difficulty is getting more and more difficult, even if it is as powerful as Intel, it has been hovering in the 14nm process for so many years, and there has been no large-scale transformation to the 10nm process.

If you think back ten years ago, the chip manufacturing process can be upgraded from 90nm to 65nm at once, and then continue to be significantly upgraded to 45nm, 22nm and other processes. However, in recent years, the chip manufacturing process has been upgraded less and less, for example After 22nm, it started to enter the 16nm process, and then 14nm, 12nm, 11nm, 10nm, 8nm, and now the most advanced is 7nm, so we see that it seems that it becomes extremely difficult to move forward 1nm.

However, this time the scientists of the Chinese Academy of Sciences made a major breakthrough in chip manufacturing. It can be said that we have done a good job of technical support in the field of chip manufacturing in the future, and the rest that we need to overcome is the last difficulty in the field of chips, which is the manufacturing of chips. Equipment, mainly lithography machines. At present, only ASML in the Netherlands can provide the most advanced lithography machines supporting extreme ultraviolet lithography technology. We believe that our scientists will surely bring us surprises in the future. We will wait and see. What’s your opinion?