Technology 3 min read

New Microscopy Method Breaks the Fluorescence Optical Imaging Color Barrier

The epr-SRS microscopy spectrum | Nicoletta Barolini | Columbia University |

The epr-SRS microscopy spectrum | Nicoletta Barolini | Columbia University |

Columbia University scientists have unveiled a new microscopy methodology. This development breaks the so-called “color barrier,” and widens the sensitivity of fluorescent microscopes by five times. 

Thanks to its extreme sensitivity, fluorescence microscopy, a part of optical microscopy, is the most used microscopy technique in biological research, particularly suitable for the study of living cells. Fluorescence microscopes enable the visualization of naturally fluorescent objects, such as chlorophyll, or biomolecules (fluorescent proteins) stained with a fluorescent chemical (fluorophore) to study them.

The Color Barrier Facing Fluorescent Microscopy

However practical and effective, fluorescent microscopy has some limits. With the problem of sample thickness aside (penetration of fluorescence), because of intrinsic properties of the fluorescence spectrum, among the shades that fluorescent proteins emit, the number of resolvable colors is limited to only up to five colors: blue, cyan, green, yellow, and red. This means that researchers are limited to seeing a maximum of only five cellular structures at the same time.

That number can reach from seven to nine colors using complex instruments and analysis methods, but a new technique takes that number up to 24.

Broader Color Palette for Fluorescent Imaging

Dr. Wei Min, Associate Professor of Chemistry at Columbia University, and his team have developed a new optical microscopy platform that addresses the problem of the color barrier which faces fluorescence microscopes.

Called epr-SRS, or electronic pre-resonance stimulated Raman Scattering Microscopy, this innovative technique breaks the color barrier and enables viewing up to 24 color structures at the same time, instead of only five.

“In the era of systems biology,” Professor Min, who leads a research team at his biophotonics lab, said, “how to simultaneously image a large number of molecular species inside cells with high sensitivity and specificity remains a grand challenge of optical microscopy.”

As described in the study published in the journal Nature, epr-SRS images cellular structures, combining high vibrational sensitivity and selectivity to create a palette of dyes that, when combined with available fluorescent probes, provides 24 resolvable colors, with the number likely to increase further.

In addition to the greater resolution of images, this 24-color system would enable scientists to increase their productivity. Researchers will be able to observe up to 24 protein structures and processes at once per tissue sample and don’t have to start over, lowering the chance of damaging sampled tissue.

Columbia University developed a new flourescence microscopy methodology.Click To Tweet

Possible Applications?

Where could this technology take us?

In the short-term, disease treatment schedules will be more detailed.

In the long-term, perhaps this microscopy methodology could give way to a more authentic medical AI. Giving a machine learning system increased ability to understand biological processes could improve our understanding of how biological processes are interconnected, especially in their relation to consciousness.

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Zayan Guedim

Trilingual poet, investigative journalist, and novelist. Zed loves tackling the big existential questions and all-things quantum.

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