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Novel Laser Technology to Analyze Molecular Makeup of Biological Samples

At the Laboratory for Attosecond Physics, researchers have created an exclusive laser technology for analyzing the molecular makeup of biological samples. The technology has the ability to detect even slight changes in the chemical composition of organic systems.

At the biochemical level, organisms can be considered as complex collections of various species of molecules. During their metabolism, biological cells produce chemical compounds and alter them in various different ways. Several of these products are discharged into the intercellular medium, finally getting accumulated in bodily fluids such as the blood.

One of the main goals of biomedical research is to perceive what these highly complex molecule mixtures can reveal about the state of the concerned organism. All multifarious types of cells contributed to this “soup.” However, malignant and precancerous cells tend to add their own particular molecular markers. Moreover, these offer the initial indications of the existence of tumor cells in the body.

However, to date, only a handful of these indicator molecules have been recognized, and those that are familiar exist in biological samples in infinitesimal amounts. Due to this reason, it is highly challenging to detect these molecules.

Several of the most informative molecular signatures are presumed to include combinations of compounds that fall in all the different types of molecules that exist in cells—sugars, proteins, fats, and their different derivatives. A single analytical method, versatile and sufficiently sensitive to detect and quantify the levels of all of them, is required to define them.

At present, an interdisciplinary team under the guidance of Prof. Ferenc Krausz has developed an innovative laser-based system designed exclusively for this purpose. The team is based at the Laboratory for Attosecond Physics (LAP), collaboratively run by Ludwig-Maximilians-Universitaet (LMU) in Munich and the Max Planck Institute for Quantum Optics (MPQ). The group includes physicists, data scientists, and biologists.

This system allows chemical fingerprints to be obtained in the form of infrared light spectra, which unravel the molecular makeup of all types of samples, such as biological samples. The technology provides unmatched sensitivity and can be applied for biomolecules of all known classes.

The new laser spectrometer has been developed based on technologies originally created in the LAP for producing ultrashort laser pulses used to analyze the ultrafast dynamics of subatomic systems.

Developed by physicist Ioachim Pupeza and his team, the instrument has been designed to release trains of highly powerful laser light pulses covering a wider segment of the spectrum in the infrared wavelength. Each of the pulses lasts only for a few femtoseconds (in scientific terms, 1 fs = 10−15 seconds, or one-millionth of a billionth of a second).

These infrared light flashes, which are very brief, make the bonds connecting atoms together to vibrate. The effect is similar to that of striking a tuning fork. As soon as the pulse passes, the vibrating molecules release coherent light at extremely characteristic wavelengths or, analogously, oscillation frequencies.

The new technology enables capturing the total ensemble of wavelengths emitted. Each unique compound in the sample vibrates at a particular set of frequencies, thus it contributes its own clearly defined “subspectrum” to the emission. None of the molecular species can hide anywhere.

With this laser, we can cover a wide range of infrared wavelengths—from 6 to 12 micrometers—that stimulate vibrations in molecules. Unlike mass spectroscopy, this method provides access to all the types of molecules found in biological samples.

Marinus Huber, Study Joint First Author, Ludwig Maximilian University of Munich

Huber is a member of biologist Mihaela Zigman’s team, which also took part in the experiments performed at the LAP.

Every ultrashort laser pulse used to vibrate the molecules includes just a few oscillations of the optical field. In addition, each pulse’s spectral brightness (i.e. its photon density) is nearly twice as high as those produced by traditional synchrotrons, which have thus far acted as radiation sources for analogous approaches to molecular spectroscopy.

Moreover, the infrared radiation is coherent spatially and temporally. Collectively, all of these physical parameters contribute to the very high sensitivity of the new laser system, thus facilitating the detection of molecules that exist in extremely low concentrations and the production of high-precision molecular fingerprints.

Besides that, for the first time, it would be possible to illuminate living tissue samples measuring up to 0.1 mm thick with infrared light and analyze them with unmatched sensitivity. As part of preliminary experiments, the group at the LAP used the approach on leaves and other living cells, in addition to blood samples.

This ability to accurately measure variations in the molecular composition of body fluids opens up new possibilities in biology and medicine, and in the future the technique could find application in the early detection of disorders.

Mihaela Zigman, Biologist, Ludwig Maximilian University of Munich


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