Infrared Frequency Comb Measures Biological Signatures

Researchers at the National Institute of Standards and Technology NIST and colla­borators have demonstrated a compact frequency-comb apparatus that rapidly measures the entire infrared band of light to detect biological, chemical and physical properties of matter. Infrared light travels in waves longer than visible light and is most familiar as the radiation associated with heat. The setup, which occupies just a few square feet of table space, has potential appli­cations such as disease diagnosis, identi­fication of chemicals used in manufacturing, and biomass energy harvesting.

This tabletop frequency comb apparatus can quickly identify molecules based on their absorption of infrared light. (Source: NIST)

Optical frequency combs measure exact frequencies of light. Various comb designs have enabled the development of next-generation atomic clocks and show promise for environ­mental appli­cations such as detecting methane leaks. Biological appli­cations have been slower to develop, in part because it’s been hard to directly generate and measure the relevant infrared light. To showcase biological appli­cations, the NIST team used the new apparatus to detect finger­prints of NIST’s monoclonal antibody reference material, a protein made of more than 20,000 atoms that is used by the biopharma­ceutical industry to ensure the quality of treatments.

“For the first time our frequency combs have simul­taneous coverage across the entire infrared molecular fingerprint region,” project leader Scott Diddams said. “Other key advantages are speed, resolution and dynamic range in acquiring data.” Mid-infrared light is an especially useful research probe because molecules usually rotate and vibrate at these frequencies. But until now it’s been difficult to probe this region due to a lack of broadband or tunable light sources and efficient detectors such as those available for visible and near-infrared light, the part of the infrared spectrum closest to visible light.

The new apparatus overcomes these problems. Simple fiber lasers generate light spanning the entire range used to identify molecules – that is, mid-infrared to far-infrared wavelengths of 3-27 micrometers. The amounts of light absorbed at specific frequencies provide a unique signature of a molecule. The new system is inno­vative in detecting the electric fields of the absorbed light using photo­diodes operating in the near-infrared range. “A unique feature is that we detect signals in real time by rapidly sampling the infrared electric field with a near-infrared laser,” Diddams explained. “This has two advantages: It shifts the detection from the infrared to the near-infrared where we can use inexpensive tele­communications photo­diodes, and we no longer suffer from the limitations of infrared detectors, which require cryogenic (liquid nitrogen) cooling.”

The researchers detected signature vibrations of three bands of amides in the monoclonal antibody reference material. Amide bands in proteins are used to determine the folding, unfolding and aggre­gating mechanisms. Specific features of the detected bands indicated that the protein has a sheet structure, agreeing with previous studies. Sheets connect chemical groups in a flat arrangement. In addition to biological applications, the new apparatus might be used to detect inter­actions between infrared light and condensed matter for quantum computing approaches that store data in molecular vibra­tions or rotations. In addition, when combined with novel imaging techniques, the tabletop system could obtain nano­meter-scale images of samples that currently require the use of a much larger synchrotron facility. (Source: NIST)

Reference: A. S. Kowligy et al.: Infrared electric field sampled frequency comb spectroscopy, Sci. Adv. 5, eaaw8794 (2019); DOI: 10.1126/sciadv.aaw8794

Link: Time and Frequency Division, NIST, Boulder, USA

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