In an advancement with the potential to transform biomarker detection, researchers at the Max Planck Institute for the Science of Light have introduced a novel technique called femtosecond fieldoscopy. This new method allows for precise measurements of extremely small liquid quantities, reaching down to the micromolar level, with unprecedented sensitivity in the near-infrared spectrum. Such a breakthrough holds significant promise for future biomedical applications by enabling label-free bio-imaging and enhancing the detection of specific molecules in aqueous environments. The findings of this study have been published in the journal Nature Photonics.
The key principle behind this innovative technology lies in the use of ultrashort laser pulses to induce vibrational responses in molecules. When exposed to these brief pulses, molecules begin to vibrate, similar to how a quick tap on a bell causes it to ring. These vibrations produce a signal, known as free-induction decay (FID), which contains valuable information about the molecules’ unique characteristics. However, this signal is fleeting—lasting only up to one-trillionth of a second—yet it effectively captures the “fingerprint” of the molecule’s vibration.
Femtosecond fieldoscopy makes it possible to detect these vibrations with remarkable clarity. By utilizing an ultrashort laser pulse, researchers have found a way to separate the molecule’s signal from the laser pulse itself. This separation removes background interference, allowing the detection of a molecule’s vibrational response with high precision and specificity. This capability is particularly useful for biomarker detection, as it enables scientists to identify specific biological molecules in complex, liquid environments without interference from surrounding signals.
In their initial demonstration of femtosecond fieldoscopy, researchers successfully measured faint combination bands of molecules in both water and ethanol. They achieved detection at concentrations as low as 4.13 micromoles, a feat that highlights the technique’s extraordinary sensitivity and suggests its potential to identify even trace amounts of biomarkers in clinical samples.
This capability relies on the generation of high-power, ultrashort light pulses. To create these pulses, researchers use photonic crystal fibers filled with gas, compressing the light waves to nearly a single cycle. For detection, these compressed light pulses are combined with phase-stable near-infrared pulses, which enhance the system’s overall sensitivity.
The team employs a sophisticated field detection method called electro-optic sampling, which can measure these ultrafast light pulses with remarkable precision. With a detection bandwidth approaching petahertz and an astounding 400 attoseconds of temporal resolution, this technology enables scientists to observe molecular interactions in real time with unprecedented accuracy. Such temporal resolution allows for the observation of molecular vibrations and other ultrafast phenomena at an almost atomic timescale.
The researchers believe that femtosecond fieldoscopy represents a major leap forward in the field of liquid sample analysis, providing a higher level of sensitivity and a broader dynamic range than previously possible. Anchit Srivastava, a Ph.D. student involved in the research, emphasized the precision of the new technique, explaining that it allows for the exclusion of signals originating from both liquid and gas phases. This capacity to filter out extraneous signals is critical, as it reduces noise and leads to cleaner, more accurate measurements.
Co-author Hanieh Fattahi notes that the simultaneous measurement of both phase and intensity in these signals creates new opportunities for high-resolution biological spectro-microscopy. This dual measurement enhances the amount of molecular information available, enabling more detailed imaging and characterization. Beyond its implications for field-resolved metrology, this advancement could be transformative for fields that rely on precise molecular detection, such as chemistry and biology.
This research not only broadens our understanding of ultrafast phenomena but also offers potential applications in diverse areas where accurate detection of molecular signatures is crucial. As femtosecond fieldoscopy continues to be refined, it could pave the way for major advances in diagnostics, environmental monitoring, and the development of new analytical tools for the life sciences.