Ioachim Pupeza

With its high molecular complexity, human breath lends itself as an information-rich sample for non-invasive biomedical diagnostics. Among emerging multi-variate analytical techniques for human breath, laser-based optical spectroscopy constitutes a particularly promising novel combination of short measurement times and high concentration dynamic range for molecular detection. Here, we present an automated system designed for continuous collection of exhaled breath directly from a respirator, and subsequent spectroscopic analysis. By obviating any additional intermediate sample storage or transport, our method minimizes setup complexity and sample contamination, while avoiding interference with the operation of the respirator. In this proof-of-principle study, we present automated and quantitative monitoring of three substances introduced in an artificial test lung ventilated by the respirator. Employing a standard Fourier-transform infrared spectrometer for molecular quantification, individual measurements were performed every 7 min over 24 h. The stability and analytical capability of the breath sampling system presented here, along with improvements in terms of spectral resolution and detection dynamic range obtainable through state-of-the-art laser-based spectroscopy promise fast and quantitative monitoring of the human breath volatilome. Coupled to state-of-the-art spectroscopy this may pave the way to monitor metabolites in real time in critically ill patients over the entire physiologically relevant molecular concentration range.

High-speed vibrational spectroscopy is a sensitive label-free approach for molecular fingerprinting in dynamic and non-repetitive systems. Field-resolved mid-IR spectroscopy based on electro-optic sampling (EOS) offers broad bandwidth and high dynamic range, but reducing the technical complexity of high-speed implementations remains challenging. Here, we demonstrate the use of a galvanometer scanner resonant at 4 kHz for high-speed EOS of mid-IR pulses with a single-scan acquisition time of 125 μs. Interferometric delay tracking and reconstruction provide femtosecond-level timing precision and spectra compatible with those of conventional slow-scan, lock-in measurements. We validate the operational functionality of the EOS resonant scanner by monitoring dimethyl sulfone concentration in water in a flow-through cuvette in real time. This approach offers advantages in reducing technical complexity, improving cost-effectiveness, and enabling flexible selection of the scanning speed.

Full characterization of electric-field waveforms in amplitude and phase is achieved across the terahertz to visible spectral range through interaction with an optical pulse shorter than a half-cycle period via the Pockels (linear electro-optic) effect. This technique of electro-optic sampling has become an indispensable tool in various areas, including ultrafast pump-probe, time-domain and frequency-comb spectroscopies, quantum optics, high-harmonic generation, and attosecond science, and holds great promise for further advances. Not only does it enable spectroscopic measurements with record dynamic range and temporal resolution, along with massively parallel real-time spectral data acquisition, but its remarkable sensitivity also allows the detection of vacuum fluctuations, i.e., “zero-point motion” of electric fields, profoundly impacting our understanding of the fundamental laws of nature.

Field-resolved infrared spectroscopy (FRS) of impulsively excited molecular vibrations can surpass the sensitivity of conventional time-integrating spectroscopies, owing to a temporal separation of the molecular signal from the noisy excitation. However, the resonant response carrying the molecular signal of interest depends on both the amplitude and phase of the excitation, which can vary over time and across different instruments. To date, this has compromised the accuracy with which FRS measurements could be compared, which is a crucial factor for practical applications. Here, we utilize a data processing procedure that overcomes this shortcoming while preserving the sensitivity of FRS. We validate the approach for aqueous solutions of molecules. The employed approach is compatible with established processing and evaluation methods for the analysis of infrared spectra and can be applied to existing spectra from databases, facilitating the spread of FRS to new molecular analytical applications.

Electro-optic sampling of infrared electric fields has set sensitivity and dynamic-range records in broadband molecular vibrational spectroscopy. Yet, in these works, the 1-second-scale single-trace acquisition time leads to intra-scan noise accumulation and restricts the throughput in measurements of multiple samples and of dynamic processes. We present a dual-laser-oscillator approach capturing 2800 mid-infrared waveforms per second by scanning the relative delay between the sampled waveform and the gate pulses using a modulated repetition-frequency lock. The new technique of electro-optic delay tracking (EODT) provides delay calibration with down to few-attosecond precision and provides a general route to high-precision dual-oscillator spectroscopy with picosecond delay ranges. Our work has immediate applications in, e.g., precision electric-field metrology and high-speed biosensing.

Parametric downconversion driven by modern, high-power sources of 10-fs-scale near-infrared pulses, in particular intrapulse difference-frequency generation (IPDFG), affords combinations of properties desirable for molecular vibrational spectroscopy in the mid-infrared range: broad spectral coverage, high brilliance, and spatial and temporal coherence. Yet, unifying these in a robust and compact radiation source has remained a key challenge. Here, we address this need by employing IPDFG in a multi-crystal in-line geometry, driven by the 100-W-level, 10.6-fs pulses of a 10.6-MHz-repetition-rate, nonlinearly post-compressed Yb:YAG thin-disk oscillator. Polarization tailoring of the driving pulses using a bichromatic waveplate is followed by a sequence of two crystals, LiIO₃ and LiGaS₂, resulting in the simultaneous coverage of the 800-cm^-1-to-3000-cm^-1 spectral range (at -30-dB intensity) with 130 mW of average power. We demonstrate that optical-phase coherence is maintained in this in-line geometry, in theory and experiment, the latter employing ultra-broadband electro-optic sampling. These results pave the way toward coherent spectroscopy schemes like field-resolved and frequency-comb spectroscopy, as well as nonlinear, ultrafast spectroscopy and optical-waveform synthesis across the entire infrared molecular fingerprint region.

The evolution of ultrafast-laser technology has steadily advanced the level of detail in studies of light-matter interactions. Here, we employ electric-field-resolved spectroscopy and quantum-chemical modelling to precisely measure and describe the complete coherent energy transfer between octave-spanning mid-infrared waveforms and vibrating molecules in aqueous solution. The sub-optical-cycle temporal resolution of our technique reveals alternating absorption and (stimulated) emission on a few-femtosecond time scale. This behaviour can only be captured when effects beyond the rotating wave approximation are considered. At a femtosecond-to-picosecond timescale, optical-phase-dependent coherent transients and the dephasing of the vibrations of resonantly excited methylsulfonylmethane (DMSO₂) are observed. Ab initio modelling using density functional theory traces these dynamics back to molecular-scale sample properties, in particular vibrational frequencies and transition dipoles, as well as their fluctuation due to the motion of DMSO₂ through varying solvent environments. Future extension of our study to nonlinear interrogation of higher-order susceptibilities is fathomable with state-of-the-art lasers.

Femtosecond enhancement cavities¹ are key to applications including high-sensitivity linear^2–4 and nonlinear^5,6 gas spectroscopy, as well as efficient nonlinear optical frequency conversion^7–10. Yet, to date, the broadest simultaneously enhanced bandwidths amount to 8,9,11–15. Here, we present an ultrabroadband femtosecond enhancement cavity comprising gold-coated mirrors and a wedged-diamond-plate input coupler, with an average finesse of 55 for optical frequencies below 40 THz and exceeding 40 in the 120–300 THz range. Resonant enhancement of a 50-MHz-repetition-rate offset-free frequency comb spanning 22–40 THz results in a waveform-stable ultrashort circulating pulse with a spectrum supporting a Fourier limit of 1.6 cycles, enabling time-domain electric-field-resolved spectroscopy of molecular samples with temporally separated excitation and molecular response¹⁶. The contrast between the two is improved by taking advantage of destructive interference at the input coupler. At an effective interaction length with a gas of up to 81 m, this concept promises parts-per-trillion-level ultrabroadband electric-field-resolved linear and nonlinear spectroscopy of impulsively excited molecular vibrations.

The evolution of ultrafast-laser technology has steadily advanced the level of detail in studies of light-matter interactions. Here, we employ electric-field-resolved spectroscopy and quantum-chemical modelling to precisely measure and describe the complete coherent energy transfer between octave-spanning mid-infrared waveforms and vibrating molecules in aqueous solution. The sub-optical-cycle temporal resolution of our technique reveals alternating absorption and (stimulated) emission on a few-femtosecond time scale. This behaviour can only be captured when effects beyond the rotating wave approximation (RWA) are included in simulations using first-order time-dependent perturbation theory. At a timescale of femtoseconds to picoseconds, other energy transfer processes are observed, namely optical-phase-dependent coherent transients and the dephasing of the vibrations of resonantly excited methylsulfonylmethane (DMSO2) molecules due to their motion through varying environments in the solvent. Ab-initio modelling using density functional theory traces these dynamic processes back to molecular-scale sample properties. The absorbed and coherently re-emitted fractions of the optical energy impinging on the sample can be used as performance metrics for spectroscopic techniques that allow for the separation of absorption and re-emission in time and/or in space. The extension of our study to nonlinear interrogation of higher-order susceptibilities is fathomable with state-of-the-art lasers in the near future.

Metallic spintronic terahertz (THz) emitters have become well-established for offering ultra-broadband, gapless THz emission in a variety of excitation regimes, in combination with reliable fabrication and excellent scalability. However, so far, their potential for high-average-power excitation to reach strong THz fields at high repetition rates has not been thoroughly investigated. In this article, we explore the power scaling behavior of tri-layer spintronic emitters using an Yb-fiber excitation source, delivering an average power of 18.5 W (7 W incident on the emitter after chopping) at 400 kHz repetition rate, temporally compressed to a pulse duration of 27 fs. We confirm that a reflection geometry with back-side cooling is ideally suited for these emitters in the high-average-power excitation regime. In order to understand limiting mechanisms, we disentangle the effects on THz power generation by average power and pulse energy by varying the repetition rate of the laser. Our results show that the conversion efficiency is predominantly determined by the incident fluence in this high-average-power, high-repetition-rate excitation regime if the emitters are efficiently cooled. Using these findings, we optimize the conversion efficiency and reach highest excitation powers in the back-cooled reflection geometry. Our findings provide guidelines for scaling the power of THz radiation emitted by spintronic emitters to the milliwatt-level by using state-of-the-art femtosecond sources with multi-hundred-Watt average power to reach ultra-broadband, strong-field THz sources with high repetition rate.