Dynamic optical response of solids following 1-fs-scale photoinjection.

Photoinjection of charge carriers profoundly changes the properties of a solid. This manipulation enables ultrafast measurements, such as electric-field sampling1,2, advanced recently to petahertz frequencies3-7, and the real-time study of many-body physics8-13. Nonlinear photoexcitation by a few-cycle laser pulse can be confined to its strongest half-cycle14-16. Describing the associated subcycle optical response, vital for attosecond-scale optoelectronics, is elusive when studied with traditional pump-probe metrology as the dynamics distort any probing field on the timescale of the carrier, rather than that of the envelope. Here we apply field-resolved optical metrology to these dynamics and report the direct observation of the evolving optical properties of silicon and silica during the first few femtoseconds following a near-1-fs carrier injection. We observe that the Drude-Lorentz response forms within several femtoseconds-a time interval much shorter than the inverse plasma frequency. This is in contrast to previous measurements in the terahertz domain8,9 and central to the quest to speed up electron-based signal processing.

Field-resolved infrared spectroscopy of biological systems.

The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge1-8. Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment. Vibrationally excited molecules emit a coherent electric field following few-cycle infrared laser excitation9-12, and this field is specific to the sample's molecular composition. Employing electro-optic sampling10,12-15, we directly measure this global molecular fingerprint down to field strengths 107 times weaker than that of the excitation. This enables transillumination of intact living systems with thicknesses of the order of 0.1 millimetres, permitting broadband infrared spectroscopic probing of human cells and plant leaves. In a proof-of-concept analysis of human blood serum, temporal isolation of the infrared electric-field fingerprint from its excitation along with its sampling with attosecond timing precision results in detection sensitivity of submicrograms per millilitre of blood serum and a detectable dynamic range of molecular concentration exceeding 105. This technique promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings.

Breast-cancer detection using blood-based infrared molecular fingerprints.

BACKGROUND: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection. METHODS: We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing. RESULTS: Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression. CONCLUSION: This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.

Molecular Origin of Blood-Based Infrared Spectroscopic Fingerprints*.

Infrared spectroscopy of liquid biopsies is a time- and cost-effective approach that may advance biomedical diagnostics. However, the molecular nature of disease-related changes of infrared molecular fingerprints (IMFs) remains poorly understood, impeding the method's applicability. Here we probe 148 human blood sera and reveal the origin of the variations in their IMFs. To that end, we supplemented infrared spectroscopy with biochemical fractionation and proteomic profiling, providing molecular information about serum composition. Using lung cancer as an example of a medical condition, we demonstrate that the disease-related differences in IMFs are dominated by contributions from twelve highly abundant proteins-that, if used as a pattern, may be instrumental for detecting malignancy. Tying proteomic to spectral information and machine learning advances our understanding of the infrared spectra of liquid biopsies, a framework that could be applied to probing of any disease.

Complementary Si/SiO2 dispersive mirrors for 2-4†µm spectral range.

Complementary pair of dispersive multilayers operating in the 2-4 µm spectral range were designed and produced for the first time. The mirrors comprise layers of Si and SiO2 thin-film materials. The pair exhibits unparalleled reflectance exceeding 99.7% and provides a group delay dispersion of (-200) fs2. The mirrors can be used in Cr:ZnS/Cr:ZnSe femtosecond lasers and amplifiers.

Directly diode-pumped, Kerr-lens mode-locked, few-cycle Cr:ZnSe oscillator.

Lasers based on Cr2+-doped II-VI material, often known as the Ti:Sapphire of the mid-infrared, can directly provide few-cycle pulses with octave-spanning spectra, and serve as efficient drivers for generating broadband mid-infrared radiation. It is expected that the wider adoption of this technology benefits from more compact and cost-effective embodiments. Here, we report the first directly diode-pumped, Kerr-lens mode-locked Cr2+-doped II-VI oscillator pumped by a single InP diode, providing average powers over 500 mW and pulse durations of 45 fs - shorter than six optical cycles at 2.4 µm. These correspond to a sixty-fold increase in peak power compared to the previous diode-pumped record, and are at similar levels with respect to more mature fiber-pumped oscillators. The diode-pumped femtosecond oscillator presented here constitutes a key step toward a more accessible alternative to synchrotron-like infrared radiation and is expected to accelerate research in laser spectroscopy and ultrafast infrared optics.

Efficient femtosecond mid-infrared generation based on a Cr:ZnS oscillator and step-index fluoride fibers.

Femtosecond light sources in the 3-5 µm region are highly sought after for numerous applications. While they can be generated by using nonlinear effects in optical fibers, the efficiencies and effectiveness of frequency conversion can be significantly enhanced by using ultrashort driving pulses. Here, we report on a few-cycle Cr:ZnS oscillator driving low-order soliton dynamics in soft-glass fibers. By selecting appropriate parameters, sub-two-cycle pulses or broad supercontinua spanning over 1.7 octaves from 1.6 to 5.1 µm can be generated at average power levels exceeding 300 mW. In the same setting, Raman-induced soliton self-frequency shifting has been exploited to generate sub-100-fs pulses continuously tunable from 2.3 to 3.85 µm with a conversion efficiency of ∼50%. These results demonstrate the vast potential of using Cr:ZnS or Cr:ZnSe lasers for powerful mid-infrared generation.

Intra-pulse difference-frequency generation of mid-infrared (2.7-20 µm) by random quasi-phase-matching.

We present a mid-infrared (MIR) source based on intra-pulse difference-frequency generation under the random quasi-phase-matching condition. The scheme enables the use of non-birefringent materials whose crystal orientations are not perfectly and periodically poled, widening the choice of media for nonlinear frequency conversion. With a 2 µm driving source based on a Ho:YAG thin-disk laser, together with a polycrystalline ZnSe element, an octave-spanning MIR continuum (2.7-20 µm) was generated. At over 20 mW, the average power is comparable to regular phase-matching in birefringent crystals. A 1 µm laser system based on a Yb:YAG thin-disk laser was also tested as a driving source in this scheme. The new approach provides a simplified way for generating coherent MIR radiation with an ultrabroad bandwidth at reasonable efficiency.

Broadband dispersive Ge/YbF3 mirrors for mid-infrared spectral range.

Broadband dispersive mirrors operating in the mid-infrared spectral range of 6.5-11.5 µm are developed for the first time, to the best of our knowledge. The mirrors comprise Ge and YbF3 layers, which have not been used before for manufacturing of multilayer dispersive optics. The design and production processes are described; mechanical stresses of the coatings are estimated based on experimental data; and spectral and phase properties of the produced mirrors are measured. The mirrors compensate group delay dispersion of ultrashort laser pulses accumulated by propagation through 4 mm ZnSe windows and additional residual phase modulation of an ultrashort laser pulse.

Controlling dielectrics with the electric field of light.

The control of the electric and optical properties of semiconductors with microwave fields forms the basis of modern electronics, information processing and optical communications. The extension of such control to optical frequencies calls for wideband materials such as dielectrics, which require strong electric fields to alter their physical properties. Few-cycle laser pulses permit damage-free exposure of dielectrics to electric fields of several volts per ångström and significant modifications in their electronic system. Fields of such strength and temporal confinement can turn a dielectric from an insulating state to a conducting state within the optical period. However, to extend electric signal control and processing to light frequencies depends on the feasibility of reversing these effects approximately as fast as they can be induced. Here we study the underlying electron processes with sub-femtosecond solid-state spectroscopy, which reveals the feasibility of manipulating the electronic structure and electric polarizability of a dielectric reversibly with the electric field of light. We irradiate a dielectric (fused silica) with a waveform-controlled near-infrared few-cycle light field of several volts per angström and probe changes in extreme-ultraviolet absorptivity and near-infrared reflectivity on a timescale of approximately a hundred attoseconds to a few femtoseconds. The field-induced changes follow, in a highly nonlinear fashion, the turn-on and turn-off behaviour of the driving field, in agreement with the predictions of a quantum mechanical model. The ultrafast reversibility of the effects implies that the physical properties of a dielectric can be controlled with the electric field of light, offering the potential for petahertz-bandwidth signal manipulation.

Optical-field-induced current in dielectrics.

The time it takes to switch on and off electric current determines the rate at which signals can be processed and sampled in modern information technology. Field-effect transistors are able to control currents at frequencies of the order of or higher than 100 gigahertz, but electric interconnects may hamper progress towards reaching the terahertz (10(12) hertz) range. All-optical injection of currents through interfering photoexcitation pathways or photoconductive switching of terahertz transients has made it possible to control electric current on a subpicosecond timescale in semiconductors. Insulators have been deemed unsuitable for both methods, because of the need for either ultraviolet light or strong fields, which induce slow damage or ultrafast breakdown, respectively. Here we report the feasibility of electric signal manipulation in a dielectric. A few-cycle optical waveform reversibly increases--free from breakdown--the a.c. conductivity of amorphous silicon dioxide (fused silica) by more than 18 orders of magnitude within 1 femtosecond, allowing electric currents to be driven, directed and switched by the instantaneous light field. Our work opens the way to extending electronic signal processing and high-speed metrology into the petahertz (10(15) hertz) domain.

Nonlinear pulse compression in a gas-filled multipass cell.

We present an efficient method for compressing sub-picosecond pulses at 200 W average power with 2 mJ pulse energy in a multipass cell filled with different gases. We demonstrate spectral broadening by more than a factor of five using neon, argon, and nitrogen as nonlinear media. The 210 fs input pulses are compressed down to 37 fs and 35 GW peak power with a beam quality factor of 1.3×1.5 at a power throughput of >93%. This concept represents an excellent alternative to hollow-core fiber-based compression schemes and optical parametric amplifiers (OPAs).

Synthesis, fabrication and characterization of a highly-dispersive mirrors for the 2 µm spectral range.

We report a challenging design, fabrication and post-production characterization problem of a dispersive mirror supporting the spectral range from 2000 nm to 2200 nm and providing a group delay dispersion of -1000 fs2. The absolute reflectance in the working range is over 99.95%. The reported mirror is a critical element for Tm and Ho based lasers and paves the way for the development of ultrafast 2 µm lasers with sub-100 fs pulse duration.

1 kW, 200 mJ picosecond thin-disk laser system.

We report on a laser system based on thin-disk technology and chirped pulse amplification, providing output pulse energies of 200 mJ at a 5 kHz repetition rate. The amplifier contains a ring-type cavity and two thin Yb:YAG disks, each pumped by diode laser systems providing up to 3.5 kW power at a 969 nm wavelength. The average output power of more than 1 kW is delivered in an excellent output beam characterized by M2=1.1. The output pulses are compressed to 1.1 ps at full power with a pair of dielectric gratings.

Near-PHz-bandwidth, phase-stable continua generated from a Yb:YAG thin-disk amplifier.

We report on the generation of a multi-octave, phase-stable continuum from the output of a Yb:YAG regenerative amplifier delivering 1-ps pulses with randomly varying carrier-envelope phase (CEP). The intrinsically CEP-stable spectral continuum spans from 450 nm to beyond 2500 nm, covering a spectral range of about 0.6 PHz. The generated coherent broadband light carries an energy of 4 µJ, which can be scaled to higher values if required. The system has been designed and is ideally suited for seeding broadband parametric amplifiers and multichannel synthesizers pumped by picosecond Yb:YAG amplifiers, obviating the need for active timing synchronization required in previous approaches. The presented concept paves the way to cost-effective, reliable all-Yb:YAG single-cycle sources with terawatt peak-power and tens-of-Watts average power.

Powerful 100-fs-scale Kerr-lens mode-locked thin-disk oscillator.

We have recently demonstrated a simple power scaling procedure for Kerr-lens mode-locked thin-disk oscillators. Here we report on the extension of this scheme to a broadband high-peak-power thin-disk oscillator, delivering 140-fs pulses with a peak and average power of 62 MW and 155 W, respectively. This result shows that reaching the emission bandwidth of the gain material in Kerr-lens mode-locked thin-disk oscillators is feasible without sacrificing output power, efficiency, or stability by relying on high intracavity nonlinearities.

Direct regenerative amplification of femtosecond pulses to the multimillijoule level.

We present a compact femtosecond nonlinear Yb:YAG thin-disk regenerative amplifier delivering pulses carried at a wavelength of 1030 nm with an average power of >200 W at a repetition rate of 100 kHz and an energy noise value of 0.46% (rms) in a beam with a propagation factor of M2<1.4. The amplifier is seeded with bandwidth-limited subpicosecond pulses without temporal stretching. We give estimates for the nonlinear parameters influencing the system and show that chirped mirrors compress the 2 mJ pulses to a near-bandwidth-limited duration of 210 fs.

High-power, 1-ps, all-Yb:YAG thin-disk regenerative amplifier.

We report a 100 W, 20 mJ, 1-ps, all-Yb:YAG thin-disk regenerative amplifier seeded by a microjoule-level Yb:YAG thin-disk Kerr-lens mode-locked oscillator. The regenerative amplifier is implemented in a chirped pulse amplification system and operates at an ambient temperature in air, delivering ultrastable output pulses at a 5 kHz repetition rate and with a root mean square power noise value of less than 0.5%. Second harmonic generation of the amplifier's output in a 1.5 mm-thick BBO crystal results in more than 70 W at 515 nm, making the system an attractive source for pumping optical parametric chirped pulse amplifiers in the visible and near-infrared spectral ranges.

Real-time observation of valence electron motion.

The superposition of quantum states drives motion on the atomic and subatomic scales, with the energy spacing of the states dictating the speed of the motion. In the case of electrons residing in the outer (valence) shells of atoms and molecules which are separated by electronvolt energies, this means that valence electron motion occurs on a subfemtosecond to few-femtosecond timescale (1 fs = 10(-15) s). In the absence of complete measurements, the motion can be characterized in terms of a complex quantity, the density matrix. Here we report an attosecond pump-probe measurement of the density matrix of valence electrons in atomic krypton ions. We generate the ions with a controlled few-cycle laser field and then probe them through the spectrally resolved absorption of an attosecond extreme-ultraviolet pulse, which allows us to observe in real time the subfemtosecond motion of valence electrons over a multifemtosecond time span. We are able to completely characterize the quantum mechanical electron motion and determine its degree of coherence in the specimen of the ensemble. Although the present study uses a simple, prototypical open system, attosecond transient absorption spectroscopy should be applicable to molecules and solid-state materials to reveal the elementary electron motions that control physical, chemical and biological properties and processes.

Highly-dispersive mirrors reach new levels of dispersion.

A highly-dispersive mirror with the unprecedented group delay dispersion of -10000 fs2 in the wavelength range of 1025-1035 nm is reported. Reproducible production of a coating with such a high dispersion was possible due to the recently developed robust synthesis technique. Successful employment of the new highly-dispersive mirror in an oscillator is demonstrated.