Mid-infrared optical parametric oscillation spanning 3.4-8.2µm in a MgF2microresonator.

Mid-infrared optical parametric oscillators (OPOs) offer a compelling route for accessing the 'molecular fingerprint' region and, thus, can find intensive applications such as precision spectroscopy and trace gas detection. Yet it still remains rather a challenge to realize broadband mid-infrared OPOs within a single cavity, usually limited by strict phase-matching conditions for wide spectral coverage and available pump power for adequate frequency generation. Here, we report the mid-infrared parametric oscillation spanning from 3.4 to 8.2µm, based on four-wave mixing in a high-QMgF2microresonator with optimized dispersion. The center wavelength at 4.78µm is determined by the continuous tunable quantum cascade laser source, which contributes to effective expansion towards longer wavelength, as well as systemic miniaturization with smaller pump module. Such results could not only shed light on new ultimates of crystal and other microresonators, but also inspire explorations on their growing potentials in near future.

Intrinsic Spectral Resolution Limitations of QEPAS Sensors for Fast and Broad Wavelength Tuning.

Quartz-enhanced photoacoustic sensing is a promising method for low-concentration trace-gas monitoring due to the resonant signal enhancement provided by a high-Q quartz tuning fork. However, quartz-enhanced photoacoustic spectroscopy (QEPAS) is associated with a relatively slow acoustic decay, which results in a reduced spectral resolution and signal-to-noise ratio as the wavelength tuning rate is increased. In this work, we investigate the influence of wavelength scan rate on the spectral resolution and signal-to-noise ratio of QEPAS sensors. We demonstrate the acquisition of photoacoustic spectra from 3.1 µm to 3.6 µm using a tunable mid-infrared optical parametric oscillator. The spectra are attained using wavelength scan rates differing by more than two orders of magnitude (from 0.3 nm s-1 to 96 nm s-1). With this variation in scan rate, the spectral resolution is found to change from 2.5 cm-1 to 9 cm-1. The investigated gas samples are methane (in nitrogen) and a gas mixture consisting of methane, water, and ethanol. For the gas mixture, the reduced spectral resolution at fast scan rates significantly complicates the quantification of constituent gas concentrations.

Waveguide-Integrated Compact Plasmonic Resonators for On-Chip Mid-Infrared Laser Spectroscopy.

The integration of nanoplasmonic devices with a silicon photonic platform affords a new approach for efficient light delivery by combining the high field enhancement of plasmonics and the ultralow propagation loss of dielectric waveguides. Such a hybrid integration obviates the need for a bulky free-space optics setup and can lead to fully integrated, on-chip optical sensing systems. Here, we demonstrate ultracompact plasmonic resonators directly patterned atop a silicon waveguide for mid-infrared spectroscopic chemical sensing. The footprint of the plasmonic nanorod resonators is as small as 2 µm2, yet they can couple with the mid-infrared waveguide mode efficiently. The plasmonic resonance is directly measured through the transmission spectrum of the waveguide with a coupling efficiency greater than 70% and a field intensity enhancement factor of over 3600 relative to the evanescent waveguide field intensity. Using this hybrid device and a tunable mid-infrared laser source, surface-enhanced infrared absorption spectroscopy of both a thin poly(methyl methacrylate) film and an octadecanethiol monolayer is successfully demonstrated.

Quantitative Evaluation of Broadband Photoacoustic Spectroscopy in the Infrared with an Optical Parametric Oscillator.

We evaluate the spectral resolution and the detection thresholds achievable for a photoacoustic spectroscopy (PAS) system in the broadband infrared wavelength region 3270 n m ≲ λ ≲ 3530 n m driven by a continuous wave optical parametric oscillator (OPO) with P ¯ ≈ 1.26 W . The absorption spectra, I PAS ( λ i ) , for diluted propane, ethane and methane test gases at low concentrations ( c ∼ 100 ppm ) were measured for ∼1350 discrete wavelengths λ i . The I PAS ( λ i ) spectra were then compared to the high resolution cross section data, σ FTIR , obtained by Fourier Transform Infrared Spectroscopy published in the HITRAN database. Deviations of 7.1(6)% for propane, 8.7(11)% for ethane and 15.0(14)% for methane with regard to the average uncertainty between I PAS ( λ i ) and the expected reference values based on σ FTIR were recorded. The characteristic absorption wavelengths λ res can be resolved with an average resolution of δ λ res ∼ 0.08 nm . Detection limits range between 7.1 ppb (ethane) to 13.6 ppb (methane). In an additional step, EUREQA, an artificial intelligence (AI) program, was successfully applied to deconvolute simulated PAS spectra of mixed gas samples at low limits of detection. The results justify a further development of PAS technology to support e.g., biomedical research.

Photoacoustic Spectroscopy for the Determination of Lung Cancer Biomarkers-A Preliminary Investigation.

With 1.6 million deaths per year, lung cancer is one of the leading causes of death worldwide. One reason for this high number is the absence of a preventive medical examination method. Many diagnoses occur in a late cancer stage with a low survival rate. An early detection could significantly decrease the mortality. In recent decades, certain substances in human breath have been linked to certain diseases. Different studies show that it is possible to distinguish between lung cancer patients and a healthy control group by analyzing the volatile organic compounds (VOCs) in their breath. We developed a sensor based on photoacoustic spectroscopy for six of the most relevant VOCs linked to lung cancer. As a radiation source, the sensor uses an optical-parametric oscillator (OPO) in a wavelength region from 3.2 µm to 3.5 µm. The limits of detection for a single substance range between 5 ppb and 142 ppb. We also measured high resolution absorption spectra of the biomarkers compared to the data currently available from the National Institute of Standards and Technology (NIST) database, which is the basis of any selective spectroscopic detection. Future lung cancer screening devices could be based on the further development of this sensor.

Enhanced Tissue Ablation Efficiency with a Mid-Infrared Nonlinear Frequency Conversion Laser System and Tissue Interaction Monitoring Using Optical Coherence Tomography.

We report development of optical parametric oscillator (OPO)-based mid-infrared laser system that utilizes a periodically poled nonlinear crystal pumped by a near-infrared (NIR) laser. We obtained a mid-infrared average output of 8 W at an injection current of 20 A from a quasi-phase-matched OPO using an external cavity configuration. Laser tissue ablation efficiency is substantially affected by several parameters, including an optical fluence rate, wavelength of the laser source, and the optical properties of target tissue. Dimensions of wavelength and radiant exposure dependent tissue ablation are quantified using Fourier domain optical coherence tomography and the ablation efficiency was compared to a non-converted NIR laser system.

Robust QRS detection based on simulated degenerate optical parametric oscillator-assisted neural network.

Accurately detecting the depolarization QRS complex in the ventricles is a fundamental requirement for cardiovascular disease detection using electrocardiography (ECG). In contrast to traditional signal enhancement algorithms, emerging neural network approaches have shown promise for QRS detection because of their generalizability on complex data. However, the inevitable noise present during ECG recording leads to a decrease in the performance of neural networks. To enhance the robustness and performance of neural network-based QRS detectors, we propose a simulated degeneration unit (SDU)-assisted convolutional neural network (CNN). An SDU simulates the physical degeneration process of interfering optical pulses, which can effectively suppress in-band noise. Through comprehensive performance evaluations on three open-source databases, the SDU-enhanced CNN-based approach demonstrated better performance in detecting QRS complexes than other recently reported QRS detectors. Furthermore, real-world noise injection tests indicate that the optimal noise robustness boundary for the CNN equipped with SDU is 167-300% higher than that for the CNN without SDU.

Widely tunable and high resolution mid-infrared laser based on BaGa4Se7 optical parametric oscillator.

The widely tunable and high resolution mid-infrared laser based on a BaGa4Se7 (BGSe) optical parametric oscillator (OPO) was demonstrated. A wavelength tuning range of 2.76-4.64 µm and a wavelength tuning resolution of about 0.3 nm were obtained by a BGSe (56.3°, 0°) OPO, which was pumped by a 1064 nm laser. It is the narrowest reported wavelength tuning resolution for BGSe OPO, and was obtained by simultaneously controlling the angle and temperature of BGSe.

Investigations of 2D PtS2's Saturable Absorption Characteristic and Its Optimization to OPO's Operation.

A 6.2 nm-thickness platinum disulfide (PtS2) film was prepared by electron beam evaporation with post vulcanization. The nonlinear transmittance was measured by power scanning method and the modulation depth is fitted to be 13%. Based on the transmittance curve, saturable absorption parameters of PtS2 are calculated with inhomogeneously broadening mechanism, including 6.4298 × 10-19 cm-2 ground-state absorption cross-section, 2.5927 × 10-19 cm-2 excited-state absorption cross-section, and 1.043 ms excited-state lifetime. The PtS2 film combined with active time management was implemented to modulate the fundamental light of optical parametric oscillator (OPO). Owing to the nonlinear absorption property of PtS2, the operation of Q-switched OPO was optimized in both the experiment and dynamical theory. In particular, the conversion efficiency was experimentally improved by 13.2%. The pump-to-signal conversion efficiency went up to 3.29%, which is the highest conversion value reported so far. The theoretical values fit the experiment well, which are from the Gaussian rate equations with PtS2's saturable-absorption characteristic.

Infrared multiple photon dissociation (IRMPD) spectroscopy and its potential for the clinical laboratory.

Infrared multiple photon dissociation (IRMPD) spectroscopy is a powerful tool used to probe the vibrational modes-and, by extension, the structure-of an ion within an ion trap mass spectrometer. Compared to traditional FTIR spectroscopy, IRMPD spectroscopy has advantages including its sensitivity and its relative ability to handle complex mixtures. While IRMPD has historically been a technique for fundamental analyses, it is increasingly being applied in a more analytical fashion. Notable recent demonstrations pertinent to the clinical laboratory and adjacent interests include analysis of modified amino acids/residues and carbohydrates, structural elucidation (including isomeric differentiation) of metabolites, identification of novel illicit drugs, and structural studies of various biomolecules and pharmaceuticals. Improvements in analysis time, coupling to commercial instruments, and integration with separations methods are all drivers toward the realization of these analytical applications. Additional improvements in these areas, along with advances in benchtop tunable IR sources and increased cross-discipline collaboration, will continue to drive innovation and widespread adoption. The goal of this tutorial article is to briefly present the fundamentals and instrumentation of IRMPD spectroscopy, as an overview of the utility of this technique for helping to answer questions relevant to clinical analysis, and to highlight limitations to widespread adoption, as well as promising directions in which the field may be heading.

Method for Multiplexed Dynamic Intravital Multiphoton Imaging.

Intravital two-photon microscopy enables monitoring of cellular dynamics and communication of complex systems, in genuine environment-the living organism. Particularly, its application in understanding the immune system brought unique insights into pathophysiologic processes in vivo. Here we present a method to achieve multiplexed dynamic intravital two-photon imaging by using a synergistic strategy combining a spectrally broad range of fluorophore emissions, a wave-mixing concept for simultaneous excitation of all targeted fluorophores, and an effective unmixing algorithm based on the calculation of spectral similarities with previously acquired fluorophore fingerprints. Our unmixing algorithm allows us to distinguish 7 fluorophore signals corresponding to various cellular and tissue compartments by using only four detector channels.

Photostability enhancement of silica-coated gold nanostars for photoacoustic imaging guided photothermal therapy.

Gold nanostars (GNSs) are promising contrast agents for simultaneous photothermal therapy and photoacoustic imaging (PAI) owing to their excellent photothermal conversion efficiency. However, GNSs are easily reshaped under transient high-intensity laser pulses, which can cause a rapid shift in the light absorption peak, resulting in a decrease in both therapeutic and monitoring effects. In this work, we synthesized GNSs without toxic surfactants and coated them with a silica shell to retain their shape, thus maintaining their photostability. The excellent performance of these silica-coated GNSs was verified through both in vitro and in vivo PAI experiments. The silica-coated GNSs exhibited a threefold improvement in photoacoustic stability, as compared with the non-coated GNSs. The proposed silica coating method for GNSs was found to improve the photostability of GNSs, making them efficient, safe, and reliable nanoparticles for PAI.

Direct measurement of neuronal ensemble activity using photoacoustic imaging in the stimulated Fos-LacZ transgenic rat brain: A proof-of-principle study.

Measuring neuroactivity underlying complex behaviors facilitates understanding the microcircuitry that supports these behaviors. We have developed a functional and molecular photoacoustic tomography (F/M-PAT) system which allows direct imaging of Fos-expressing neuronal ensembles in Fos-LacZ transgenic rats with a large field-of-view and high spatial resolution. F/M-PAT measures the beta-galactosidase catalyzed enzymatic product of exogenous chromophore X-gal within ensemble neurons. We used an ex vivo imaging method in the Wistar Fos-LacZ transgenic rat, to detect neuronal ensembles in medial prefrontal cortex (mPFC) following cocaine administration or a shock-tone paired stimulus. Robust and selective F/M-PAT signal was detected in mPFC neurons after both conditions (compare to naive controls) demonstrating successful and direct detection of Fos-expressing neuronal ensembles using this approach. The results of this study indicate that F/M-PAT can be used in conjunction with Fos-LacZ rats to monitor neuronal ensembles that underlie a range of behavioral processes, such as fear learning or addiction.

Optical Frequency Combs in Quadratically Nonlinear Resonators.

Optical frequency combs are one of the most remarkable inventions in recent decades. Originally conceived as the spectral counterpart of the train of short pulses emitted by mode-locked lasers, frequency combs have also been subsequently generated in continuously pumped microresonators, through third-order parametric processes. Quite recently, direct generation of optical frequency combs has been demonstrated in continuous-wave laser-pumped optical resonators with a second-order nonlinear medium inside. Here, we present a concise introduction to such quadratic combs and the physical mechanism that underlies their formation. We mainly review our recent experimental and theoretical work on formation and dynamics of quadratic frequency combs. We experimentally demonstrated comb generation in two configurations: a cavity for second harmonic generation, where combs are generated both around the pump frequency and its second harmonic and a degenerate optical parametric oscillator, where combs are generated around the pump frequency and its subharmonic. The experiments have been supported by a thorough theoretical analysis, aimed at modelling the dynamics of quadratic combs, both in frequency and time domains, providing useful insights into the physics of this new class of optical frequency comb synthesizers. Quadratic combs establish a new class of efficient frequency comb synthesizers, with unique features, which could enable straightforward access to new spectral regions and stimulate novel applications.

Continuous wave laser diodes enable fast optoacoustic imaging.

Pulsed laser diodes may offer a smaller, less expensive alternative to conventional optoacoustic laser sources; however they do not provide pulse rates faster than a few tens of kHz and emit at wavelengths only within the near-infrared region. We investigated whether continuous wave (CW) laser diodes, which are available in visible and near-infrared regions, can be good optoacoustic light sources when overdriven with a peak current >40-fold higher than the CW absolute maximum. We found that overdriven CW diodes provided ∼10 ns pulses of ∼200 nJ/pulse and repetition rates higher than 600 kHz without being damaged, outperforming many pulsed laser diodes. Using this system, we obtained images of phantoms and mouse ear and human arm in vivo, confirming their use in optoacoustic imaging and sensing.