Design and testing of an optical instrument for skin flap monitoring.

Flap procedures are complex surgical tools widely used in reconstructive surgery. Flap ischemia is one of the most dangerous complications, both during the surgical procedure and during the patient's recovery, which can quickly lead to tissue necrosis (flap loss) with serious medical and psychological consequences. Today, bedside clinical assessment remains the gold standard for flap monitoring, but timely detection of flap ischemia is a difficult and challenging task, so auxiliary techniques are needed to support flap monitoring. Here we present a prototype of a new optical diagnostic tool, based on visible light absorption in diffuse reflectance spectroscopy, for non-invasive, continuous, real-time monitoring of flaps. The proposed approach is assessed by monitoring flap ischemic scenarios induced on pig animal models. The results obtained support that the proposed approach has great potential, not only for prompt detection of ischemia (in seconds), but also for clear differentiation between an arterial occlusion and venous occlusion.

Experimental demonstration of a new near-infrared spectroscopy technique based on optical dual-comb: DC-NIRS.

We present a novel near-infrared spectroscopy technique based on Dual-Comb optical interrogation (DC-NIRS) applied to dispersive media. The technique recovers the frequency response of the medium under investigation by sampling its spectral response in amplitude and phase. The DC-NIRS reference and sample signals are generated using electro-optic modulation which offers a cost-effective, integrable solution while providing high adaptability to the interrogated medium. A careful choice of both line spacing and optical span of the frequency comb ensures that the retrieved information enables the reconstruction of the temporal impulse response of the medium, known as the diffuse-time-of-flight (DTOF), to obtain its optical properties with a 70 µs temporal resolution and 32 ps photon propagation delay resolution. Furthermore, the DC-NIRS technique also offers enhanced penetration due to noiseless optical amplification (interferometric detection). The presented technique was demonstrated on a static bio-mimetic phantom of known optical properties reproducing a typical brain's optical response. The DTOF and optical properties of the phantom were measured, showing the capabilities of this new technique on the estimation of absolute optical properties with a deviation under 3%. Compared to current technologies, our DC-NIRS technique provides enhanced temporal resolution, spatial location capabilities, and penetration depth, with an integrable and configurable cost-effective architecture, paving the way to next-generation, non-invasive and portable systems for functional brain imaging, and brain-computer interfaces, among other. The system is patent pending PCT/ES2022/070176.

Direct hyperspectral dual-comb gas imaging in the mid-infrared.

In this Letter, we present and experimentally validate the first direct hyperspectral dual-comb gas imaging system operating in the mid-infrared region. This method provides an unmatched combination of super-fine spectral characterization and high temporal resolution without the need for thermal contrast between the target molecules and the background. In a proof-of-concept experiment, the system has allowed us to perform precision hyperspectral imaging of butane in the 3.4 µm band with a time resolution of 1 s.

Design of a Multipurpose Photonic Chip Architecture for THz Dual-Comb Spectrometers.

In this work, we present a multipurpose photonic integrated circuit capable of generating multiheterodyne complex Dual-Combs (DC) THz signals. Our work focuses on translating the functionality of an electro-optic tunable DC system into a photonic chip employing standard building blocks to ensure the scalability and cost efficiency of the integrated device. The architecture we analyze for integration is based on three stages: a seed comb, a mode selection stage and a DC stage. This final DC stage includes a frequency shifter, a key element to improve the final detection of the THz signals and obtain real-time operation. This investigation covers three key aspects: (1) a solution for comb line selection on GHz spaced combs using OIL or OPLL on photonic chips is studied and evaluated, (2) a simple and versatile scheme to produce a frequency shift using the double sideband suppressed carrier modulation technique and an asymmetric Mach Zehnder Interferometer to filter one of the sidebands is proposed, and (3) a multipurpose architecture that can offer a versatile effective device, moving from application-specific PICs to general-purpose PICs. Using the building blocks (BBs) available from an InP-based foundry, we obtained simulations that offer a high-quality Dual-Comb frequency shifted signal with a side mode suppression ratio around 21 dB, and 41 dB after photodetection with an intermediate frequency of 1 MHz. We tested our system to generate a Dual-Comb with 10 kHz of frequency spacing and an OOK modulation with 5 Gbps which can be down-converted to the THz range by a square law detector. It is also important to note that the presented architecture is multipurpose and can also be applied to THz communications. This design is a step to enable a commercial THz photonic chip for multiple applications such as THz spectroscopy, THz multispectral imaging and THz telecommunications and offers the possibility of being fabricated in a multi-project wafer.

Hyperspectral terahertz imaging with electro-optic dual combs and a FET-based detector.

In this paper, a terahertz hyperspectral imaging architecture based on an electro-optic terahertz dual-comb source is presented and demonstrated. In contrast to single frequency sources, this multi-heterodyne system allows for the characterization of the whole spectral response of the sample in parallel for all the frequency points along the spectral range of the system. This hence provides rapid, highly consistent results and minimizes measurement artifacts. The terahertz illumination signal can be tailored (in spectral coverage and resolution) with high flexibility to meet the requirements of any particular application or experimental scenario while maximizing the signal-to-noise ratio of the measurement. Besides this, the system provides absolute frequency accuracy and a very high coherence that allows for direct signal detection without inter-comb synchronization mechanisms, adaptive acquisition, or post-processing. Using a field-effect transistor-based terahertz resonant 300 GHz detector and the raster-scanning method we demonstrate the two-dimensional hyperspectral imaging of samples of different kinds to illustrate the remarkable capabilities of this innovative architecture. A proof-of-concept demonstration has been performed in which tree leaves and a complex plastic fragment have been analyzed in the 300 GHz range with a frequency resolution of 10 GHz.

A Quantum Cascade Laser-Based Multi-Gas Sensor for Ambient Air Monitoring.

A quantum cascade laser-based sensor for ambient air monitoring is presented and five gases, affecting the air quality, can be quantified. The light sources are selected to measure CO, NO, NO2, N2O and SO2. The footprint of the measurement setup is designed to fit in two standard 19" rack (48 cm × 65 cm) with 4 height units (18 cm) whereas one is holding the optical components and the other one contains the electronics and data processing unit. The concentrations of the individual analytes are measured using 2f-Wavelength Modulation Spectroscopy (2f-WMS) and a commercially available multipass gas cell defines the optical path. In addition, CO can also be measured with a dispersion-based technique, which allows one to cover a wider concentration range than 2f-WMS. The performance of this prototype has been evaluated in the lab and detection limits in the range of 1ppbv have been achieved. Finally, the applicability of this prototype for ambient air monitoring is shown in a five-week measurement campaign in cooperation with the Municipal Department for Environmental Protection (MA 22) of Vienna, Austria.

Early, Non-Invasive Sensing of Sustained Hyperglycemia in Mice Using Millimeter-Wave Spectroscopy.

Diabetes is a very complex condition affecting millions of people around the world. Its occurrence, always accompanied by sustained hyperglycemia, leads to many medical complications that can be greatly mitigated when the disease is treated in its earliest stage. In this paper, a novel sensing approach for the early non-invasive detection and monitoring of sustained hyperglycemia is presented. The sensing principle is based on millimeter-wave transmission spectroscopy through the skin and subsequent statistical analysis of the amplitude data. A classifier based on functional principal components for sustained hyperglycemia prediction was validated on a sample of twelve mice, correctly classifying the condition in diabetic mice. Using the same classifier, sixteen mice with drug-induced diabetes were studied for two weeks. The proposed sensing approach was capable of assessing the glycemic states at different stages of induced diabetes, providing a clear transition from normoglycemia to hyperglycemia typically associated with diabetes. This is believed to be the first presentation of such evolution studies using non-invasive sensing. The results obtained indicate that gradual glycemic changes associated with diabetes can be accurately detected by non-invasively sensing the metabolism using a millimeter-wave spectral sensor, with an observed temporal resolution of around four days. This unprecedented detection speed and its non-invasive character could open new opportunities for the continuous control and monitoring of diabetics and the evaluation of response to treatments (including new therapies), enabling a much more appropriate control of the condition.

Implementation and characterization of a thermal infrared laser heterodyne radiometer based on a wavelength modulated local oscillator laser.

This article presents the first implementation and the experimental characterization of a thermal infrared wavelength modulation laser heterodyne radiometer (WM-LHR) based on an external cavity quantum cascade laser. This novel WM-LHR system has demonstrated calibration-free operation, a superior signal to noise ratio and, more importantly, has opened the door for cost-efficient wide spectral range laser heterodyne radiometry in the near future.

High frequency modulation and (quasi) single-sideband emission of mid-infrared ring and ridge quantum cascade lasers.

We investigate the high frequency modulation characteristics of mid-infrared surface-emitting ring and edge-emitting ridge quantum cascade lasers (QCLs). In particular, a detailed comparison between circular ring devices and ridge-QCLs from the same laser material, which have a linear waveguide in a "Fabry-Pérot (FP) type" cavity, reveals distinct similarities and differences. Both device types are single-mode emitting, based on either 2 nd- (ring-QCL) or 1 st-order (ridge-QCL) distributed feedback (DFB) gratings with an emission wavelength around 7.56 µm. Their modulation characteristics are investigated in the frequency-domain using an optical frequency-to-amplitude conversion technique based on the ro-vibrational absorptions of CH 4. We observe that the amplitude of frequency tuning Δf over intensity modulation index m as function of the modulation frequency behaves similarly for both types of devices, while the ring-QCLs typically show higher values. The frequency-to-intensity modulation (FM-IM) phase shift shows a decrease starting from ∼72 ∘ at a modulation frequency of 800 kHz to about 0 ∘ at 160 MHz. In addition, we also observe a quasi single-sideband (qSSB) regime for modulation frequencies above 100 MHz, which is identified by a vanishing -1 st-order sideband for both devices. This special FM-state can be observed in DFB QCLs and is in strong contrast to the behavior of regular DFB diode lasers, which do not achieve any significant sideband suppression. By analyzing these important high frequency characteristics of ring-QCLs and comparing them to ridge DFB-QCLs, it shows the potential of intersubband devices for applications in e.g. novel spectroscopic techniques and highly-integrated and high-bitrate free-space data communication. In addition, the obtained results close an existing gap in literature for high frequency modulation characteristics of QCLs.

Electro-optic THz dual-comb architecture for high-resolution, absolute spectroscopy.

An absolute-frequency terahertz (THz) dual-frequency comb spectrometer based on electro-optic modulators for tunable, high-resolution, and real-time rapid acquisition is presented. An optical line of a master frequency comb (filtered via optical injection locking) serves as the seed to electro-optically generate a pair of new frequency combs (probe and local oscillator). Photomixing both combs with another coherent line from the same original master comb generates a narrow linewidth THz dual-comb with teeth frequencies that can be referenced to a radio-frequency standard. The system is validated with a proof-of-principle measurement of a microwave filter in the W-band.

Wavelength modulation laser heterodyne radiometry.

A novel method is proposed for improving the performance of traditional laser heterodyne radiometry. The technique, which is based on the use of a wavelength modulated local oscillator laser, provides baseline-free spectra, lower limits of detection, and better precision and consistency than the conventional approach. This tool could, therefore, boost the accuracy of current terrestrial and planetary atmospheric studies.

Frequency accurate coherent electro-optic dual-comb spectroscopy in real-time.

Electro-optic dual-comb spectrometers have proved to be a promising technology for sensitive, high-resolution and rapid spectral measurements. Electro-optic combs possess very attractive features like simplicity, reliability, bright optical teeth, and typically moderate but quickly tunable optical spans. Furthermore, in a dual-comb arrangement, narrowband electro-optic combs are generated with a level of mutual coherence that is sufficiently high to enable optical multiheterodyning without inter-comb stabilization or signal processing systems. However, this valuable tool still presents several limitations; for instance, on most systems, absolute frequency accuracy and long-term stability cannot be guaranteed; likewise, interferometer-induced phase noise restricts coherence time and limits the attainable signal-to-noise ratio. In this paper, we address these drawbacks and demonstrate a cost-efficient absolute electro-optic dual-comb instrument based on a frequency stabilization mechanism and a novel adaptive interferogram acquisition approach devised for electro-optic dual-combs capable of operating in real-time. The spectrometer, completely built from commercial components, provides sub-ppm frequency uncertainties and enables a signal-to-noise ratio of 10000 (intensity noise) in 30 seconds of integration time.

Frequency-tunable photonic frequency synthesis from an optical frequency comb reference.

We present an architecture for photonic-assisted RF signal synthesization that uses as a reference the optical repetition frequency of an optical frequency comb. The setup, which is based on a multiharmonic photonic phase frequency detector, enables a perfect phase-locking of a voltage-controlled oscillator to multiples and submultiples of the repetition frequency of the reference comb, operating hence as an optically referenced phase-locked frequency-tunable synthesizer. The design of the system, which is also capable of operating with RF reference inputs, is very well suited for highly stable signal generation and optical clock distribution networks, as signal synthesization is performed directly from the provided optical reference.

Classification of skin phenotypes caused by diabetes mellitus using complex scattering parameters in the millimeter-wave frequency range.

The pathological skin phenotype caused by hyperglycemia is an important indicator for the progress of diabetes mellitus. An early detection of diabetes assures an early intervention to regulate the carbohydrate metabolism. In this publication a non-invasive detection principle based on the measurement of complex scattering parameters in the millimeter-wave frequency range is presented. The measurement principle provides evidence of the applicability for the identification of different glycemic states in animal models. The method proposed here can be used to predict diabetes status in animal models and is interesting for application on humans in view of safeness of millimeter-wave radiation. Furthermore the complex scattering parameters give important information about the anatomic varieties between the analyzed skin samples of the different mice strains. In contrast to other methods, our approach is less sensitive to skin variations between animals.

Heterodyne Phase-Sensitive Dispersion Spectroscopy in the Mid-Infrared with a Quantum Cascade Laser.

Molecular dispersion spectroscopy encompasses a group of spectroscopic techniques for gas analysis that retrieve the characteristics of the sample from the measurement of the profile of its refractive index in the vicinity of molecular resonances. This approach, which is in clear contrast to traditional methods based on the detection of absorption, provides inherent immunity to power fluctuations, calibration-free operation, and an output that is linearly dependent on gas concentration. Heterodyne phase-sensitive dispersion spectroscopy (HPSDS) is a very recently proposed technique for molecular dispersion spectroscopy based on tunable lasers that is characterized by a very simple architecture in which data processing and concentration retrieval are straightforward. Different HPSDS implementations have been experimentally validated in the near-IR. Here, we present the first demonstration of HPSDS in the mid-IR using a directly modulated quantum cascade laser for the measurement of CO. The setup is put under test to characterize its response to changing concentrations, pressures, and levels of optical intensity on the detector, and the limit of detection is estimated. Besides this, an experimental comparison with wavelength modulation spectroscopy with second-harmonic detection (2f-WMS) is performed and discussed in detail in order to offer a clear view of the benefits and drawbacks that HPSDS can provide over what we could consider the reference method for gas analysis based on tunable laser spectroscopy.

In-vivo, non-invasive detection of hyperglycemic states in animal models using mm-wave spectroscopy.

Chronic or sustained hyperglycemia associated to diabetes mellitus leads to many medical complications, thus, it is necessary to track the evolution of patients for providing the adequate management of the disease that is required for the restoration of the carbohydrate metabolism to a normal state. In this paper, a novel monitoring approach based on mm-wave spectroscopy is comprehensively described and experimentally validated using living animal models as target. The measurement method has proved the possibility of non-invasive, in-vivo, detection of hyperglycemia-associated conditions in different mouse models, making possible to clearly differentiate between several hyperglycemic states.

Gain-switching injection-locked dual optical frequency combs: characterization and optimization.

In this work, the generation of dual optical frequency combs based on gain-switching and optical injection locking is experimentally examined. The study reveals that an effective process of optical injection can lead to optimized RF combs in terms of span and signal-to-noise ratio. The system also minimizes the overlap of lines and reduces the number of optical components involved, eliminating the need for any external modulator (electro-optic, acousto-optic). The validation of the system was performed as a dual-comb spectrometer, which allowed for determination of the absorption and dispersion profiles of the molecular transition of H13CN at 1538.523 nm.

Dual optical frequency comb architecture with capabilities from visible to mid-infrared.

In this paper, a new approach to dual comb generation based on well-known optical techniques (Gain-Switching and Optical Injection Locking) is presented. The architecture can be implemented using virtually every kind of continuous-wave semiconductor laser source (DFB, VCSEL, QCL) and without the necessity of electro-optic modulators. This way, a frequency-agile and adaptive dual-comb architecture is provided with potential implementation capabilities from mid-infrared to near ultraviolet. With a RF comb comprising around 70 teeth, the system is validated in the 1.5 µm region measuring the absorption feature of H13CN at 1538.523 nm with a minimum integration time of 10 µs.

Dual electro-optic optical frequency combs for multiheterodyne molecular dispersion spectroscopy.

In this paper, a multiheterodyne architecture for molecular dispersion spectroscopy based on a coherent dual-comb source generated using a single continuous wave laser and electro-optic modulators is presented and validated. The phase-sensitive scheme greatly simplifies previous dual-comb implementations by the use of an electro-optic dual comb and by phase-locking all the signal generators of the setup eliminating, in this way, the necessity of any reference optical path currently mandatory in absorption-based instruments. The architecture is immune to the classical baseline and normalization problems of absorption-based analyzers and provides an output linearly dependent on the gas concentration. In addition, the simultaneous parallel multi-wavelength measurement approach has the ability to deliver an improved output bandwidth (measurement speed) over gas analyzers based on tunable lasers.

Remote diffuse reflectance spectroscopy sensor for tissue engineering monitoring based on blind signal separation.

In this study the first results on evaluation and assessment of grafted bioengineered skin substitutes using an optical Diffuse Reflectance Spectroscopy (DRS) system with a remote optical probe are shown. The proposed system is able to detect early vascularization of skin substitutes expressing the Vascular Endothelial Growth Factor (VEGF) protein compared to normal grafts, even though devitalized skin is used to protect the grafts. Given the particularities of the biological problem, data analysis is performed using two Blind Signal Separation (BSS) methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). These preliminary results are the first step towards point-of-care diagnostics for skin implants early assessment.