The emerging mid-infrared photoacoustic microscopy (MIR-PAM) is a potential imaging modality in revealing special biomolecules compositions in thick samples by utilizing the light-excited ultrasound signals. The development of a nanosecond and high-energy MIR fiber laser source is still at an early age, facing the challenges of either low peak power or large footprint. This work aims to develop a new Raman laser source for MIR-PAM based on the gas-filled anti-resonant hollow core fiber (ARHCF) technology. As a proof of concept, a MIR laser source at 3.4 μm is developed and combined with PAM for the first time targeting at the lipid-rich mouse brain sample due to main absorption band of myelin sheaths. This laser source is based on the cascading of two ARHCFs, where a high-energy (~26.5 μJ) Raman Stokes line at 1409 nm is generated through the 1st-stage nitrogen-filled ARHCF with a pump fiber laser at 1060 nm. The output Raman laser from the 1st stage ARHCF is used as a pump for the 2nd-stage hydrogen-filled ARHCF, to generate the Raman laser at 3.4 μm with ~2.7 μJ pulse energy. Our label-free ex-vivo imaging depicted the lipid-rich myelin region in the mouse brain, showing the feasibility of extending the novel gas-filled laser platform into PAM imaging modalities.
This report presents a state-of-the-art multimodality imaging device that combines multi-spectral optoacoustic microscopy (OAM) and optical coherence tomography (OCT) to chart absorbers in live tadpoles (Xenopus laevis) accurately. The OAM channel captures maps of five internal contrast agents: melanin, hemoglobin, collagen, glucose, and lipids. A novel method was developed to achieve this by assuming that each voxel in the 3D-OAM image exhibits a single chromophore contributing to the optoacoustic signal. The device is powered by a single optical source (SuperK Compact, NKT Photonics) that operates across an ultra-wide spectral range of 450 to 2400 nm. The set-up was optimized by minimizing optical aberrations and attenuation on optical components to stimulate the sample effectively. Using optical pulses of 2 ns duration and a repetition rate of 20 kHz, the device imaged tadpoles in their embryonic stage at multiple wavelengths, using narrow spectral windows of 25 nm bandwidth within the broad spectrum of the supercontinuum source at a time. In addition, an ultra-high-resolution OCT imaging channel operating at 1300 nm (spectral bandwidth 180 nm) was created and incorporated into the device. The OCT channel, also powered by a commercial supercontinuum source (SuperK EXTREME EXR9, NKT Photonics), was used for guidance purposes and to help determine the location of the chromophores.
In conventional optoacoustic microscopy, nanosecond pulse duration lasers are employed. When a laser delivering shorter pulse durations is used, it is expected that, from a theoretical point of view, broader, higher-frequency acoustic waves to be generated, therefore a better axial resolution of the instrument. In the present report, this advantage, offered by a picosecond duration pulse laser, to experimentally demonstrate that the axial resolution of an optoacoustic microscopy instrument can be enhanced was exploited. In comparison to a 2 ns pulse duration, an improvement in the axial resolution of ~50% is demonstrated by using excitations with pulses of duration ⪅100 ps. Details of an optoacoustic microscopy instrument, operating at 532 nm, capable to provide high-resolution axial and lateral optoacoustic images, are also presented. The capabilities of the instrument are demonstrated by in-vivo images of Xenopus laevis brain with a similar ~ 3.8 μm lateral resolution throughout the whole axial imaging range.
Unraveling the scientific and technological importance of the mid-infrared (mid-IR) region remains yet a long-standing challenge. Despite the significant efforts on mid-IR light sources, development of high-energy, narrow-linewidth and compact lasers still constitutes the main obstacle towards novel spectroscopic, imaging and sensing devices. Photoacoustic modality is known as one of the most powerful tools enabling high signal-to-noise ratio gas detection and albeit its wide use in the mature near-infrared (near-IR) region, further research has to be carried out in the mid-IR in order to “unlock” its full potential. In this work, we aim on tracing CO2 based on the innovative combination of the emerging gas-filled mid-IR silica anti-resonant hollow-core fiber (ARHCF) Raman laser technology with the powerful photoacoustic modality. The laser source adopts the stimulated Raman scattering effect of H2 filled in a piece of ARHCF, to enable the generation of first-order vibrational Raman Stokes from a 1533 nm Er-doped fiber laser pump. With this configuration, a nanosecond laser pulses with micro-joule level pulse energy is achieved at ~ 4.25 μm wavelength, which is located within the strongest absorption band of CO2. The laser’s linewidth is estimated to be tens GHz level. This laser source is used to drive an in-house developed photoacoustic sensor, revealing a 1.78 ppm level CO2 detection limit in laboratory condition. This work provides a valuable reference for the development of high-sensitivity gas detectors.
Conventional optoacoustic microscopy (OAM) instruments have at their core a nanosecond pulse duration laser. If lasers with a shorter pulse duration are used, broader, higher frequency ultrasound waves are expected to be generated and as a result, the axial resolution of the instrument is improved. Here, we exploit the advantage offered by a picosecond duration pulse laser to enhance the axial resolution of an OAM instrument. In comparison to an instrument equipped with a 2-ns pulse duration laser, an improvement in the axial resolution of 50% is experimentally demonstrated by using excitation pulses of only 85 ps. To illustrate the capability of the instrument to generate high-quality optoacoustic images, en-face, in-vivo images of the brain of Xenopus laevis tadpole are presented with a lateral resolution of 3.8 μm throughout the entire axial imaging range.
We will present our recent work using noble and Raman-active gas-filled anti-resonant hollow-core fiber (ARHCF) technology. First, we will present the generation of supercontinuum spanning from 200 nm to 4000 nm based on nonlinear effects of soliton self-compression and phase-matched deep‑ultraviolet (DUV) dispersive wave (DW) emission in Argon (Ar)-filled ARHCFs pumped at 2.46 μm wavelength with 100 fs pulses and ~8μJ pulse energy. Then we will discuss our recent work on stimulated Raman scattering (SRS) effect in a hydrogen (H2)-filled ARHCF, to achieve near- and MIR Raman lasers. By employing the single-stage vibrational SRS effect, a 4.22 μm Raman laser line is directly converted from a linearly polarized 1.53 μm pump laser. A quantum efficiency as high as 74% was achieved, to yield 17.6 µJ pulse energy. The designed 4.22 μm wavelength is well overlapped with the strongest CO2 absorption, therefore constituting a promising way for CO2 detection. In addition, we report a multi-wavelength Raman laser based on the cascaded rotational SRS effect. Four Raman lines at 1683 nm, 1868 nm, 2100 nm, and 2400 nm are generated, with pulse energies as high as 18.25 µJ, 14.4 µJ, 14.1 µJ, and 8.2 µJ, respectively. The energy of these Raman lines can be controlled by tuning the H2 pressure from 1 bar to 20 bar.
We demonstrate a high repetition rate (3 MHz) Mid-IR supercontinuum (SC) source spanning whose spectrum spanning 1000-4200 nm using a cascade of different nonlinear fibers. Multi-tone absorption spectroscopy measurements are subsequently carried out using this source and a scanning spectrometer probing various concentrations and a combination of different analytes. We further explore a novel algorithm for rearranging the absorption in the IR-region and the NIR region for three-dimensional modeling. We show this method of analyzing the data is robust, that is being able to predict newly added samples of slightly different nature without having to the recalibrate the model.
Supercontinuum (SC) lasers are of high interest for applications like multispectral photoacoustic imaging (MSPAI), where the wide optical bandwidth of the SC laser system facilitates functional investigations on top of the structural information of various endogenous agents inside the human body. The current work addresses a promising attempt at devising high pulse energy SC laser source using telecom-range diode laser systems and few meters of standard single-mode fibers for various MSPAI applications in near-infrared (NIR) and extended-NIR wavelength regions.
An all-fiberized tunable repetition rate (50kHz-10MHz) SC source for photoacoustic microscopy (PAM) and optical coherence tomography (OCT) is developed. OCT is a scattering based imaging technique, requiring low spectral noise. Noise level requirement in OCT is usually mitigated using high repetition rate (MHz) laser sources. On the other hand, PAM is a hybrid imaging modality based on optical absorption that requires high pulse energies, thus, sources operating at lower repetition rates (kHz) are preferred. Nevertheless, it is always important to quantify and understand the RIN dynamics of the SC sources for good quality PAM and OCT images.
We demonstrate a robust photoacoustic medium for measuring the concentration of ammonia in an aqueous solution. We target the near-infrared (NIR) overtone absorption band (~1540 nm) of ammonia with a supercontinuum (SC) laser-based excitation system and an immersion-based acoustic transducer as the detection system. We further present how such a simple system can be used to perform effective in-situ measurements of ammonia over a range of concentrations with a sensitivity of parts per million (ppm) by volume and linearity of <96%. We demonstrate how the sensing system can be readily tailored to monitor the concentrations of other miscible gases in the aqueous solution.
Detection of ammonia based on an all-fiber configuration is reported. The system consists of a hollowcore photonic-bandgap (HC-PBG) fiber with 20μm core diameter and transmission window from 1490 to 1680 nm. Absorption bands of ammonia at ~1538 nm are targeted using a supercontinuum source with central wavelength at 1550 nm. We present the method of achieving a complete fiber system while addressing the gas entry/exit path through the HC-PBG. Analysis of the ammonia absorbance in the fiber with respect to fiber length and response time is investigated. By operating in the near infrared, we demonstrate how the proposed system addresses several challenges associated with fiber-based gas-sensing, using readily available commercial components.
In this work, we report a cost-effective supercontinuum (SC) laser-based multispectral photoacoustic spectroscopy (MSPAS) system for studying spectral characteristics of various analytes. We demonstrate an in vitro label-free monitoring of the analytes in the extended near-infrared (NIR) (1540–1840 nm) spectral range. We further demonstrate how a simple ratiometric analysis in conjunction with linear regression can be used for accurate prediction of glucose over commonly encountered physiological levels inside the human body (0–400 mg/dL). Looking forward, the proposed SC-based MSPAS system provides a framework for the development of label-free and non-invasive monitoring multiple bio-analytes accurately, with potential translation to clinical in vivo applications.
Concatenating fibers to extend supercontinuum generation beyond the multiphonon absorption edge of silica to access longer wavelengths in the mid infrared region has received much attention due to the various molecular fingerprints that exist in this region. Thulium doped (Tm) fiber has been used as an intermediate fiber to get above the multiphonon absorption edge of silica through absorption (900 and 1600 nm) and emission processes between (1800 – 2100 nm) and (2200 - 2600 nm). The advantages of the Tm-doped fiber is not only limited to generating SC above the multiphonon edge of silica but also reducing the high peak power which easily damages the facet of soft glass fibers whose transmission window extends well into the longer mid infrared region. The mechanisms governing the generation of SC in active fibers is quite different from passive fibers as there is interplay of the nonlinear processes that are commonly observed in passive fibers as well as energy transition contributions by the dopants in the fiber.
SC generation and its application are hindered by pulse-to-pulse fluctuations as the generation is initiated by noise seeded processes especially in the long pumped regime (> 1ps). In this work we have experimentally studied the pulse fluctuations in thulium gain fiber whose SC spans 1550 – 2700 nm at three different repetition rates (10 KHz , 100 KHz, 200 KHz). We have illustrated the relative intensity noise across the whole spectrum most importantly within the absorption and emission regions of the Tm-doped fiber.
In this work, we employ frequency-domain photoacoustic microscopy to obtain photoacoustic images of labeled and unlabeled cells. The photoacoustic microscope is based on an intensity-modulated diode laser in combination with a focused piezo-composite transducer and allows imaging of labeled cells without severe photo-bleaching. We demonstrate that frequency-domain photoacoustic microscopy realized with a diode laser is capable of recording photoacoustic images of single cells with sub-µm resolution. As examples, we present images of undyed human red blood cells, stained human epithelial cells, and stained yeast cells.
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