Dual-modality thermoacoustic and photoacoustic imaging

Diagnosis of early breast cancer is the key to survival. The combined contrasts from thermoacoustic and photoacoustic tomography: TAT and PAT) can potentially predict early stage breast cancer. We have designed and engineered a breast imaging system integrating both thermoacoustic and photoacoustic imaging techniques to achieve dual-contrast: microwave and light absorption), non-ionizing, low-cost, high-resolution, three-dimensional breast imaging. We have also developed a novel concept of using a negative acoustic lens to increase the acceptance angle of an unfocused large-area ultrasonic transducer: detector), leading to more than twofold improvement of the tangential resolution in both TAT and PAT when the object is far from the scanning center. A contrast agent could be greatly beneficial for early cancer diagnosis using TAT/PAT, because the early stage intrinsic contrast can be low. We have developed a carbon nanotube-based contrast agent for both TAT and PAT. In comparison with deionized water, single-walled carbon nanotubes: SWNTs) exhibited more than twofold signal enhancement for TAT at 3 GHz, and in comparison with blood, they exhibited more than sixfold signal enhancement for PAT at 1064 nm wavelength. Using PAT in conjunction with an intradermal injection of SWNTs, we also showed the feasibility of noninvasive in vivo sentinel lymph node imaging in a rat model. We have also developed and demonstrated molecular photoacoustic imaging using unique soft-type colloidal gold nanobeacons: GNBs) in the near-infrared region. GNBs represent a novel class of stable, colloidal gold nanoparticles, incorporating small metallic gold nanoparticles that can clear from the body when the particles are metabolically disrupted. We have also imaged the sentinel lymph node using different sizes of GNBs, showing that size plays an important role in their in vivo behavior and uptake to the lymph nodes. In addition to providing diagnostic imaging, TAT and PAT can be used in therapy for real-time temperature monitoring with high spatial resolution and high temperature sensitivity, which are both needed for safe and efficient thermotherapy. Using a tissue phantom, these noninvasive methods have been demonstrated to have a high temperature sensitivity of 0.15 0C at 2 s temporal resolution: 20 signal averages)

Cantilever enhanced gas sensing using photoacoustic spectroscopy

Monet sovellukset vaativat erittäin pienten kaasumäärien tunnistamista. Tähän tarkoitukseen on kehitetty monia tekniikoita, joista fotoakustisella spektroskopialla on saavutettu kaikkein herkimpiä tuloksia. Menetelmä perustuu näytekaasun synnyttämään akustiseen aaltoon, joka syntyy kaasun absorboidessa valoa. Kalvomikrofonien herkkyyttä rajoittaa mittaukseen kytkeytyvä elektroninen kohina, sekä kalvon mekaanisen liikkeen epälineaarisuus suuria optisia tehoja käytettäessä. Tästä syystä herkimpiä mittauksia varten kalvomikrofonit on korvattu optisesti mitattavalla, oven tavoin toimivalla, palkilla. Palkki on erotettu kehyksestä kolmelta sivulta kapealla raolla. Vaikka mikromekaanisilla palkeilla onkin saavutettu pienimmät mitatut herkkyydet, vaatii niiden vahvuuksien täydellinen hyödyntäminen vielä lisää tutkimusta. Tämä työ muodostuu kahdesta osasta. Ensimmäisessä osassa tehdään kirjallisuuskatsaus fotoakustiseen ilmiöön ja sitä hyödyntävän laitteiston vaatimiin osiin. Lisäksi esitellään piipalkkien valmistukseen käytetty prosessi. Toisessa osassa Micronovaan kootulla järjestelmällä mitattuja signaalispektrejä verrataan teoreettiseen malliin. Vaikka mallin antamat tulokset vastaavatkin mitattuja arvoja käytettäessä kapeita rakoja, huomattiin mallin ja kokeellisten tulosten välillä suuria poikkeamia sekä signaali- että kohinaspektrissä, kun raon leveyttä kasvatettiin. Piipalkkien herkkyyttä rajoittaa pääasiassa näytekaasun aiheuttama kaasujousi. Kaasujousen vaikutuksen vähentämiseksi työssä mallinnetaan elementtimenetelmällä (FEM) erimuotoisia antureita. Mallien perusteella palkin perforointi pienentää efektiivistä jousivakiota tehokkaasti.The ability to detect small amount of trace gases is vital in many applications. The photo acoustic spectroscopy is one of the methods that produce the most sensitive detection schemes. It is based on detecting a gas specific acoustic wave generated in the absorption of light. The sensitivity of the traditional membrane microphones is limited by electrical noise and the nonlinearity of the displacement of the mechanical sensor at high optical power levels. Membrane microphones have been therefore replaced with optically measured cantilevers in the most sensitive systems. Even though a MEMS cantilever has shown the best sensitivity to date, further work is needed to fully exploit its full potential. This thesis consists of two parts. The first part gives a review of the photo acoustic effect and the components used to build a photo acoustic system based on the literature. In addition, a brief review of the fabrication process of cantilevers is given. In the second part, a photo acoustic setup assembled at Micronova is used to compare the theoretical model with the measured signal spectra of the cantilevers. The cantilever design is like a tight micro machined "door" in which the gas leakage through the gap between the moving door and the frame is of crucial importance. The used model could explain the experimental data very well when this narrow gap is in a few µm range. For larger gaps, the gas leakage and dynamics change the overall behaviour so much that the agreement becomes worse. The sensitivity of the micro fabricated cantilevers is mainly limited by a gas spring. Therefore various shapes for the component were modelled with the finite element method (FEM) showing that the effective spring constant can be efficiently altered by perforating the cantilever

カーボンナノチューブの光音響イメージング増強剤への応用

Tohoku University西條芳文課

Laser-based optical activity detector for high performance liquid chromatography

The identification of chromatographic peaks is simplified when multiple detectors are used, particularly those that monitor entirely different physical properties. A concept that has recently been demonstrated is detection based on the rotation of polarized light by optically active molecules. One can make use of the presence or absence of optical activity, the sign of the optical rotation, as well as the wavelength dependence of the rotation, to aid in the identification of peaks. The working system is based on the use of a laser and high quality optics. A detection limit approaching that of the conventional UV absorption detector can be achieved in a small volume flow cell. Three specific applications will be discussed. In human urine, the determination of various sugars, except glucose, has been a problem. The detector based on optical activity is ideal in this case. The other optically active components can be separated by the use of a heavy-metal ion exchange column. In human plasma, the determination of the lipid profile is of interest. While some success has been reported using far UV absorption, interference between triglycerides and free cholesterol is a problem. Furthermore, important species like cholestanol has no convenient absorption bands. The optical activity detector once again can be used to overcome these problems;Also, chromatograms are obtained for various saturated fractions of shale oil, having different particle sizes and from different sources. Separation is accomplished by reversed-phase high performance liquid chromatography and the eluate is monitored by the optical activity detector. The chromatograms show an abundance of optically active components, which may be good fingerprints for the various shale oils

Liquid-Phase and Evanescent-Wave Cavity Ring-Down Spectroscopy in Analytical Chemistry

Due to its simplicity, versatility, and straightforward interpretation into absolute concentrations, molecular absorbance detection is widely used in liquidphase analytical chemistry. Because this method is inherently less sensitive than zero-background techniques such as fluorescence detection, alternative, more sensitive measurement principles are being explored. This review discusses one of these: cavity ring-down spectroscopy (CRDS). Advantages of this technique include its long measurement pathlength and its insensitivity to light-source-intensity fluctuations. CRDS is already a wellestablished technique in the gas phase, so we focus on two new modes: liquidphase CRDS and evanescent-wave (EW)-CRDS. Applications of liquidphase CRDS in analytical chemistry focus on improving the sensitivity of absorbance detection in liquid chromatography. Currently, EW-CRDS is still in early stages: It is used to study basic interactions between molecules and silica surfaces. However, in the future this method may be used to develop, for instance, biosensors with high specificity. Copyright © 2009 by Annual Reviews

Cavity Enhanced Optical Refrigeration and Spectroscopy

This dissertation is mainly concerned with increasing the pump power absorption in optical refrigeration of solids and photo-acoustic spectroscopy of trace gases using optical cavities. Enhancing the absorption is key to reaching lower temperatures in optical refrigeration and achieving better sensitivity in photo-acoustic spectroscopy. We have used intra-cavity and coupled-cavity absorption enhancement techniques to increase the absorption in Ytterbium doped Yttrium Lithium Fluoride (Yb3+:YLF) crystals. For this purpose, we have developed tunable high-power narrow-linewidth InGaAs/GaAs vertical external-cavity surface-emitting lasers (VECSELs) operating at 1020 nm, the optimal cooling wavelength for Yb:YLF. By inserting a 7% Yb:YLF sample inside the resonator of the VECSEL, we have cooled it to 130±1 K. It has been shown that due to high intra-cavity power, saturation of pump absorption reduces the absorbed power in intra-cavity cooling. We have also utilized a coupled-cavity geometry to enhance the absorption. In this method, the cooling sample is placed inside a Fabry-Perot cavity which is used as an effective output coupler for the VECSEL. With this technique we have been able to cool a 10% Yb:YLF crystal to 145±1 K. Advantages and challenges, including cavity design, wavelength stabilization techniques, and cooling sample choice for optimal cooling are discussed in both cases. We have also utilized critical coupling (or impedance) matching condition in two coherently coupled Fabry-Perot cavities to enhance the absorption in photo-acoustic detection of trace gases. In this novel technique, by adjusting the reflectivity of the first Fabry-Perot cavity, the impedance matching can be achieved for a wide range of absorption coefficients for the second cavity, where the acoustic detection is performed. Normalized noise-equivalent absorption coefficient of 5×10^(-10) cm^(-1) W∕√Hz is measured

Development, characterization and miniaturization of a trace gas detection system for NO₂ in air based on photoacoustic spectroscopy

This thesis provides a detailed theoretical discussion about common absorption spectroscopy (AS) and, in particular, about photoacoustic spectroscopy (PAS). The physical concepts of signal generation are illustrated in view of amplitude modulation (AM) and wavelength modulation (WM). Furthermore the advantages and disadvantages of the techniques are presented. As a result, PAS was identified to outclass AS, thus it turned out to be the method of choice in view of developing a miniaturized trace gas sensing application. The theoretical part of this work further outlines various approaches of signal enhancement, e.g. by acoustic and/or mechanical resonance amplification. Besides, several phenomena of signal attenuation are addressed, e.g. acoustic detuning, vibrational-translational (VT) relaxation and vibrational-vibrational (VV) energy transfer processes, which have to be considered with regard to the individual measuring conditions. Simulation and experimental chapters illustrate the pre-development and the practical implementation of a laboratory photoacoustic setup, a portable trace gas monitoring device and various photoacoustic cell (PAC) designs. These include a conventional bulky design, an optimized low-cost 3D printed PAC, a miniaturized quartz enhanced photoacoustic spectroscopic (QEPAS) scheme and a further integrated microelectromechanical system (MEMS) based sensor chip, respectively. Although several parts of this thesis also provide preparatory work for multi-component analysis, nitrogen dioxide (NO2) was used as primary analyte in order to characterize the above mentioned photoacoustic cell designs. This involves acoustic resonance and noise analysis, determination of optimal operating parameters (e.g. gas flow rate and lock-in time constant), performance evaluation (e.g. response behavior, optical performance, calibration characteristics and long-term signal stability) as well as interference studies towards oxygen (O2), carbon dioxide (CO2), humidity (H2O) and acoustic noise. In conclusion, NO2 detection by means of the low-cost 3D printed PAC and the QEPAS configuration even revealed two world record detection limits (1sigma) of 33 pptV and 600 pptV, respectively

Glossary of methods and terms used in analytical spectroscopy (IUPAC Recommendations 2019)

Recommendations are given concerning the terminology of concepts and methods used in spectroscopy in analytical chemistry, covering nuclear magnetic resonance spectroscopy, atomic spectroscopy, and vibrational spectroscopy. © 2021 IUPAC and De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/ 2021

Development of High-speed Photoacoustic Imaging technology and Its Applications in Biomedical Research

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of this dissertation is to develop high-speed PA microscopy (PAM) technologies. Novel optical scanning, ultrasonic detection, and laser source techniques are introduced in this dissertation to advance the performance of PAM systems. These upgrades open up new avenues for PAM to be applicable to address important biomedical challenges and enable fundamental physiological studies.First, we investigated the feasibility of applying high-speed PAM to the detection and imaging of circulating tumor cells (CTCs) in melanoma models, which can provide valuable information about a tumor’s metastasis potentials. We probed the melanoma CTCs at the near-infrared wavelength of 1064 nm, where the melanosomes absorb more strongly than hemoglobin. Our high-speed PA flow cytography system successfully imaged melanoma CTCs in travelling trunk vessels. We also developed a concurrent laser therapy device, hardware-triggered by the CTC signal, to photothermally lyse the CTC on the spot in an effort to inhibit metastasis.Next, we addressed the detection sensitivity issue in the previous study. We employed the stimulated Raman scattering (SRS) effect to construct a high-repetition-rate Raman laser at 658 nm, where the contrast between a melanoma CTC and the blood background is near the highest. Our upgraded PA flow cytography successfully captured sequential images of CTCs in mouse melanoma xenograft model, with a significantly improved contrast-to-noise ratio compared to our previous results. This technology is readily translatable to the clinics to extract the information of a tumor’s metastasis risks.We extended the Raman laser technology to the field of brain functional studies. We developed a MEMS (micro-electromechanical systems) scanner for fast optical scanning, and incorporated it to a dual-wavelength functional PAM (fPAM) for high-speed imaging of cerebral hemodynamics in mouse. This fPAM system successfully imaged transient changes in blood oxygenation at cerebral micro-vessels in response to brief somatic stimulations. This fPAM technology is a powerful tool for neurological studies.Finally, we explored some approaches of reducing the size the PAM imaging head in an effort to translate our work to the field of wearable biometric monitors. To miniaturize the ultrasonic detection device, we fabricated a thin-film optically transparent piezoelectric detector for detecting PA waves. This technology could enable longitudinal studies on free-moving animals through a wearable version of PAM