Terahertz spectroscopy and imaging of potential phantoms with defect classification

Summary form only given. The terahertz (THz) band of the electromagnetic spectrum has long held interest in the science and engineering community for its unique applications in imaging and spectroscopy. However, due to the difficulty in generating and receiving THz radiation, only very recently practical and efficient THz systems become available. Due to recent advances in the development and manufacturing of commercially available THz spectroscopy and imaging system many of these applications are coming to fruition. As such, the practical implementation of THz in applications needs to be investigated in order to determine the advantages of THz technology. In this work, THz spectroscopy of photovoltaic semiconductor devices will be performed throughout various critical stages in the fabrication process. Due to the few millimeter penetrating and none-destructive properties of THz radiation it will be possible to monitor semiconductor wafers using THz spectroscopy. This technology has a potential to provide insight into the development of wafer defects earlier in the fabrication process. Using a pulsed Terahertz imaging and spectroscopy system at the University of Arkansas, our group will investigate the electrical properties of semiconductor photovoltaics and will conduct THz imaging of defected ones. Testing the wafers throughout various key steps in fabrication is a process known to produce a functional device. This will then be repeated for the same process, only now with a critical fatal defect such as a buried crack, surface crack or a defect in the doping level. These defects will be intentionally inserted at an early stage to determine if THz spectroscopy can be used to detect them early on. THz characterization of the semiconductors for the impurity doping levels and crystal orientation to be studied will be performed to determine the electrical properties in this frequency range. This will allow for accurate numerical simulation to compare with the experimental results.

This study describes terahertz (THz) imaging of hydration changes in physiological tissues with high water concentration sensitivity. A fast-scanning, pulsed THz imaging system (centered at 525 GHz; 125 GHz bandwidth) was utilized to acquire a 35 mm x 35 mm field-of-view with 0.5 mm x 0.5 mm pixels in less than two minutes. THz time-lapsed images were taken on three sample systems: (1) a simple binary system of water evaporating from a polypropylene towel, (2) the accumulation of fluid at the site of a sulfuric acid burn on ex vivo porcine skin, and (3) the evaporative dehydration of an ex vivo porcine cornea. The diffusion-regulating behavior of corneal tissue is elucidated, and the correlation of THz reflectivity with tissue hydration is measured using THz spectroscopy on four ex vivo corneas. We conclude that THz imaging can discern small differences in the distribution of water in physiological tissues and is a good candidate for burn and corneal imaging.

This paper presents an image morphing algorithm for quantitative evaluation methodology of terahertz (THz) images of excised breast cancer tumors. Most current studies on the assessment of THz imaging rely on qualitative evaluation, and there is no established benchmark or procedure to quantify the THz imaging performance. The proposed morphing algorithm provides a tool to quantitatively align the THz image with the histopathology image. Freshly excised xenograft murine breast cancer tumors are imaged using the pulsed THz imaging and spectroscopy system in the reflection mode. Upon fixing the tumor tissue in formalin and embedding in paraffin, an FFPE tissue block is produced. A thin slice of the block is prepared for the pathology image while another THz reflection image is produced directly from the block. We developed an algorithm of mesh morphing using homography mapping of the histopathology image to adjust the alignment, shape, and resolution to match the external contour of the tissue in the THz image. Unlike conventional image morphing algorithms that rely on internal features of the source and target images, only the external contour of the tissue is used to avoid bias. Unsupervised Bayesian learning algorithm is applied to THz images to classify the tissue regions of cancer, fat, and muscles present in xenograft breast tumors. The results demonstrate that the proposed mesh morphing algorithm can provide more effective and accurate evaluation of THz imaging compared with existing algorithms. The results also showed that while THz images of FFPE tissue are highly in agreement with pathology images, challenges remain in assessing THz imaging of fresh tissue.

The terahertz (THz) time-domain spectroscopy technique was used to characterize the cooling process of solid n-alkanes. The THz waveforms of n-octadecane, n-nonadecane, n-eicosane, n-heneicosane, n-docosane, and n-pentacosane were obtained with the cooling time using the aforementioned noncontact optical method. The peak values of the THz signal were found to be related to the cooling temperature of n-alkanes. The THz wave was sensitive to the size and structure of particles in the liquid; therefore, the crystallization process of n-alkanes was monitored. An empirical equation based on signal attenuation was proposed to quantitatively distinguish the content change of structural order in the samples. Results present a new noncontact optical approach for characterizing wax crystallization via THz time-domain spectroscopy.

In the past few decades, the applications of terahertz (THz) spectroscopy and imaging technology have seen significant developments in the fields of biology, medical diagnosis, food safety, and nondestructive testing. Label-free diagnosis of malignant tumours has been obtained and also achieved significant development in THz biomedical imaging. This review mainly presents the research status and prospects of several common continuous-wave (CW) THz medical imaging systems and applications of THz medical imaging in biological tissues. Here, we first introduce the properties of THz waves and how these properties play a role in biomedical imaging. Then, we analyse both the advantages and disadvantages of the CW THz imaging methods and the progress of these methods in THz biomedical imaging in recent ten years. Finally, we summarise the obstacles in the way of the application of THz bio-imaging application technology in clinical detection, which need to be investigated and overcome in the future.

Terahertz (THz) is an electromagnetic spectrum with a frequency range from 0.1 to 10 THz, which is located in between the microwave and infrared regions. The unique features of THz waves make them eligible for use in various medical applications. The THz imaging is one of them, which is mainly based on the analysis and processing of the transmission and reflection spectrum information of the sample. This chapter mainly presents the research status and prospects of several THz medical imaging systems and their applications for medical imaging in biological tissues. As the demand for technology grows, high-performance THz imaging systems are becoming indispensable. The ability of the THz time-domain spectroscopy (THz-TDS) system to extract spectra from amplitude and phase information opens virtually unlimited possibilities for imaging applications. The performance achievements of THz-TDS-based imaging with potential research on its fast-imaging components for solving the existing limitations of imaging speed are also presented. Furthermore, the latest developments of several THz-TDS-based imaging methods, including tomography imaging and near-field imaging, are highlighted with their performance improvement. Additionally, the rapid development of THz-TDS as a highly versatile analytical tool for the characterisation of pharmaceutical materials has drawn considerable attention. One of the greatest biomedical potentials of THz imaging is the use of molecular spectroscopy for diagnostics, which is exponentially advanced and moving closer to progress. It is now evident that different types of biomolecules leave distinctive spectral fingerprints in the THz region, which considerably widens the coverage of its technology application including in-vitro and in-vivo measurements of small molecules of clinical importance in point of care and diagnostic systems. In-vivo molecular imaging is considered the next frontier in medical diagnostics, which would be ideally performed non-invasively. Recent achievements in the field of medical imaging have dramatically enhanced the early detection and treatment of many pathological conditions. THz imaging systems can help in detecting early cancer before it is visible or sensitive to any other identification resources. The THz images can distinguish between healthy tissue and basal cell carcinoma and therefore help in mapping the exact margins of early-stage tumours. By obtaining both frequency and time-domain information, the THz imaging can ensure enhanced detection of cancer and provide sharper imaging and molecular fingerprinting. THz biomedical imaging has become a modality of interest due to its ability to simultaneously acquire both image and spectral information. Advanced digital image processing algorithms are greatly needed to assist in screening, diagnosis and treatment. Finally, we summarise the obstacles in the way of the application of THz biomedical imaging application technology in clinical detection, which need to be investigated and overcome in the future.

The purpose of this paper is to construct an identification model that can discriminate different transgenic cotton seeds with similar characteristics based on terahertz (THz) spectroscopy. An improved support vector machine (SVM) which using genetic algorithm (GA) to optimize parameters is proposed in this paper. Principal Component Analysis is applied to extract relevant features from original spectrum information and eliminate the anomalous samples. Instead of original spectral information, the feature spectrum is selected to be fed into the model of GA-SVM, where an improved SVM method to identify those samples. The results demonstrate that the GA-SVM method can effectively identify the distinct transgenic cottons, and THz spectroscopy can provide a nondestructive, rapid and reliable method to distinguish different transgenic cottons.

Terahertz (THz) spectroscopy has high sensitivity for the interaction between molecules and vibration of large molecules. Besides, it is well known that infrared (IR) spectroscopy can be used to detect the vibration of functional groups. Hence, the comparison of the conventional diagnosis method using IR spectroscopy and THz spectroscopy is expected for more potential diagnosis. In this study, the comparison between THz spectroscopy and IR spectroscopy for deteriorated hydrocarbon liquids has been conducted for the degraded insulating oils. The surveyed samples are pure dodecane and mineral oil. The degraded samples are made by heating in the oxygen atmosphere. In addition, we also measured the breakdown voltage and the volume resistivity to know the states of degraded insulating oil. The experimental results show that oxidation causes spectral changes in the both of THz and IR regions. The spectral change in the IR region is due to carbonyl group and hydroxyl group vibrations. Whereas, in the THz region, the spectral change originates from the modification of intermolecular interaction. The degradation phenomena of the insulating oil contribute to higher carbonyl/hydroxyl content and associated by stronger intermolecular interaction that leads to its lower breakdown voltage.

Terahertz (THz) and sub-terahertz imaging and spectroscopy are becoming increasingly popular nondestructive evaluation techniques for damage detection and characterization of materials. THz radiation is being used for inspecting ceramic foam tiles used in TPS (Thermal Protection System), thick polymer composites and polymer tiles that are not good conductors of ultrasonic waves. Capability of THz electromagnetic waves in detecting heat induced damage in porous materials is investigated in this paper. Porous pumice stone blocks are subjected to long time heat exposures to produce heat induced damage in the block. The dielectric properties extracted from THz TDS (Time Domain Spectroscopy) measurements are compared for different levels of heat exposure. Experimental results show noticeable and consistent change in dielectric properties with increasing levels of heat exposure, well before its melting point.

Terahertz (THz) spectroscopy is a nondestructive method that has the ability to identify many hazardous materials by investigating their low frequency vibrational modes (0.1-6.0 THz). Ammonium nitrate (AN), often used in improvised explosives, exhibits featureless reflection/transmission spectrum at THz frequencies at room temperature. However, the low frequency vibrational modes exhibit strong temperature dependence below room temperature (<240k) due to the polymorphic phase transitions. In this work, we study the effective dielectric properties of AN embedded in a polytetrafluoroethylene (PTFE) host medium using terahertz time domain spectroscopy in the temperature ranging from 5K to 300K. The dielectric properties of pure AN were extracted using three different effective medium theories (EMT): (i) the simple effective medium approach, (ii) the Maxwell-Garnett (MG) model, and (iii) the Bruggeman (BR) model. The dielectric properties obtained from theoretical approximations agree well with the experimental values. We identified six lattice vibrational modes between 0.2-3.0 THz that are associated with the polymorphic phase transitions at low temperature.

Terahertz (THz) spectroscopy and imaging were used to differentiate brain gliomas in a mouse model at different temperatures. The THz spectral difference between brain glioma and normal brain tissues at -10°C and 20°C was obtained in the 0.4-2.53 THz range. The absorption coefficient and refractive index values varied with both temperature and frequency. The fresh ex vivo brain glioma tissues were mapped by THz attenuated total reflection (ATR) imaging at 2.52 THz in the temperature range from -20°C to 35°C. Compared with histological examination, THz-ATR imaging could better display the tumor areas at a higher temperature. And the averaged reflectivity of normal tissue was increased with the increase of temperature, whereas the tumor region showed a decreasing trend. Thus, the larger THz imaging difference between glioma and normal tissues could be obtained. Moreover, in vivo brain gliomas in mouse models could also be differentiated clearly from normal brain tissues using THz-ATR imaging at 2.52 THz under room temperature. The THz-ATR images corresponded well with those of visual and hematoxylin and eosin (H&E) stained images. Therefore, this pilot study demonstrated that temperature dependence THz spectroscopy and imaging are helpful to the brain gliomas in mouse model detection.

Owing to the unique characteristics of terahertz (THz) waves and their interaction with matter, THz imaging has significant potential in diverse fields, including life sciences, non-destructive quality control, and security. However, today’s THz technology faces major obstacles in providing the cost, compactness, and functional scope that is required to facilitate a wide-reaching use outside the laboratory. Therefore, the general aim of this thesis is to increase the societal impact of THz technology by exploring novel THz imaging modalities with integrated circuits (ICs) based on conventional silicon technolgy. Previous research in THz ICs mostly focused on building compact integrated source and detector components for far-field imaging systems that exploit the ability of THz waves to penetrate through diverse dielectric materials. One part of this thesis joins this research and demonstrates low-cost volumetric THz imaging based on computed tomography with silicon components for the first time. To this end, a high-power 0.43 THz source in 0.13 μm silicon-germanium heterojunction bipolar transistor (SiGe HBT) technology is developed in this thesis. However, the resolution of THz far-field imaging is limited by diffraction to the millimeter range, whereas some of the most promising THz applications in life sciences, such as intraoperative imaging of cancerous tissue, are in need for a microscopic resolution to resolve material properties on the cellular level. This thesis presents the realization of microscopic THz imaging with a silicon-based sensor system. The central contribution of this work is the development and analysis of a 128-pixel THz near-field sensor System-on-a-Chip (SoC) operating at 0.55 THz and showing a spatial resolution around 10 μm. The sensor exploits the capacitive near-field interaction between split-ring-resonator probes and imaging objects, giving an imaging contrast based on the dielectric permittivity. To simultaneously enable real-time image acquisition, high sensor sensitivity, and an integration level that is comparable to conventional consumer electronics, the full integration capabilities of a high-speed 0.13 μm SiGe bipolar CMOS (SiGe-BiCMOS) technology are exploited. In particular, the presented SoC employs cointegration of a chip-scale one-dimensional THz sensor front-end, analog signal processing, and digital circuitry for controlling the chip and external communication. The achieved results in terms of imaging speed, system cost, and integration level reach well beyond the state of the art in THz near-field imaging. The ability to rapidly acquire THz images with micrometer-scale resolution will be of benefit to fundamental research into material properties in the THz range and lays the foundation for the exploration of THz bioimaging applications on the cellular level. In particular, the sensor enables the conduction of large-scale clinical studies on the relevance of microscopic THz imaging to ex vivo tumor margin assessment in breast cancer surgeries for the first time.

Investigations were initiated for developing a rapid and nondestructive detection method to measure the illegal additive of melamine into milk powder by using terahertz (THz) spectroscopy and the correlation analysis algorithm. The absorption coefficients exhibited a maximum absorption peak at 2.04 THz, which would normally increase along with the concentration of melamine additive. In the current study, correlation analysis was carried out to select a pair-variable at 2.04 and 2.34 THz for improving the predictive ability of the multiple linear regression (MLR) model. Compared with the partial least square (PLS) model in full spectrum, the MLR model for powder samples could be considered successful in terms of quality control of milk powder with correlation coefficient R2 of 0.97 and root mean square error of prediction (RMSEP) of 1.38%. At the same time, the MLR model was simple and easier to interpret than the PLS one. The results of the research suggested that THz spectroscopy in combination with the correlation analysis algorithm has a significant potential in the quantitative analysis of the illegal additive of melamine in milk powder.

Simple SummaryIn order to realize rapid and complete pre-screening in the pathological examination of gastric cancer and assist in quickly determining the boundary between cancerous and healthy cells, we developed a fast-scanning near-field terahertz (THz) imaging system. This imaging system is compact, low-cost, and easy to operate. THz examination does not need any processing after sectioning, and the diagnostic results are directly displayed in images within one minute. Compared with the H&E staining method, THz imaging diagnosis uses a quantitative absorption coefficient to distinguish cancer tissue and healthy tissue, which makes the automation of the tissue sampling pre-screening procedure possible and will save valuable time to help quickly define cancer tissue. At the same time, the spatial resolution of our near-field imaging system reaches λ/17. Using THz imaging to accurately define the margins of cancer can not only conserve healthy tissues but also minimize the number of second surgical procedures, which would save a lot of additional hospital resources.The distinguishable absorption contrast among healthy gastric tissues, carcinoma in situ and cancer tissues in the THz frequency range is one of the keys to realizing gastric cancer diagnosis by THz imaging. Based on microwave devices and a sub-wavelength fiber, we developed a fast-scanning THz imaging system combined with the principle of surface plasmon resonance enhancement. This imaging system has a near-field λ/17 spatial resolution and imaging S/N ratio as high as 108:1, and the image results are directly displayed within 1 min. We also successfully demonstrated the image diagnostic capability on sliced tissues from eight patients with gastric cancer. The results indicate that THz absorption images can not only clearly distinguish cancer tissue from healthy tissues but also accurately define the margins of cancer. Through a medical statistical study of 40 sliced tissues from 40 patients, we prove that THz imaging can be used as a standalone method to diagnose gastric cancer tissues with a diagnostic specificity and sensitivity of 100%. Compared with the H&E staining method, THz imaging diagnosis makes the automation of tissue-sampling pre-screening procedure possible and assists in quickly determining the boundary between cancerous and healthy tissues.

Metal-organic frameworks (MOFs) are porous crystalline materials. Their large pores make them particularly interesting for membranes, gas separation, and gas storage. Furthermore, MOFs are ultralight, making them suitable for a large realm of exciting applications ranging from wearable devices to space technology. Optimizing MOFs for these applications demands a detailed understanding of their low energy dynamics and photophysics, which can be provided by terahertz (THz) spectroscopy. MOFs exhibit structural modes, or phonons, with energies in the meV range, which corresponds to the THz spectral range (0.1–10 THz, 0.4–40 meV). Understanding these modes is crucial in determining how a MOF interacts with guest molecules in the process of gas capture and storage. In this perspective, we discuss how gas-MOF interactions alter the MOFs’ spectral fingerprints. We demonstrate that THz spectroscopy can be used for gas adsorption monitoring and explain how density functional theory, together with THz spectra, can illuminate the dynamic structure of MOFs, providing unique insight into their functionality. THz is also a contact free probe for conductivity and allows us to measure short range conductivity within an individual MOF crystal. We will discuss the advantages of THz as a conductivity probe for MOFs as compared to more established direct current techniques. We will then expand our view to incorporate ultrafast photoconductivity in MOFs measured via optical pump-THz probe spectroscopy, in comparison to more established ultrafast spectroscopic tools such as optical transient absorption and photoluminescence. We will supplement this section with a discussion of THz studies on perovskites, which unveiled electron–phonon interactions not yet explored in MOFs.