Terahertz refractive index-based morphological dilation for breast carcinoma delineation

 Cassar, Quentin, Samuel Caravera, Gaëtan MacGrogan, Thomas Bücher, Philipp Hillger, Ullrich Pfeiffer, Thomas Zimmer, Jean-Paul Guillet, and Patrick Mounaix. "Terahertz refractive index-based morphological dilation for breast carcinoma delineation." Scientific reports 11, no. 1 (2021): 1-16.

Abstract

This paper reports investigations led on the combination of the refractive index and morphological dilation to enhance performances towards breast tumour margin delineation during conserving surgeries. The refractive index map of invasive ductal and lobular carcinomas were constructed from an inverse electromagnetic problem. Morphological dilation combined with refractive index thresholding was conducted to classify the tissue regions as malignant or benign. A histology routine was conducted to evaluate the performances of various dilation geometries associated with different thresholds. It was found that the combination of a wide structuring element and high refractive index was improving the correctness of tissue classification in comparison to other configurations or without dilation. The method reports a sensitivity of around 80% and a specificity of 82% for the best case. These results indicate that combining the fundamental optical properties of tissues denoted by their refractive index with morphological dilation may open routes to define supporting procedures during breast-conserving surgeries.

for full paper see https://www.nature.com/articles/s41598-021-85853-8

.....Time-domain terahertz pulsed images were acquired with a TPS3000 spectrometer (TeraView Ltd, Cambridge, UK) operating in reflection geometry. In such systems, terahertz pulses are generated from the activation of a GaAs photoswitch.....

Enhanced dielectric and conductivity properties of carbon-coated SiC nanocomposites in the terahertz frequency range

 Huang, Feirong, Shuting Fan, Xiyang Li, Xinghao Qu, Yuqi Tian, Xuefeng Zhang, Zhidong Zhang, Xinglong Dong, and Tun Cao. "Enhanced dielectric and conductivity properties of carbon-coated SiC nanocomposites in the terahertz frequency range." Nanotechnology 32, no. 26 (2021): 265705.

Abstract

C-coated SiC nanocomposites (SiC@C NCs) were one-step synthesized under a mixture atmosphere of Ar and CH4 using a DC arc-discharge plasma method. The microstructure of the composites could be controlled by varying the volume ratio of Ar and CH4. A strong response to the terahertz (THz) field was observed due to the existence of a graphite shell. The dielectric properties of SiC@C NCs can be enhanced by altering the thickness of the graphite shell. The thicker graphite shell results in a stronger absorption of THz waves and an enhanced real part of conductivity. Fitting the measured conductivity data using the Drude–Smith model reveals that the carrier transport in the SiC@C NCs and its counterpart, the SiC nanoparticles, is dominated by backscattering. The SiC@C NCs with enhanced conductivity are believed to be fundamental materials for various functionalized optoelectronic devices.

for full paper see https://iopscience.iop.org/article/10.1088/1361-6528/abf070/meta

… Optical and dielectric properties of all the samples were characterized using a commercial THz- TDS system, TeraPulse 4000 (TeraView Ltd, Cambridge, UK) [15, 16], in transmission configuration which has a useable bandwidth extending from 0.06 to 4 THz …

TeraView @ IRMMW 2021 Chengdu

Please for listen to the following talks at the conference #IRMMW2021

17:45 Mo-PM2-5-5 5098030

Terahertz Waveform Selection Of A Pharmaceutical Film Coating Process Using Recurrent Network
Xiaoran Li1 ; Bryan Williams 2 ; Robert May 3 ; Michael Evans 3 ; Shuncong Zhong 4 ; Lynn Gladden 5 ; Axel Zeitler 5 ; Yaochun Shen 6 ; Hungyen Lin 1

1University of Lancaster, Engineering department, University of Lancaster, Lancaster, United Kingdom; 2University of Lancaster, Department of Computing and Communications, Lancaster, United Kingdom; 3TeraView Ltd, Enterprise Cambridge Research Park, Cambridge, United Kingdom; 4Fuzhou University, School of Mechanical Engineering and Automation, Fuzhou, China; 5University of Cambridge, Department of Chemical Engineering and Biotechnol, Cambridge, United Kingdom; 6University of Liverpool, Department of Electrical Engineering and Electron, Liverpool, United Kingdom

10:15 Th-AM-6-2 5103981 

Detecting Capacity Of THz Method Applied To Art Painting 
Olga Smolyanskaya 1 ; Sergey Sirro 2 ; Alexander Minin 3 ; Vyacheslav Toropov 3 ; Olga Kravtsenyuk 4 ; Anastasiya Lykina 4 ; Alessia Portieri5 ; Phil Taday 5 ; Donald Arnone 5 ; Jean-Paul Guillet 6 ; Vincent Detalle 7 ; Michel Menu 7 

1 ITMO University, Kronverksky Pr. 49, bldg. A, Saint-Petersburg, Russian Federation; 22The State Russian Museum, Inzhenernaya, 4, Saint-Petersburg, Russian Federation; 3The State Russian Museum, Inzhenernaya, 4, Saint-Petersburg, Russian Federation; 4 ITMO University, ITMO University, Saint-Petersburg, Russian Federation; 5TeraView, Cambridge Research Park, Cambridge C25 9PD, Cambridge, United Kingdom; 6Bordeaux University, 351 Cours de la libération, 33405 Talence, Bordeaux, France; 7C2RMF, 14 Quai François Mitterrand, Paris, France

Key Differences of the Hydrate Shell Structures of ATP and Mg· ATP Revealed by Terahertz Time-Domain Spectroscopy and Dynamic Light Scattering

 Penkov, Nikita V., and Nadezda Penkova. "Key Differences of the Hydrate Shell Structures of ATP and Mg· ATP Revealed by Terahertz Time-Domain Spectroscopy and Dynamic Light Scattering." The Journal of Physical Chemistry B 125, no. 17 (2021): 4375-4382.

Abstract

ATP is one of the main biological molecules. Many of its biological and physicochemical properties, such as energy capacity of the phosphate bonds, significantly depend on hydration. However, the structure of the hydration shell of the ATP molecule is still a matter of discussion. In this work, the hydration shells of ATP in water and MgCl2 solutions were examined by terahertz time-domain spectroscopy and dynamic light scattering. Terahertz spectroscopy reveals the distorted water structure in the ATP water solution displaying tightly bound water molecules, which could be explained by the hydration of phosphate groups. Upon ATP binding to a Mg2+ ion, the situation is principally different: Instead of the distorted water structure, its arranged structure with increased hydrogen bond number is observed. Dynamic light scattering showed that the hydrodynamic diameter of ATP increases by 0.5 nm after Mg2+ binding. Meanwhile, according the characteristics of scattering, the increase of the shell size occurs via formation of a layer with a refraction coefficient similar to water. This layer can be interpreted as hydration shell differing from unaltered water by increased number of hydrogen bonds.

for full paper see https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.1c02276

Possible Effect of Human-Experimenter on Homeopathic-Like Aqueous Preparations

Korenbaum, Vladimir, Tatiana Chernysheva, Victorya Galay, Roman Galay, Alexandr Ustinov, Sergei Zakharkov, and Nikolai Bunkin. "Possible Effect of Human-Experimenter on Homeopathic-Like Aqueous Preparations." Water 13, no. 11 (2021): 1475.

Abstract

Homeopathy is one of the applications in structured water influencing human health. The objective is to search for the physical basis of homeopathy. This methodology includes a study of absorption in the far IR spectral range, absorption and refraction in THz diapason, dynamic light scattering in the UV–near IR spectral range for the blinded samples of homeopathic-like preparations (HLP) of several parent substances and hidden/apparent controls, and statistical analysis on the significance of distinctions in spectral data between ensembles of HLP of each parent substance and ensembles of hidden/apparent controls. The analysis of nine independent blind studies of aqueous HLP of several parent substances gave statistically significant spectral differences in some preparations with an apparent control (25 comparisons of 35) and a hidden control (11 comparisons of 40). The revealed dominance in the occurrence frequency of differences in any HLP with an apparent control can be treated as involving most of these changes to the samples by the spectral measuring process. This allows interpreting the main mechanism of manifestation of the spectral changes found as the “observer effect”. The therapeutic effect of HLP may be assumed as a combination of the “observer effect” from the physician side and a “placebo effect” from the patient side

for full paper see https://doi.org/10.3390/w13111475

Application of terahertz pulses to solid dosage forms recent papers

 

Year	Ref	Paper title	Abstract
2021	[i]	Terahertz time-domain spectroscopy for powder compact porosity and pore shape measurements: An error analysis of the anisotropic bruggeman model	Terahertz time-domain spectroscopy (THz-TDS) is a novel technique which has been applied for pore structure analysis and porosity measurements. For this, mainly the anisotropic Bruggeman (AB-EMA) model is applied to correlate the effective refractive index (neff) of a tablet and the porosity as well as to evaluate the pore shape based on the depolarisation factor L. This paper investigates possible error sources of the AB-EMA for THz-TDS based tablet analysis. The effect of absorption and tablet anisotropy – changes of pore shape with porosity and density distribution – have been investigated. The results suggest that high tablet absorption has a negligible effect on the accuracy of the AB-EMA. In regards of tablet anisotropy the accuracy of the porosity determination is not impaired significantly. However, density distribution and variations in the pore shape with porosity resulted in an unreliable extraction of the tablet pore shape. As an extension of the AB-EMA a new concept was introduced to convert the model into bounds for L. This new approach was found useful to investigate tablet pore shape but also the applicability of the AB-EMA for an unknown set of data.
2021	[ii]	A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets	There is a clear need for a robust process analytical technology tool that can be used for on-line/in-line prediction of dissolution and disintegration characteristics of pharmaceutical tablets during manufacture. Tablet porosity is a reliable and fundamental critical quality attribute which controls key mass transport mechanisms that govern disintegration and dissolution behavior. A measurement protocol was developed to measure the total porosity of a large number of tablets in transmission without the need for any sample preparation. By using this fast and non-destructive terahertz spectroscopy method it is possible to predict the disintegration and dissolution of drug from a tablet in less than a second per sample without the need of a chemometric model. The validity of the terahertz porosity method was established across a range of immediate release (IR) formulations of ibuprofen and indomethacin tablets of varying geometries as well as with and without debossing. Excellent correlation was observed between the measured terahertz porosity, dissolution characteristics (time to release 50% drug content) and disintegration time for all samples. These promising results and considering the robustness of the terahertz method pave the way for a fully automated at-line/on-line porosity sensor for real time release testing of IR tablets dissolution.
2020	[iii]	Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial	Porosity, one of the important quality attributes of pharmaceutical tablets, directly affects the mechanical properties, the mass transport and hence tablet disintegration, dissolution and ultimately the bioavailability of an orally administered drug. The ability to accurately and quickly monitor the porosity of tablets during manufacture or during the manufacturing process will enable a greater assurance of product quality. This tutorial systematically outlines the steps involved in the terahertz-based measurement method that can be used to quantify the porosity of a tablet within seconds in a non-destructive and non-invasive manner. The terahertz-based porosity measurement can be performed using one of the three main methods, which are (i) the zero-porosity approximation (ZPA); (ii) the traditional Bruggeman effective medium approximation (TB-EMA); and (iii) the anisotropic Bruggeman effective medium approximation (AB-EMA). By using a set of batches of flat-faced and biconvex tablets as a case study, the three main methods are compared and contrasted. Overall, frequency-domain signal processing coupled with the AB-EMA method was found to be most suitable approach in terms of accuracy and robustness when predicting the porosity of tablets over a range of complexities and geometries. This tutorial aims to concisely outline all the necessary steps, precautions and unique advantages associated with the terahertz-based porosity measurement method.
2020	[iv]	Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis	Terahertz pulsed imaging (TPI) was introduced approximately fifteen years ago and has attracted a lot of interest in the pharmaceutical industry as a fast, non-destructive modality for quantifying film coatings on pharmaceutical dosage forms. In this topical review, we look back at the use of TPI for analysing pharmaceutical film coatings, highlighting the main contributions made and outlining the key challenges ahead.
2018	[v]	A quantitative comparison of in-line coating thickness distributions obtained from a pharmaceutical tablet mixing process using discrete element method and terahertz pulsed imaging	The application of terahertz pulsed imaging (TPI) in an in-line configuration to monitor the coating thickness distribution of pharmaceutical tablets has the potential to improve the performance and quality of the spray coating process. In this study, an in-line TPI method is used to measure coating thickness distributions on pre-coated tablets during mixing in a rotating pan, and compared with results obtained numerically using the discrete element method (DEM) combined with a ray-tracing technique. The hit rates (i.e. the number of successful coating thickness measurements per minute) obtained from both terahertz in-line experiments and the DEM/ray-tracing simulations are in good agreement, and both increase with the number of baffles in the mixing pan. We demonstrate that the coating thickness variability as determined from the ray-traced data and the terahertz in-line measurements represents mainly the intra-tablet variability due to relatively uniform mean coating thickness across tablets. The mean coating thickness of the ray-traced data from the numerical simulations agrees well with the mean coating thickness as determined by the off-line TPI measurements. The mean coating thickness of in-line TPI measurements is slightly higher than that of the off-line measurements. This discrepancy can be corrected based on the cap-to-band surface area ratio of the tablet and the cap-to-band sampling ratio obtained from ray-tracing simulations: the corrected mean coating thickness of the in-line TPI measurements shows a better agreement with that of the off-line measurements.
2018	[vi]	Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy	Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, Sa, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The Sa parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The Sa parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product.
2018	[vii]	A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging	Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets were imaged by TPI and the results were compared to X-ray microtomography. The terahertz pulse beam propagates through the tablets and is back-reflected at the interface between the MCC matrix and the coated pellets within the tablet causing a peak in the terahertz waveform. Cross-section images of the tablets were extracted at different depths and parallel to the tablet faces from 3D terahertz data to visualise the surface-near structure of the MUPS tablets. The images of the surface-near structure of the MUPS tablets were compared to X-ray microtomography images at the same depths. The surface-near structure could be clearly resolved by TPI at depths between 24 and 152 μm below the tablet surface. An increasing amount of pellets within the MUPS tablets appears to slightly decrease the detectability of the pellets within the tablets by TPI. TPI was shown to be a non-destructive method for the detection of pellets within the tablets and could resolve structures thicker than 30 μm. In conclusion, a proof-of-concept was provided for TPI as a method of quality control for MUPS tablets.
2017	[viii]	Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements	The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale.
2017	[ix]	On the role of API in determining porosity, pore structure and bulk modulus of the skeletal material in pharmaceutical tablets formed with MCC as sole excipient	The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties.

---

[i] Anuschek, Moritz, Prince Bawuah, and J. Axel Zeitler. "Terahertz time-domain spectroscopy for powder compact porosity and pore shape measurements: An error analysis of the anisotropic bruggeman model." International Journal of Pharmaceutics: X (2021): 100079.

 

[ii] Bawuah, Prince, Daniel Markl, Alice Turner, Mike Evans, Alessia Portieri, Daniel Farrell, Ralph Lucas, Andrew Anderson, Daniel J. Goodwin, and Axel Zeitler. "Data supporting'A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets'." (2021).

 

[iii] Bawuah, Prince, Daniel Markl, Daniel Farrell, Mike Evans, Alessia Portieri, Andrew Anderson, Daniel Goodwin, Ralph Lucas, and J. Axel Zeitler. "Terahertz-based porosity measurement of pharmaceutical tablets: a tutorial." Journal of Infrared, Millimeter, and Terahertz Waves (2020): 1-20.

 

[iv] Alves-Lima, Décio, Jun Song, Xiaoran Li, Alessia Portieri, Yaochun Shen, J. Axel Zeitler, and Hungyen Lin. "Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis." Sensors 20, no. 5 (2020): 1441.

 

[v] Pei, Chunlei, Hungyen Lin, Daniel Markl, Yao-Chun Shen, J. Axel Zeitler, and James A. Elliott. "A quantitative comparison of in-line coating thickness distributions obtained from a pharmaceutical tablet mixing process using discrete element method and terahertz pulsed imaging." Chemical Engineering Science 192 (2018): 34-45.

 

[vi] Markl, Daniel, Prince Bawuah, Cathy Ridgway, Sander van den Ban, Daniel J. Goodwin, Jarkko Ketolainen, Patrick Gane, Kai-Erik Peiponen, and J. Axel Zeitler. "Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy." International journal of pharmaceutics 537, no. 1-2 (2018): 102-110.

 

[vii] Novikova, Anna, Daniel Markl, J. Axel Zeitler, Thomas Rades, and Claudia S. Leopold. "A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging." European Journal of Pharmaceutical Sciences 111 (2018): 549-555.

 

[viii] Markl, Daniel, Johanna Sauerwein, Daniel J. Goodwin, Sander van den Ban, and J. Axel Zeitler. "Non-destructive determination of disintegration time and dissolution in immediate release tablets by terahertz transmission measurements." Pharmaceutical research 34, no. 5 (2017): 1012-1022.

 

[ix] Ridgway, Cathy, Prince Bawuah, Daniel Markl, J. Axel Zeitler, Jarkko Ketolainen, Kai-Erik Peiponen, and Patrick Gane. "On the role of API in determining porosity, pore structure and bulk modulus of the skeletal material in pharmaceutical tablets formed with MCC as sole excipient." International journal of pharmaceutics 526, no. 1-2 (2017): 321-331.

 

Supervised Bayesian learning for breast cancer detection in terahertz imaging

 Chavez, Tanny, Nagma Vohra, Keith Bailey, Magda El-Shenawee, and Jingxian Wu. "Supervised Bayesian learning for breast cancer detection in terahertz imaging." Biomedical Signal Processing and Control 70 (2021): 102949.

Abstract

This paper proposes a supervised multinomial Bayesian learning algorithm for breast cancer detection using terahertz (THz) imaging of freshly excised murine tumors. The proposed algorithm utilizes a multinomial Bayesian probit regression approach, which establishes the link between THz data and classification results by using two different models, a polynomial regression model and a kernel regression model. Such a model-based learning approach employs only a small number of model parameters, thus it requires much less training data when compared with alternative deep learning methods. The training phase of the algorithm is performed by using the histopathology results of formalin-fixed, paraffin embedded (FFPE) samples as ground truth. There is usually a considerable shape mismatch between the freshly excised sample and its FFPE counterpart due to sample dehydration, and such mismatch negatively impacts the quality of the training data. We propose to address this challenge by using an innovative reliability-based training data selection method, where the reliability of the training data is quantified and estimated by using an unsupervised expectation maximization (EM) classification algorithm with soft probabilistic output. Experiment results demonstrate that the proposed multinomial Bayesian probit regression models with reliability-based training data selection achieve better performance than existing methods. Overall, these results demonstrate that the proposed supervised segmentation models represent a promising technique for the region detection with THz imaging of freshly excised breast cancer samples.

… The TPS Spectra 3000 THz pulse reflection imaging system (TeraView, Ltd., UK) at the University of Arkansas was used [26]. ...

for full paper see https://www.sciencedirect.com/science/article/abs/pii/S1746809421005462

Investigating the low-frequency vibrations of chlorophyll derivatives using terahertz spectroscopy

Coquillat, Dominique, Emma O'Connor, Etienne V. Brouillet, Yoann Meriguet, Cedric Bray, David J. Nelson, Karen Faulds, Jeremie Torres, and Nina Dyakonova. "Investigating the low-frequency vibrations of chlorophyll derivatives using terahertz spectroscopy." In Terahertz Emitters, Receivers, and Applications XII, vol. 11827, p. 118270F. International Society for Optics and Photonics, 2021.

Abstract

The terahertz absorption spectra of sodium magnesium chlorophyllin (Chl-Mg-Na) and sodium copper chlorophyllin (Cu-Chl), two major members of the chlorophyll derivative family, have been measured in the range 0.2−3.0 THz (6.6−100 cm^-1), at room temperature. Additionally, surface-enhanced Raman scattering spectroscopy was used to supplement data in the higher frequency range. The capability of terahertz spectroscopy for quantitative characterization of Chl-Mg-Na intermolecular vibrations was investigated and the sensitivity of the 1.82-THz feature with degree of hydration by changes in the molecular environment was examined. For Cu-Chl derivative, a broad feature was observed around 1.8 THz which currently hinders clear Cu-Chl identification and quantification.

for full paper see https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11827/118270F/Investigating-the-low-frequency-vibrations-of-chlorophyll-derivatives-using-terahertz/10.1117/12.2593589.short?SSO=1

… The maximum laser power was 40 mW and the average scan time 1 s. The THz-TDS spectra were acquired using a commercial TeraPulse 4000 instrument across the spectral range of 0.1-3.5 THz (TeraView Ltd …

TeraView and ACE Solution receives the first order of EOTPR system

TeraView is pleased to announce a sale of the Company’s proprietary Electro Optical Terahertz Pulse Reflectometry (EOTPR) Platform to a leading independent failure analysis lab in Taiwan, through TeraView’s Taiwanese distributor ACE Solution. The EOTPR technology has been sold to many FA labs of leading semiconductor companies and OSATs around the world, but this is the first time an independent FA lab has purchased the technology.

Mr. Steve Hsu, CEO of ACE Solution commented on the sale: “We are pleased to offer the EOTPR technology to another fine Taiwanese technology company as part of ACE Solution’s portfolio of advanced technology offering. We have been working closely with TeraView to ensure that our customers are well supported in Taiwan.”

Dr Don Arnone, Chief Executive Officer of TeraView, commented: “Selected by a leading independent FA lab, this EOTPR purchase signifies that the EOTPR technology is recognized as not only a productive technology but also it helps our customers to be more profitable. We are also pleased to increase our installation base in Taiwan.”

Martin Igarashi, TeraView’s Vice President of Semiconductor Business, further added “This EOTPR 3000 system sale to a major independent FA lab has a significant meaning to TeraView and the failure analysis industry since the EOTPR technology is recognized as a de-facto industry standard in advanced IC package fault isolation solution, and it is proof that independent FA labs can use the technology to promote their business.”

About EOTPR

Boasting a 5 µm fault isolation accuracy, TeraView developed the Electro Optical Terahertz Pulse Reflectometry (EOTPR) technology with Intel and launched in 2010. This product has been accepted by the semiconductor packaging industry as the de-facto standard for isolating faults in the advanced IC packages, and TeraView has shipped many systems around the world to major semiconductor and OSAT companies since its inception.

About TeraView

Founded in 2001, TeraView (https://teraview.com/) is the world’s first and leading company solely focused on the application of terahertz light to provide solutions to customer issues. A spin out from the Toshiba Corporation and Cambridge University, TeraView has developed its proprietary technology across a number of markets. These include fault analysis and quality assurance for semiconductor chips used in mobile computing and communications, as well as non-destructive inspection of high value coatings used in the automotive, pharmaceutical, food and solar industries. With the largest number of systems in the field, as well as applications know-how made available to customers via a team of dedicated scientists using intellectual property and knowledge in peer-reviewed scientific publications, TeraView is uniquely placed to deliver the business benefits of terahertz to customers. Headquartered in Cambridge UK, sales and customer support are available throughout the Far East, North America and Europe either directly or through a network of distributors.

For more information please click here

About ACE Solution

Founded in 2000, ACE Solution is located in Hsinchu City, Taiwan with branch offices in Suzhou and Shenzhen in China. Our mission is to provide customized test solutions to meet customer needs in electrical components, devices and system manufactures, as well as providing technology solutions through our partners. We are focused on RF, mmWave and terahertz with the expert technical support team. ACE Solution provides professional, innovative and multi-functional integrated techniques and solutions.

ACE Solution’s web site can be found here.

Continuously tunable intensity modulators with large switching contrasts using liquid crystal elastomer films that are deposited with terahertz metamaterials

 Chiang, Wei-Fan, Harry Miyosi Silalahi, Yu-Chih Chiang, Mi-Chia Hsu, Yan-Song Zhang, Jui-Hsiang Liu, Yanlei Yu, Chia-Rong Lee, and Chia-Yi Huang. "Continuously tunable intensity modulators with large switching contrasts using liquid crystal elastomer films that are deposited with terahertz metamaterials." Optics Express 28, no. 19 (2020): 27676-27687.

For full paper see: https://www.osapublishing.org/DirectPDFAccess/697A3814-1A2D-47DD-B931C558EE48A56E_437870/oe-28-19-27676.pdf?da=1&id=437870&seq=0&mobile=no

Abstract 

A liquid crystal elastomer (LCE) film is successfully deposited with a terahertz metamaterial using thermal evaporation via a programmed electronic shutter and high-efficiency cooling system. The transmittance of the metamaterial at its resonance frequency is monotonically increased from 0.0036 to 1.0 as a pump beam bends the LCE film, so the metamaterial has a large switching contrast of 277 at the frequency. The monotonic increase in the resonance transmittance arises from the constant resonance frequency of the metamaterial at the transmittance modulation and depicts that the metamaterial-deposited LCE film can continuously tune the transmitted intensity of a terahertz beam. The metamaterial-deposited LCE film has potential in developing continuously tunable intensity modulators with large switching contrasts for the application of terahertz imaging and terahertz communication. Therefore, the thermal evaporation expands the application of metamaterials and improves their optical properties.

......The metal plate with the metamaterial-deposited LCE film and pump laser are placed in the chamber of a terahertz spectrometer (TPS 3000, TeraView) for studying the effect of the bending of the film on the resonance transmittance of the metamaterial..... 

BaSrTiO3 ceramic-polymer composite material lens antennas at 220–330 GHz telecommunication applications

 Myllymäki, S., M. Teirikangas, and M. Kokkonen. "BaSrTiO3 ceramic-polymer composite material lens antennas at 220–330 GHz telecommunication applications." Electronics Letters 56, no. 22 (2020): 1165-1167.

for full paper see https://digital-library.theiet.org/content/journals/10.1049/el.2020.1875

Abstract 

Ceramic (Ba_0.55Sr_0.45Ti_1.01O₃) – polypropylene polymer ER182 composites-based materials were applied for sub-THz range antenna lens application in telecommunications. Typical plano-convex -shaped lenses were simulated and measured with a standard rectangular waveguide at 220–330 GHz frequency band and applied on 150 mm on-air distance. The lens fabricated with ER182 polymer material increased the signal strength by 15 dB, ER182/7 vol% BST by 6 dB and ER182/30 vol% BST by −23 dB. Material loss tangent values were 0.008 for ER182, 0.034 for ER182/7%BST and 0.081 for ER182/30%BST. The directivity of ER182 material lens and WR3 waveguide combination was 26 dBi at 300 GHz.

… The BST was selected as filler due to its high relative permittivity with moderately low losses at high frequencies. The dielectric properties of the fabricated material samples were measured with TeraView TPS Spectra 3000 THZ spectroscopy equipment …

Terahertz Birefringence and Dichroism of KTA Crystal

 Huang, Jingguo, Yang Li, Yanqing Gao, Zhiming Huang, Nazar Nikolaev, Alexander Mamrashev, Grigory Lanskii, and Yury Andreev. "Terahertz birefringence and dichroism of KTA crystal." Crystals 10, no. 9 (2020): 730.

for full paper see https://www.mdpi.com/2073-4352/10/9/730

Abstract

For the first time, we present the spectra of all three components of the refractive index and absorption coefficient of the KTiOAsO4 (KTA) crystal measured by the means of terahertz time-domain spectroscopy in the range of 0.3–2.1 THz. The dispersion of the refractive index is approximated and presented in the form of the Sellmeier equation. We observe a large birefringence ∆nZ-X ≈ 0.76 and dichroism which is attributed to a strong absorption peak in the vicinity of ~1.23–1.25 THz for the Z-axis. However, the crystal can be considered as almost uniaxial due to a close value of nX and nY as well as αX ≈ αY in the region below 0.5 THz. Moreover, KTA crystals can satisfy the phase-matching condition in principal XZ-plane for THz emission on difference frequency generation mechanism. Therefore, the crystal could be considered as an efficient candidate for terahertz wave generator under intense laser pump. 

.....The polarized transmission spectra in the terahertz range were carried out via terahertz time-domain spectrometer (THz-TDS) TeraPulse 4000 (TeraView, Cambridge, UK) at the temperature of 17 ◦C......

Non-destructive quantification of fragmentation within tablets after compression from scattering analysis of terahertz transmission measurements

Skelbæk-Pedersen, Anne Linnet, Moritz Anuschek, Thomas Kvistgaard Vilhelmsen, Jukka Rantanen, and J. Axel Zeitler. "Non-destructive quantification of fragmentation within tablets after compression from scattering analysis of terahertz transmission measurements." International Journal of Pharmaceutics 588 (2020): 119769.

for full paper see https://www.sciencedirect.com/science/article/abs/pii/S0378517320307535

Abstract

Material deformation behaviour has a critical impact on tablet formation. Fragmentation is one of the key mechanisms affecting the strength of a final compact, however, quantitative methods for estimating fragmentation are often complex, destructive and time-consuming. The purpose of this study was to investigate the applicability of terahertz time-domain spectroscopy (THz-TDS) to quantify fragmentation upon tableting. Up to five size fractions of microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP), and lactose monohydrate (lactose) in the range of <125 µm up to the range of 355–500 µm were compressed into tablets and analysed with THz-TDS. The effective refractive index and absorbance spectra of whole tablets were measured in transmission, and the optical properties were clearly affected by fragmentation upon compression. The scattering observed from the absorbance spectra was fitted into a power law equation (y = AνB). It was observed that up to pressures of 50 MPa the values of parameter A that were extracted from the power law fit decreased exponentially with increasing compression pressure. For higher compression pressures the value of A remained constant. This observation was more pronounced for DCP, followed by lactose and then MCC and the effect was more pronounced for larger compared to smaller initial particles. The non-destructive measurements correlated with previously obtained results based on particle size distribution measurements of the particles before compression and those obtained from destructive analysis of tablets. The terahertz method can resolve similar differences in fragmentation behaviour upon compression compared to the particle size analysis but requires no sample preparation.

Terahertz time domain spectroscopy (THz-TDS). Terahertz time-domain spectroscopy (THz-TDS) measurements were acquired in a transmission setup using a Terapulse 4000 spectrometer (Teraview Ltd., Cambridge, UK) … 

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Dielectric ordering of water molecules arranged in a dipolar lattice

Belyanchikov, M. A., M. Savinov, Z. V. Bedran, P. Bednyakov, P. Proschek, J. Prokleska, V. A. Abalmasov et al. "Dielectric ordering of water molecules arranged in a dipolar lattice." Nature communications 11, no. 1 (2020): 1-9.

for full paper see https://www.nature.com/articles/s41467-020-17832-y

Abstract

Intermolecular hydrogen bonds impede long-range (anti-)ferroelectric order of water. We confine H2O molecules in nanosized cages formed by ions of a dielectric crystal. Arranging them in channels at a distance of ~5 Å with an interchannel separation of ~10 Å prevents the formation of hydrogen networks while electric dipole-dipole interactions remain effective. Here, we present measurements of the temperature-dependent dielectric permittivity, pyrocurrent, electric polarization and specific heat that indicate an order-disorder ferroelectric phase transition at T0 ≈ 3 K in the water dipolar lattice. Ab initio molecular dynamics and classical Monte Carlo simulations reveal that at low temperatures the water molecules form ferroelectric domains in the ab-plane that order antiferroelectrically along the channel direction. This way we achieve the long-standing goal of arranging water molecules in polar order. This is not only of high relevance in various natural systems but might open an avenue towards future applications in biocompatible nanoelectronics.

A time-domain TeraView 3000 terahertz spectrometer was employed to determine the dielectric spectra up to few terahertz. 

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Defect Localization in Through-Si-Interposer Based 2.5D ICs

Gourikutty, Sajay Bhuvanendran Nair, Yew Meng Chow, Jesse Alton, Ratan Bhimrao Umralkar, Haonan Bai, Kok Keng Chua, and Surya Bhattacharya. "Defect localization in through-Si-interposer based 2.5 D ICS." In 2020 IEEE 70th Electronic Components and Technology Conference (ECTC), pp. 1180-1185. IEEE, 2020.

for full paper see  https://ieeexplore.ieee.org/abstract/document/9159199

Abstract:

Advanced packaging solutions using Through Silicon Interposers (TSI) are an attractive option to create 2.5D ICs. In many applications such as GPU and FPGA, 2.5D ICs can overcome the power, performance, and form-factor limitations of traditional IC packages. Investigating yield-loss and reliability mechanisms of such packages is made particularly challenging by the multitude of possible failure locations such as in TSV, micro-bumps, underfill, solder ball joints and RDL layers. Existing electrical and physical failure analysis tools do not have adequate resolution to accurately localize the failure in 2.5D IC. In this paper, we present a non-destructive methodology to carry out the failure analysis by localizing the defects which are entirely internal to the package and inaccessible from the exterior. In a through silicon interposer based FPGA package, a short failure has been successfully located with an accuracy of less than 10μm without the need for any sample preparation. The testing, fault localization and physical failure analysis of advanced package demonstrated here will provide a cost-effective method for improving manufacturing yield.

Crystal Structure-Free Method for Dielectric and Polarizability Characterization of Crystalline Materials at Terahertz Frequencies

Zhang, Tianyao, Zhaohui Zhang, and Mark A. Arnold. "Crystal Structure-Free Method for Dielectric and Polarizability Characterization of Crystalline Materials at Terahertz Frequencies." Applied Spectroscopy 75, no. 6 (2021): 647-653.

for full paper see https://journals.sagepub.com/doi/abs/10.1177/0003702821991594

Abstract

Terahertz (THz) time-domain spectroscopy provides a direct and nondestructive method for measuring the dielectric properties of materials directly from the phase delay of coherent electromagnetic radiation propagating through the sample. In cases when crystals are embedded within an inert polymeric pellet, the Landau, Lifshitz, and Looyenga (LLL) effective medium model can be used to extract the intrinsic dielectric constant of the crystalline sample. Subsequently, polarizability can be obtained from the Clausius–Mossotti (CM) relationship. Knowledge of the crystal structure density is required for an analytical solution to the LLL and CM relationships. A novel crystal structure-free graphical method is presented as a way to estimate both dielectric constants and polarizability values for the situation when the crystal structure density is unknown, and the crystals are embedded within a pellet composed of a non-porous polymer. The utility of this crystal structure-free method is demonstrated by analyzing THz time-domain spectra collected for a set of amino acids (L-alanine, L-threonine, and L-glutamine) embedded within pellets composed of polytetrafluoroethylene. Crystal structures are known for each amino acid, thereby enabling a direct comparison of results using the analytical solution and the proposed crystal structure-free graphical method. For each amino acid, the intrinsic dielectric constant is extracted through the LLL effective medium model without using information of their crystal structure densities. THz polarizabilities are then calculated with the CM relationship by using the determined intrinsic dielectric constant for each amino acid coupled with its crystal density as determined graphically. Comparison between the analytical and graphical solutions reveal relative differences between dielectric constants of 3.7, 5.1, and 13.6% for threonine, alanine, and glutamine, respectively, and relative differences between polarizability of 0.6, 0.9, and 5.4%, respectively. These values were determined over the 10–20 cm⁻¹ THz frequency range. The proposed method requires no prior knowledge of crystal structure information.