Research into terahertz technology is now receiving increasing attention around the world, and devices exploiting this waveband are set to become increasingly important in a very diverse range of applications. Here, an overview of the status of the technology, its uses and its future prospects are presented.

Cutting-edge terahertz technology

Terahertz spectroscopy systems use far-infrared radiation to extract molecular spectral information in an otherwise inaccessible portion of the electromagnetic spectrum. Materials research is an essential component of modern terahertz systems: novel, higher-power terahertz sources rely heavily on new materials such as quantum cascade structures. At the same time, terahertz spectroscopy and imaging provide a powerful tool for the characterization of a broad range of materials, including semiconductors and biomolecules.

Materials for terahertz science and technology

1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4

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Cell-free nucleic acids as biomarkers in cancer patients

During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA - arguably the most clinically advanced approach.

Integrating liquid biopsies into the management of cancer

Terahertz irradiation and sensing is being applied for the first time to a wide range of fields outside the traditional niches of space science, molecular line spectroscopy, and plasma diagnostics. This paper surveys some of the terahertz measurements and applications of interest in the biological and medical sciences.

Terahertz technology in biology and medicine

The invention relates to a method for detecting a polynucleotide sequence A in a sample containing a plurality of identical or different polynucleotide sequences X in the form of individual strands. The polynucleotide sequence A can be identical to one of the polynucleotide sequences X or can be contained in one of the polynucleotide sequences X in the form of a sequence segment. The method determines the binding status of the polynucleotide sequences X contained in the sample in relation to a known test polynucleotide sequence B which is complementary to polynucleotide sequence A; and comprises the following steps: preparing a test medium which contains test polynucleotide sequences B which are complementary to the polynucleotide sequence A to be detected, in the form of individual strands; and bringing the sample into contact with the test medium by introducing the sample into the test medium or applying the sample to the test medium, so that the individual strands of the polynucleotide sequences X contained in the sample can bind to the complementary test polynucleotide sequences B contained in the test medium. The following step c) is carried out in order to detect the binding of the polynucleotide sequences X to the test polynucleotide sequences B: determining at least one component of the complex index of refraction or an equivalent variable of the sample in contact with the test medium using interaction with incident electromagnetic radiation with a frequency of between 0.1 terahertz (THz) and 20 THz, preferably between 1 THz and 10 THz and then analyzing the properties of the electromagnetic radiation after the interaction, especially in terms of the time or phase delay, absorption, refraction or dispersion of the incident electromagnetic radiation caused by the interaction.

Method for detecting polynucleotide sequences

Thromboemoblism is the most feared complication of atrial fibrillation. Percutaneous left atrial appendage occlusion is a new interventional procedure for reducing thromboembolic risk in patients with atrial fibrillation. The paper reports of a post mortem analysis of the device demonstrating that one year after implantation the atrial surface of the device is completely covered by neo-endothelium and the device occludes the appendage completely.

Post mortem analysis of a left atrial appendage occlusion device (PLAATO) in a patient with permanent atrial fibrillation.

Extraskeletal osteosarcoma (EOS) is a highly aggressive and exceedingly rare mesenchymal tumor. Due to the rare nature of the disease, the diagnosis can be difficult and is often confirmed only after diagnostic laparotomy and histopathology. We describe the clinical history, radiologic and histomorphologic presentation, and clinical management of a 61-year-old patient who presented with abdominal pain. Abdominal ultrasound and computerized tomography (CT) scan revealed a calcified intra-abdominal mass. Following an explorative laparotomy, histology showed a large extraosseous osteosarcoma of the small bowel mesentery. Therapy according to the Cooperative Sarcoma Study-96 (COSS-96) was commenced. Diagnosis, management, and outcome in the context of the current literature are discussed. To our knowledge, this is the first description of an extraosseous osteosarcomas in the small bowel mesentery in the literature.

Extraosseous osteosarcoma arising from the small intestinal mesentery.

Hintergrund
Inflammatorische fibroide Polypen (IFP) sind Proliferationen CD34-positiver Spindelzellen vor einem inflammatorischen Hintergrund in der Submukosa und Mukosa des Gastrointestinaltrakts. IFP kommen vor allem im Magen, aber auch im Dunndarm, Kolon und Osophagus vor. Atiologie und Pathogenese sind bislang unklar.

Inflammatorische fibroide Polypen sind echte Neoplasien mit PDGFRA-Mutationen

We present a new approach for the label-free characterization of genetic material. Time-resolved THz transmission analysis of polynucleotides demonstrates a strong dependence of the complex refractive index on the binding state (hybridized / denatured) of DNA molecules. By monitoring THz transients one can thus infer the binding state of oligo-and polynucleotides. A broadband experimental demonstration in a free-space configuration is presented. The integration into higher-sensitivity approaches in planar structures, as well as the potential application for next generation gene chips are discussed.

Reinhard Büttner

Papers

Method for detecting polynucleotide sequences

Post mortem analysis of a left atrial appendage occlusion device (PLAATO) in a patient with permanent atrial fibrillation.

Extraosseous osteosarcoma arising from the small intestinal mesentery.

Inflammatorische fibroide Polypen sind echte Neoplasien mit PDGFRA-Mutationen

Label-free probing of the binding state of DNA by time-domain THz sensing