Volume 72, Issue 3-4 - Special Issue: ESSENCE

Breath gas analysis is a promising non-invasive tool for medical diagnosis as there are thousands of Volatile Organic Compounds (VOCs) in human breath that can be used as health monitoring markers. Millimeter-wave/terahertz molecular spectroscopy is highly suitable for breath gas analysis due to unique fingerprint spectra of many VOCs in that frequency range. We present our recent work on sensor systems for gas spectroscopy based on integrated transmitters (TX) and receivers (RX) fabricated in IHP’s 0.13 μm SiGe BiCMOS technology. For a single-band system, spectroscopic measurements and beam profiles are presented. The frequency is tuned by direct voltage-frequency tuning and by a fractional-n PLL, respectively. The spectroscopic system includes a folded gas absorption cell with gas pre-concentration abilities demonstrating the detection of a 50 ppm mixture of ethanol in ambient air corresponding to a minimum detectable concentration of 260 ppb. Finally, the design of a 3-band system covering frequencies from 225 to 273 GHz is introduced.

Breast Cancer is one of the most frequently diagnosed cancer diseases worldwide, and the most common invasive tumour for women. As with all cancers, early detection plays a major role in reducing the mortality and morbidity rate. Currently, most breast cancers are detected due to clinical symptoms, or by screening mammography. The limitations of these techniques have resulted in research of alternative methods for imaging and detecting breast cancer. Apart from this, it is essential to define precise tumour margins during breast-conserving surgeries to reduce the re-excision rate. This study presents the advances in the development of a silicon-based THz sub-wavelength imager usable in life science applications, especially for tumour margin identification.

Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) for which adequate therapeutic and diagnostic measures are still lacking. Causative agent of HAT is the African trypanosome, a single-cell parasite, which propagates in the blood and cerebrospinal fluid of infected patients. Although different testing methods for the pathogen exist, none is robust, reliable and cost-efficient enough to support large-scale screening and control programs. Here we propose the design of a new sensor-type for the detection of infective-stage trypanosomes. The sensor exploits the highly selective binding capacity of nucleic acid aptamers to the surface of the parasite in combination with passive sensor structures to allow an electromagnetic remote read-out using terahertz (THz)-radiation. The short wavelength provides a superior interaction with the parasite cells than longer wavelengths, which is essential for a high sensitivity. We present two different sensor structures using both, micro- and nano-scale elements, as well as different measurement principles.

A Terahertz protein sensing concept based on subwavelength Ge resonators is presented. Ge bowtie resonators, compatible with CMOS fabrication technology, have been designed and characterized with a resonance frequency of 0.5 THz and calculated local intensity enhancement of 10.000. Selective biofunctionalization of Ge resonators on Si wafer was achieved in one step using lipoic acid-HaloTag ligand (LA-HTL) for biofunctionalization and passivation. The results lay the foundation for future investigation of protein tertiary structure and the dynamics of protein hydration shell in response to protein conformation changes.

In this work three disciplines – microfluidics, microbiology and microwave engineering – are utilized to develop a system for analyzing subpopulations of biofilms and their reaction to antibiotic treatment. We present handling strategies to destabilize a biofilm inside a microfluidic system down to aggregate sizes of<10 µm 2 as well as microfluidic structures for the flow-through filtration of the resulting cell suspensions. For the analysis of the cell populations by microwave electrical impedance spectroscopy, two novel calibration schemes are demonstrated to cover both, reflection as well as transmission measurements of dielectric fluids. The broadband calibration strategies are solely based on liquid standards and allow a precise long-term monitoring with a resolution up to  Δε=6 ${\text{ }}\Delta \varepsilon = 6$ ‰, while the error is kept below Δ=1.5 $\Delta = 1.5$ ‰ at 5 GHz ${\ }5{\ }{\rm GHz}$. Combining these three research topics therefore will open up new ways for analyzing biofilm effects.

Radio-frequency fields in the GHz range are increasingly applied in biotechnology and medicine. In order to fully exploit both their potential and their risks detailed information about the dielectric properties of biological material is needed. For this purpose a measuring system is presented that allows the acquisition of complex dielectric spectra over 4 frequency decade up to 110 GHz. Routines for calibration and for data evaluation according to physicochemical interaction models have been developed. The frequency dependent permittivity and dielectric loss of some proteins and nucleic acids, the main classes of biomolecules, and of their sub-units have been determined. Dielectric spectra are presented for the amino acid alanine, the proteins lysozyme and haemoglobin, the nucleotides AMP and ATP, and for the plasmid pET-21, which has been produced by bacterial culture. Characterisation of a variety of biomolecules is envisaged, as is the application to studies on protein structure and function.

The concept of a novel dual-mode microwave applicator for diagnosis and thermal ablation treatment of tumorous tissue is presented in this paper. This approach is realized by integrating a planar resonator array to, firstly, detect abnormalities by a relative dielectric analysis, and secondly, perform a highly localized thermal ablation. A further essential advantage is addressed by designing the applicator to be MRI compatible to provide a multimodal imaging procedure. Investigations for an appropriate frequency range lead to the use of much higher operating frequencies between 5 GHz and 10 GHz, providing a significantly lower power consumption for microwave ablation of only 20 W compared to commercial available applicators.

Millimeter-wave imaging is a promising technology for diagnosing skin burns, that may make it easier to assess and determine the burn depth in the near future. However, up to now, it has not yet been brought to clinical use due to the lack of clinical trails on patients and a millimeter-wave-aided classification of skin burns. In this paper, in a preliminary step, ex-vivo burned porcine skin is utilized to visualize and quantify skin that has been burned in different ways, and to access its effect on millimeter-wave images. For the first time, a 24 hour study of in-vivo human skin visualizes the effect of wound dressings using a fast imaging system operating at frequencies from 70 to 80 GHz. For validation, the effective relative permittivity of the skin and the dressings are measured using a open-ended coaxial probe. An analytical model is applied to calculate the reflection coefficient which are compared to the intensity of the millimeter-wave images to validate the model.

The aim of this article is to give a broad overview of current methods for the identification and quantification of the human dehydration level. Starting off from most common clinical setups, including vital parameters and general patients’ appearance, more quantifiable results from chemical laboratory and electromagnetic measurement methods will be reviewed. Different analysis methods throughout the electromagnetic spectrum, ranging from direct current (DC) conductivity measurements up to neutron activation analysis (NAA), are discussed on the base of published results. Finally, promising technologies, which allow for an integration of a dehydration assessment system in a compact and portable way, will be spotted.