Priority Program ESSENCE SPP1857

The Senate of the „Deutsche Forschungsgesellschaft, DFG“ (German Research Foundation) has decided to fund the Priority Program “Elektromagnetische Sensoren für Life Sciences: Neuartige Sensorkonzepte und Technologien für biomedizinische Analytik und Diagnostik, Prozess- und Umweltmonitoring” (Electromagnetic Sensors for Life Sciences: New sensor concepts and technologies for biomedical analysis and diagnostics, process- and environmental monitoring), SPP1857, acronym: ESSENCE. The program is designed to run for six years, consisting of two funding periods of three years each.

The central idea of the Priority Program ESSENCE is to establish interdisciplinary research in the field of electromagnetic sensors, whose principle of sensing or measurement is based on the interaction between the electromagnetic fields of the sensor and the matter to be detected or analyzed with a special focus in life sciences. The matter of interest could be biomolecules, cells, tissues and organs or other parts of the body of animals or humans in biology and medicine as well as materials, chemical substances and mixtures of it in pharmacology, food chemistry, agricultural engineering, environmental analysis and monitoring. Therefore, senor elements at micro-, millimeter- and THz waves are very promising because of their high-performance potential, combining a high sensitivity, good penetration and spatial resolution as well as marker- and reactionless operation.

According to an IUPAC definition, a biosensor, in contrast to biotic sensors or bio-tests, is a self-contained, integrated receptor-transducer device, which is capable of providing selective quantitative or semi-quantitative analytical information, using a combination of biological recognition element (bio-receptor) and a transducer. Transducer based on electrochemical, electrical, optical and piezoelectric principles are well established since years, and their development has been pushed to physical limits, concerning their sensitivity and spatial resolution. An example for the static and low frequency electrical methods are the ampero-, potentio- and conductometry. These approaches have difficulties with the necessary sensitivity to detect pathogenic agents in complex matrices like blood. On the other hand, methods based on optical techniques evaluate the change of the index of refraction, spectroscopic properties or fluorescence effects. The use of fluorescence markers leads to additional preparation times and often does not offer the necessary sensitivity due to bleaching effects. Electromagnetic sensors at micro-, millimeter- and THz-waves offer possibilities to overcome some of these limitations. They combine a high sensitivity, good spatial resolution and marker- and reactionless operation. So far, they have been studied only rudimentary, but they are very promising, since in this region of the electromagnetic spectrum, many frequency-specific electromagnetic effects can be observed on a molecular and cellular level, for example due to the resonances of weak chemical bonds such as hydrogen bonds, which show resonance effects in the THz region. Since they play an important role in the folding process of proteins, conformal changes of proteins can be identified as specific resonance in the THz spectrum.

Compared to low frequency methods like Ampero-/Potentiometry based on electric and electrochemical transducers, electromagnetic sensors can offer a higher sensitivity, faster measurements and higher signal to noise ratios. In comparison to optical methods, the electromagnetic fields show a deeper penetration into the matter of interest and they are usable for optically opaque materials. In contrast to ultraviolet light and x-rays they are not ionizing. Furthermore, they offer the possibility of contact- and wireless measurements. The combination of these properties open up various applications, which might be complementary to established methods or which open up new possibilities not accessible so far.

Besides the practical application in the fields of medicine, biology, pharmacology, food chemistry, agricultural engineering and environmental analysis/monitoring, which reach from clinical through point-of-care applications to laboratory- and on-site diagnostics, there is a special interest as well in fundamental research, for example in molecular biology and toxicology. The high (social and commercial) relevance of this subject arises from the potential to directly increase the quality of life through faster, easier and more precise ways of analyzing and diagnosing. Beyond that, it might enable new forms of treatments as well.

Hence, the major scientific objective of ESSENCE is to foster fundamental interdisciplinary research on new principles, concepts and technologies of electromagnetic sensors at micro-, millimeter or terahertz wavelengths (300 MHz up to 10 THz) with specific focus on life sciences. The sensors under investigation could range from single, dedicated sensors through sensor arrays to complex multifunctional sensors, partly in combination with specifically tailored microfluidc structures or new dedicated surface functionalization for electromagnetic transducers in the stated frequency range. Another classification of sensors for life science applications could be according to the scale of the involved sensing object of interest, somehow arbitrarily classified into three categories, namely molecules, isolated cells and united cell structures and tissues.

Molecular level

The smallest scale for a biosensor is the molecular level, which opens up many applications, ranging from very basic research in the field of molecular biology, environmental monitoring by means of pollutant monitoring or the detection of poisonous impurities in the food and agricultural industry. Many resonances of low energy bonds such as hydrogen bonds can be identified in the range of a few THz, and might be used by appropriate sensors for real-time detection of conformal changes in proteins without any markers. As well, many functional groups, organic as well as inorganic and larger structures such as ring systems and long protein sequences show a multitude of specific resonances in the millimeter- and THz-wave regime. Again, this might enable the direct detection or the real-time observation of molecular processes or the detection of (un)wanted substances without further labeling. This can be of great relevance for the understanding of bio-molecular processes with relevance for the development of new drugs, for the research on human diseases. Depending on the actual application, many limitations of actual sensors have to be overcome by enhancing its performances. This might be (1.) the necessary sensitivity for the detection of very small quantities, (2.) the selectivity to distinguish between the effects due to the aimed sensing object and the spurious influence of other substances present in the given sample or (3.) the exploitation of novel interaction principles between a proposed electromagnetic structures and the matter under investigation, in order to develop new electromagnetic sensor elements.

Cellular level

The next scale is the cellular level. It is well known, that single cells show characteristic electromagnetic properties over a wide range of frequencies from micro- to millimeter waves. These properties can be exploited to inquire information about the cells, e.g. health, activity or specific metabolic processes inside the cell. Again, since this is possible without the use of specific markers or even dyes, there is no reaction of the cell to the actual measurement and therefore the measurement can be repeated various times with the same cell or cell culture. In addition, electromagnetic signals are not ionizing like UV- and X-rays, thus, supporting the approach of non-reactive measurements. The question of completely reactionless interaction between electromagnetic fields and cells, however, is not answered yet. This is mainly due to the lack of repeatability, the lack of precise experimental conditions which guaranty for example a well-known exposure in terms of electromagnetic field strength in the vicinity of the studied cells or the separation of different effects such as thermal influence or changes in the culture medium of the cell. For these reasons, further research in this area is necessary in order to guarantee reactionless measurements, which seems to be possible under certain conditions. Some of the challenges in the field of cellular sensing include, but are not limited to, the necessary selectivity in order to differentiate certain metabolic activities, the suppression of the influence of the culture medium and the appropriate cell handling during the measurements. Possible applications of such measurement techniques range from toxicological essays, to basic biological experiments where established methods like fluorescence-based or optical methods do not deliver the desired information about the involved cells up to the automated culturing of cells and the continuous monitoring of their health in the pharmaceutical industry.

United cells and tissue level

The third scale in this scheme is the observation of large amounts of united cells and tissues. Many biological materials have already been studied with respect to their electromagnetic properties. These studies indicate, that electromagnetic measurements can reveal significant differences between healthy, modified and malignant samples. For example, this has been shown for teeth, many different types of carcinoma and many human organs. One of the great advantages of electromagnetic sensors in this area is the low preparatory work necessary for diagnoses. For example, many changes of healthy tissue turning into malignant forms include a significant change of water content or a drastic change of cell organelles or cell structure. These changes can be detected without the need of optical microscopy, and hence, the necessary sample preparation for visual inspection. With that, electromagnetic sensor-based methods might support the treatment of cancer during the surgery. The advantage compared to a result obtained by classical histological methods carried out after the surgery are obvious, the suffering of the patients might be reduced by obsolete secondary surgeries and a higher chance of healing. As well, the possibility of reactionless in-vivo measurements close to vital areas without the need of excision seems very attractive for the reduction of risks during both, diagnose and treatment.

To summarize, the major objective of the priority program is to stimulate and foster interdisciplinary research on electromagnetic sensors specifically applied for life sciences, including fundamental investigations on effects usable for electromagnetic sensors, the interaction between sensor element structures and the material/tissue under test as well as on novel electromagnetic sensor principles, approaches, concepts and technologies. According to the classification above, this includes for example new approaches for sensors used for the observation or detection of specific molecules of organic or inorganic nature, e.g. proteins and biomedical metabolism products, food impurities, pollutants and pharmaceutical substances. Moreover, the observation of isolated cells and cell cultures using (automated) electromagnetic measurement setups is of high relevance, for example in the field of (human) biological and medical test series as commonly used in basic research as well as in applied analytics and diagnostics and for plant protection. Lastly, these sensors can be used to characterize large united cell structures and biological tissues, for example to prevent and to treat cancer, for mobile medical on-site tests or manifold minimally invasive diagnostic procedures in the clinical area such as vascular diagnosis for assessing the risk of heart attack.

Therefore, in the framework of this DFG Priority Program SPP 1857, particularly scientific projects shall be promoted with research approaches in the field of electromagnetic sensors at micro-, millimeter- or terahertz wavelengths, which combine several (at least two) of the following topics:

• Dedicated sensor structures with optimized selectivity and/or sensitivity
• Non-invasive or minimal invasive sensors for diagnostics
• EM sensor based/supported medical treatment methods
• Accelerated or real-time non-destructive reactionless test methods for life sciences
• In- and ex-vivo characterization methods for biological tissues and tissue differences as well as for medically relevant substances
• Techniques to handle very small sample volumes in combination with specifically designed sensors or sensor arrays
• Tailored biological, chemical or physical surface functionalization for electromagnetic transducers
• Characterization of electromagnetic properties of healthy and pathologically altered cells, biological tissues and substances in biology and medicine (in- as well as ex-vivo) and chemical substances, for example in the field of environmental and food diagnostics
• Investigation of non-thermal effects of (weak) electromagnetic fields on biological systems
• Basic research of biological processes on a molecular level using electromagnetic sensors

These topics should be handled in multi- and interdisciplinary projects, involving researchers from different disciplines such as electrical engineering, mechanical engineering, physics, medical technology, chemistry, biology and medicine. Project proposals made by two applicants, should represent two different disciplines. One of these two applicants must be from the core discipline of electrical engineering, having expertise in the field of electromagnetic sensors. Projects with three applicants should cover at least two different disciplines and one applicant must be from the core discipline of electrical engineering. To foster a great variety, strong interdisciplinary and balance between the participating disciplines, the priority program is organized such that in each project every PI should not be funded with more than one research assistant position. Furthermore, for dissemination of the research results, special sessions related to the topics of the Priority Program will be held at international conferences and workshops. In addition, a suitable web portal will be established to foster contacts, to distribute and share knowledge and results gained from the scientists of the Priority Program. The coordinator and the deputy coordinators are the contact point for postgraduate students, junior scientists and applicants. In the framework of the coordination project, funds for the support of female scientists and young families as well as for promising young scientists to get them started on their way to independent researchers will be proposed for.