Volume 90, Issue 12 - Special Issue: Dresdner Sensor Symposium 2022; Guest Editor: Andreas Schütze

This review provides an overview on bio- and chemosensors based on a thermal transducer platform that monitors the thermal interface resistance R th between a solid chip and the supernatant liquid. The R th parameter responds in a surprisingly strong way to molecular-scale changes at the solid–liquid interface, which can be measured thermometrically, using for instance thermocouples in combination with a controllable heat source. In 2012, the effect was first observed during on-chip denaturation experiments on complementary and mismatched DNA duplexes that differ in their melting temperature. Since then, the concept is addressed as heat-transfer method , in short HTM , and numerous applications of the basic sensing principle were identified. Functionalizing the chip with bioreceptors such as molecularly imprinted polymers makes it possible to detect neurotransmitters, inflammation markers, viruses, and environmental pollutants. In combination with aptamer-type receptors, it is also possible to detect proteins at low concentrations. Changing the receptors to surface-imprinted polymers has opened up new possibilities for quantitative bacterial detection and identification in complex matrices. In receptor-free variants, HTM was successfully used to characterize lipid vesicles and eukaryotic cells (yeast strains, cancer cell lines), the latter showing spontaneous detachment under influence of the temperature gradient inherent to HTM. We will also address modifications to the original HTM technique such as M-HTM, inverted HTM, thermal wave transport analysis TWTA, and the hot-wire principle. The article concludes with an assessment of the possibilities and current limitations of the method, together with a technological forecast.

Zusammenfassung Es wird ein neues Instrument für labelfreie Messungen auf der Basis von optischen Low Q-Whispering Gallery Modes vorgestellt, bei der mit miniaturisierten Sensorbeads verschiedene Anwendungsfelder adressiert werden. Als Sensoren dienen fluoreszente sphärische Beads mit Durchmessern von 7–12 Mikrometern, die unabhängig vom Messgerät in kleinsten Räumen eingesetzt werden können und mit Analytmengen im Femtogrammbereich auskommen. Die sphärischen Beads mit einer sehr glatten Oberfläche und hohem Brechungsindex dienen als Resonatoren für zirkulare Lichtwellen. Für die Messung wird der Fluoreszenzfarbstoff in den Sensoren mit einem Laser angeregt. Ein Teil der Fluoreszenz wird an der Partikeloberfläche total ins Partikel zurück reflektiert, so dass sich zirkulierende Wellen bilden, die bis zu 10,000 Mal umlaufen. Ihre Resonanzfrequenz hängt empfindlich vom Partikeldurchmesser und der Brechungsindexdifferenz zwischen Partikel und Medium ab. Bei Adsorbtion von Molekülen verschiebt sich die Resonanzfrequenz, da sich beide Parameter ändern. Für die Messung dieser Verschiebung wurde ein kompaktes Gerät mit Anregungslaser, hochauflösendem Spektrometer, CCD-Zeile, XYZ -Stage, Mikroskop, Kamera, Gerätesteuerung und Auswertesoftware entwickelt. Es werden einige Anwendungsbeispiele in der Biosensorik, der Layer-by-Layer Beschichtung, der Wirkstofffreisetzung und der Lösungsmittelsensorik präsentiert, die das breite Potential und Vorteile gegenüber auf dem Markt befindlicher, alternativer Meßmethoden demonstrieren.

Zusammenfassung Brechzahlsensitive plasmonische Sensoren mit nanostrukturierten Goldoberflächen bieten viele Vorteile für die kontinuierliche Vor-Ort-Überwachung in komplexen Prozessflüssigkeiten. In Kombination mit stimulus-responsiven Hydrogelen haben diese Potential für die selektive Detektion von Einzelparametern, hier der Ethanolkonzentration, bei sich gleichzeitig ändernden Stoffkonzentrationen anderer Komponenten. Ein erster Schritt zur Ausnutzung dieser selektiven Eigenschaften ist die Differenzierung des ethanolinduzierten Quelleffekts im eingesetzten Polyacrylamid-Hydrogel von der Brechzahländerung der zu analysierenden Flüssigkeit in Folge von Konzentrationsänderungen. Dies wurde durch die Anwendung einer mit Hydrogel funktionalisierten Messfläche und einer nicht funktionalisierten Referenzfläche erreicht. Das hier vorgestellte Sensorkonzept ermöglicht so die Bestimmung der Ethanolkonzentration wässriger Lösungen zwischen 40 und 60 vol%. Dabei wird gezeigt, dass von der Entquellung des Hydrogelvolumens nicht direkt auf das oberflächennahe Verhalten geschlossen werden kann, sondern eine individuelle Kalibrierung des optischen Signals notwendig ist.

Cochlear implants are hearing prostheses for patients with severe to total hearing loss but intact auditory nerve. An external speech processor captures sound from the environment, which is subsequently converted into electrical signals and transmitted to an electrode array in the patient’s inner ear. The metallic stimulation electrodes of the electrode array electrically stimulate the spiral ganglion cells of the auditory nerve. The functionality of cochlear implants strongly depends on the possible maximum current stimulating the spiral ganglion cells, which can be affected by, e.g., cell growth around the stimulation electrodes. This in turn decreases the stimulation efficiency leading to decreased hearing. Cell growth, implant position and other changes in the surrounding medium are reflected in a change of the impedance of the stimulation electrodes. The impedance measurement of the stimulation electrodes is already implemented in all common cochlear implant systems to check functionality of the stimulation electrodes after implantation, but the frequency spectrum is normally not analyzed. Although this method can detect cell growth on the stimulation electrodes, it faces limitations when other interfering effects, such as changes in the perilymph and implant position, influence the impedance. This work shows impedance spectroscopic measurements using enlarged cochlear implant models to electrically analyze the surrounding medium, the perilymph, to understand changes in electrode impedance and to later monitor the stimulation efficiency of cochlear implants and to identify possible reasons for decreased hearing ability by impedance spectroscopy. In addition, we use FEM simulations to numerically model the influence of the perilymph composition on the impedance measurement. As shown by a final validation, this model can serve as a basis for an extended simulation model including implant position and cell growth monitoring to predict hearing deterioration in cochlear implant patients. In this context, this work serves as a basis for the development of a holistic prediction model and considers in the first step exclusively the influence of the perilymph composition on the impedance between two stimulation electrodes.

A gas mixing apparatus (GMA) can provide well-defined gas mixtures, which are necessary to calibrate gas sensors for quantitative measurements. This article presents a novel modular GMA and especially the representative measurements carried out to qualify and quantify its performance. New methods were developed to optimise the GMA’s settling speed and to enable self-monitoring. The GMA is able to provide up to 14 individual test gases, each in a large concentration range from sub-parts-per-billion to hundreds of parts-per-million. Additionally, the relative humidity can be set. The system is able to provide stable gas mixtures in approximately 6 min. The entire control software is realised in Python, which determines the control setpoints of all relevant system components based on the concentration input of the user. A major focus was placed on minimising the time of a gas mixture exchange to confirm design and additional software optimisation. Also, a number of techniques are shown for the analytical quantification of the system, including analysis of thermal desorption tubes by an accredited laboratory, showing maximal contaminations of e.g. only 4.18 ppb ethanol. Finally, self-monitoring of the system using photoionization detectors (PID) is demonstrated as an addition to flow readback for internal leakage detection.

The measurement of the spatially distributed flow field in large industrial vessels, e.g. biogas fermenters, is not possible with commercially available measurement equipment. Therefore the concept of flow following sensor particles has been developed. They act as data loggers within the vessel. The sensor particles are equipped with a pressure sensor and an inertial measurement unit to measure their motion. The measurements are taken in the coordinate frame of the sensor particle and need to be transformed into the vessel’s coordinate frame to analyze the flow field. This is done by an error-state Kalman filter which estimates the orientation of the sensor particle with respect to the vessel based on the direction of the gravitational acceleration and the local magnetic field. Since no other aiding sensors are available or usable within an industrial vessel, particular emphasis was given to the inertial sensors’ stochastic modelling and the accelerometer’s calibration. Based on the orientation estimation, the measured acceleration is transformed into the vessel frame. We performed two experiments in a 1.4 m 3 lab reactor to qualify this approach. The results show, that the transformed acceleration is in good qualitative agreement with the known flow field inside the lab reactor.