Bioanalytical sensors using the heat-transfer method HTM and related techniques
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Patrick Wagner
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Soroush Bakhshi Sichani
Abstract
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
Dieser Artikel gibt eine Übersicht zu thermischen Bio- und Chemosensoren die den Wärmeleitungswiderstand R th zwischen einem Chip und einer Flüssigkeit messen. Der R th Parameter reagiert überraschend stark auf Veränderungen, die auf molekularer Ebene an der Grenzschicht zwischen dem Festköper und der Flüssigkeit stattfinden. Dies kann thermometrisch nachgewiesen werden, zum Beispiel mit Thermoelementen und einer regelbaren Heizquelle. Der Effekt wurde zuerst im Jahr 2012 bei der thermischen Denaturierung von chip-gebundenen, komplementären und mutierten DNA Fragmenten beobachtet, die sich in ihrer Schmelztemperatur unterscheiden. Seitdem wird das Konzept als heat-transfer method, bzw. als HTM bezeichnet und es wurden zahlreiche andere Anwendungsmöglichkeiten des Basisprinzips identifiziert. Funktionalisieren des Chips mit Biorezeptoren wie z. B. molekular geprägten Polymeren ermöglicht den quantitativen Nachweis von Neurotransmittern, Entzündungsmarkern, Viren und toxischen Stoffen in der Umwelt. Durch die Verwendung von Aptameren als Rezeptoren lassen sich auch Proteine bis zu niedrigen Konzentrationen nachweisen. Ein weiterer Rezeptortyp, die oberflächengeprägten Polymere, ermöglicht die selektive und quantitative Bestimmung von bakteriellen Kontaminationen in komplexen Proben. In rezeptorfreien Varianten wurde HTM erfolgreich für die Charakterisierung von Lipidbläschen und eukaryoten Zellen verwenden (Hefestämme, Krebszelllinien), die ein spontanes Ablöseverhalten unter Einfluss des HTM-typischen Temperaturgradienten zeigen. Des weiteren werden Modifikationen der originalen HTM-Methode behandelt wie M-HTM, invertiertes HTM, die Transportanalyse thermischer Wellen (TWTA) und das Hitzdraht-Prinzip. In der Zusammenfassung werden die Möglichkeiten und vorläufigen Beschränkungen dieser Methoden besprochen, zusammen mit einem technologischen Ausblick.
Funding source: Fonds Wetenschappelijk Onderzoek
Award Identifier / Grant number: SmartNano / G.0E3618.18N
Funding source: HORIZON EUROPE Health
Award Identifier / Grant number: Remedia / 874753
Funding source: Agentschap Innoveren en Ondernemen
Award Identifier / Grant number: SIPORE / HBC.2021.0804
Funding source: Austrian Science Fund
Award Identifier / Grant number: SmartNano / I3568-N28
About the authors
Soroush Bakhshi Sichani obtained his MSc in micro- and nano-electromechanical systems engineering (MEMS & NEMS) from the University of Tehran, Iran. Currently, he is a PhD student at the Laboratory of Soft Matter and Biophysics, KU Leuven, Belgium. His research focuses on developing a multi-parametric label free sensing platform based on electrochemical impedance spectroscopy (EIS), quartz crystal microbalance (QCM), and heat transfer method (HTM).
Mehran Khorshid obtained his Doctorate of Veterinary Medicine (DVM) from the Azad University, Karaj branch, Iran in 2009. Afterwards, he obtained a Master of Biomedical Sciences at Hasselt University in 2014. Since completing his PhD in Science (2018) from KU Leuven, Belgium, he has been working as a post-doctoral researcher at the Laboratory for Soft Matter and Biophysics, KU Leuven. His research interest covers engineering of biosensors for medical and biomedical applications, as well as study of complex biophysical systems.
Peter A. Lieberzeit obtained his PhD in Chemistry in 1999 at the University of Vienna and his postdoctoral lecture qualification (habilitation) in 2007. Since 2011 he is a Full Professor at the Faculty of Chemistry of the University of Vienna. His research focuses on generating biomimetic recognition systems for sensing chemical and biological analytes, mainly based on molecularly imprinted polymers and mass-sensitive sensors. He is a member of the editorial board of Sensors and Actuators B: Chemical, of the editorial advisory board of Analytical and Bioanalytical chemistry and chairman of the International Steering Committee of IMCS conferences.
Patricia Losada-Pérez obtained her PhD in physics in 2009 at the University of Vigo. She has been a postdoctoral researcher at the Laboratory of Soft Matter and Biophysics at the KU Leuven and a research associate at the Institute of Materials Research of Hasselt University. She is currently an associate professor in the Experimental Soft Matter and Thermal Physics group of the Université libre de Bruxelles, Belgium. Her research interests include soft-condensed matter physics, thermodynamics, lipid biophysics, and biosensors.
Derick Yongabi obtained his PhD in Physics in 2021 from KU Leuven, Belgium. Before then, he received a Master of Science in Research Methods in 2011 from the University of Leeds, UK, and a Master of Biomedical Science – Bioelectronics and Nanotechnology from the University of Hasselt, Belgium (2015). He also holds a Postgraduate Certificate in Advanced Medical Imaging from KU Leuven (2018). He is currently a postdoctoral researcher at KU Leuven, laboratory for Soft Matter and Biophysics. His research focuses on unraveling fundamental cell-material interactions towards biomedical and biosensor applications, as well as development of synthetic receptors and bio(mimetic) sensors.
Acknowledgments
The authors are grateful for stimulating scientific discussions with Profs. Marloes Peeters (Newcastle University, UK), Kasper Eersels and Bart van Grinsven (both in Maastricht University, The Netherlands), as well as Ronald Thoelen and Jef Hooyberghs (both in Hasselt University, Belgium). Patrick Wagner and Peter Lieberzeit wish to dedicate this article to Univ.-Prof. Dr. Franz L. Dickert (University of Vienna) on the occasion of his 80th birthday.
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Research ethics: Not applicable.
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Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors state no conflict of interest.
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Research funding: Copied from the Acknowledgements section of the manuscript: D. Yongabi acknowledges financial support by the VLAIO (Flanders Innovation & Entrepreneurship) project SIPORE, grant no. HBC.2021.0804. S. Bakhshi Sichani is supported by the project SmartNano G.0E3618.18N of the Research Foundation Flanders FWO in cooperation with the Austrian Science Fund FWF, project no. I3568-N28. M. Khorshid was supported by the H2020 project REMEDIA, grant no. 874753.
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Data availability: The raw data can be obtained on request from the corresponding author.
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© 2023 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- 16th Dresden Sensor Symposium
- Review Article
- Bioanalytical sensors using the heat-transfer method HTM and related techniques
- Research Articles
- Miniaturisierung von labelfreier Oberflächenanalytik mittels Whispering Gallery Modes
- Hydrogelbasierte plasmonische Sensoren zur Ethanoldetektion: Einfluss des Quellverhaltens auf das optische Signal
- Impedance spectroscopy of enlarged cochlear implant stimulation electrodes – FEM simulations considering the perilymph
- Qualification and optimisation of a gas mixing apparatus for complex trace gas mixtures
- Orientation resolved measurements of accelerations with sensor particles in bioreactors
Articles in the same Issue
- Frontmatter
- Editorial
- 16th Dresden Sensor Symposium
- Review Article
- Bioanalytical sensors using the heat-transfer method HTM and related techniques
- Research Articles
- Miniaturisierung von labelfreier Oberflächenanalytik mittels Whispering Gallery Modes
- Hydrogelbasierte plasmonische Sensoren zur Ethanoldetektion: Einfluss des Quellverhaltens auf das optische Signal
- Impedance spectroscopy of enlarged cochlear implant stimulation electrodes – FEM simulations considering the perilymph
- Qualification and optimisation of a gas mixing apparatus for complex trace gas mixtures
- Orientation resolved measurements of accelerations with sensor particles in bioreactors
