Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration

Label-free optical biosensors are an invaluable tool for molecular interaction analysis. Over the past 30 years, refractometric biosensors and, in particular, surface plasmon resonance have matured to the <i>de facto</i> standard of this field despite a significant cross reactivity to en...

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Main Authors: Andreas Frutiger, Karl Gatterdam, Yves Blickenstorfer, Andreas Michael Reichmuth, Christof Fattinger, János Vörös
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Sensors
Subjects:
Online Access:https://www.mdpi.com/1424-8220/21/1/9
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author Andreas Frutiger
Karl Gatterdam
Yves Blickenstorfer
Andreas Michael Reichmuth
Christof Fattinger
János Vörös
author_facet Andreas Frutiger
Karl Gatterdam
Yves Blickenstorfer
Andreas Michael Reichmuth
Christof Fattinger
János Vörös
author_sort Andreas Frutiger
collection DOAJ
description Label-free optical biosensors are an invaluable tool for molecular interaction analysis. Over the past 30 years, refractometric biosensors and, in particular, surface plasmon resonance have matured to the <i>de facto</i> standard of this field despite a significant cross reactivity to environmental and experimental noise sources. In this paper, we demonstrate that sensors that apply the spatial affinity lock-in principle (part I) and perform readout by diffraction overcome the drawbacks of established refractometric biosensors. We show this with a direct comparison of the cover refractive index jump sensitivity as well as the surface mass resolution of an unstabilized diffractometric biosensor with a state-of-the-art Biacore 8k. A combined refractometric diffractometric biosensor demonstrates that a refractometric sensor requires a much higher measurement precision than the diffractometric to achieve the same resolution. In a conceptual and quantitative discussion, we elucidate the physical reasons behind and define the figure of merit of diffractometric biosensors. Because low-precision unstabilized diffractometric devices achieve the same resolution as bulky stabilized refractometric sensors, we believe that label-free optical sensors might soon move beyond the drug discovery lab as miniaturized, mass-produced environmental/medical sensors. In fact, combined with the right surface chemistry and recognition element, they might even bring the senses of smell/taste to our smart devices.
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spelling doaj.art-71bfb78fff76414c83391bb1ef86784b2023-11-21T02:02:06ZengMDPI AGSensors1424-82202020-12-01211910.3390/s21010009Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental DemonstrationAndreas Frutiger0Karl Gatterdam1Yves Blickenstorfer2Andreas Michael Reichmuth3Christof Fattinger4János Vörös5Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zürich, 8092 Zürich, SwitzerlandInstitute of Structural Biology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyLaboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zürich, 8092 Zürich, SwitzerlandLaboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zürich, 8092 Zürich, SwitzerlandRoche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, SwitzerlandLaboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zürich, 8092 Zürich, SwitzerlandLabel-free optical biosensors are an invaluable tool for molecular interaction analysis. Over the past 30 years, refractometric biosensors and, in particular, surface plasmon resonance have matured to the <i>de facto</i> standard of this field despite a significant cross reactivity to environmental and experimental noise sources. In this paper, we demonstrate that sensors that apply the spatial affinity lock-in principle (part I) and perform readout by diffraction overcome the drawbacks of established refractometric biosensors. We show this with a direct comparison of the cover refractive index jump sensitivity as well as the surface mass resolution of an unstabilized diffractometric biosensor with a state-of-the-art Biacore 8k. A combined refractometric diffractometric biosensor demonstrates that a refractometric sensor requires a much higher measurement precision than the diffractometric to achieve the same resolution. In a conceptual and quantitative discussion, we elucidate the physical reasons behind and define the figure of merit of diffractometric biosensors. Because low-precision unstabilized diffractometric devices achieve the same resolution as bulky stabilized refractometric sensors, we believe that label-free optical sensors might soon move beyond the drug discovery lab as miniaturized, mass-produced environmental/medical sensors. In fact, combined with the right surface chemistry and recognition element, they might even bring the senses of smell/taste to our smart devices.https://www.mdpi.com/1424-8220/21/1/9label-free biosensorsoptical diffractionshot noise limitfocal molography
spellingShingle Andreas Frutiger
Karl Gatterdam
Yves Blickenstorfer
Andreas Michael Reichmuth
Christof Fattinger
János Vörös
Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
Sensors
label-free biosensors
optical diffraction
shot noise limit
focal molography
title Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
title_full Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
title_fullStr Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
title_full_unstemmed Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
title_short Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration
title_sort ultra stable molecular sensors by submicron referencing and why they should be interrogated by optical diffraction part ii experimental demonstration
topic label-free biosensors
optical diffraction
shot noise limit
focal molography
url https://www.mdpi.com/1424-8220/21/1/9
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