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

Frutiger, Andreas; Gatterdam, Karl; Blickenstorfer, Yves; Reichmuth, Andreas Michael; Fattinger, Christof; Vörös, János

doi:10.3390/s21010009

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

Andreas Frutiger

Karl Gatterdam

Yves Blickenstorfer

¹,

Andreas Michael Reichmuth

¹,

Christof Fattinger

^3,* and

János Vörös

^1,*

Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zürich, 8092 Zürich, Switzerland

Institute of Structural Biology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany

Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland

Authors to whom correspondence should be addressed.

Sensors 2021, 21(1), 9; https://doi.org/10.3390/s21010009

Received: 17 November 2020 / Revised: 7 December 2020 / Accepted: 8 December 2020 / Published: 22 December 2020

(This article belongs to the Special Issue Advanced Biophotonic Sensors)

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Abstract

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 de facto 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. View Full-Text

Keywords: label-free biosensors; optical diffraction; shot noise limit; focal molography

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MDPI and ACS Style

Frutiger, A.; Gatterdam, K.; Blickenstorfer, Y.; Reichmuth, A.M.; Fattinger, C.; Vörös, J. Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration. Sensors 2021, 21, 9. https://doi.org/10.3390/s21010009

AMA Style

Frutiger A, Gatterdam K, Blickenstorfer Y, Reichmuth AM, Fattinger C, Vörös J. Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration. Sensors. 2021; 21(1):9. https://doi.org/10.3390/s21010009

Chicago/Turabian Style

Frutiger, Andreas, Karl Gatterdam, Yves Blickenstorfer, Andreas M. Reichmuth, Christof Fattinger, and János Vörös. 2021. "Ultra Stable Molecular Sensors by Submicron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part II. Experimental Demonstration" Sensors 21, no. 1: 9. https://doi.org/10.3390/s21010009

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

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