Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier
Label-free optical biosensors, such as surface plasmon resonance, are sensitive and well-established for the characterization of molecular interactions. Yet, these sensors require stabilization and constant conditions even with the use of reference channels. In this paper, we use tools from signal p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Sensors |
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| Online Access: | https://www.mdpi.com/1424-8220/21/2/469 |
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| author | Andreas Frutiger Christof Fattinger János Vörös |
| author_facet | Andreas Frutiger Christof Fattinger János Vörös |
| author_sort | Andreas Frutiger |
| collection | DOAJ |
| description | Label-free optical biosensors, such as surface plasmon resonance, are sensitive and well-established for the characterization of molecular interactions. Yet, these sensors require stabilization and constant conditions even with the use of reference channels. In this paper, we use tools from signal processing to show why these sensors are so cross-sensitive and how to overcome their drawbacks. In particular, we conceptualize the spatial affinity lock-in as a universal design principle for sensitive molecular sensors even in the complete absence of stabilization. The spatial affinity lock-in is analogous to the well-established time-domain lock-in. Instead of a time-domain signal, it modulates the binding signal at a high spatial frequency to separate it from the low spatial frequency environmental noise in Fourier space. In addition, direct sampling of the locked-in sensor’s response in Fourier space enabled by diffraction has advantages over sampling in real space as done by surface plasmon resonance sensors using the distributed reference principle. This paper and part II hint at the potential of spatially locked-in diffractometric biosensors to surpass state-of-the-art temperature-stabilized refractometric biosensors. Even simple, miniaturized and non-stabilized sensors might achieve the performance of bulky lab instruments. This may enable new applications in label-free analysis of molecular binding and point-of-care diagnostics. |
| first_indexed | 2024-03-09T05:13:05Z |
| format | Article |
| id | doaj.art-7b94ecb33ecb4f179ce3daaba4f52c8b |
| institution | Directory Open Access Journal |
| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-03-09T05:13:05Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Sensors |
| spelling | doaj.art-7b94ecb33ecb4f179ce3daaba4f52c8b2023-12-03T12:47:38ZengMDPI AGSensors1424-82202021-01-0121246910.3390/s21020469Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in AmplifierAndreas Frutiger0Christof Fattinger1János Vörös2Laboratory of Biosensors and Bioelectronics, Institute of 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 of Biomedical Engineering, University and ETH Zürich, 8092 Zürich, SwitzerlandLabel-free optical biosensors, such as surface plasmon resonance, are sensitive and well-established for the characterization of molecular interactions. Yet, these sensors require stabilization and constant conditions even with the use of reference channels. In this paper, we use tools from signal processing to show why these sensors are so cross-sensitive and how to overcome their drawbacks. In particular, we conceptualize the spatial affinity lock-in as a universal design principle for sensitive molecular sensors even in the complete absence of stabilization. The spatial affinity lock-in is analogous to the well-established time-domain lock-in. Instead of a time-domain signal, it modulates the binding signal at a high spatial frequency to separate it from the low spatial frequency environmental noise in Fourier space. In addition, direct sampling of the locked-in sensor’s response in Fourier space enabled by diffraction has advantages over sampling in real space as done by surface plasmon resonance sensors using the distributed reference principle. This paper and part II hint at the potential of spatially locked-in diffractometric biosensors to surpass state-of-the-art temperature-stabilized refractometric biosensors. Even simple, miniaturized and non-stabilized sensors might achieve the performance of bulky lab instruments. This may enable new applications in label-free analysis of molecular binding and point-of-care diagnostics.https://www.mdpi.com/1424-8220/21/2/469molecular sensorschemosensors, biosensorslock-in amplifiersnoise rejectionnoise analysisoptical diffraction |
| spellingShingle | Andreas Frutiger Christof Fattinger János Vörös Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier Sensors molecular sensors chemosensors, biosensors lock-in amplifiers noise rejection noise analysis optical diffraction |
| title | Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier |
| title_full | Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier |
| title_fullStr | Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier |
| title_full_unstemmed | Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier |
| title_short | Ultra-Stable Molecular Sensors by Sub-Micron Referencing and Why They Should Be Interrogated by Optical Diffraction—Part I. The Concept of a Spatial Affinity Lock-in Amplifier |
| title_sort | ultra stable molecular sensors by sub micron referencing and why they should be interrogated by optical diffraction part i the concept of a spatial affinity lock in amplifier |
| topic | molecular sensors chemosensors, biosensors lock-in amplifiers noise rejection noise analysis optical diffraction |
| url | https://www.mdpi.com/1424-8220/21/2/469 |
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