Image reversal reactive immersion lithography improves the detection limit of focal molography

Frutiger, Andreas; Tschannen, Cla Duri; Blickenstorfer, Yves; Reichmuth, Andreas M.; Fattinger, Christof; Vörös, János

doi:10.1364/ol.43.005801

Cited by 9 publications

(22 citation statements)

References 6 publications

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“…This achieves an effective separation of signal and environmental noise by a high-frequency spatial affinity lock-in [28]. Second, the grating lines composed of the binding sites are not straight and equidistant but rather chirped and curved to form a focusing grating coupler (diffractive lens) [26,27,[46][47][48][49][50]. The lens constructs the Fourier plane necessary for the analog spatial lock-in in close proximity to the chip without any additional optical components [27,28,46].…”

Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

“…The class of diffractometric biosensors that incorporates a high spatial frequency affinity lock-in, a diffractive lens and darkfield illumination was termed focal molography [46]. The name originates from a combination of the words molecule and holography given that the analyte molecules form a focusing hologram in which the Airy disk intensity serves as the sensor output [26,27,33,46,50].…”

Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

“…where K is the coupling coefficient [31], A is the area, dn dc is the refractive index increment for proteins in water [46], n c is the refractive index of the cover medium and Γ coh is the coherent mass density. The total mass density Γ tot can be obtained from Γ coh by division with the analyte efficiency η [A] , which is discussed in [27,31,50]. The coupling coefficient for an incident-guided TE mode and outgoing free space mode into the substrate reads…”

Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

“…The diffractometric biosensor measures the refractive index difference, i.e., the coherent mass density Γ coh , between ridges and grooves. [27,31,50] (an image of the focal plane is shown in the insets; the scale bar is 30 µm). (d) The binding of molecules, irrespective of whether they bind on the ridge or the groove, increases the average refractive index of the cover medium close to the waveguide surface.…”

Section: Experimental Noise Rejection Performance Of a Spatial Lock-imentioning

confidence: 99%

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

Frutiger

Gatterdam

Blickenstorfer

et al. 2020

Sensors

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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.

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Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

Section: A Combined Refractometric and Diffractometric Biosensormentioning

confidence: 99%

Section: Experimental Noise Rejection Performance Of a Spatial Lock-imentioning

confidence: 99%

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

Frutiger

Gatterdam

Blickenstorfer

et al. 2020

Sensors

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“…In addition, a low-cost diffractometric readout and patterning system based on compact disk technology [36] has been demonstrated. The recently introduced diffractometric biosensing method, focal molography [7,8,37,38], allows ultrasensitive detection due to focusing of the sensor signal and a photolithographic method for synthesis of a submicron diffractive structure of receptors. Because of the inherent robustness of the submicron referencing, even interactions in the membrane of living cells can be monitored in real time and new applications in real-time diagnostics are possible with focal molography [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Diffractometric Biosensing

et al. 2021

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Diffractometric biosensing is a promising technology to overcome critical limitations of refractometric biosensors, the dominant class of label-free optical transducers. These limitations manifest themselves by higher noise and drifts due to insufficient rejection of refractive index fluctuations caused by variation in temperature, solvent concentration, and, most prominently, nonspecific binding. Diffractometric biosensors overcome these limitations with inherent self-referencing on the submicron scale with no compromise on resolution. Despite this highly promising attribute, the field of diffractometric biosensors has only received limited recognition. A major reason is the lack of a general quantitative analysis. This hinders comparison to other techniques and amongst different diffractometric biosensors. For refractometric biosensors, on the other hand, such a comparison is possible by means of the refractive index unit (RIU). In this paper, we suggest the coherent surface mass density, coh , as a quantity for label-free diffractometric biosensors with the same purpose as the RIU in refractometric sensors. It is easy to translate coh to the total surface mass density tot , which is an important parameter for many assays. We provide a generalized framework to determine coh for various diffractometric biosensing arrangements that enables quantitative comparison. Additionally, the formalism can be used to estimate background scattering in order to further optimize sensor configurations. Finally, a practical guide with important experimental considerations is given to enable readers of any background to apply the theory. Therefore, this paper provides a powerful tool for the development of diffractometric biosensors and will help the field to mature and unveil its full potential.

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