High-speed label-free detection by spinning-disk micro-interferometry

Varma, Manoj M.; Inerowicz, Halina D.; Regnier, Fred E.; Nolte, David D.

doi:10.1016/j.bios.2003.12.033

Cited by 67 publications

(50 citation statements)

References 14 publications

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“…We introduced the biological compact disc (BioCD) 4 to incorporate the advantages of direct optical detection into a sensitive and scalable immunoassay platform (1,2 ). The 1st BioCD demonstration was related in structure to conventional optical compact discs, but rather than operating in digital mode, it was modified to operate in interferometric phase quadrature (3 ), in which the signal and reference beams have a 90°relative phase difference.…”

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High-Speed Interferometric Detection of Label-Free Immunoassays on the Biological Compact Disc

et al. 2006

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Background:We describe a direct-detection immunoassay that uses high-speed optical interferometry on a biological compact disc (BioCD). Methods: We fabricated phase-contrast BioCDs from 100-mm diameter 1.1-mm thick borosilicate glass disks coated with a 10-layer dielectric stack of Ta 2 O 5 /SiO 2 that serves as a mirror with a center wavelength at 635 nm. The final layer is a /4 layer of SiO 2 onto which protein patterns are immobilized through several different chemical approaches. Protein on the disc is scanned by a focused laser spot as the disc spins. Interaction of the light with the protein provides both a phase-modulated signal and a local reference that are combined interferometrically to convert phase into intensity. A periodic pattern of protein on the spinning disc produces an intensity modulation as a function of time that is proportional to the surface-bound mass. The binding of antigen or antibodies is detected directly, without labels, by a change in the interferometric intensity. The technique is demonstrated with a reverse assay of immobilized rabbit and mouse IgG antigen incubated against anti-IgG antibody in a casein buffer. Results: The signal increased with increased concentration of analyte. The current embodiment detected a concentration of 100 ng/L when averaged over ϳ3000 100-micron-diameter protein spots. Conclusions: High-speed interferometric detection of label-free protein assays on a rapidly spinning BioCD is

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High-Speed Interferometric Detection of Label-Free Immunoassays on the Biological Compact Disc

et al. 2006

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“…A CPI has been used extensively in quantitative phase measurements since Dyson's seminal paper in 1953 [9]. A CPI scheme at quadrature condition (i.e., the phase difference between the reference and signal beams is centered around π∕2) is very sensitive to minute changes in the phase of the signal beam [10][11][12]. At this condition, a CPI provides a linear relationship between the observed intensity modulation and the change in the optical phase that induces the intensity change.…”

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“…A CPI scheme at quadrature condition (i.e., the phase difference between the reference and signal beams is centered around π∕2) is very sensitive to minute changes in the phase of the signal beam [10][11][12]. At this condition, a CPI provides a linear relationship between the observed intensity modulation and the change in the optical phase that induces the intensity change.One successful application of CPI at quadrature condition is in spinning-disk interferometry (SDI) [10][11][12]. SDI is used primarily in microimmunoassay wherein specific antigens attach to engineered substrates that fulfil the quadrature condition.…”

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Nanostep height measurement via spatial mode projection

et al. 2014

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We demonstrate an optical scheme for measuring the thickness of thin nanolayers with the use of light beam's spatial modes. The novelty in our scheme is the projection of the beam reflected by the sample onto a properly tailored spatial mode. In the experiment described below, we are able to measure a step height smaller than 10 nm, i.e., oneeightieth (1∕80) of the wavelength with a standard error in the picometer scale. Since our scheme enhances the signal-to-noise ratio, which effectively increases the sensitivity of detection, the extension of this technique to the detection of subnanometric layer thicknesses is feasible. The search for new optical methods to measure thickness in the range of a few nanometers or even hundreds of picometers is a topic of great interest. This is fuelled not only by the desire to reach the limit of resolution on the use of light in the nanoworld but also to develop new methods that can complement and/or substitute some well-established techniques, such as x-ray spectroscopy, atomic force microscopy, and ellipsometry [1][2][3]. Moreover, the continuous shrinking of all kinds of optical and electronic devices and the explosive growth of the exploration of the inner working of cells and molecular bio machines demand detection techniques that apart from being highly sensitive, must also be noninvasive, faster, and easy to implement in different scenarios. These requirements can be met by photonics technologies. Most of the time, high-resolution optical metrology is closely related to the evaluation of the phase of an electromagnetic field. In general, phases cannot be readily obtained and the desired information must be extracted indirectly by some other methods. The most widely used of these methods is interferometry. By looking at the intensity produced at the output port of an interferometer, the relative phase can be measured and consequently, the relative thickness of a layer. Hugely small global phase differences between two independent beams up to ∼1 × 10 −7 rad can be detected [4,5]. The detection of small structures, such as a step [6], is more cumbersome since the reflected beam contains a spatially varying phase instead of a global phase which should be resolved.A major problem in interferometry is the presence of uncontrollable disturbances that can also introduce phase differences. This is especially critical when tiny phase changes are being measured. A way to circumvent this problem is by using a common path interferometer (CPI) where an unperturbed part of the beam acts as a reference beam and travels the same path as the signal beam [7,8]. A CPI has been used extensively in quantitative phase measurements since Dyson's seminal paper in 1953 [9]. A CPI scheme at quadrature condition (i.e., the phase difference between the reference and signal beams is centered around π∕2) is very sensitive to minute changes in the phase of the signal beam [10][11][12]. At this condition, a CPI provides a linear relationship between the observed intensity modulation and the change in ...

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“…Water film, as a constituent of the biochemical analytes or as a dielectric layer, may contribute background signals to mass-sensitive biosensors which detect label-free biomaterials on microarrays, especially when the detection is performed after the sample has been dried. [4][5][6] Therefore, the quantitative measurement of water on biosensor surfaces is essential to understand how water affects the sensitivity and accuracy of mass-sensitive biosensors. However, this measurement is a challenging metrology problem because the water film is usually extremely thin and is present on all surfaces.…”

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Ambient molecular water accumulation on silica surfaces detected by a reflectance interference optical balance

Wang

Zhao

Nolte

2010

Applied Physics Letters

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Water is a persistent background in virtually all biosensors, yet is difficult to quantify. We apply an interferometric optical balance to measure water film accumulation from air onto several types of prepared silica surfaces. The optical balance uses in-line common-path interferometry with balanced quadratures to measure the real-time accumulation of molecular films. The accumulated water thickness is sensitive to ambient conditions, with thicknesses that vary from picometers up to nanometers, even on hydrophobic silanized surfaces. These results demonstrate that water adsorption contributes an excess signal in dry label-free protein microarray optical biosensors and presents a fundamental limit to assay sensitivity.

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High-speed label-free detection by spinning-disk micro-interferometry

Cited by 67 publications

References 14 publications

High-Speed Interferometric Detection of Label-Free Immunoassays on the Biological Compact Disc

High-Speed Interferometric Detection of Label-Free Immunoassays on the Biological Compact Disc

Nanostep height measurement via spatial mode projection

Ambient molecular water accumulation on silica surfaces detected by a reflectance interference optical balance

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