Label-free monitoring of multiple biomolecular binding interactions in real-time with diffraction-based sensing

Goh, Jane Betty; Loo, Richard W.; Goh, M. Cynthia

doi:10.1016/j.snb.2004.08.003

Cited by 48 publications

(36 citation statements)

References 13 publications

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“…Recently, optical sensors based on diffraction gratings have been developed as a new sensing platform [1][2][3][4][5][6][7][8][9][10][11][12][13]. In this sensing protocol, sensitive substrates or materials are patterned into period arrays by soft lithography or other methods.…”

Section: Introductionmentioning

confidence: 99%

Surface-relief-gratings based on molecularly imprinted polymer for 2,4-dichlorophenoxyacetic acid detection

Wang

Liu

Wang

2015

Sensors and Actuators B: Chemical

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Section: Introductionmentioning

confidence: 99%

Surface-relief-gratings based on molecularly imprinted polymer for 2,4-dichlorophenoxyacetic acid detection

Wang

Liu

Wang

2015

Sensors and Actuators B: Chemical

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“…Examples include on-chip embodiments of a Mach-Zehnder (11)(12)(13)(14) and Young Interferometer (15), dual polarization interferometer (16), porous Si (17) and nanoporous Al (18) sensors, diffraction optics technology (19), and the biological compact disk (BioCD) (20,21), as well as BSI (9,10,22). The Mach-Zehnder and Young dual polarization interferometers use wave guiding to monitor binding with surface interaction sensing, which requires relatively long sections of the channel to be coated with the target and large sample volumes to be introduced to facilitate micromolar to nanomolar detection limits.…”

mentioning

confidence: 99%

Free-Solution, Label-Free Molecular Interactions Studied by Back-Scattering Interferometry

Bornhop

Latham

Kussrow

et al. 2007

Science

191

216

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Free-solution, label-free molecular interactions were investigated with back-scattering interferometry in a simple optical train composed of a helium-neon laser, a microfluidic channel, and a position sensor. Molecular binding interactions between proteins, ions and protein, and small molecules and protein, were determined with high dynamic range dissociation constants (K d spanning six decades) and unmatched sensitivity (picomolar K d 's and detection limits of 10,000s of molecules). With this technique, equilibrium dissociation constants were quantified for protein A and immunoglobulin G, interleukin-2 with its monoclonal antibody, and calmodulin with calcium ion Ca 2+ , a small molecule inhibitor, the protein calcineurin, and the M13 peptide. The high sensitivity of back-scattering interferometry and small volumes of microfluidics allowed the entire calmodulin assay to be performed with 200 picomoles of solute.

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“…A movable stage allows monitoring and potential patterning with different capture reagents for 8 discrete diffraction spots. In addition, each individual spot can be cross-patterned to perform intraspot multiplexing and assays, as we have previously demonstrated (5,6 ).…”

mentioning

confidence: 99%

Diffractive Optics Technology: A Novel Detection Technology for Immunoassays

Borisenko

Tam

et al. 2006

Clinical Chemistry

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There is an increasing need for high-sensitivity immunoassays that can be used in point-of-care patient testing of complex media. For example, analytes such as the natriuretic peptides and recently discovered sepsis markers are found in blood in very low picomolar concentrations (1, 2 ). Although advances have been made in the use of fluorescent, chemiluminescent, and other labels to measure markers at lower detection limits, background interference from biological samples and detection instrumentation remains problematic. Optical biosensors offer the promise of label-free real-time measurements, but their application to quantification of analytes in complex media is impaired by higher detection limits and is susceptible to changes in refractive indices or nonspecific surface binding. Moreover, the costliness of these devices has largely prohibited bedside implementation. In this report, we detail the use of a novel diffractive optics technology (dot™) that takes advantage of the inherent properties of diffractive optics to deliver a cost-effective, portable, robust, optical biosensor that detects analytes at picomolar concentrations in complex media.In the dotLab TM System, coherent light striking a nonrandom pattern of capture molecules on the dotLab Sensor creates constructive and destructive interferences that produce a well-defined diffraction image. As molecules bind to the capture molecules, the height of the diffraction pattern is increased, which in turn increases the diffraction efficiency and the diffractive order intensity. A photodiode monitors the intensity of the diffractive order, which is correlated to analyte concentrations. Because diffraction is inherently self-referencing, the transduction of binding events is dependent on the initial pattern, and an increase in diffractive order intensity will occur only if molecules bind exclusively to the patterned capture reagents. Therefore, nonspecific binding to both the patterned and nonpatterned regions will not affect the signal, a characteristic that offers an important advantage over other optical biosensor systems in which any surfacebinding event will cause an increase in signal.Previous diffraction-based immunosensors have used silicon wafer chips that were in contact with analytecontaining solutions and required washing and drying before analysis by a simple reader (3 ). The dotLab system uses a plastic consumable, the dotLab Sensor, with an integrated prism situated below the flow channel so that the light source interrogates the diffraction grating without passing through the bulk solution. Previous studies suggest that this total internal reflection scheme allows for 95% of the laser intensity to be measured, whereas in a nontotal internal reflection set-up only 5% is measured (4 ). Moreover, with this configuration, our system monitors biomolecule binding in real time and in complex media.We tested the beta prototype of the dotLab instrument, which incorporates the core dot technology in an integrated package intended for in-house and con...

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Label-free monitoring of multiple biomolecular binding interactions in real-time with diffraction-based sensing

Cited by 48 publications

References 13 publications

Surface-relief-gratings based on molecularly imprinted polymer for 2,4-dichlorophenoxyacetic acid detection

Surface-relief-gratings based on molecularly imprinted polymer for 2,4-dichlorophenoxyacetic acid detection

Free-Solution, Label-Free Molecular Interactions Studied by Back-Scattering Interferometry

Diffractive Optics Technology: A Novel Detection Technology for Immunoassays

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