Holographic molecular binding assays

Zagzag, Yvonne; Soddu, M. Francesca; Hollingsworth, Andrew D.; Grier, David G.

doi:10.1038/s41598-020-58833-7

Cited by 13 publications

(21 citation statements)

References 24 publications

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“…Holographic microscopy has recently been demonstrated as being sensitive enough for this task. 176 One of the inventors of the technique has suggested that it can be used for detecting antibodies from COVID-19 infection or whole virions of SARS-CoV-2. 177 For completeness, we mention the state of aggregation of viruses, which must be known, e.g., in order to understand the meaning of viral titre measurements in terms of plague forming units.…”

Section: Detectionmentioning

confidence: 99%

Soft matter science and the COVID-19 pandemic

et al. 2020

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Section: Detectionmentioning

confidence: 99%

Soft matter science and the COVID-19 pandemic

et al. 2020

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“…Measurements on emulsion droplets demonstrate precision and reproducibility in the refrac-tive index of ±1 part per thousand [27]. The former is fine enough to detect the formation of a molecular coating on a bead through the associated change in the bead's diameter [5,28]. The latter is useful for distinguishing different types of beads on the basis of their composition [29].…”

Section: Holographic Particle Characterizationmentioning

confidence: 99%

“…Holographic particle characterization [1] is a fast and robust technique for measuring the size and refractive index of colloidal spheres and has a wide variety of applications in basic research [2][3][4][5], industrial materials analysis [6] and medical diagnostics [5,7]. As illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

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Holographic characterization and tracking of colloidal dimers in the effective-sphere approximation

Altman¹,

Quddus²,

Cheong³

et al. 2020

Preprint

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An in-line hologram of a colloidal sphere can be analyzed with the Lorenz-Mie theory of light scattering to measure the sphere's three-dimensional position with nanometer-scale precision while also measuring its diameter and refractive index with part-per-thousand precision. Applying the same technique to aspherical or inhomogeneous particles yields the position, diameter and refractive index of an effective sphere that represents an average over the particle's geometry and composition. This effective-sphere interpretation has been applied successfully to porous, dimpled and coated spheres, as well as to fractal clusters of nanoparticles, all of whose inhomogeneities appear on length scales smaller than the wavelength of light. Here, we combine numerical and experimental studies to investigate effective-sphere characterization of symmetric dimers of micrometer-scale spheres, a class of aspherical objects that appear commonly in real-world dispersions. Our studies demonstrate that the effective-sphere interpretation usefully identifies dimers in holographic characterization studies of monodisperse colloidal spheres. The effective-sphere estimate for a dimer's axial position closely follows the ground truth for its center of mass. Trends in the effective-sphere diameter and refractive index, furthermore, can be used to measure a dimer's three-dimensional orientation. When applied to colloidal dimers transported in a Poiseuille flow, the estimated orientation distribution is consistent with expectations for Brownian particles undergoing Jeffery orbits.

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“…Holographic particle characterization works by recording the in-line hologram of a colloidal particle [1] and then analyzing it pixel-by-pixel [2] with a generative model based on the Lorenz-Mie theory of light scattering [3][4][5]. This analysis yields the particle's diameter with nanometer-scale precision and its refractive index to within a part per thousand [2,6], which should be fine enough to detect nanometer-scale molecules binding to the surfaces of micrometer-scale colloidal beads [7,8]. The resulting label-free assay for molecular binding, shown schematically in Fig.…”

Section: Introductionmentioning

confidence: 99%

Interpreting Holographic Molecular Binding Assays with Effective Medium Theory

Altman¹,

Grier²

2020

Preprint

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Holographic molecular binding assays use holographic video microscopy to directly detect molecules binding to the surfaces of micrometer-scale colloidal beads by monitoring associated changes in the beads' light-scattering properties. Holograms of individual spheres are analyzed by fitting to a generative model based on the Lorenz-Mie theory of light scattering. Each fit yields an estimate of a probe bead's diameter and refractive index with sufficient precision to watch the beads grow as molecules bind. Rather than modeling the molecular-scale coating, however, these fits use effective medium theory, treating the coated sphere as if it were homogeneous. This effectivesphere analysis is rapid and numerically robust and so is useful for practical implementations of label-free immunoassays. Here, we assess how effective-sphere properties reflect the properties of molecular-scale coatings by modeling coated spheres with the discrete-dipole approximation and analyzing their holograms with the effective-sphere model.

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Holographic molecular binding assays

Cited by 13 publications

References 24 publications

Soft matter science and the COVID-19 pandemic

Soft matter science and the COVID-19 pandemic

Holographic characterization and tracking of colloidal dimers in the effective-sphere approximation

Interpreting Holographic Molecular Binding Assays with Effective Medium Theory

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