Publications by authors named "David Grier"

In-line holographic video microscopy records a wealth of information about the microscopic structure and dynamics of colloidal materials. Powerful analytical techniques are available to retrieve that information when the colloidal particles are well separated. Large assemblies of close-packed particles create holograms that are substantially more challenging to interpret.

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Acoustic trapping uses forces exerted by sound waves to transport small objects along specified trajectories in three dimensions. The structure of the time-averaged acoustic force landscape acting on an object is determined by the amplitude and phase profiles of the sound's pressure wave. These profiles typically are sculpted by deliberately selecting the amplitude and relative phase of the sound projected by each transducer in large arrays of transducers, all operating at the same carrier frequency.

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Emulsion droplets on the colloidal length scale are a model system of frictionless compliant spheres. Direct imaging studies of the microscopic structure and dynamics of emulsions offer valuable insights into fundamental processes, such as gelation, jamming, and self-assembly. A microscope, however, can only resolve the individual droplets in a densely packed emulsion if the droplets are closely index-matched to their fluid medium.

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Acoustic traps use forces exerted by sound waves to confine and transport small objects. The dynamics of an object moving in the force landscape of an acoustic trap can be significantly influenced by the inertia of the surrounding fluid medium. These inertial effects can be observed by setting a trapped object in oscillation and tracking it as it relaxes back to mechanical equilibrium in its trap.

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Holographic particle characterization treats holographic microscopy of colloidal particles as an inverse problem whose solution yields the diameter, refractive index and three-dimensional position of each particle in the field of view, all with exquisite precision. This rich source of information on the composition and dynamics of colloidal dispersions has created new opportunities for fundamental research in soft-matter physics, statistical physics and physical chemistry, and has been adopted for product development, quality assurance and process control in industrial applications. Aberrations introduced by real-world imaging conditions, however, can degrade performance by causing systematic and correlated errors in the estimated parameters.

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Shear flows cause aspherical colloidal particles to tumble so that their orientations trace out complex trajectories known as Jeffery orbits. The Jeffery orbit of a prolate ellipsoid is predicted to align the particle's principal axis preferentially in the plane transverse to the axis of shear. Holographic microscopy measurements reveal instead that colloidal ellipsoids' trajectories in Poiseuille flows strongly favor an orientation inclined by roughly π/8 relative to this plane.

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Holographic particle characterization uses in-line holographic video microscopy to track and characterize individual colloidal particles dispersed in their native fluid media. Applications range from fundamental research in statistical physics to product development in biopharmaceuticals and medical diagnostic testing. The information encoded in a hologram can be extracted by fitting to a generative model based on the Lorenz-Mie theory of light scattering.

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The mobility of a colloidal particle in a slit pore is modified by the particle's hydrodynamic coupling to the bounding surfaces and therefore depends on the particle's position within the pore and its direction of motion. We report holographic particle tracking measurements of colloidal particles' diffusion and sedimentation between parallel horizontal walls that yield the mobility for motions perpendicular to the walls, including its dependence on height within the channel. These measurements complement previous studies that probed colloidal mobility parallel to confining surfaces.

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Holographic particle characterization uses quantitative analysis of holographic microscopy data to precisely and rapidly measure the diameter and refractive index of individual colloidal spheres in their native media. When this technique is applied to inhomogeneous or aspherical particles, the measured diameter and refractive index represent properties of an effective sphere enclosing each particle. Effective-sphere analysis has been applied successfully to populations of fractal aggregates, yielding an overall fractal dimension for the population as a whole.

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The intensity distribution of a holographically-projected optical trap can be tailored to the physical properties of the particles it is intended to trap. Dynamic optimization is especially desirable for manipulating dark-seeking particles that are repelled by conventional optical tweezers, and even more so when dark-seeking particles coexist in the same system as light-seeking particles. We address the need for dexterous manipulation of dark-seeking particles by introducing a class of "dark" traps created from the superposition of two out-of-phase Gaussian modes with different waist diameters.

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mutations have recently been implicated in congenital neutropenia (CN) and the in-frame deletion, p.Thr117del, is the most common pathogenic mutation reported. The largest study of -mutated CN to-date followed 23 patients for a median of 15 years.

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The measurement of polydisperse protein aggregates and particles in biotherapeutics remains a challenge, especially for particles with diameters of ≈ 1 µm and below (sub-micrometer). This paper describes an interlaboratory comparison with the goal of assessing the measurement variability for the characterization of a sub-micrometer polydisperse particle dispersion composed of five sub-populations of poly(methyl methacrylate) (PMMA) and silica beads. The study included 20 participating laboratories from industry, academia, and government, and a variety of state-of-the-art particle-counting instruments.

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ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized.

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Background: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening hyperinflammatory syndrome that occurs after primary SARS-CoV-2 infection. The pathogenesis of MIS-C remains undefined, and whether specific inflammatory biomarker patterns can distinguish MIS-C from other hyperinflammatory syndromes, including Kawasaki disease and macrophage activation syndrome (MAS), is unknown. Therefore, we aimed to investigate whether inflammatory biomarkers could be used to distinguish between these conditions.

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The programmability of DNA oligonucleotides has led to sophisticated DNA nanotechnology and considerable research on DNA nanomachines powered by DNA hybridization. Here, we investigate an extension of this technology to the micrometer-colloidal scale, in which observations and measurements can be made in real time/space using optical microscopy and holographic optical tweezers. We use semirigid DNA origami structures, hinges with mechanical advantage, self-assembled into a nine-hinge, accordion-like chemomechanical device, with one end anchored to a substrate and a colloidal bead attached to the other end.

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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 measurements of 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.

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The size of a probe bead reported by holographic particle characterization depends on the proportion of the surface area covered by bound target molecules and so can be used as an assay for molecular binding. We validate this technique by measuring the kinetics of irreversible binding for the antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) as they attach to micrometer-diameter colloidal beads coated with protein A. These measurements yield the antibodies' binding rates and can be inverted to obtain the concentration of antibodies in solution.

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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 a population of beads grow as molecules bind.

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Background: To initiate the development of a machine learning algorithm capable of comparing segments of pre and post pamidronate whole body MRI scans to assess treatment response and to compare the results of this algorithm with the analysis of a panel of paediatric radiologists.

Methods: Whole body MRI of patients under the age of 16 diagnosed with CNO and treated with pamidronate at a tertiary referral paediatric hospital in United Kingdom between 2005 and 2017 were reviewed. Pre and post pamidronate images of the commonest sites of involvement (distal femur and proximal tibia) were manually selected (n = 45).

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We demonstrate the use of holographic video microscopy to detect individual subvisible particles dispersed in biopharmaceutical formulations and to differentiate them based on material characteristics measured from their holograms. The result of holographic analysis is a precise and accurate measurement of the concentrations and size distributions of multiple classes of subvisible contaminants dispersed in the same product simultaneously. We demonstrate this analytical technique through measurements on model systems consisting of human IgG aggregates in the presence of common contaminants such as silicone oil emulsion droplets and fatty acids.

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Article Synopsis
  • The TRPV6 channel is essential for transporting calcium from mother to fetus, and mutations in this channel can lead to severe skeletal dysplasia in infants.
  • A case report describes a female infant with significant skeletal abnormalities detected as early as 20 weeks gestation, who faced a challenging postnatal course, including reliance on ventilation and subsequent cardiac arrest.
  • Genetic testing revealed two TRPV6 variants, and post-mortem examinations showed specific skeletal issues along with some recovery indicators, including improved bone density and changes in rib and long bone structure.
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In-line holographic microscopy provides an unparalleled wealth of information about the properties of colloidal dispersions. Analyzing one colloidal particle's hologram with the Lorenz-Mie theory of light scattering yields the particle's three-dimensional position with nanometer precision while simultaneously reporting its size and refractive index with part-per-thousand resolution. Analyzing a few thousand holograms in this way provides a comprehensive picture of the particles that make up a dispersion, even for complex multicomponent systems.

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