Microfluidic multipoles: theory and applications

Microfluidic multipoles (MFMs) have been realized experimentally and hold promise for "open-space" biological and chemical surface processing. Whereas convective flow can readily be predicted using hydraulic-electrical analogies, the design of advanced MFMs is constrained by the lack of simple, accurate models to predict mass transport within them. In this work, we introduce the first exact solutions to mass transport in multipolar microfluidics based on the iterative conformal mapping of 2D advection-diffusion around a simple edge into dipoles and multipolar geometries, revealing a rich landscape of transport modes. The models were validated experimentally with a library of 3D printed MFM devices and found in excellent agreement. Following a theory-guided design approach, we further ideated and fabricated two new classes of spatiotemporally reconfigurable MFM devices that are used for processing surfaces with time-varying reagent streams, and to realize a multistep automated immunoassay. Overall, the results set the foundations for exploring, developing, and applying open-space MFMs.Comment: 16 pages, 5 figure

Slide spatial bias in antibody microarrays: from characterization to minimization

Antibody microarrays enable multiplexed protein detection with minimal reagent consumption, and although quality appears adequate when characterized using local replicates, they continue to be plagued by lack of reproducibility. Chemically-functionalized glass slides are the foundation of antibody microarrays, yet spatial inhomogeneity and its effect on assay variability has not been analyzed. Here, we (i) characterize spatial bias in antibody microarrays by measuring signal variation across the surface of 5 commercial slide models, and (ii) develop an experimental approach to minimize bias and optimize assay reproducibility. We used PBS and the 2 optimal buffers (among 28) for each slide to print 3 different antibodies as 9 overlapping arrays across the slide. The fluorescence for antibody immobilization and assay signal of 5 different slide models was used to generate 270 heatmaps characterizing the spatial bias and variability, which varied significantly across models. We then compared reproducibility measures obtained with local, random, and structured random replicates; local replicates poorly estimated the whole-slide mean signal and gave misleading CV values up to 7 times less than the 'true' whole-slide CV, while structured random replicates distributed throughout the slide gave the most accurate estimates. When using a slide model with low spatial bias, assays achieved good intra-slide CV of 7.3% and inter-slide of 6.3%. Our results highlight spatial bias as an underappreciated source of variability and the inadequacy of commonly used local replicates in assessing assay performance, leading us to recommend the use of distributed replicates to ensure reproducibility of antibody microarray results.Les biopuces d'anticorps permettent la détection multiplexée de protéines avec consommation minimale de réactifs, et bien que leur qualité paraisse adéquate lorsqu'elles sont caractérisées à l'aide de répétitions locales, elles continuent d'être atteintes d'un manque de reproductibilité. Les lames de verre fonctionnalisées chimiquement constituent le fondement des biopuces d'anticorps, mais l'inhomogénéité spatiale et son impact sur la variabilité de ces tests immunologiques n'ont pas été analysés. Dans ce travail, nous (i) caractérisons le biais spatial des biopuces d'anticorps en mesurant la variation du signal à la surface de cinq modèles de lames de verre commerciales, et (ii) nous développons une approche expérimentale pour minimiser le biais et optimiser la reproductibilité du test immunologique. Nous avons utilisé du PBS et deux solutions tampons optimales (parmi 28) pour chaque lame afin d'imprimer trois anticorps différents, créant neuf biopuces superposées à la surface des lames. Les signaux fluorescents associés à l'immobilisation des anticorps et au test immunologique menés sur cinq modèles de lames ont été utilisés pour générer 270 cartes thermiques qui caractérisent le biais spatial et la variabilité, lesquels diffèrent significativement d'un modèle de lame à l'autre. Nous avons ensuite comparé la reproductibilité obtenue avec des répétitions locales, aléatoires, et aléatoires-structurées; les répétitions locales ont mal estimé les « vraies » valeurs de la moyenne et du CV de la lame complète et ont produit des valeurs de CV trompeuses, jusqu'à 7 fois inférieures aux « vraies » valeurs, tandis que les répétitions aléatoires-structurées ont produit les estimations les plus précises. En utilisant un modèle de lame avec un biais spatial faible, nous avons mesuré la concentration d'une protéine avec une biopuce d'anticorps et obtenu un bon CV intra-lame de 7,3 % et inter-lame de 6,3 %. Nos résultats mettent en évidence que le biais spatial est une source de variabilité sous-estimée et que les répétitions locales sont insuffisantes pour mesurer la performance des tests immunologiques, ce qui nous mène à suggérer l'utilisation de répétitions distribuées pour assurer la reproductibilité des résultats de biopuces d'anticorps

Preschool behavior and first-grade achievement : the mediational role of cognitive self-control

The purpose of this study was to test a model of school achievement that included children's intellectual abilities, preschool behavior, and cognitive self-control. It suggested that teacher-rated preschool behavior such as aggressive, anxious-withdrawn, and prosocial behaviors influence cognitive self-control, which in turn positively determines school achievement at the end of first grade (when controlling for intellectual abilities). Participants were 291 kindergarten children. Results from structural equation modeling demonstrated that all hypothesized path models were significant, except the one between anxious-withdrawn behavior and cognitive self-control. A second model was thus specified in which a path between anxious-withdrawn behavior and school achievement was estimated. The second model offered a better representation of the sample data (comparative fit index = .99, nonnormed fit index = .98), χ²(19, N = 286) = 29.43, p > .05, and the path between anxious-withdrawn behavior and school achievement was found significant. The role of preschool behavior and cognitive self-control in first-grade school achievement is discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved