3,102 research outputs found
Optimization of micropillar sequences for fluid flow sculpting
Inertial fluid flow deformation around pillars in a microchannel is a new
method for controlling fluid flow. Sequences of pillars have been shown to
produce a rich phase space with a wide variety of flow transformations.
Previous work has successfully demonstrated manual design of pillar sequences
to achieve desired transformations of the flow cross-section, with experimental
validation. However, such a method is not ideal for seeking out complex
sculpted shapes as the search space quickly becomes too large for efficient
manual discovery. We explore fast, automated optimization methods to solve this
problem. We formulate the inertial flow physics in microchannels with different
micropillar configurations as a set of state transition matrix operations.
These state transition matrices are constructed from experimentally validated
streamtraces. This facilitates modeling the effect of a sequence of
micropillars as nested matrix-matrix products, which have very efficient
numerical implementations. With this new forward model, arbitrary micropillar
sequences can be rapidly simulated with various inlet configurations, allowing
optimization routines quick access to a large search space. We integrate this
framework with the genetic algorithm and showcase its applicability by
designing micropillar sequences for various useful transformations. We
computationally discover micropillar sequences for complex transformations that
are substantially shorter than manually designed sequences. We also determine
sequences for novel transformations that were difficult to manually design.
Finally, we experimentally validate these computational designs by fabricating
devices and comparing predictions with the results from confocal microscopy
Shape-design for stabilizing micro-particles in inertial microfluidic flows
Design of microparticles which stabilize at the centerline of a channel flow
when part of a dilute suspension is examined numerically for moderate Reynolds
numbers (). Stability metrics for particles with arbitrary
shapes are formulated based on linear-stability theory. Particle shape is
parametrized by a compact, Non-Uniform Rational B-Spline (NURBS)-based
representation. Shape-design is posed as an optimization problem and solved
using adaptive Bayesian optimization. We focus on designing particles for
maximal stability at the channel-centerline robust to perturbations. Our
results indicate that centerline-focusing particles are families of
characteristic "fish"/"bottle"/"dumbbell"-like shapes, exhibiting fore-aft
asymmetry. A parametric exploration is then performed to identify stable
particle-designs at different k's (particle chord-to-channel width ratio) and
Re's (). Particles at high-k's and Re's
are highly stabilized when compared to those at low-k's and Re's. A comparison
of the modified dumbbell designs from the current framework also shows better
performance to perturbations in Fluid-Structure Interaction (FSI) when compared
to the rod-disk model reported previously (Uspal & Doyle 2014) for low-Re
Hele-Shaw flow. We identify basins of attraction around the centerline, which
span larger release-angle-ranges and lateral locations (tending to the channel
width) for narrower channels, which effectively standardizes the notion of
global focusing in such configurations using the current stability-paradigm.
The present framework is illustrated for 2D cases and is potentially
generalizable to stability in 3D flow-fields. The current formulation is also
agnostic to Re and particle/channel geometry which indicates substantial
potential for integration with imaging flow-cytometry tools and microfluidic
biosensing-assays.Comment: 27 pages, 18 figures, modified the LaTeX document template, corrected
typo
Optimized design of obstacle sequences for microfluidic mixing in an inertial regime
Mixing is a basic but challenging step to achieve in high throughput microfluidic applications such as organic synthesis or production of particles. A common approach to improve micromixer performance is to devise a single component that enhances mixing through optimal convection, and then sequence multiple such units back-to-back to enhance overall mixing at the end of the sequence. However, the mixing units are often optimized only for the initial non-mixed fluid composition, which is no longer the input condition for each subsequent unit. Thus, there is no guarantee that simply repeating a single mixing unit will achieve optimally mixed fluid flow at the end of the sequence. In this work, we analyzed sequences of 20 cylindrical obstacles, or pillars, to optimize the mixing in the inertial regime (where mixing is more difficult due to higher Péclet number) by managing their interdependent convection operations on the composition of the fluid. Exploiting a software for microfluidic design optimization called FlowSculpt, we predicted and optimized the interfacial stretching of two co-flowing fluids, neglecting diffusive effects. We were able to quickly design three different optimal pillar sequences through a space of 32^(20) possible combinations of pillars. As proof of concept, we tested the new passive mixer designs using confocal microscopy and full 3D CFD simulations for high Péclet numbers (Pe ≈O(10^(5-6)), observing fluid flow shape and mixing index at several cross-sections, reaching mixing efficiencies around 80%. Furthermore, we investigated the effect of the inter-pillar spacing on the most optimal design, quantifying the tradeoff between mixing performance and hydraulic resistance. These micromixer designs and the framework for the design in inertial regimes can be used for various applications, such as lipid nanoparticle fabrication which has been of great importance in vaccine scale up during the pandemic
Scheduling of space to ground quantum key distribution
Satellite-based platforms are currently the only feasible way of achieving intercontinental range for quantum communication, enabling thus the future global quantum internet. Recent demonstrations by the Chinese spacecraft Micius have spurred an international space race and enormous interest in the development of both scientific and commercial systems. Research efforts so far have concentrated upon in-orbit demonstrations involving a single satellite and one or two ground stations. Ultimately satellite quantum key distribution should enable secure network communication between multiple nodes, which requires efficient scheduling of communication with the set of ground stations. Here we present a study of how satellite quantum key distribution can service many ground stations taking into account realistic constraints such as geography, operational hours, and most importantly, weather conditions. The objective is to maximise the number of keys a set of ground stations located in the United Kingdom could share while simultaneously reflecting the communication needs of each node and its relevance in the network. The problem is formulated as a mixed-integer linear optimisation program and solved to a desired optimality gap using a state of the art solver. The approach is presented using a simulation run throughout six years to investigate the total number of keys that can be sent to ground stations
Development of the first 18F-labeled radiohybrid-based minigastrin derivative with high target affinity and tumor accumulation by substitution of the chelating moiety
In order to optimize elevated kidney retention of previously reported minigastrin derivatives, we substituted (R)-DOTAGA by DOTA in (R)-DOTAGA-rhCCK-16/-18. CCK-2R-mediated internalization and affinity of the new compounds were determined using AR42J cells. Biodistribution and µSPECT/CT imaging studies at 1 and 24 h p.i. were carried out in AR42J tumor-bearing CB17-SCID mice. Both DOTA-containing minigastrin analogs exhibited 3- to 5-fold better IC50 values than their (R)-DOTAGA-counterparts. natLu-labeled peptides revealed higher CCK-2R affinity than their natGa-labeled analogs. In vivo, tumor uptake at 24 h p.i. of the most affine compound, [19F]F-[177Lu]Lu-DOTA-rhCCK-18, was 1.5- and 13-fold higher compared to its (R)-DOTAGA derivative and the reference compound, [177Lu]Lu-DOTA-PP-F11N, respectively. However, activity levels in the kidneys were elevated as well. At 1 h p.i., tumor and kidney accumulation of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 and [18F]F-[natLu]Lu-DOTA-rhCCK-18 was high. We could demonstrate that the choice of chelators and radiometals has a significant impact on CCK-2R affinity and thus tumor uptake of minigastrin analogs. While elevated kidney retention of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 has to be further addressed with regard to radioligand therapy, its radiohybrid analog, [18F]F-[natLu]Lu-DOTA-rhCCK-18, might be ideal for positron emission tomography (PET) imaging due to its high tumor accumulation at 1 h p.i. and the attractive physical properties of fluorine-18
Micropillar sequence designs for fundamental inertial flow transformations
The ability to control the shape of a flow in a passive microfluidic device enables potential applications in chemical reaction control, particle separation, and complex material fabrication. Recent work has demonstrated the concept of sculpting fluid streams in a microchannel using a set of pillars or other structures that individually deform a flow in a predictable pre-computed manner. These individual pillars are then placed in a defined sequence within the channel to yield the composition of the individual flow deformations – and ultimately complex user-defined flow shapes. In this way, an elegant mathematical operation can yield the final flow shape for a sequence without an experiment or additional numerical simulation. Although these approaches allow for programming complex flow shapes without understanding the detailed fluid mechanics, the design of an arbitrary flow shape of interest remains difficult, requiring significant design iteration. The development of intuitive basic operations (i.e. higher-level functions that consist of combinations of obstacles) that act on the flow field to create a basis for more complex transformations would be useful in systematically achieving a desired flow shape. Here, we show eight transformations that could serve as a partial basis for more complex transformations. We initially used in-house, freely available custom software (uFlow), which allowed us to arrive at these transformations that include making a fluid stream concave and convex, tilting, stretching, splitting, adding a vertex, shifting, and encapsulating another flow stream. The pillar sequences corresponding to these transformations were subsequently fabricated and optically analyzed using confocal imaging – yielding close agreement with uFlow-predicted shapes. We performed topological analysis on each transformation, characterizing potential sequences leading to these outputs and trends associated with changing diameter and placement of the pillars. We classify operations into four sets of sequence-building concatenations: stacking, recursion, mirroring, and shaping. The developed basis should help in the design of microfluidic systems that have a phenomenal variety of applications, such as optofluidic lensing, enhanced heat transfer, or new polymer fiber design
Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping.
Tissue clearing methods promise to provide exquisite three-dimensional imaging information; however, there is a need for simplified methods for lower resource settings and for non-fluorescence based phenotyping to enable light microscopic imaging modalities. Here we describe the simplified CLARITY method (SCM) for tissue clearing that preserves epitopes of interest. We imaged the resulting tissues using light sheet microscopy to generate rapid 3D reconstructions of entire tissues and organs. In addition, to enable clearing and 3D tissue imaging with light microscopy methods, we developed a colorimetric, non-fluorescent method for specifically labeling cleared tissues based on horseradish peroxidase conversion of diaminobenzidine to a colored insoluble product. The methods we describe here are portable and can be accomplished at low cost, and can allow light microscopic imaging of cleared tissues, thus enabling tissue clearing and imaging in a wide variety of settings
Sequential Array Cytometry: Multi-Parameter Imaging with a Single Fluorescent Channel
Heterogeneity within the human population and within diseased tissues necessitates a personalized medicine approach to diagnostics and the treatment of diseases. Functional assays at the single-cell level can contribute to uncovering heterogeneity and ultimately assist in improved treatment decisions based on the presence of outlier cells. We aim to develop a platform for high-throughput, single-cell-based assays using well-characterized hydrodynamic cell isolation arrays which allow for precise cell and fluid handling. Here, we demonstrate the ability to extract spatial and temporal information about several intracellular components using a single fluorescent channel, eliminating the problem of overlapping fluorescence emission spectra. Integrated with imaging technologies such as wide field-of-view lens-free fluorescent imaging, fiber-optic array scanning technology, and microlens arrays, use of a single fluorescent channel will reduce the cost of reagents and optical components. Specifically, we sequentially stain hydrodynamically trapped cells with three biochemical labels all sharing the same fluorescence excitation and emission spectrum. These markers allow us to analyze the amount of DNA, and compare nucleus-to-cytoplasm ratio, as well as glycosylation of surface proteins. By imaging cells in real-time we enable measurements of temporal localization of cellular components and intracellular reaction kinetics, the latter is used as a measurement of multi-drug resistance. Demonstrating the efficacy of this single-cell analysis platform is the first step in designing and implementing more complete assays, aimed toward improving diagnosis and personalized treatments to complex diseases
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