Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

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Microfluidics: Fluid physics at the nanoliter scale

1. Introduction 2. Theoretical foundations 3. Propagation and focusing of optical fields 4. Spatial resolution and position accuracy 5. Nanoscale optical microscopy 6. Near-field optical probes 7. Probe-sample distance control 8. Light emission and optical interaction in nanoscale environments 9. Quantum emitters 10. Dipole emission near planar interfaces 11. Photonic crystals and resonators 12. Surface plasmons 13. Forces in confined fields 14. Fluctuation-induced phenomena 15. Theoretical methods in nano-optics Appendices Index.

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Principles of nano-optics

Differently from passive Brownian particles, active particles, also known as self-propelled Brownian particles or microswimmers and nanoswimmers, are capable of taking up energy from their environment and converting it into directed motion. Because of this constant flow of energy, their behavior can be explained and understood only within the framework of nonequilibrium physics. In the biological realm, many cells perform directed motion, for example, as a way to browse for nutrients or to avoid toxins. Inspired by these motile microorganisms, researchers have been developing artificial particles that feature similar swimming behaviors based on different mechanisms. These man-made micromachines and nanomachines hold a great potential as autonomous agents for health care, sustainability, and security applications. With a focus on the basic physical features of the interactions of self-propelled Brownian particles with a crowded and complex environment, this comprehensive review will provide a guided tour through its basic principles, the development of artificial self-propelling microparticles and nanoparticles, and their application to the study of nonequilibrium phenomena, as well as the open challenges that the field is currently facing.

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Active Particles in Complex and Crowded Environments

This review reports the progress on the recent development of micromixers. The review first presents the different micromixer types and designs. Micromixers in this review are categorized as passive micromixers and active micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, passive micromixers will be the focus of this review. Next, the review discusses the operation points of the micromixers based on characteristic dimensionless numbers such as Reynolds number Re, Peclet number Pe, and in dynamic cases the Strouhal number St. The fabrication technologies for different mixer types are also analysed. Quantification techniques for evaluation of the performance of micromixers are discussed. Finally, the review addresses typical applications of micromixers.

https://iopscience.iop.org/article/10.1088/0960-1317/15/2/R01/pdf

Micromixers?a review

Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome–DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain ∼50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.

http://absimage.aps.org/image/MAR08/MWS_MAR08-2008-020581.pdf

The Genomic Code for Nucleosome Positioning

We report a direct measurement of the hydrodynamic interaction between two colloidal particles. Two micron-sized latex beads were held at varying distances in optical tweezers while their Brownian displacements were measured. In spite of the fact that fluid systems at low Reynolds number are generally considered to have no “memory,” the cross-correlation function of the bead positions shows a pronounced, time-delayed anticorrelation. We show that the anticorrelations can be understood in terms of the standard Oseen tensor hydrodynamic coupling.

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Direct Measurement of Hydrodynamic Cross Correlations between Two Particles in an External Potential

Mixing two liquids on a microfluidic chip is notoriously hard because the small dimensions and velocities on the chip effectively prevent turbulence. We present a topological mixing scheme that exploits the laminarity of the flow to repeatedly fold the flow and exponentially increase the concentration gradients to obtain fast and efficient mixing by diffusion. It is based on helical flow channels with opposite chiralities that split, rotate, and recombine the fluid stream in a topology reminiscent of a series of Mobius bands. This geometry is realized in a simple six-stage, two-layer elastomer structure with a footprint of 400 μm×300 μm per stage that mixes two solutions efficiently at Reynolds numbers between 0.1 and 2. This represents more than an order of magnitude reduction in the size of microfluidic mixers that can be manufactured in standard multilayer soft lithography techniques.

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Topologic mixing on a microfluidic chip

We studied the thermal fluctuations of single DNA molecules with a novel optical tweezer based force spectroscopy technique. This technique combines femtonewton sensitivity with millisecond time resolution, surpassing the sensitivity of previous force measurements in aqueous solution with comparable bandwidth by a hundredfold. Our data resolve long-standing questions concerning internal hydrodynamics of the polymer and anisotropy in the molecular relaxation times and friction coefficients. The dynamics at high extension show interesting nonlinear behavior.

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Femtonewton force spectroscopy of single extended DNA molecules.

We have studied the adsorption of poly(styrene-b-2-vinylpyridine) block copolymers from a selective solvent onto a flat solid substrate, resulting in the formation of laterally ordered microdomains. We address the question whether the lateral domain structure is due to adsorption of entire micelles from the solution. Dynamic light scattering, atomic force microscopy, surface plasmon spectroscopy, and transmission electron microscopy were used to characterize the polymer solution, the adsorption process, and the resulting polymer layer, respectively. A quantitative comparison of the results obtained with different techniques strongly indicates direct adsorption of whole micelles onto a brush formed from free copolymer chains. Furthermore, the adsorption process is found to depend strongly on the velocity at which the samples are withdrawn from the solution.

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Adsorption of Block-Copolymer Micelles from a Selective Solvent

Multilayer soft lithography was used to prepare a poly(dimethylsiloxane) microfluidic chip that allows for in vivo sampling of amino acid neurotransmitters by low-flow push−pull perfusion. The chip incorporates a pneumatically actuated peristaltic pump to deliver artificial cerebrospinal fluid to a push−pull perfusion probe, pull sample from the probe, perform on-line derivatization with o-phthaldialdehyde, and push derivatized amino acids into the flow-gated injector of a high-speed capillary electrophoresis−laser-induced fluorescence instrument. Peristalsis was achieved by sequential actuation of six, 200 μm wide by 15 μm high control valves that drove fluid through three fluidic channels of equal dimensions. Electropherograms with 100 000 theoretical plates were acquired at ∼20-s intervals. Relative standard deviations of peak heights were 4% in vitro, and detection limits for the excitatory amino acids were ∼60 nM. For in vivo measurements, push−pull probes were implanted in the striatum of anesthetiz...

Jens-Christian Meiners

Papers

Direct Measurement of Hydrodynamic Cross Correlations between Two Particles in an External Potential

Topologic mixing on a microfluidic chip

Femtonewton force spectroscopy of single extended DNA molecules.

Adsorption of Block-Copolymer Micelles from a Selective Solvent

Microfluidic chip for low-flow push-pull perfusion sampling in vivo with on-line analysis of amino acids