3D capillary stop valves for versatile patterning inside microfluidic chips.

The patterning of antibodies in microfluidics chips is always a delicate process that is usually done in an open chip before bonding. Typical bonding techniques such as plasma treatment can harm the antibodies with as result that they are removed from our fabrication toolbox. Here we propose a method, based on capillary phenomena using 3D capillary valves, that autonomously and conveniently allows us to pattern liquids inside closed chips. We theoretically analyse the system and demonstrate how our analysis can be used as a design tool for various applications. Chips patterned with the method were used for simple immunodetection of a cardiac biomarker which demonstrates its suitability for antibody patterning.

Filling of charged cylindrical capillaries.

We provide an analytical model to describe the filling dynamics of horizontal cylindrical capillaries having charged walls. The presence of surface charge leads to two distinct effects: It leads to a retarding electrical force on the liquid column and also causes a reduced viscous drag force because of decreased velocity gradients at the wall. Both these effects essentially stem from the spontaneous formation of an electric double layer (EDL) and the resulting streaming potential caused by the net capillary-flow-driven advection of ionic species within the EDL. Our results demonstrate that filling of charged capillaries also exhibits the well-known linear and Washburn regimes witnessed for uncharged capillaries, although the filling rate is always lower than that of the uncharged capillary. We attribute this to a competitive success of the lowering of the driving forces (because of electroviscous effects), in comparison to the effect of weaker drag forces. We further reveal that the time at which the transition between the linear and the Washburn regime occurs may become significantly altered with the introduction of surface charges, thereby altering the resultant capillary dynamics in a rather intricate manner.

Nanofluidics in point of care applications.

Nanofluidics is generally described as the study of liquid flow in or around structures of 100 nm or smaller, and its use for lab on a chip devices has now been actively studied for two decades. Here a brief review is given of the impact that this nanofluidics research has had on point of care applications. Four areas are identified where nanofluidics has brought the largest contributions: single nanopores, nanoporous membranes, nanoconfinement and the use of concentration polarization. The sometimes revolutionary developments in these areas are briefly treated and finally challenges and future perspectives are described.

A modular versatile chip carrier for high-throughput screening of cell-biomaterial interactions.

The field of biomaterials research is witnessing a steady rise in high-throughput screening approaches, comprising arrays of materials of different physico-chemical composition in a chip format. Even though the cell arrays provide many benefits in terms of throughput, they also bring new challenges. One of them is the establishment of robust homogeneous cell seeding techniques and strong control over cell culture, especially for long time periods. To meet these demands, seeding cells with low variation per tester area is required, in addition to robust cell culture parameters. In this study, we describe the development of a modular chip carrier which represents an important step in standardizing cell seeding and cell culture conditions in array formats. Our carrier allows flexible and controlled cell seeding and subsequent cell culture using dynamic perfusion. To demonstrate the application of our device, we successfully cultured and evaluated C2C12 premyoblast cell viability under dynamic conditions for a period of 5 days using an automated pipeline for image acquisition and analysis. In addition, using computational fluid dynamics, lactate and BMP-2 as model molecules, we estimated that there is good exchange of nutrients and metabolites with the flowing medium, whereas no cross-talk between adjacent TestUnits should be expected. Moreover, the shear stresses to the cells can be tailored uniformly over the entire chip area. Based on these findings, we believe our chip carrier may be a versatile tool for high-throughput cell experiments in biomaterials sciences.

Concentration polarization in translocation of DNA through nanopores and nanochannels.

In this Letter we provide a theory to show that high-field electrokinetic translocation of DNA through nanopores or nanochannels causes large transient variations of the ionic concentrations in front and at the back of the DNA due to concentration polarization (CP). The CP causes strong local conductivity variations, which can successfully explain the nontrivial current transients and ionic distributions observed in molecular dynamics simulations of nanopore DNA translocations as well as the transient current dips and spikes measured for translocating hairpin DNA. Most importantly, as the future of sequencing of DNA by nanopore translocation will be based on time-varying electrical conductance, CP, must be considered in experimental design and interpretation--currently these studies are mostly based on the incomplete pore conductance models that ignore CP and transients in the electrical conductance.

Nanofluidic technology for biomolecule applications: a critical review.

In this review, we present nanofluidic phenomena, particularly as they relate to applications involving analysis of biomolecules within nanofabricated devices. The relevant length scales and physical phenomena that govern biomolecule transport and manipulation within nanofabricated nanofluidic devices are reviewed, the advantages of nanofabricated devices are presented, and relevant applications are cited. Characteristic length scales include the Debye length, the Van der Waals radius, the action distance of hydrogen bonding, the slip length, and macromolecular dimensions. On the basis of the characteristic lengths and related nanofluidic phenomena, a nanofluidic toolbox will be assembled. Nanofluidic phenomena that affect biomolecule behavior within such devices can include ion depletion and enrichment, modified velocity and mobility, permselectivity, steric hindrance, entropy, adsorption, and hydrodynamic interaction. The complex interactions and coupled physics of such phenomena allow for many applications, including biomolecule separation, concentration, reaction/hybridization, sequencing (in the case of DNA) and detection. Examples of devices for such applications will be presented, followed by a discussion of near-term challenges and future thoughts for the field.

Principles and applications of nanofluidic transport.

The evolution from microfluidic to nanofluidic systems has been accompanied by the emergence of new fluid phenomena and the potential for new nanofluidic devices. This review provides an introduction to the theory of nanofluidic transport, focusing on the various forces that influence the movement of both solvents and solutes through nanochannels, and reviews the applications of nanofluidic devices in separation science and energy conversion.

Electrophoretic separation of DNA in gels and nanostructures.

The development of nanostructure devices has opened the door to new DNA separation techniques and fundamental investigations. With advanced nanotechnologies, artificial gels (e.g. nanopillar arrays, nanofilters) can be manufactured with controlled and ordered geometries. This contrast with gels, where the pores are disordered and the range of available pore sizes is limited by the level of cross-linking and the mechanical properties of the gel. In this review, we recall the theories developed for free-solution and gel electrophoresis (extended Ogston model, biased reptation and entropic trapping) and from this perspective, suggestions for future concepts for fast DNA separation using nanostructures will be given.

Strongly accelerated and humidity-independent drying of nanochannels induced by sharp corners.

Measurements are shown indicating that the drying rate of nanochannels can be enhanced by up to 3 orders of magnitude relative to drying by vapor diffusion, and that the drying rate is independent of the relative humidity of the environment up to a relative humidity of more than 90%. Micromachined Pyrex glass nanochannels of 72 nm height and with sharp corners (corner angles 7 degrees) were used. Available theory shows that the sharp corners function as a low-resistance pathway for liquid water, siphoning (wicking) the water to a location close to the channel exit before it evaporates. The described phenomena are of importance for the understanding of drying processes in industry and agriculture. The introduction of sharp corners or grooves can furthermore be beneficial for the functioning of microheat pipes and capillary-pumped loops.

Technologies for nanofluidic systems: top-down vs. bottom-up--a review.

This paper gives an overview of the most commonly used techniques for nanostructuring and nanochannel fabrication employed in nanofluidics. They are divided into two large categories: top-down and bottom-up methods. Top-down methods are based on patterning on large scale while reducing the lateral dimensions to the nanoscale. Bottom-up methods arrange atoms and molecules in nanostructures. Here, we review the advantages and disadvantages of those methods and give some future perspectives. It is concluded that technology in the region of 1-10 nm is lacking and potentially can be covered by using the pulsed-laser deposition method as a controlled way for thin film deposition (thickness of a few nanometers) and further structuring by the top-down method.

An AC electroosmotic micropump for circular chromatographic applications.

Flow rates of up to 50 microm s(-1) have been successfully achieved in a closed-loop channel using an AC electroosmotic pump. The AC electroosmotic pump is made of an interdigitated array of unequal width electrodes located at the bottom of a channel, with an AC voltage applied between the small and the large electrodes. The flow rate was found to increase linearly with the applied voltage and to decrease linearly with the applied frequency. The pump is expected to be suitable for circular chromatography for the following reasons: the driving forces are distributed over the channel length and the pumping direction is set by the direction of the interdigitated electrodes. Pumping in a closed-loop channel can be achieved by arranging the electrode pattern in a circle. In addition the inherent working principle of AC electroosmotic pumping enables the independent optimisation of the channel height or the flow velocity.

A wireless electrochemiluminescence detector applied to direct and indirect detection for electrophoresis on a microfabricated glass device.

A novel electrochemiluminescence (ECL) detector is presented in this article. The detector is applied for micellar electrokinetic chromatographic separation of dichlorotris(2,2'-bipyridyl)ruthenium(II) hydrate [Ru-(bpy)] and dichlorotris(1,10-phenanthroline)ruthenium-(II) hydrate [Ru(phen)] on a microfabricated glass device. It consists of a microfabricated "U"-shape floating platinum electrode placed across the separation channel. The legs of the U function respectively as working and counter electrode. The required potential difference for the ECL reaction is generated at the Pt electrode by the electric field available in the separation channel during electrophoretic separation. Initial experiments demonstrate a micellar electrokinetic separation and direct ECL detection of 10(-16) mol of Ru(phen) (10(-6) M) and 4.5 x 10(-16) mol of Ru(bpy) (5 x 10(-6) M). Also, preliminary results show the indirect detection of three amino acids. The high voltage at the location of detection does not interfere with the electrochemistry.

Wavelet transform for Shah convolution velocity measurements of single particles and solutes in a microfluidic chip.

Wavelet transform analysis is applied to determine the speed of fluorescent polystyrene microspheres and fluorescent solutes in a microchip. The data analysed consist of the periodical signal (Shah convolution) obtained when fluorescent particles or solute plugs move in a channel that is covered with a chromium grid pattern. This setup converts velocity into a (fluorescence emission) frequency, and previous analyses therefore used Fourier transform to extract the frequency information. In this paper it is shown that wavelet transform has some advantages over Fourier transform. With wavelet transform, time information can be obtained in addition to frequency information. Thus the speed of individual particles was determined together with their moments of appearance and disappearance in the system. With solutes small changes of velocity during the analysis were detected, and an improvement in peak frequency resolution was obtained.