Two-dimensional paper networks: programmable fluidic disconnects for multi-step processes in shaped paper

Most laboratory assays take advantage of multi-step protocols to achieve high performance, but conventional paper-based tests (e.g., lateral flow tests) are generally limited to assays that can be carried out in a single fluidic step. We have developed two-dimensional paper networks (2DPNs) that use materials from lateral flow tests but reconfigure them to enable programming of multi-step reagent delivery sequences. The 2DPN uses multiple converging fluid inlets to control the arrival time of each fluid to a detection zone or reaction zone, and it requires a method to disconnect each fluid source in a corresponding timed sequence. Here, we present a method that allows programmed disconnection of fluid sources required for multi-step delivery. A 2DPN with legs of different lengths is inserted into a shared buffer well, and the dropping fluid surface disconnects each leg at in a programmable sequence. This approach could enable multi-step laboratory assays to be converted into simple point-of-care devices that have high performance yet remain easy to use.     

Layer-to-layer parallel fluidic transportation system by addressable fluidic gate arrays

This paper presents addressable fluidic gate arrays for a layer-to-layer parallel fluidic transportation system. The proposed addressable fluidic gate consists of double valves driven by pneumatic pressure. One of the double valves is controlled by the row channel and the other is controlled by the column channel for row/column addressing. Our study applies addressable fluidic gate arrays to layer-to-layer transportation beyond a typical in-plane fluidic network system. The layer-to-layer transportation makes it possible to collect targeted samples from a testing well plate. 3 x 3 fluidic gate arrays based on the proposed concept are developed and tested. A single PDMS valve (phi400 microm) can be closed by 75.0 kPa. The demonstrated fluidic system is based on all PDMS structures by taking account of its disposable use. This paper also reports a dome-shaped chamber for robust sealing and a switching valve with a bistable diaphragm for memory function.     

Thermally controlled fluidic self-assembly

A novel approach for the fluidic self-assembly (FSA) of microparts in a multibatch process utilizing the thermal behavior of the carrier fluid as a means for selecting binding sites is presented. In the system studied, fluidic assembly takes place due to a capillary bridge between hexadecane deposited on a hydrophobic patch on a substrate and a hydrophobic surface on a micropart suspended in a carrier fluid. When desired, FSA of microparts is prevented by causing the surrounding carrier fluid to form a gel when heated, offering a method for directing self-assembly to sites that are not heated. It is shown that a suitable carrier fluid is 15 wt % Pluronic F127, which gels at about 40 degrees C when tested in the geometry used to demonstrate the concept. Experimental results demonstrating FSA and thermally controlled fluidic assembly (TCFSA) of plastic microparts dispersed in Pluronic F127 solution are presented. Potentially, TCFSA offers a general method for directed assembly as it relies on restricting the transport of microparts to a site rather than interfering with the fundamental attractive forces responsible for self-assembly.     

Dielectrophoresis-based cellular microarray chip for anticancer drug screening in perfusion microenvironments

We present a dielectrophoresis (DEP)-based cellular microarray chip for cell-based anticancer drug screening in perfusion microenvironments. Human breast cancer cells, MCF7, were seeded into the chip and patterned via DEP forces onto the planar interdigitated ring electrode (PIRE) arrays. Roughly, only one third of the cell amount was required for the chip compared to that for a 96-well plate control. Drug concentrations (cisplatin or docetaxel) were stably generated by functional integration of a concentration gradient generator (CGG) and an anti-crosstalk valve (ACV) to treat cells for 24 hours. Cell viability was quantified using a dual staining method. Results of cell patterning show substantial uniformity of patterned cells (92 ± 5 cells per PIRE). Furthermore, after 24 hour drug perfusion, no statistical significance in dose-responses between the chip and the 96-well plate controls was found. The IC(50) value from the chip also concurred with the values from the literature. Moreover, the perfusion culture exhibited reproducibility of drug responses of cells on different PIREs in the same chamber. The chip would enable applications where cells are of limited supply, and supplement microfluidic perfusion cultures for clinical practices.     

Dielectrophoresis-based particle exchanger for the manipulation and surface functionalization of particles

We present a microfluidic device where micro- and nanoparticles can be continuously functionalized in flow. This device relies on an element called "particle exchanger", which allows for particles to be taken from one medium and exposed to some reagent while minimizing mixing of the two liquids. In the exchanger, two liquids are brought in contact and particles are pushed from one to the other by the application of a dielectrophoretic force. We determined the maximum flow velocity at which all the particles are exchanged for a range of particle sizes. We also present a simple theory that accounts for the behaviour of the device when the particle size is scaled. Diffusion mixing in the exchanger is also evaluated. Finally, we demonstrate particle functionalization within the microfluidic device by coupling a fluorescent tag to avidin-modified 880 nm particles. The concept presented in this paper has been developed for synthesis of modified particles but is also applicable to on-chip bead-based chemistry or cellular biology.     

Dielectrophoretic fluidic cell fractionation system

This paper presents the development and experimental verification of a DEP fluidic system capable of fractionation of intact biological cells in suspension into purer subpopulations. This was accomplished by employing a specially shaped nonuniform electric field, synthesized by microfabricated planar microelectrode arrays, housed on an insulating glass substrate. To improve the efficiency of cell sorting, the microelectrodes are individually biased by a variable frequency alternating current (ac) voltage source, which allows us to exploit both positive and negative dielectrophoresis (DEP) to affect cell separation. Furthermore, through suitable establishment of a cell stream supported by sheath flow, such fractionation is achieved in a continuous fashion. The proposed DEP fluidic fractionation may be configured to operate in three (3) different modes. In this work, however, a detailed account is only presented for one mode of operation. The simulation of the electric field and force profiles, together with the experimental results obtained on model cells (plant protoplasts), confirm our theoretical predictions and furthermore demonstrate improvements in both separation efficiency and throughput over a wide range of frequencies (10 Hz to 5 kHz).     

Modular fluidic resistors to enable widely tunable flow rate and fluidic switching period in a microfluidic oscillator

Microfluidic systems with modular components are attractive alternatives to monolithically integrated microfluidic systems because of their flexibility. In this study, we apply the modular concept on a water‐head‐pressure‐driven microfluidic oscillator and obtain a widely tunable flow rate and fluidic switching period. Modular fluidic resistors can be easily mounted onto and demounted from a main chip by means of plastic male connectors. The connectors enable a leak‐free connection between the modular resistors and main chip (leakage pressure > 140 kPa). With modular resistors, we show independent control of the flow rate and flow switching period of the oscillator system in a wide range (2.5 s–6.4 h and 2 μL/min–2 mL/min). This modular approach can be used to enhance the flexibility of instruction‐embedded microfluidic circuits in which their operational range is limited.     

Pressure-driven flow in open fluidic channels

Arsenic is an element that exists naturally in many rocks and minerals around the world. It also accumulates in petroleum, shale, oil sands, and coal deposits as a result of biogeochemical processes, and it has been found in fly ash from the combustion of solid biofuels. Arsenic compounds in their organic and inorganic forms pose both a health and an environmental risk, and continue to be a challenge to the energy industry. The environmental fate and removal technologies of arsenic compounds are controlled to a large extent by their surface interactions with inorganic and organic adsorbents. We report thermodynamic binding constants, K(binding), from applying the triple-layer surface complexation model to adsorption isotherm and pH envelope data for dimethylarsinic acid (DMA) and p-arsanilic acid (p-AsA) on hematite and goethite. Ligand exchange reactions were constructed based on the interpretation of ATR-FTIR spectra of DMA and p-AsA surface complexes. Surface coverage of adsorbates was quantified in situ from the spectral component at 840 cm(-1). The best fit to the DMA adsorption data was obtained using outer-sphere complex formation, whereas for p-AsA, the best fit was obtained using two monodentate inner-sphere surface complexes. The significance of the results is discussed in relation to improving modeling tools used by environmental regulators and the energy sector for optimum control of arsenic content in fuels.     

Non-equilibrium electrokinetic micro/nano fluidic mixer

We propose a new type of micro/nano fluidic mixer based on non-equilibrium electrokinetics and demonstrate its mixing performance. We fabricate the device with two-step reactive ion etching, one for nanochannels and one for microchannels. Mixing is achieved by strong vortex structures formed near the micro/nano channel interface. We expect the proposed device to be beneficial in the development of micro total analysis systems, since it is simple in its design with minimal fabrication complications.     

Electrokinetic transport and separations in fluidic nanochannels

This article presents a summary of theory, experimental studies, and results for the electrokinetic transport in small fluidic nanochannels. The main focus is on the effect of the electric double layer on the EOF, electric current, and electrophoresis of charged analytes. The double layer thickness can be of the same order as the width of the nanochannels, which has an impact on the transport by shaping the fluid velocity profile, local distributions of the electrolytes, and charged analytes. Our theoretical consideration is limited to continuum analysis where the equations of classical hydrodynamics and electrodynamics still apply. We show that small channels may lead to qualitatively new effects like selective ionic transport based on charge number as well as different modes for molecular separation. These new possibilities together with the rapid development of nanofabrication capabilities lead to an extensive experimental effort to utilize nanochannels for a variety of applications, which are also discussed and analyzed in this review.     

Pressure-driven fluidic delivery through carbon tube bundles

The aim of this work is to demonstrate controlled flow through macroscopically long (approximately 1 cm) carbon tubes (0.5-1.8 microm in radius). A model, high-throughput, pressure-driven fluidic setup, which features a large number of parallel carbon tubes forming a bundle, is fabricated and tested. The carbon tubes are synthesized and self-assembled via co-electrospinning and subsequent carbonization. The setup accommodates pressure-driven flows with flow discharge rates of the order of 1 nL s(-1) (73 x 10(-11) kg s(-1)) for low-viscosity liquids and 30 nL s(-1) (36.3 x 10(-12) kg s(-1)) for gases into a water pool under imposed pressure drops below 4 bar. The measurements demonstrate the ability to sustain well-controlled laminar flows through these long carbon tube bundles and elucidate the main transport features. A novel procedure is also formulated to recover the flow-carrying tube inner-diameter distribution from the measured dependence of the fluid volumetric or mass flow rate on the imposed pressure drop.     

Electrokinetic molecular separation in nanoscale fluidic channels

This report presents a study of electrokinetic transport in a series of integrated macro- to nano-fluidic chips that allow for controlled injection of molecular mixtures into high-density arrays of nanochannels. The high-aspect-ratio nanochannels were fabricated on a Si wafer using interferometric lithography and standard semiconductor industry processes, and are capped with a transparent Pyrex cover slip to allow for experimental observations. Confocal laser scanning microscopy was used to examine the electrokinetic transport of a negatively charged dye (Alexa 488) and a neutral dye (rhodamine B) within nanochannels that varied in width from 35 to 200 nm with electric field strengths equal to or below 2000 V m-1. In the negatively charged channels, nanoconfinement and interactions between the respective solutes and channel walls give rise to higher electroosmotic velocities for the negatively charged dye than for the neutral dye, towards the negative electrode, resulting in an anomalous separation that occurs over a relatively short distance (<1 mm). Increasing the channel widths leads to a switch in the electroosmotic transport behavior observed in microscale channels, where neutral molecules move faster because the negatively charged molecules are slowed by the electrophoretic drag. Thus a clear distinction between "nano-" and "microfluidic" regimes is established. We present an analytical model that accounts for the electrokinetic transport and adsorption (of the neutral dye) at the channel walls, and is in good agreement with the experimental data. The observed effects have potential for use in new nano-separation technologies.     

Superelastic metal microsprings as fluidic sensors and actuators

Superelastic metal microsprings fabricated by deterministic rolling of nanomembranes have been anisotropic-strain-engineered via glancing angle deposition. The advantageous applications of metal microsprings in liquid flow rate sensors and chemical-stimulated actuators due to their reliable superelasticity are demonstrated. Theoretical calculation of microspring elongation as a function of flow rate agrees with our experimental observation and reveals that the sensitivity can be well tuned by the geometrical design of the microsprings. Such outstanding mechanical properties of rolled-up metal microsprings should find important applications in future fluidic micro-/nano-devices.     

Vortex fluidic induced mass transfer across immiscible phases

Mixing immiscible liquids typically requires the use of auxiliary substances including phase transfer catalysts, microgels, surfactants, complex polymers and nano-particles and/or micromixers. Centrifugally separated immiscible liquids of different densities in a 45° tilted rotating tube offer scope for avoiding their use. Micron to submicron size topological flow regimes in the thin films induce high inter-phase mass transfer depending on the nature of the two liquids. A hemispherical base tube creates a Coriolis force as a ‘spinning top’ (ST) topological fluid flow in the less dense liquid which penetrates the denser layer of liquid, delivering liquid from the upper layer through the lower layer to the surface of the tube with the thickness of the layers determined using neutron imaging. Similarly, double helical (DH) topological flow in the less dense liquid, arising from Faraday wave eddy currents twisted by Coriolis forces, impact through the less dense liquid onto the surface of the tube. The lateral dimensions of these topological flows have been determined using ‘molecular drilling’ impacting on a thin layer of polysulfone on the surface of the tube and self-assembly of nanoparticles at the interface of the two liquids. At high rotation speeds, DH flow also occurs in the denser layer, with a critical rotational speed reached resulting in rapid phase demixing of preformed emulsions of two immiscible liquids. ST flow is perturbed relative to double helical flow by changing the shape of the base of the tube while maintaining high mass transfer between phases as demonstrated by circumventing the need for phase transfer catalysts. The findings presented here have implications for overcoming mass transfer limitations at interfaces of liquids, and provide new methods for extractions and separation science, and avoiding the formation of emulsions.

Micron to submicron size Coriolis and Faraday wave induced high shear topological flow regimes in 45° titled rapidly rotating tubes result in high inter-phase mass transfer of immiscible liquids and spontaneous demixing.     

Vortex fluidic exfoliation of graphite and boron nitride

Graphite is exfoliated into graphene by shearing vortex fluidic films of N-methyl-pyrrolidone (NMP), as a controlled process for preparing oxide free graphene, and for exfoliating the corresponding boron nitride sheets.     

Programmable fluidic production of microparticles with configurable anisotropy

We report a technique for continuous production of microparticles of variable size with new forms of anisotropy including alternating bond angles, configurable patchiness, and uniform roughness. The sequence and shape of the anisotropic particles are configured by exploiting a combination of confinement effects and microfluidics to pack precursor colloids with different properties into a narrow, terminal channel. The width and length of the channel relative to the particle size fully specify the configuration of the anisotropic particle that will be produced. The precursor spheres packed in the production zone are then permanently bonded into particles by thermal fusing. The flow in the production zone is reversed to release the particles for collection and use. Particles produced have linear chain structure with precisely configured, repeatable bond angles. With software programmable microfluidics, sequence and shape anisotropy are combined to yield synthesized homogeneous (type "A"), surfactantlike (type "A-B") or triblock (type "A-B-A") internal sequences in a single device. By controlling the dimensions of the microfluidic production zone, triangular prisms and particles with controlled roughness and patchiness are produced. The fabrication method is performed with precursors spheres with diameter as small as 3.0 microm.     

Acoustic control of suspended particles in micro fluidic chips

A method to separate suspended particles from their medium in a continuous mode at microchip level is described. The method combines an ultrasonic standing wave field with the extreme laminar flow properties obtained in a silicon micro channel. The channel was 750 microm wide and 250 microm deep with vertical side walls defined by anisotropic wet etching. The suspension comprised "Orgasol 5 microm" polyamide spheres and distilled water. The channel was perfused by applying an under pressure (suction) to the outlets. The channel was ultrasonically actuated from the back side of the chip by a piezoceramic plate. When operating the acoustic separator at the fundamental resonance frequency the acoustic forces were not strong enough to focus the particles into a well defined single band in the centre of the channel. The frequency was therefore changed to about 2 MHz, the first harmonic with two pressure nodes in the standing wave, and consequently two lines of particles were formed which were collected via the side outlets. Two different microchip separator designs were investigated with exit channels branching off from the separation channel at angles of 90 degrees and 45 degrees respectively. The 45 degrees separator displayed the most optimal fluid dynamic properties and 90% of the particles were gathered in 2/3 of the original fluid volume.     

3-D microarray and its microfabrication-free fluidic immunoassay device

Conventional 2-D microarray is known to have high-throughput detection capability; however, the sensing spots density is significantly hindered by the spot-to-spot distance (gap) requirement for eliminating cross-talks between adjacent spots. Herein a new conceptual 3-D microarray device is proposed to significantly improve the spots density. To demonstrate advantages of the 3-D array, a microfabrication-free fluidic immunoassay device is further made by simply coupling an antibodies-arrayed glass cuboid into a circular glass tube. Rapid, sensitive and high-throughput flow-through immunoassays were accomplished with the 3-D array-based device for detection limits of 10–100 pg mL⁻¹ and wide dynamic range over 4–5 orders of magnitude in human serum with cancer biomarkers α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as model targets, holding great promise for practical clinical applications. The 3-D microarray device not only significantly increases the density of sensing spots, but also greatly enhances the mass transport for rapid immunoassay when using in a flow-through device.     

Large-domain colloidal crystal films fabricated using a fluidic cell

The growth of colloidal crystal films from a dispersion of monodispersed silica spheres using a simple cell with one opening was investigated. Colloidal crystal films with large domain sizes were successfully fabricated almost over the cell (approximately 10 cm2) without applying any external force at room temperature. During the drying process, three distinct conditions were observed, in each of which the films exhibited different optical properties. Films with high transmittance were formed in the first stage. Upon further solvent evaporation, the films entered a medium transmittance state via an extremely low transmittance state. Angle-resolved reflection spectroscopy, which was used to analyze the three conditions, revealed that close-packed arrays with water-filled spaces between were formed in the first stage. One-directional flow was generated in the cell because water evaporation occurred only at the opening. The flow caused the spheres to be arranged epitaxially, resulting in a large domain size.