Experimental study of the separation behavior of nanoparticles in micro- and nanochannels

In this article, we investigate the effects of pH, ionic strength, and channel height on the mobility and diffusivity of charged spherical particles within planar microfluidic channels. Specifically, we report results of a broad experimental study on the transport and separation behavior of 50 and 100 nm spherical carboxylated polystyrene nanoparticles, confined in 20 μm, 1 μm, and 250 nm deep fluidic channels. We find that pH, ionic strength, and channel height have coupled impacts on mobility changes. In particular, we show that, depending on pH, the dependence of particle mobility on channel size can have opposing behavior. In addition, we also show that at the nanoscale, at lower ionic strengths, there is a substantial increase in mobility, due to enhanced electric fields within the nanochannels. These effects are important to understand in order to avoid potential downfalls in terms of separation efficiency as well as design for better tuning of separation performance in micro- and nanochannels. Finally, we propose a method to estimate the effective zeta potential of spherical particles from measured electrophoretic mobility data. This could prove useful in characterizing a heterogeneous collection of particles having a distribution over a range of values of the zeta potential.     

Multilayer patterning technique for micro- and nanofluidic chip fabrication

Polymer micro- and nanofluidic chips become increasingly significant for medical and biological applications. However, it is difficult to fabricate micro- and nanochannels integrately into a polymer substrate due to the reflow and insufficient flow of the polymer. In the present paper, micro- and nanochannels were hot embossed into a multilayer substrate by micromold and nanomold, respectively. To replicate high replication precision nanochannels without damaging the fabricated microchannels, the embossing parameters were optimized by Taguchi and analytic hierarchy process methods. The fabricated micro- and nanochannels were fully sealed at bonding parameters optimized according to the bonding rate of the chip. The fluorescence image indicates that there is no blocking or leakage over the entire micro- and nanochannels. With presented fabrication method, low-cost polymer micro- and nanostructures can be fabricated, which allows for commercial manufacturing of micro- and nanofluidic chips.     

One-dimensional axial simulation of electric double layer overlap effects in devices combining micro- and nanochannels

This paper presents a numerical steady-state model of ion transport in micro- and nanofluidic devices with widely varying geometric scale, such as transitions between micro- and nanochannels. Finite element or finite volume simulation of such problems is challenging, due to the number of elements needed to produce a satisfactory mesh. Here, only the lengthwise channel dimension is meshed; standard analytical approximations are used to incorporate cross-channel properties. Singularly perturbed cases are built up by continuation. The method is shown to reproduce our previously reported measurements of electric double-layer effects on conductivity, ion concentration, and ion enhancement and depletion. Comparison with 2-D simulations reported in the literature shows that effects on accuracy due to the 1-D approximation are small. The model incorporates analytical models of surface charge density taken from the literature. This enables predictive simulation with reasonable accuracy using published parameter values, or these values may be tuned based on experiment to give improved results. Use of the model for iterative design and parameter estimation is demonstrated.     

Fabrication of high-aspect-ratio polymer nanochannels using a novel Si nanoimprint mold and solvent-assisted sealing

We present a low cost nanofabrication method to fabricate high-aspect-ratio (HAR) polymer nanochannels using a novel silicon nanoimprint mold fabrication technique and a solvent-assisted sealing method. These nanofluidic channels are being developed for single biomolecule detection. The silicon nanoimprint mold fabrication process is based on the combination of anisotropic etching of silicon by potassium hydroxide (KOH) solution and the local oxidation of silicon (LOCOS) process. The resulting high-aspect-ratio silicon mold has smooth sidewalls owing to the anisotropic KOH etching process along the silicon crystalline geometry as well as the LOCOS process. The nanostructures in the nanoimprint molds that form the nanochannels can be easily controlled by the initial micropattern sizes defined using conventional UV lithography and the oxidation time, making this technique a practical solution for low cost and high-throughput HAR silicon nanoimprint mold fabrication. Nanoimprint molds having aspect ratios of more than 1:5.5 (width: 200 nm, height: 1.1 μm, length: 1 cm) were successfully fabricated. Nanoimprinting technique was used to create poly(methyl methacrylate) (PMMA) nanotrenches out of this nanoimprint mold. A novel solvent-assisted sealing technique was developed in order to seal the HAR PMMA nanotrenches. This technique enables the generation of nanochannels with various nanoscale dimensions without the need for complicated and expensive nanolithography tools.     

Monolithic fabrication of nanochannels using core–sheath nanofibers as sacrificial mold

A simple and reliable approach for fabricating circular nanofluidic channels in polydimethylsiloxane (PDMS) microfluidic systems is described, which uses core–sheath nanofibers as sacrificial molds. The core–sheath structures consist of an electrospun polyvinylpyrrolidone (PVP) core and a sputtered aluminum sheath. The rupture of the sheath during master template releasing allows easy removal of the nanofibers to form the nanochannels. Straight nanochannels with the diameter as small as 390 nm are demonstrated. This technology is advantageous over existing nanochannel fabrication approaches in reduced risks of fluidic leakage and channel blocking, simpler fabrication process, lower cost and easier dimension control. This work provides a solid technical basis that enables development of various on-chip analytical devices for investigation of the unique transport phenomena at nanoscale.     

Nano- and microsized metal oxide thin film gas sensors

Functional micro- and nanosized metal oxide thin film structures are very promising candidate for future gas-sensors. Their reduced size offers an increased surface to volume ratio thus improving sensitivity and sensor performance. Whilst most experimental nanostructures are produced using a bottom-up approach, a top-down sputtering technique for structuring nano-sized gas sensitive metal oxide areas is presented in this letter. Oxidised silicon wafers were used as substrates. The silicon dioxide film of 1 μm thickness was prepared by thermal oxidation in order to insulate the gas sensing elements from the substrate. The sensor chips had an overall size of (1.5 × 1.5) mm² onto which a Ta/Pt film (20/200 nm thickness) was deposited and patterned to act as electrodes, heater and temperature sensor. In a second step micro-scaled tin dioxide layers (60 nm thick, 5 μm width) were deposited by sputtering techniques and photolithographical patterning between the platinum micro-electrodes (4 μm gap). Finally, the width of the stripes was reduced using focused ion beam technology to obtain the desired size and structure. This enables the control of the dimensions of the structures down to the resolution limit of the FIB-system which is about 10 nm. The structural and electrical characterisation of the sensors and their responses during exposure to several test gases including O₂, CO, NO₂ and H₂O are presented as well.     

DSMC investigation of rarefied gas flow through diverging micro- and nanochannels

Direct simulation Monte Carlo (DSMC) method with simplified Bernoulli trials (SBT) collision scheme has been used to study the rarefied pressure-driven nitrogen flow through diverging micro- and nanochannels. The fluid behaviours flowing between two plates with different divergence angles ranging between 0° and 17° are described at different pressure ratios (1.5 ≤ Π ≤ 2.5) and Knudsen numbers (0.03 ≤ Kn ≤ 12.7). The primary flow field properties, including pressure, velocity, and temperature, are presented for divergent micro- and nanochannels and are compared with those of a micro- and nanochannel with a uniform cross section. The variations of the flow field properties in divergent micro- and nanochannels which are influenced by the area change, the channel pressure ratio, and the rarefication are discussed. The results show no flow separation in divergent micro- and nanochannels for all the range of simulation parameters studied in the present work. It has been found that a divergent channel can carry higher amounts of mass in comparison with an equivalent straight channel geometry. A correlation between the mass flow rate through micro- and nanochannels, the divergence angle, the pressure ratio, and the Knudsen number has been suggested. The present numerical findings prove the occurrence of Knudsen minimum phenomenon in micro- and nanochannels with non-uniform cross sections.     

Effect of dispersed phase viscosity on maximum droplet generation frequency in microchannel emulsification using asymmetric straight-through channels

Uniformly sized droplets of soybean oil, MCT (medium-chain fatty acid triglyceride) oil and n-tetradecane with a Sauter mean diameter of d _3,2 = 26–35 μm and a distribution span of 0.21–0.25 have been produced at high throughputs using a 24 × 24 mm silicon microchannel plate consisting of 23,348 asymmetric channels fabricated by photolithography and deep reactive ion etching. Each channel consisted of a 10-μm diameter straight-through micro-hole with a length of 70 μm and a 50 × 10 μm micro-slot with a depth of 30 μm at the outlet of each channel. The maximum dispersed phase flux for monodisperse emulsion generation increased with decreasing dispersed phase viscosity and ranged from over 120 L m⁻² h⁻¹ for soybean oil to 2,700 L m⁻² h⁻¹ for n-tetradecane. The droplet generation frequency showed significant channel to channel variations and increased with decreasing viscosity of the dispersed phase. For n-tetradecane, the maximum mean droplet generation frequency was 250 Hz per single active channel, corresponding to the overall throughput in the device of 3.2 million droplets per second. The proportion of active channels at high throughputs approached 100% for soybean oil and MCT oil, and 50% for n-tetradecane. The agreement between the experimental and CFD (Computational Fluid Dynamics) results was excellent for soybean oil and the poorest for n-tetradecane.     

Microfluidic phase change valve with a two-level cooling/heating system

A phase change (PC) microvalve with an integrated two-level cooling/heating system is developed for microfluidic applications in this article. This PC microvalve utilizes the liquid–solid PC of a small portion of the working medium in a microchannel to switch on/off the flow in the microchannel. The size of the working medium for the PC microvalve is 5-mm long, 50-μm high, and 80-μm wide (50 μm × 80 μm is the cross-sectional area of the channel) in this study. The switch is actuated by using a two-level cooling/heating system integrated on the chip. The first-level cooling/heating unit keeps the working medium in the valve area in the temperature range of supercooling state. Based on the supercooling state, the second-level cooling/heating unit either heats up or cools down the medium in the valve area to trigger its PC between liquid and solid for valving purposes. The proposed microfluidic PC microvalve is characterized experimentally in microfluidic chips. The thermal impact of one PC microvalve in one particular microchannel on its adjacent channels is discussed by establishing a preliminary analytical model and a numerical model. In addition to no leakage and no moving element, this PC microvalve with a two-level cooling/heating system can achieve a very short cooling time (i.e., 2.72 s).     

Efficient prototyping of large-scale pdms and silicon nanofluidic devices using pdms-based phase-shift lithography

In this study, we explore the potential of poly-dimethylsiloxane (PDMS)-based phase-shift lithography (PPSL) for the fabrication of nanofluidic devices. We establish that this technology, which was already shown to allow for the generation of 100?nm linear or punctual features over squared centimeter surfaces with conventional photolithography systems, is readily adequate to produce some of the most popular nanofluidic systems, namely nanochannels and nanoposts arrays. We also demonstrate that PPSL technology enables to generate PDMS and silicon nanofluidic systems. This technological achievement allows us to perform single DNA molecule manipulation experiments in PDMS and silicon nanochannels, and we observe an unexpectedly slow migration of DNA in PDMS devices, which is independent on salt or pH conditions. Our data in fact hint to the existence of an anomalous response of DNA in PDMS nanofluidic devices, which is likely associated to transient nonspecific interactions of DNA with PDMS walls. Overall, our work demonstrates the efficiency and the performances of PPSL for prototyping nanofluidic systems.     

Fabrication and electrical characterization of integrated nano-scale fluidic channels

We present the fabrication and characterization of nanoscale fluidic channels with embedded electrodes. Arrays of 2.25 μm long and 60 nm tall nanochannels with widths ranging from 60 to 500 nm were microfabricated in SiO₂ with Au electrodes embedded inside and outside of the nanochannels. The built-in electrodes were able to probe nanochannel conductance via a redox reaction of \textFe(\textCN)₆^{3 - /4 -} {\text{Fe}}({\text{CN}})_{6}^{3 - /4 - } . Amperometric characterization showed that conductance of nanochannel arrays varied linearly both with the width and number of nanochannels and was in the 10–100 pS range. Further, we show that electrical current was largely diffusion based and could be predicted from channel geometry using standard diffusion equations. We also discuss the potential of such nanochannel arrays as electronic biomolecular sensors and show preliminary streptavidin detection results.     

Development of a nanofluidic preconcentrator with precise sample positioning and multi-channel preconcentration

A nanofluidic preconcentrator with the capability of rapidly preconcentrating and precisely positioning protein bands in multiple microchannels has been developed for highly sensitive detection of biomolecules. A novel electrical resistive network model is developed to guide the design of the nanofluidic preconcentrator which consists of a PDMS slab bonded with a glass slide. In the prototype design, two microchannels (23 mm long, 25–50 μm wide, and 5–15 μm deep), one preconcentration microchannel and one ground microchannel are connected in the middle via 16 nanochannels (25–50 μm long, 25 μm wide, and 50–80 nm deep). With two sets of optimal voltage settings applied on the opposite ends of the nanofluidic chip, the ion depletion region and electrokinetic trapping were generated to carry out the preconcentration. With the optimal voltage settings (30–30 V) predicted by the model, the ionic current of the nanochannel in our optimized preconcentrator was adjusted to be greater than the threshold value (3.9 nA) needed for the occurrence of the preconcentration, and a preconcentration factor >10⁵ was achieved in 5 min. The sample positioning capability of the preconcentrator was demonstrated by adjusting the applied voltages and moving the preconcentrated protein bands to multiple sites by a distance from several micrometers to several millimeters in the preconcentration channel. The multi-channel preconcentration capability was also demonstrated by preconcentrating two protein bands in two separate microchannels. In this work, the resistive network model was developed and validated to optimize nanofluidic preconcentrators for rapid, high throughput and highly sensitive sensing of low abundance analytes.     

Numerical investigation of micro- and nanochannel deformation due to discontinuous electroosmotic flow

Large pressures can induce detrimental deformation in micro- and nanofluidic channels. Although this has been extensively studied for systems driven by pressure and/or capillary forces, deflection in electrokinetic systems due to internal pressure gradients caused by non-uniform electric fields has not been widely explored. For example, applying an axial electric field in a channel with a step change in conductivity and/or surface charge can lead to internally generated pressures large enough to cause cavitation, debonding, and/or channel collapse. Finite electric double layers within nanofluidic channels can further complicate the physics involved in the deformation process. In order to design devices and experimental procedures that avoid issues resulting from such deformation, it is imperative to be able to predict deformation for given system parameters. In this work, we numerically investigate pressures resulting from a step change in conductivity and/or surface charge in micro- and nanofluidic channels with both thin and thick double layers. We show an explicit relation of pressure dependence on concentration ratio and electric double layer thickness. Furthermore, we develop a numerical model to predict deformation in such systems and use the model to unearth trends in deformation for various electric double layer thicknesses and both glass and PDMS on glass channels. Our work is particularly impactful for the development and design of micro- and nanofluidic-based devices with gradients in surface charge and/or conductivity, fundamental study of electrokinetic-based cavitation, and other systems that exploit non-uniform electric fields.     

Fabrication of sealed nanofluidic channels using site-selective direct write (maskless) X-ray lithography

Sealed nanofluidic channels with cross-sections as small as 60 nm × 60 nm were created in polymer bilayers using the focused X-rays of a scanning transmission X-ray microscope. These structures were then characterized by near-edge X-ray absorption fine structure spectromicroscopy, atomic force microscopy and scanning electron microscopy. The cross-sectional area of the nanochannels could be tuned by adjusting the area patterned in x and y and/or manipulating the bottom layer thickness. The maximum length was found to be limited by the efficiency of excavation of patterned material out of the channel, and the stability of the polymer overlayer which seals the channel. Schemes toward interfacing these nanochannels with conventional microfluidics are discussed.     

Gas–liquid dynamics at low Reynolds numbers in pillared rectangular micro channels

Most heterogeneously catalyzed gas–liquid reactions in micro channels are chemically/kinetically limited because of the high gas–liquid and liquid–solid mass transfer rates that can be achieved. This motivates the design of systems with a larger surface area, which can be expected to offer higher reaction rates per unit volume of reactor. This increase in surface area can be realized by using structured micro channels. In this work, rectangular micro channels containing round pillars of 3 μm in diameter and 50 μm in height are studied. The flow regimes, gas hold-up, and pressure drop are determined for pillar pitches of 7, 12, 17, and 27 μm. Flow maps are presented and compared with flow maps of rectangular and round micro channels without pillars. The Armand correlation predicts the gas hold-up in the pillared micro channel within 3% error. Three models are derived which give the single-phase and the two-phase pressure drop as a function of the gas and liquid superficial velocities and the pillar pitches. For a pillar pitch of 27 μm, the Darcy-Brinkman equation predicts the single-phase pressure drop within 2% error. For pillar pitches of 7, 12, and 17 μm, the Blake-Kozeny equation predicts the single-phase pressure drop within 20%. The two-phase pressure drop model predicts the experimental data within 30% error for channels containing pillars with a pitch of 17 μm, whereas the Lockhart–Martinelli correlation is proven to be non-applicable for the system used in this work. The open structure and the higher production rate per unit of reactor volume make the pillared micro channel an efficient system for performing heterogeneously catalyzed gas–liquid reactions.     

Micro-mixer device with deep channels in silicon using modified RIE process: fabrication,packaging and characterization

In the present work, silicon based micromixer microfluidic devices have been fabricated in silicon substrates of 2-inch diameter. These devices are of 2-input and 1-output port configuration bearing channel depth in the range 80–280 µm. Conventional reactive ion etching (RIE) process used in integrated circuit fabrication was modified to get reasonably high silicon etch rate (~1.2 µm/min). It was anticipated that devices with channel depth in excess of 150 µm would become weak and susceptible to breakage. For such devices, a bonded pair of silicon having a 0.5 µm SiO₂ at the bonded interface was used as the starting substrate. The processed silicon wafer bearing channels was anodically bonded to a Corning^® 7740 glass plate of identical size for fluid confinement. Through-holes for input/output ports were made either in Si substrate or in glass plate before carrying out anodic bonding. Micro-channels were characterized using stylus and optical profiler. Surface roughness of the channel was observed to increase with increasing channel depth. The devices were packaged in a polycarbonate housing and pressure drop versus flow rate measurements were carried out. Reynolds number and friction factor were calculated for devices with 82 µm deep channels. It was observed that up to 25 sccm of gas and 10 ml/min of liquid, the flow was laminar in nature. It is envisaged that using bonded silicon wafer pair and combination of RIE and wet etching, it is possible to get an etch stop at the SiO₂ layer of the bonded silicon interface with much smaller value of surface roughness rendering smooth channel surface.     

Fibre-optical MEMS switches based on bulk silicon micromachining

 Fibre-optical micro-electro-mechanical systems (MEMS) switches for optical communication systems require high-precision mechanical subassemblies due to the sensitivity of single-mode fibre coupling against misalignments. The fibre diameter of 125 μm also demands for actuators with at least ±62.5-μm travel range. Bulk micromachining based on wet anisotropic etching of crystalline silicon allows fabricating actuators and alignment structures with the required accuracy. Two concepts for lensless moving-fibre switches with thermo-mechanical and electrostatic Si-micromachined actuators with large displacements are demonstrated. Received: 14 January 2002/Accepted: 1 February 2002 This paper was presented at the Workshop “Optical MEMS and Integrated Optics” in June 2001.     

Geometrical strengthening and tip-sharpening of a microneedle array fabricated by X-ray lithography

A novel fabrication method for LIGA (from the German “Lithographie”, “Galvanik”, and “Abformung”) microneedles with through holes is presented. Such microneedles are in demand by most bio-medical MEMS applications and in some fluidic MEMS applications. We propose a technique that combines conventional deep X-ray lithography, plane-pattern to cross-section transfer (PCT) process, and alignment X-ray lithography. The technique provides precise hole alignment with ± 3 μm tolerance. Finite-element simulations on various hole locations were performed to determine the optimum position. We previously fabricated a microneedle with a 100-μm base and a 300-μm height by a right-triangular mask. The resultant microneedle had a very sharp tip but was excessively steep, and thus resulted in a very low strength. Improved strength and tip sharpness was consequently achieved by changing the mask-pattern from a triangular pattern to a polygonal mask and changing the dimensions of the microneedle to have a 300-μm base with various heights between 350 and 800 μm. Using the proposed technique, we could produce a total of 100 hollow microneedles on a 5 × 5 mm² chip. Moreover, we successfully fabricated sharpened microneedles that were stronger than that we have fabricated so far. The molding process or electroplating and the cost list of the LIGA microneedle will also be included.     

Theoretical investigation of enzymatic hydrolysis of polypeptides in nanofluidic channels

Label-free detection of enzymes using nanofluidic channels requires enzymes to diffuse into a nanochannel and react with substrates already immobilized on the nanochannel surfaces. A theoretical model is necessary to predict the reaction progress in the confined space and translate it to the electrical readouts of the nanochannel. In this paper, enzymatic hydrolysis of polypeptides in nanofluidic channels is considered and a 1-D model is developed that accounts for various reaction kinetics, enzyme diffusion and non-specific adsorption. The polypeptides have multiple cleavage sites which can be cleaved in different orders depending on the type of enzyme. Here it is shown that this process creates two types of reaction fronts inside the nanochannel which advance linearly with time once they are fully developed. Such constant reaction rates can be predicted by an analytical model. The numerical simulations are validated against the experimental results of trypsin–polylysine reaction in nanochannels, and a good agreement between the two is observed. This study deepens our understandings of enzymatic reactions in nanoscale-confined spaces and can guide the development of a fast-response, label-free enzyme sensor based on nanochannels.     

Roll manufacturing of flexible microfluidic devices in thin PMMA and COC foils by embossing and lamination

Microfluidics on foil is gaining momentum due to a number of advantages of employing thin films combined with the capability of cost-effective high-volume manufacturing of devices. In this work, ultra-thin, flexible Y-microreactors with microchannels of 100 μm width and 30 μm depth were fabricated in thermoplastic polymer foils. The fluidic pattern was hot roll embossed in 125 μm thick poly-methyl-methacrylate (PMMA) and 130 μm thick cyclic-olefin-copolymer (COC) films using a dry-etched microstructured silicon wafer as a flat embossing tool in a laminator. The sealing of the channels was performed with two different techniques, one based on lamination of SU8 dry film resist (DFR) and the other one based on spin-coated poly-dimethylsiloxane (PDMS). Testing of the interconnected microreactor was carried out using two dye colorant solutions to demonstrate mixing.