Fabrication of nanofluidic biochips with nanochannels for applications in DNA analysis

With the development of nanotechnology, great progress has been made in the fabrication of nanochannels. Nanofluidic biochips based on nanochannel structures allow biomolecule transport, bioseparation, and biodetection. The domain applications of nanofluidic biochips with nanochannels are DNA stretching and separation. In this Review, the general fabrication methods for nanochannel structures and their applications in DNA analysis are discussed. These representative fabrication approaches include conventional photolithography, interference lithography, electron-beam lithography, nanoimprint lithography and polymer nanochannels. Other nanofabrication methods used to fabricate unique nanochannels, including sub-10-nm nanochannels, single nanochannels, and vertical nanochannels, are also mentioned. These nanofabrication methods provide an effective way to form nanoscale channel structures for nanofluidics and biosensor devices for DNA separation, detection, and sensing. The broad applications of nanochannels and future perspectives are also discussed.     

Real-time template-assisted manipulation of nanoparticles in a multilayer nanofluidic chip

The ability to control dynamically the flow and placement of nanoscale particles and biomolecules in a biocompatible, aqueous environment will have profound impact in advancing the fields of nanoplasmonics, nanophotonics, and medicine. Here, an approach based on electrokinetic forces is demonstrated that enables dynamically controlled placement of nanoparticles into a predefined pattern. The technique uses an applied voltage to manipulate nanoparticles in a multilayer nanofluidic chip architecture. Simulations of the nanoparticles' motion in the nanofluidic chip validate the approach and are confirmed by experimental demonstration to produce uniform 200-nm-diameter spherical nanoparticle arrays. The results are important as they provide a new method that is capable of dynamically capturing and releasing nanoscale particles and biomolecules in an aqueous environment, which could lead to the creation of reconfigurable nanostructure patterns for nanoplasmonic, nanophotonic, biological sensing, and drug-delivery applications.     

DNA-functionalized nanochannels for SNP detection

We have developed ultrahigh density array of functionalized nanochannels by using a block copolymer having end di-COOH group. This approach provides a facile route for direct functionalization of wall surface of the nanochannels and immobilization site for molecular recognition agents (MRAs). By using overhanging single-stranded DNA as MRAs, the DNA-functionalized nanochannels showed high resolution to detect a single-base mismatch as well as to discriminate single-mismatched sequence at various locations by hybridization preference with MRAs.     

A nanofluidic railroad switch for DNA

We present a metamaterial consisting of a two-dimensional, asymmetric lattice of crossed nanochannels in fused silica, with channel diameters of 80 nm to 140 nm. When DNA is introduced, it is stretched and linearized. We show that the asymmetry in channel dimensions gives rise to a preferred direction for DNA orientation and a preferred direction for transport under dc electrophoresis. Interestingly, the preferred axis of orientation and transport can be switched by 90 degrees through application of an ac voltage. We explain the results in terms of an energy landscape for polyelectrolytes that consists of entropic and dielectrophoretic contributions and whose strength and sign can be tuned by changing the ac field strength.     

Biomimetic smart nanochannels for power harvesting

With the increasing requirements of reliable and environmentally friendly energy resources, porous materials for sustainable energy conversion technologies have attracted intensive interest in the past decades. As an important block of porous materials, biomimetic smart nanochannels (BSN) have been developed rapidly into an attractive field for their well-tunable geometry and chemistry. With inspiration from nature, many works have been reported to utilize BSN to harvest clean energy. In this review, we summarize recent progress in the BSN for power harvesting from four parts of brief introduction of BSN, biological prototypes for power harvesting, BSN-based energy conversion, and conclusion and outlook. Overall, by learning from nature, exploiting new avenues and improving the performance of BSN, a number of exciting developments in the near future may be anticipated.

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Gateable nanofluidic interconnects for multilayered microfluidic separation systems

The extension of microfluidic devices to include three-dimensional fluidic networks allows complex fluidic and chemical manipulations but requires innovative methods to interface fluidic layers. Externally controllable interconnects, employing nuclear track-etched polycarbonate membranes containing nanometer-diameter capillaries, are described that produce hybrid three-dimensional fluidic architectures. Controllable nanofluidic transfer is achieved by controlling applied bias, polarity, and density of the immobile nanopore surface charge and the impedance of the nanocapillary array relative to the microfluidic channels. Analyte transport between vertically separated microchannels has three stable transfer levels, corresponding to zero, reverse, and forward bias. The transfer can even depend on the properties of the analyte being transferred such as the molecular size, illustrating the flexible character of the analyte transfer. In a specific analysis implementation, nanochannel array gating is applied to capillary electrophoresis separations, allowing selected separated components to be isolated for further manipulation, thereby opening the way for preparative separations at attomole analyte mass levels.     

Self-sealed vertical polymeric nanoporous-junctions for high-throughput nanofluidic applications

We developed a reliable but simple integration method of polymeric nanostructure in a poly(dimethylsiloxane) (PDMS)-based microfluidic channel, for nanofluidic applications. The Nafion polymer junction was creased by infiltrating polymer solution between the gaps created by mechanical cutting, without any photolithography or etching processes. The PDMS can seal itself with the heterogeneous polymeric nanoporous material between the PDMS/PDMS gap due to its flexibility without any (covalent) bonding between PDMS and the polymer materials. Thus, one can easily integrate the nanoporous-junction into a PDMS microchip in a leak-free manner with excellent repeatability. We demonstrated nanofluidic preconcentration of proteins (beta-phycoerythrin) using the device. Because the polymeric junction spans across the entire microchannel height, the preconcentration was achieved with high-pressure field or even in large channels, with the dimensions of 1000 microm width x 100 microm depth.     

Tuneable Heterodyne Infrared Spectrometer for atmospheric and astronomical studies

The transportable setup of the Cologne Tuneable Heterodyne Infrared Spectrometer (THIS) is presented. Frequency tuneability over a wide range provided by the use of tuneable diode lasers as local oscillators (LO) allows a variety of molecules in the mid-infrared to be observed. Longtime integration, which is essential for astronomical observations, is possible owing to tight frequency control of the LO with optical feedback from an external cavity. THIS is developed to fly on the Stratospheric Observatory for Infrared Astronomy beginning in 2006 but can also be used on different types of ground-based telescopes.     

Optically fabricated three dimensional nanofluidic mixers for microfluidic devices

This paper describes a simple technique for fabricating complex, but well defined, three-dimensional (3D) networks of nanoscale flow paths in the channels of microfluidic systems. Near field scanning optical measurements reveal the optics associated with the fabrication process and the key features that enable its application to the area of microfluidics. Confocal studies of microfluidic devices that incorporate 3D nanostructures formed using this approach show that they function as efficient passive mixing elements, particularly at low Reynolds numbers. This application and others such as separation and extraction inmicrofluidic total analysis systems or lab on a chip devices represent promising areas for 3D nanostructures of this general type.     

Attoliter-scale dispensing in nanofluidic channels

As fabrication techniques improve, functional fluidic devices with nanometer scale dimensions are rapidly being developed for chemical analysis. Here, we present fluid dispensing in nanochannels with injection volumes ranging from 42 aL to 4.1 fL. Devices with hybrid poly(dimethylsiloxane) and glass nanochannels, 130 nm deep and 580 nm wide or 130 nm deep and 670 nm wide, were used to evaluate two sample dispensing schemes, modified pinched and gated injections. Electrokinetic transport was achieved by applying up to 10 V directly from an analog output board without amplification, producing modest electric field strengths in the nanochannels (0.2-2 kV/cm) and enabling rapid dispensing and analysis (10-100 ms).     

Non-planar nanofluidic devices for single molecule analysis fabricated using nanoglassblowing

A method termed 'nanoglassblowing' is presented for fabricating integrated microfluidic and nanofluidic devices with gradual depth changes and wide, shallow nanochannels. This method was used to construct fused silica channels with out-of-plane curvature of channel covers from over ten micrometers to a few nanometers, nanochannel aspect ratios smaller than 2 × 10(-5):1 (depth:width), and nanochannel depths as shallow as 7?nm. These low aspect ratios and shallow channel depths would be difficult to form otherwise without collapse of the channel cover, and the gradual changes in channel depth eliminate abrupt free energy barriers at the transition from microfluidic to nanofluidic regions. Devices were characterized with atomic force microscopy (AFM), white light interferometry, scanned height measurements, fluorescence intensity traces, and single molecule analysis of double-stranded deoxyribonucleic acid (DNA) velocity and conformation. Nanochannel depths and aspect ratios formed by nanoglassblowing allowed measurements of the radius of gyration, R(g), of single λ?DNA molecules confined to slit-like nanochannels with depths, d, ranging from 11?nm to 507?nm. Measurements of R(g) as a function of d agreed qualitatively with the scaling law R(g)∝d(-0.25) predicted by Brochard for nanochannel depths from 36?nm to 156?nm, while measurements of R(g) in 11?nm and 507?nm deep nanochannels deviated from this prediction.     

纳米通道中电渗流的分子动力学模拟

采用分子动力学(MD)方法,模拟了纳米通道中NaCl溶液的电渗现象.模拟结果表明,与上下两板带同性电荷相比,当纳米通道的上下壁面所带电荷电性相反时,通道中水的浓度分布大致相同,而离子浓度分布,水的速度及通道中的电势分布相差很大.具体表现在:Na 主要聚集在带负电的硅板附近,cl-主要聚集在带正电的硅板附近,通道中部出现电荷倒置现象;在通道下部的区域水的速度为负值,而在上部区域速度为正值;电势在硅板附近呈指数分布,其值在下硅板附近为正,在上硅板附近为负,在模拟区域中段,电势在通道下部区域由正值变为负值,在通道上部区域由负值变为正值.此外,模拟结果还表明:纳米通道中的速度流型随通道壁面电荷分布的改变而改变.     

A constitutive model for compressible elastomeric solids

A non-linear thermo-elastic constitutive model for the large deformations of isotropic materials is formulated. This model is specialized to account for the physics and thermodynamics of the elastic deformation of rubber-like materials, and based on these molecular considerations a constitutive model for compressible elastomeric solids is proposed. The new constitutive model generalizes the incompressible and isothermal model of Arruda and Boyce (1993) to include the compressibility and thermal expansion of these materials. The model is fit to existing experimental data on vulcanized natural rubbers to determine the material parameters for the rubbers examined. The fit between the simple model and the data is found to be very good for large stretches and moderate volume changes.List of symbols x\s=f(p) Deformation function - p Material point of a body in a reference configuration - x Place occupied by material point p in the current configuration - F(p)\eq(\t6/\t6p) f(p) Deformation gradient - J\s=det F\s>0 Determinant of F - F\s=RU\s=VR Polar decompositions of F - U, V Right and left stretch tensors; positive definite and symmetric - R Rotation tensor; proper orthogonal - U= _1–1 ³ ₁ ² r₁r₁ Spectral representation of U - V= ₁₌₁ ³ _t ² 1_t1₁ Spectral representation of V - _t > 0 Principal stretches - {r_i} Right principal basis - {l_i} Left principal basis - C\s=F ^T F, B\s=FF ^T Right and left Cauchy-Green strain tensors - \gq\s>0 Absolute temperature - \ge Internal energy density/unit reference volume - \gh Entropy density/unit reference volume - \gy\s=\ge\t-\gq\gh Helmholtz free energy/unit reference volume     

Polymer nanochannels fabricated by thermomechanical deformation for single-molecule analysis

A simple method for fabricating nanoscale channels based on thermomechanical deformation of rigid polymer substrates is demonstrated. Polycarbonate preforms containing microchannels with cross-sectional dimensions on the order of tens of micrometers are controllably deformed to produce submicrometer dimensions. The reduced channel dimensions are achieved by heating the preform while applying a uniaxial tensile force to reduce channel cross sections through the Poisson effect. Nanochannels with circular or elliptical cross sections are defined by varying the channel position and preform geometry prior to deformation. Arrays of parallel nanochannels with critical dimensions down to 400 nm are described. Using the fabrication method, a nanochannel network is fabricated for the detection of single protein molecules via confocal fluorescence microscopy. The chip includes a detection channel with cross-sectional dimensions approaching the confocal volume dimensions of the detection optics and a larger adjacent reference channel used to optimize focusing. Detection of fluorescently labeled bovine serum albumin at 15 and 150 nM concentrations is presented, demonstrating the ability to perform single-molecule fluorescence measurements in polycarbonate chips using visible wavelengths for excitation and detection.     

Ionic selectivity of single nanochannels

There has been an increasing interest in single nanochannel ionic devices, such as ionic filters that control the type of transported ions and ionic diodes that rectify the ionic flow. In this article, we theoretically investigate the importance of the dimensions, surface charge, electrolyte concentration, and applied bias on nanopore performance. We compare numerical solutions of the Poisson, Nernst-Planck (PNP), and Navier-Stokes (NS) equations with their one-dimensional, analytical approximations. We show that by decreasing the length of the nanopore, the ionic current and ionic selectivity become affected by processes outside the nanochannel. The contribution of electroosmosis is noticeable, especially for highly charged nanochannels, but is insignificant, justifying the use of the simple one-dimensional approximation in many cases. Estimates for the critical electric field at which the nanopore selectivity decreases and the ion current starts to saturate are provided.     

Tuneable peak deformations in chiral liquid chromatography

Modern chiral stationary phases are often combined with eluents comprising a mixture of organic solvents and polar additives. The latter may cause extreme deformations of the eluted enantiomer bands in both analytical and preparative separations. In this work, we give a theoretical background for these deformations. As an experimental verification, we separate the enantiomers of different beta-blockers on a teicoplanin stationary phase (Chirobiotic T) in the presence of triethylamine/acetic acid. We show that it is possible to tune the peak shapes of the two enantiomers by varying the organic solvent composition. An advantageous situation occurs when the first eluted peak is transformed to an anti-Langmuirian shape while keeping the second enantiomer in a normal Langmuirian shape. In this situation, the two peaks tail in opposite directions with their sharp sides pointing closely to each other. It is then possible to obtain baseline resolution at higher load than when both enantiomer peaks tail in the same direction. Adsorption isotherm parameters were determined using the inverse method; no other method could be used due to the system complexity. Computer simulations, based on these parameters, agreed very well with the observed deformations, thus confirming our hypothesis of their origin.     

High energy conversion efficiency in nanofluidic channels

It is proposed that the layering of large ions at the wall/liquid interface of nanofluidic channels can be used to achieve high efficiency (possibly >50%) in the conversion of hydrostatic energy into electrical power. Large ions tend to produce peaks and troughs in their concentration profiles at charged walls, producing high concentrations far from the walls where the ions' pressure-driven velocity is high. This increases the streaming conductance and the energy conversion efficiency.     

Nanogap detector inside nanofluidic channel for fast real-time label-free DNA analysis

We report fabrication and characterization of a novel real-time, label-free DNA detector, that uses a long nanofluidic channel to stretch a DNA strand and a nanogap detector (with a gap as small as 9 nm) inside the channel to measure the electrical conduction perpendicular to the DNA backbone as it moves through the gap. We have observed electrical signals caused by 1.1 kilobase-pair (kbp) double-stranded (ds)-DNA passing through the gap in the nanogap detectors with a gap equal to or less than 13 nm.