Micro-nanofluidic Systems Research Articles

Effect of nanochannel geometry on electrokinetic ion transport in a micro-nanofluidic system

In this paper, the electrokinetic ion transportation in a micro-nanofluidic system is demonstrated through employing Poisson-Nernst-Planck equations coupled with Navier-Stokes equations. The effects of nanochannel geometry, volumic surface charge density, nanochannel length and nanochannel radius on the electric field, ion transport field, and fluid field are investigated. Theoretical research shows that the potential drop relies mainly on the nanochannel’s volume instead of nanochannel geometry. Two acute-angle structures in a trapezoid nanochannel relative to a right-angle structure in a semicircular or rectangular nanochannel can intensify the electric double layer field. For a cross sectional shape of the trapezoid, a higher ion concentration is obtained through enhancing the volumic surface electric charge, increasing the nanochannel length, and decreasing the radius. The results enabled the provision of a beneficial method for better understanding the design principle of the nanochannel structure.

Nano-electrokinetic ion enrichment in a micro-nanofluidic preconcentrator with nanochannel’s Cantor fractal wall structure

The detection of ultra-low concentration of biomacromolecules remains the focus of research in micro-nanofluidic systems. Sample enrichment is primarily targeted at very low concentration of sample detection tasks. The use of ion concentration polarization principle is the most efficient means to solve the problem of electrokinetic ion enrichment. In this paper, numerical simulation of nano-electrokinetic ion enrichment in a micro-nanofluidic preconcentrator with nanochannel’s Cantor fractal wall structure was performed based on Poisson–Nernst–Planck equation combined with the Navier–Stokes equation. The results show that reducing the initial length L0, increasing the initial height h0, increasing the fractal step n and using the unstaggered structure in the Cantor fractal principle can increase the ion enrichment concentration and peak voltage. The initial ion concentration is 0.1 mol/m3. When the applied voltage is 30 V and the initial height h0 increases from 35 to 45 nm, the ion enrichment concentration drastically increases from 1.007 to 1.410 mol/m3 by 40%. This study provides a theoretical basis and a novel design method for improving the sensitivity of micro-nanofluidic chips and the design of ultra-low concentration sample testing equipment.

The Need for Physiological Micro-Nanofluidic Systems of the Brain.

In this article, we review brain-on-a-chip models and associated underlying technologies. Micro-nanofluidic systems of the brain can utilize the entire spectrum of organoid technology. Notably, there is an urgent clinical need for a physiologically relevant microfluidic platform that can mimic the brain. Brain diseases affect millions of people worldwide, and this number will grow as the size of elderly population increases, thus making brain disease a serious public health problem. Brain disease modeling typically involves the use of in vivo rodent models, which is time consuming, resource intensive, and arguably unethical because many animals are required for a single study. Moreover, rodent models may not accurately predict human diseases, leading to erroneous results, thus rendering animal models poor predictors of human responses to treatment. Various clinical researchers have highlighted this issue, showing that initial physiological descriptions of animal models rarely encompass all the desired human features, including how closely the model captures what is observed in patients. Consequently, such animal models only mimic certain disease aspects, and they are often inadequate for studying how a certain molecule affects various aspects of a disease. Thus, there is a great need for the development of the brain-on-a-chip technology based on which a human brain model can be engineered by assembling cell lines to generate an organ-level model. To produce such a brain-on-a-chip device, selection of appropriate cells lines is critical because brain tissue consists of many different neuronal subtypes, including a plethora of supporting glial cell types. Additionally, cellular network bio-architecture significantly varies throughout different brain regions, forming complex structures and circuitries; this needs to be accounted for in the chip design process. Compartmentalized microenvironments can also be designed within the microphysiological cell culture system to fulfill advanced requirements of a given application. On-chip integration methods have already enabled advances in Parkinson's disease, Alzheimer's disease, and epilepsy modeling, which are discussed herein. In conclusion, for the brain model to be functional, combining engineered microsystems with stem cell (hiPSC) technology is specifically beneficial because hiPSCs can contribute to the complexity of tissue architecture based on their level of differentiation and thereby, biology itself.

Ion concentration polarization and its application in molecular preconcentration in micro-nanofluidic systems

The combination of ion concentration polarization (ICP) phenomenon and micro-nanofluidic technologies provided novel solutions to the problems of biomolecular detection, ion separations and desalinations etc. This paper makes a brief introduction to ICP and the latest advances in the related theoretical and simulation research, with especial emphases on electroosmotic flow of the second kind and its deterministic role in the formation of over limiting currents. Subsequently, ICP in dumbbell-shaped and H-shaped micro-nanofluidics systems is introduced, along with its application in preconcentration, seawater desalination and current rectification systems. Latest theoretical advances ICP-based electrokinetic concentration is reviewed. Lastly, future work in terms of new functionalities, industrial development and theoretical investigations are suggested.

Fabrication of multifunctional components in a glass chip with femtosecond laser direct writing

Femtosecond lasers have opened up new avenues in materials processing due to their unique characteristics of ultrashort pulse widths and extremely high peak intensities. The short pulse width suppresses the formation of a heat-affected zone, which is vital for ultrahigh precision fabrication, whereas the high peak intensity allows multiphoton absorption to be induced in materials that are transparent to the laser wavelength. More interestingly, irradiation with tightly focused femtosecond laser pulses inside transparent materials provides a facile route to modify the interior of transparent materials in a spatially selective manner, enabling three-dimensional (3D) fabrication and integration of multifunctional micro-/nano-structures and components in a monolithic substrate. For instance, femtosecond laser pulses have been used to write optical waveguides in both passive and active materials by locally modifying their refractive indices. In combination with wet chemical etching, femtosecond laser direct writing has also been used to fabricate microfluidic structures, including microchannels and chambers, microvalves, and micropumps. The same technique has been extended to fabricate free-space optics such as micromirrors and micro-optical lenses in glass materials. By virtue of its unique ability to build different types of functional components into a monolithic substrate, femtosecond laser direct writing offers a flexible approach to fabricate a wide variety of integrated devices and microsystems. Although femtosecond laser micromachining have indeed shown extreme flexibility for fabrication and integration of 3D multifunctional micro- components in bulk transparent materials, several major issues still exist, such as the limited size of the microfluidic structures, the limited fabrication resolution, high surface roughness, and so on. This review focuses primarily on the recent efforts to tackle the two issues as mentioned above. By use of femtosecond laser direct writing in porous glass immersed in water followed by post-annealing, we demonstrated microfluidic channels with nearly unlimited lengths and arbitrary 3D geometries. By controlling the laser peak intensity and polarization, a single nanoplane with sub-50-nm feature size could be achieved inside porous glass based on these strategies, several functional devices and their applications have been demonstrated, including 3D passive microfluidic mixer and an integrated micro-nanofluidic system for single DNA analysis. Furthermore, we demonstrate fabrication of 3D whispering gallery microcavities with quality (Q)-factors on the level of ~1×106 in glass chips by femtosecond laser direct writing followed by CO2 laser reflow.

Femtosecond Laser 3D Fabrication in Porous Glass for Micro- and Nanofluidic Applications

The creation of complex three-dimensional (3D) fluidic systems composed of hollow micro- and nanostructures embedded in transparent substrates has attracted significant attention from both scientific and applied research communities. However, it is by now still a formidable challenge to build 3D micro- and nanofluidic structures with arbitrary configurations using conventional planar lithographic fabrication methods. As a direct and maskless fabrication technique, femtosecond laser micromachining provides a straightforward approach for high-precision, spatially-selective, modification inside transparent materials through nonlinear optical absorption. In this paper, we demonstrate rapid fabrication of high-aspect-ratio micro- and/or nanofluidic structures with various 3D configurations by femtosecond laser direct writing in porous glass substrates. Based on this approach, we demonstrate several functional micro- and nanofluidic devices including a 3D passive microfluidic mixer, a capillary electrophoresis (CE) analysis chip, and an integrated micro-nanofluidic system for single DNA analysis. The possible mechanisms behind the formation of high-aspect-ratio micro- and nanochannels are also discussed. This technology offers new opportunities to develop novel 3D micro-nanofluidic systems for a variety of lab-on-a-chip applications.

Direct laser writing of sub-50 nm nanofluidic channels buried in glass for three-dimensional micro-nanofluidic integration

We report on the fabrication of nanofluidic channels directly buried in silicate glass with transverse widths down to less than 50 nm using three-dimensional (3D) femtosecond laser direct writing. Using this technique, integrated micro-nanofluidic systems have been produced by simultaneously writing micro- and nanofluidic channels arranged into various 3D configurations in glass substrates. The fabricated micro- and nanofluidic systems have been used to demonstrate DNA analysis, e.g. stretching of DNA molecules. Our technique offers new opportunities to develop novel 3D micro-nanofluidic systems for a variety of lab-on-a-chip applications.

Sensitive sequence-specific molecular identification system comprising an aluminum micro-nanofluidic chip and associated real-time confocal detector

We developed a micro-nanofluidic bioreactor-detector system for isothermal DNA amplification and sensitive real-time detection of the amplified products for sequence-specific molecular identification. Aluminum (Al) chips with a range of volumes from 7.07 μL to 39 nL and an associated real-time confocal optical detector are described. The detector provided highly sensitive fluorescence detection and low background noise. One of the important aspects of the system was the development of a surface processing technique that afforded chips with an inert surface to improve amplification stability in micro-nanoliter reaction assays. The micro-nanofluidic system exhibited more sensitive exponential DNA amplification characteristics than a standard PCR tube amplification system with a volume of 25 μL, the response time was clearly reduced at the same DNA template concentration, and the sensitivity in the number of copies of the DNA template was improved by >600-fold. Efficient amplification of nucleic acid was achieved with as few as three copies of the DNA template. This system may be useful for the development of novel lab-on-a-chip devices and shows promise for single-molecule amplification in droplet assays, with potential applications in nanobiotechnology, nanomedicine, and clinical molecular diagnostics.

Microfluidics in biology and genosensor construction

We describe key stages in the development of a genosensor-based bioanalytical complex capable of functioning in a micro/nanofluidic system (MNFS), which is intended for detecting damaging agents in liquid media. Using the LIGA technology, we have developed an MNFS with a channel width of a few microns or more. Methods of (i) processing microfluid channels for positioning bacterial cells-genosensors and (ii) detecting fluorescent signals in a microfluid module are developed. A search for promoters ensuring the response of genosensor structures to a broad range of damaging factors of the external environment is carried out using a bioinformatics approach (based on GenSensor database). An experimental genosensor has been constructed based on the dps gene promoter of E. coli and the pRS-GFPvaa vector plasmid. It is shown that an E. coli/pDps-gfp genosensor in a microfluid module responds by GFPvaa protein synthesis to the presence of oxidative stress agents and agents capable of penetrating membranes in the same range of concentrations as those outside the module. The results of our investigation show that the proposed interdisciplinary approach can be used for obtaining bacterial cells-genosensors capable of functioning in MNFSs and detecting damaging factors of the external environment.