Selective Capture and Manipulation of DNA through Double Charged Nanopores.

In the past few decades, nanometer-scale pores have been employed as powerful tools for sensing biological molecules. Owing to its unique structure and properties, solid-state nanopores provide interesting opportunities for the development of DNA sequencing technology. Controlling DNA translocation in nanopores is an important means of improving the accuracy of sequencing. Here we present a proof of principle study of accelerating DNA captured across targeted graphene nanopores using surface charge density and find the intrinsic mechanism of the combination of electroosmotic flow induced by charges of nanopore and electrostatic attraction/repulsion between the nanopore and ssDNA. The theoretical study performed here provides a new means for controlling DNA transport dynamics and makes better and cheaper application of graphene in molecular sequencing.

Electroosmotic flow in soft clay and measures to promote movement under direct current electric field.

Electroosmosis has been proposed as a technique to reduce moisture and thus increase the stability of soft clay. However, its high energy consumption and uneven reinforcement effect has limited its popularization and application in practical engineering. This paper presents the results of some electrokinetic tests performed on clayey specimens with different electrification time and anode boundary conditions. The results indicate that the timing of the formation of electroosmotic flow (EF) by the water originally contained in different soil cross sections, from the anode to the cathode, varies. The measuring soil cross section nearest the anode first reached the limiting water content of 22%±3% and electroosmosis had to be stopped. Water injection into the anode during electroosmosis enhanced further drainage of other four measuring soil cross sections until the second soil cross section from the anode reached the limiting water content of 30%±2%. Electroosmosis with water injection into the anode technique provides more uniform reinforcement, increasing EF, and environmental protection. The experimental results highlighted the relevant and expected contribution of water injection into the anode on the effectiveness of the electroosmotic treatment as a soft clay improvement technique.

Conformation Influence of DNA on the Detection Signal through Solid-State Nanopores.

The detection and identification of nanoscale molecules are crucial, but traditional technology comes with a high cost and requires skilled operators. Solid-state nanopores are new powerful tools for discerning the three-dimensional shape and size of molecules, enabling the translation of molecular structural information into electric signals. Here, DNA molecules with different shapes were designed to explore the effects of electroosmotic forces (EOF), electrophoretic forces (EPF), and volume exclusion on electric signals within solid-state nanopores. Our results revealed that the electroosmotic force was the main driving force for single-stranded DNA (ssDNA), whereas double-stranded DNA (dsDNA) was primarily dominated by electrophoretic forces in nanopores. Moreover, dsDNA caused greater amplitude signals and moved faster through the nanopore due to its larger diameter and carrying more charges. Furthermore, at the same charge level and amount of bases, circular dsDNA exhibited a tighter structure compared to brush DNA, resulting in a shorter length. Consequently, circular dsDNA caused higher current-blocking amplitudes and faster passage speeds. The characterization approach based on nanopores allows researchers to get molecular information about size and shape in real time. These findings suggest that nanopore detection has the potential to streamline nanoscale characterization and analysis, potentially reducing both the cost and complexity.

Surface Reaction of Electroosmotic Flow-Driven Free Antigens With Immobilized Magnetic-Microbeads-Tagged-Antibodies in Microchannels.

Immunoassays based on reactions between target pathogen (antigen; Ag) and antibody (Ab) are frequently used for Ag detection. An external magnetic field was used to immobilize magnetic microbeads-tagged-antibodies (mMB-Ab) on the surface of a microchannel in the capture zone. The mMB-Ab was subsequently used for Ag detection. The objective of this numerical study, with experimental validation, is to assess the surface reaction between mMB-Ab and Ag in the presence of electro-osmotic flow (EOF). First, immobilization of mMB-Ab complex in the wall of the capture zone was achieved. Subsequently, the Ag was transported by EOF toward the capture zone to bind with the immobilized mMB-Ab. Lastly, mMB-Ab:Ag complex was formed and immobilized in the capture zone. A finite volume solver was used to implement the above steps. The surface reaction between the mMB-Ab and Ag was investigated in the presence of electric fields (E): 150 V/cm-450 V/cm and Ag concentrations: 0.001 M-1000 M. The depletion of mMB-Ab increases with time as the E decreases. Furthermore, as the concentration of Ag decreases, the depletion of mMB-Ab increases with time. These results quantify the detection of Ag using the EOF device; thus, signifying its potential for rapid throughput screening of Ag. This platform technology can lead to the development of portable devices for the detection of target cells, pathogens, and biomolecules for testing water systems, biological fluids, and biochemicals.

Bidirectional and Stepwise Rotation of Cells and Particles Using Induced Charge Electroosmosis Vortexes.

The rotation of cells is of significant importance in various applications including bioimaging, biophysical analysis and microsurgery. Current methods usually require complicated fabrication processes. Herein, we proposed an induced charged electroosmosis (ICEO) based on a chip manipulation method for rotating cells. Under an AC electric field, symmetric ICEO flow microvortexes formed above the electrode surface can be used to trap and rotate cells. We have discussed the impact of ICEO and dielectrophoresis (DEP) under the experimental conditions. The capabilities of our method have been tested by investigating the precise rotation of yeast cells and K562 cells in a controllable manner. By adjusting the position of cells, the rotation direction can be changed based on the asymmetric ICEO microvortexes via applying a gate voltage to the gate electrode. Additionally, by applying a pulsed signal instead of a continuous signal, we can also precisely and flexibly rotate cells in a stepwise way. Our ICEO-based rotational manipulation method is an easy to use, biocompatible and low-cost technique, allowing rotation regardless of optical, magnetic or acoustic properties of the sample.

Confined Transport Behavior of Biomolecules within Tilted Nanopores.

The transport behavior of biomolecules at the confined nanoscale is very different from that of the bulk state. Numerous disease diagnostics and targeted drug treatments are performed based on nanochannels in cells. The specific structure and shape of nanochannels play an important role in the behavior and efficiency of substance transport. In this paper, we fabricated nanopores with different tilt angles and the same diameters using focused ion beam. The capture frequency and the blocking current amplitude of λ-DNA within large-angle nanopores decrease obviously, suggesting an increase in the energy barrier of large-angle nanopores and the fact that they stretch biomolecules to thinness. Most importantly, large-angle nanopores slow down λ-DNA transport by 2-4 times. MD simulations find that the sloped electroosmotic flow inside the tilted nanopores is the main factor contributing to the transport phenomena. The increase in the capture time of biomolecules by nanopores assists in obtaining more biological information from the current trajectories. Our study provides a new understanding of substance transport in specially shaped nanopores, which can be instrumental in providing fresh inspiration and approaches to the biomedical field.

Electroosmotic and Gyrotactic Microorganisms Effects on MHD Al2O3-Cu/Blood Hybrid Nanofluid Flow through Multi-Stenosed Bifurcated Artery.

BACKGROUND: The purpose of this study is to investigate the electroosmotic flow of a hybrid nanofluid (Al2O3-Cu/Blood) with gyrotactic microorganisms through a bifurcated artery with mild stenosis in both parent and daughter arteries. The flow is subjected to a uniform magnetic field, viscous dissipation, and a heat source. METHODS: The governing equations undergo the non-dimensional transformation and coordinate conversion to regularize irregular boundaries, then solve the resulting system using the Crank-Nicolson method. RESULTS: In both sections of the bifurcated artery (parent and daughter artery), the wall shear stress (WSS) profile decreases with increasing stenotic depth. Nusselt profile increases with an increase in the heat source parameter. CONCLUSIONS: The present endeavour can be beneficial for designing better biomedical devices and gaining insight into the hemodynamic flow for therapeutic applications in the biomedical sciences.

Analytical solutions for viscoelectric effects in electrokinetic nanochannels.

Understanding electrokinetic transport in nanochannels and nanopores is essential for emerging biological and electrochemical applications. The viscoelectric effect is an important mechanism implicated in the increase of local viscosity due to the polarization of a solvent under a strong electric field. However, most analyses of the viscoelectric effect have been limited to numerical analyses. In this work, we present a set of analytical solutions applicable to the physical description of viscoelectric effects in nanochannel electrokinetic systems. To achieve such closed-form solutions, we employ the Debye-Hückel approximation of small diffuse charge layer potentials compared to the thermal potential. We analyze critical parameters, including electroosmotic flow profiles, electroosmotic mobility, flow rate, and channel conductance. We compare and benchmark our analytical solutions with published predictions from numerical models. Importantly, we leverage these analytical solutions to identify essential thermophysical and nondimensional parameters that govern the behavior of these systems. We identify scaling parameters and relations among surface charge density, ionic strength, and nanochannel height.

Transdermal drug delivery using a porous microneedle device driven by a hydrogel electroosmotic pump.

Integrating a hydrogel electroosmotic pump with a parylene C-coated porous microneedle (PMN) is developed for transdermal drug delivery applications. The hydrogel pump is fabricated by combining an anionic and a cationic hydrogel to generate enhanced electroosmosis flow (EOF) to drive the transportation of molecules via PMN.

Lithium Chloride Effects Field-Induced Protein Unfolding and the Transport Energetics Inside a Nanopipette.

The tapered geometry of nanopipettes offers a unique perspective on protein transport through nanopores since both a gradual and fast confinement are possible depending on the translocation direction. The protein capture rate, unfolding, speed of translocation, and clogging probability are studied by toggling the LiCl concentration between 2 and 4 M. Interestingly, the proteins in this study could be transported with or against electrophoresis and offer vastly different attributes of sensing. Herein, a ruleset for studying proteins is developed that prevents irreversible pore clogging and yields upward of >100,000 events/nanopore. The extended duration of experiments further revealed that the capture rate takes ∼2 h to reach a steady state, emphasizing the importance of reaching equilibrated transport for studying the energetics and kinetics of protein transport (i.e., diffusion vs barrier-limited). Even in the equilibrated transport state, improper lowpass filtering was shown to distort the classification of diffusion-limited vs barrier-limited transport. Finally, electric-field-induced protein unfolding was found to be most prominent in electroosmotic-dominant transport, whereas electrophoretic-dominant events show no evidence of unfolding. Thus, our findings showcase the optimal conditions for protein translocations and the impact on studying protein unfolding, transporting energetics, and acquiring high bandwidth data.

Joule heating and electroosmotic flow in cellular micro/nano electroporation.

Localized micro/nano-electroporation (MEP/NEP) shows tremendous potential in cell transfection with high cell viability, precise dose control, and good transfection efficacy. In MEP/NEP, micro or nanochannels are used to tailor the electric field distribution. Cells are positioned tightly by a micron or nanochannel, and the cargoes are delivered into the cell via the channel by electrophoresis (EP). Such confined geometries with micro and nanochannels are also widely used in sorting, isolation, and condensing of biomolecules and cells. Theoretical studies on the electrokinetic phenomena in these applications have been well established. However, for MEP/NEP applications, electrokinetic phenomena and their impact on the cell transfection efficiency and cell survival rate have not been studied comprehensively. In this work, we reveal the coupling between electric field, Joule heating, electroosmosis (EO), and EP in MEP/NEP at different channel sizes. A microfluidic biochip is used to investigate the electrokinetic phenomena in MEP/NEP on a single cell level. Bubble formation is observed at a threshold voltage due to Joule heating. The bubble is pushed to the cargo side due to EO and grows at the outlet of the nanochannel. As the voltage increases, the cargo transport efficiency decreases due to more intense EO, particularly for plasmid DNAs (3.5 kbp) with a low EP mobility. An 'electroporation zone' is defined for NEP/MEP systems with different channel sizes to avoid bubble formation and excessive EO velocity that may reduce the cargo delivery efficiency.

Three-dimensional rotation of deformable cells at a bipolar electrode array using a rotating electric field.

Three-dimensional rotation of cells is imperative in a variety of applications such as biology, medicine, and chemistry. We report for the first time a versatile approach for executing controllable 3D rotation of cells or particles at a bipolar electrode (BPE) array using a rotating electric field. The versatility of this method is demonstrated by 3D rotating various cells including yeast cells and K562 cells and the cells can be rotated to a desired orientation and immobilized for further operations. Our results demonstrate how electrorotation torque, induced charge electroosmosis (ICEO) flow and dielectrophoresis can be exerted on certain cells for modulating the rotation axis, speed, and direction. ICEO-based out-of-plane rotation is capable of rotating various cells in a vertical plane regardless of their shape and size. It can realize cell orientation by rotating cells toward a specific angle and enable cell rotation by steadily rotating multiple cells at a controllable speed. The rotation spectrum for in-plane rotation is further used to extract the cellular dielectric properties. This work offers a flexible method for controllable, contactless and precise rotation of different cells or particles, offering a rapid, high-throughput, and nondestructive rotation method for cell analysis and drug discovery.

An Alternating Current Electroosmotic Flow-Based Ultrasensitive Electrochemiluminescence Microfluidic System for Ultrafast Monitoring, Detection of Proteins/miRNAs in Unprocessed Samples.

Early diagnosis of acute diseases is restricted by the sensitivity and complex process of sample treatment. Here, an ultrasensitive, rapid, and portable electrochemiluminescence-microfluidic (ECL-M) system is described via sandwich-type immunoassay and surface plasmonic resonance (SPR) assay. Using a sandwich immunoreaction approach, the ECL-M system employs cardiac troponin-I antigen (cTnI) as a detection model with a Ru@SiO2 NPs labeled antibody as the signal probe. For miR-499-5p detection, gold nanoparticles generate SPR effects to enhance Ru(bpy)3 2+ ECL signals. The system based on alternating current (AC) electroosmotic flow achieves an LOD of 2 fg mL-1 for cTnI in 5 min and 10 aM for miRNAs in 10 min at room temperature. The point-of-care testing (POCT) device demonstrated 100% sensitivity and 98% specificity for cTnI detection in 123 clinical serum samples. For miR-499-5p, it exhibited 100% sensitivity and 97% specificity in 55 clinical serum samples. Continuous monitoring of these biomarkers in rats' saliva, urine, and interstitial fluid samples for 48 hours revealed observations rarely documented in biotic fluids. The ECL-M POCT device stands as a top-performing system for ECL analysis, offering immense potential for ultrasensitive, rapid, highly accurate, and facile detection and monitoring of acute diseases in POC settings.

A bioinspired approach for the modulation of electroosmotic flow and protein-surface interactions in capillary electrophoresis using silylated amino-amides blocks and covalent grafting.

We explore a bioinspired approach to design tailored functionalized capillary electrophoresis (CE) surfaces based on covalent grafting for biomolecules analysis. First, the approach aims to overcome well-known common obstacles in CE protein analysis affecting considerably the CE performance (asymmetry, resolution, and repeatability) such as the unspecific adsorption on fused silica surface and the lack of control of electroosmotic flow (EOF). Then, our approach, which relies on new amino-amide mimic hybrid precursors synthesized by silylation of amino-amides (Si-AA) derivatives with 3-isocyanatopropyltriethoxysilane, aims to recapitulate the diversity of protein-protein interactions (π-π stacking, ionic, Van der Waals…) found in physiological condition (bioinspired approach) to improve the performance of CE protein analysis (electrochromatography). As a proof of concept, these silylated Si-AA (tyrosinamide silylation, serinamide silylation, argininamide silylation, leucinamide silylation, and isoglutamine silylation acid) have been covalently grafted in physiological conditions in different amount on bare fused silica capillary giving rise to a biomimetic coating and allowing both the modulation of EOF and protein-surface interactions. The analytical performances of amino-amide functionalized capillaries were assessed using lysozyme, cytochrome C and ribonuclease A and compared to traditional capillary coatings poly(ethylene oxide), poly(diallyldimethylammonium chloride), and sodium poly(styrenesulfonate). EOF, protein adsorption rate, protein retention factor k, and selectivity were determined for each coating. All results obtained showed this approach allowed to modulate the EOF, reduce unspecific adsorption, and generate specific interactions with proteins by varying the nature and the amount of Si-AA in the functionalization mixture.

Multilayer track-etched membrane-based electroosmotic pump for drug delivery.

Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400 mmH2 O) of a fundamental pump unit was obtained at 0.8 mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7 µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7 µW. Thus, EOP-3 can run stably over 35 h at a pulse current of 0.1 mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.

Characterization of Extracellular Vesicles by Resistive-Pulse Sensing on In-Plane Multipore Nanofluidic Devices.

Extracellular vesicles (EVs) are cell-derived, naturally produced, membrane-bound nanoscale particles that are linked to cell-cell communication and the propagation of diseases. Here, we report the design and testing of in-plane nanofluidic devices for resistive-pulse measurements of EVs derived from bovine milk and human breast cancer cells. The devices were fabricated in plane with three nanopores in series to determine the particle volume and diameter, two pore-to-pore regions to measure the electrophoretic mobility and zeta potential, and an in-line filter to prevent cellular debris and aggregates from entering the nanopore region. Devices were tested with and without the channels coated with a short-chain PEG silane to minimize electroosmotic flow and permit an accurate measurement of the electrophoretic mobility and zeta potential of the EVs. To enhance throughput of EVs, vacuum was applied to the waste reservoir to increase particle frequencies up to 1000 min-1. The nanopores had cross-sections 200 nm wide and 200 nm deep and easily resolved EV diameters from 60 to 160 nm. EVs from bovine milk and human breast cancer cells had similar particle size distributions, but their zeta potentials differed by 2-fold, -8 ± 1 and -4 ± 1 mV, respectively.

Modulated complexed stenosed region consequences under the electroosmotic stimulation.

The present study analyzes the theoretical consequences of slip effects in a complex stenosed region. The flow of blood in a stenosed region is incorporated with hybrid nanofluid features which are being prepared with copper and copper oxide nanoparticles. The flow is also intensified by applying an electric field in the axial direction. The governing equations for the proposed paradigm are solved and the corresponding closed-form solutions are obtained for the cases of mild stenosis. Parameters such as Electro-osmotic, velocity slip and Helmholtz-Smoluchowski are specially focused in this study. The heat transfer, hemodynamic velocity, wall shear stress and resistance impedance for the flow are precisely determined. The various parameters that influence the physical characteristics of flow are plotted, and their effects are discussed in detail. The present model has the potential application in medical pumps for drug delivery systems.

Enrichment of cinnamaldehyde from Cinnamomum cassia by electroosmotic coupled particle-assisted solvent flotation.

Cinnamaldehyde has been widely applied in various fields due to its special flavor and various pharmacological activities, such as antioxidant, anti-inflammatory and antibacterial properties. The strategy of quick and efficient enrichment for cinnamaldehyde is imperative. In this study, an electroosmotic coupled particle-assisted solvent flotation (ECPASF) system was designed for the cinnamaldehyde enrichment from cinnamon. The response surface method was used to optimize extraction parameters. Under optimal operating conditions, its yield was 9.33 ± 0.11 mg/g. Such high yield of cinnamaldehyde using the ECPASF might be because electroosmosis effectively alters the permeability of plant cells, which facilitates the release of cinnamaldehyde. In addition, both the crude extract of cinnamon and pure cinnamaldehyde showed good antioxidant activity. The results demonstrated that the ECPASF system is a sustainable and effective method for the extraction of cinnamaldehyde from cinnamon. It also has the prospect of being extended to the extraction of other natural products.

Entropy generation optimization for the electroosmotic MHD fluid flow over the curved stenosis artery in the presence of thrombosis.

The present study deals with the entropy generation analysis on the flow of an electrically conductive fluid (Blood) with [Formula: see text]-suspended nanoparticles through the irregular stenosed artery with thrombosis on the catheter. The fluid flow can be actuated by the interactions of different physical phenomena like electroosmosis, radiation, Joule heating and a uniform radial magnetic field. The analysis of different shapes and sizes of the nanoparticle is considered by taking the Crocine model. The velocity, temperature, and concentration distributions are computed using the Crank-Nicholson method within the framework of the Debye-Huckel linearization approximation. In order to see how blood flow changes in response to different parameters, the velocity contour is calculated. The aluminium oxide nanoparticles employed in this research have several potential uses in biomedicine and biosensing. The surface's stability, biocompatibility, and reactivity may be enhanced by surface engineering, making the material effective for deoxyribonucleic acid sensing. It may be deduced that the velocity profile reduces as the nanoparticle's size grows while depicts the reverse trend for the shape size. In a region close to the walls, the entropy profile decreases, while in the region in the middle, it rises as the magnetic field parameter rises. The present endeavour can be beneficial in biomedical sciences in designing better biomedical devices and gaining insight into the hemodynamic flow for treatment modalities.

Nanopore actuation of a DNA-tracked nanovehicle.

As a kind of nanomachine that has great potential for applications in nanoscale sensing and manipulation, nanovehicles with unique shapes and functions have received extensive attention in recent years. Different from the existing common method of using synthetic chemistry to design and manufacture a nanovehicle, here we theoretically report a molecularly assembled DNA-tracked nanovehicle that can move on a solid-state surface using molecular dynamics simulations. A graphene membrane with four nanopores acts as the chassis of the nanoscale vehicle, and two circular ssDNAs across the nanopores serve as the wheels. The electroosmotic flows induced by independently charged nanopores with different surface charge densities under external electric fields were found to be the main power to actuate the controlled rotary motion of circular ssDNAs across every two nanopores. By tuning the rotary speed of each circular ssDNA, the linear and turning movements of the designed nanovehicle were realized. The designed nanovehicle makes it possible to have access to almost everywhere in the human body, which would lead to significant breakthroughs in the fields of nanoscale surgery, drug delivery and so on. The research not only enriches the family of nanorobots, but also opens another way for designing nanovehicles.