Nanoscale Flow Research Articles

A design method for nanofluidic circuits

A design method is proposed for nanofluidic circuits, based on the flow equation for a nanoscale fluid flow. This method incorporates the use of the concepts of the flow resistance, the flow rate, the pressure drop and the power loss, as like in electric circuits. The equations for calculating the flow resistance and the power loss in exemplary nanofluidic circuits including in a nanotube tree are presented. It was found that the nanotube size and the fluid-tube wall interaction both have great influences on the flow resistance and the power loss in nanochannel flow. Exemplary design analysis is given for some nanofluidic circuits, based on the proposed method.

TEM Tomography of Pores with Application to Computational Nanoscale Flows in Nanoporous Silicon Nitride (NPN).

Silicon nanomembrane technologies (NPN, pnc-Si, and others) have been used commercially as electron microscopy (EM) substrates, and as filters with nanometer-resolution size cut-offs. Combined with EM, these materials provide a platform for catching or suspending nanoscale-size structures for analysis. Usefully, the nanomembrane itself can be manufactured to achieve a variety of nanopore topographies. The size, shapes, and surfaces of nanopores will influence transport, fouling, sieving, and electrical behavior. Electron tomography (ET) techniques used to recreate nanoscale-sized structures would provide an excellent way to capture this variation. Therefore, we modified a sample holder to accept our standardized 5.4 mm × 5.4 mm silicon nanomembrane chips and imaged NPN nanomembranes (50–100 nm thick, 10–100 nm nanopore diameters) using transmission electron microscopy (TEM). After imaging and ET reconstruction using a series of freely available tools (ImageJ, TomoJ, SEG3D2, Meshlab), we used COMSOL Multiphysics™ to simulate fluid flow inside a reconstructed nanopore. The results show flow profiles with significantly more complexity than a simple cylindrical model would predict, with regions of stagnation inside the nanopores. We expect that such tomographic reconstructions of ultrathin nanopores will be valuable in elucidating the physics that underlie the many applications of silicon nanomembranes.

Methods to improve electro kinetic energy conversion efficiency in nanoscale channel

With the help of MD simulation in a Lennard jones system, Argon fluid flowing through a Platinum channel, we have demonstrated a practical approach to tune slip length in nanoscale flows. It was found that the presence of solid obstacles in the channel can manipulate the slip length similar to the variation of slip length with respect to fluid solid interaction potential. These results can act as a guidance to improve the electro kinetic energy conversion efficiency in nanoscale flows which will have immense application in the development of nanofluidic battery.

Numerical investigation of the nano-scale solutal Marangoni convections

Abstract Marangoni convection driven by surface tension gradient plays an important role in nano-scale processes and also the processes under microgravity in space, where the effect of surface tension may become significant compared with that of the gravitational body force. For a better understanding of Marangoni convection occurring in a nano-scale process, Molecular Dynamics (MD) and Computational Fluid Dynamics (CFD) simulations were carried out for a thin liquid film with concentration gradient. The computed flow structures by these methods were compared. The results show quantitative differences in the magnitudes of the flow velocity and the deformation of the liquid film. It was also found that a stronger driving force would be needed to generate nano-scale flows compared with that required for macro-scale flows. This is due to the fact that a stronger surface force may be needed to overcome the random movements of molecules.

Isolation and analysis of plasma-derived exosomes in patients with glioblastoma

Abstract Gliomas including glioblastoma (GBM) are the most common malignant brain tumors. Glioma extracellular vesicles (EVs), especially exosomes in plasma have biological effects such as mediating immunosuppression and contain signature tumor-specific cargo, therefore could serve as liquid biopsies and as a non-invasive biomarker. However, isolation of glioma plasma exosomes has not been optimized. The purpose of this study is to develop an optimized method for plasma-derived exosomes isolation and study the immunosuppressive capacity of these particles. Plasma exosomes from glioma patients and normal donors were isolated by brief centrifugation to remove cells/debris followed by one or two-step density gradient ultracentrifugation (DGU). EV size and concentration were determined by NanoSight analysis. Nanoscale Flow Cytometry analysis quantified and characterized the resulting exosome and microvesicle populations isolated by DGU. Protein cargo was screened by Western blot, protein array, and ELISA. One-step DGU efficiently isolated exosomes for NanoSight analysis. Isocitrate dehydrogenase (IDH) WT glioma patients’ plasma exosomes were smaller but higher concentration than normal donors. A second DGU efficiently concentrated exosomes for subsequent cargo analysis. Nanoscale Flow cytometry analysis confirmed that DGU allows isolation and purification of exosomes, not microvesicles. Exosome-specific markers and the immunosuppressive molecule programmed death-ligand 1 (PD-L1), were present in both glioma patient and normal donor exosomes. Screening cytokine and checkpoint molecule arrays suggested reduced pro-inflammatory molecules are found in GBM patients’ plasma exosomes compared to normal donors.

Effect of nanostructure on heat transfer between fluid and copper plate: a molecular dynamics simulation study

A molecular simulation is developed to study the effect of surface nanostructures on nanoscale flows. Based on this method, particles equation of motion is solved through the Verlet algorithm. Meanwhile, a physically sound method is applied to control the momentum and temperature of the simulation box. By adding an external force on the top copper plate according to the velocity difference between on-the-fly and desired velocities, simulations on convection of argon flows between two solid walls are performed. The top wall, which holds a higher temperature, moves at a constant velocity relative to bottom one along with the streamwise direction. These simulation results show that the nanostructures particularly affect fluid density oscillations adjacent to solid wall and nanostructures. In addition, these nanostructures also have significant effects on temperature and velocity distributions in simulation system.

An integrated fractional partial differential equation and molecular dynamics model of anomalously diffusive transport in heterogeneous nano-pore structures

Fluid flows confined in nano-pore structures exhibit physical behaviors that are not observed in large-scale structures. Molecular dynamics simulation has been used for modeling nano-scale fluid flows at nanoscale, but is deemed to be computationally very expensive and is often limited to problems with simple geometry.We develop an integrated fractional partial differential equation and molecular dynamics upscaling modeling of anomalously diffusive transport in heterogeneous nano-pore structures, which has a significantly improved computational efficiency and memory requirement over the molecular dynamics simulation. Representative applications demonstrate the usage of the new model, which takes the model a few hours on a laptop that would otherwise require a molecular dynamics simulation in the matter of at least 100 years of CPU time on a parallel computer.

Nanoscale multi-phase flow and its application to control nanofiber diameter

Nanoscale multi-phase flow and its application to control nanofiber diameter

Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic Landscape of Oligodendrocytes.

Oligodendrocytes are a type of neuroglia that provide trophic support and insulation to axons in the central nervous system. The genesis and maturation of oligodendrocytes are essential processes for myelination and the course of CNS development. Using ion mobility-enhanced, data-independent acquisitions and 2D-nanoUPLC fractionation operating at nanoscale flow rates, we established a comprehensive data set of proteins expressed by the human oligodendroglia cell line MO3.13. The final dataset incorporating all fractions comprised 223 531 identified peptides assigned to 10 390 protein hits, an improvement of 4.5 times on identified proteins described previously by our group using the same cell line. Identified proteins play pivotal roles in many biological processes such as cell growth and development and energy metabolism, providing a rich resource for future studies on oligodendrocyte development, myelination, axonal support, and the regulation of such process. Our results can help further studies that use MO3.13 cells as a tool of investigation, not only in relation to oligodendrocyte maturation, but also to diseases that have oligodendrocytes as key players. All MS data have been deposited in the ProteomeXchange with identifier PXD004696.

Supercritical CO2-induced atomistic lubrication for water flow in a rough hydrophilic nanochannel.

A fluid flow in a nanochannel highly depends on the wettability of the channel surface to the fluid. The permeability of the nanochannel is usually very low, largely due to the adhesion of fluid at the solid interfaces. Using molecular dynamics (MD) simulations, we demonstrate that the flow of water in a nanochannel with rough hydrophilic surfaces can be significantly enhanced by the presence of a thin layer of supercritical carbon dioxide (scCO2) at the water-solid interfaces. The thin scCO2 layer acts like an atomistic lubricant that transforms a hydrophilic interface into a super-hydrophobic one and triggers a transition from a stick- to- a slip boundary condition for a nanoscale flow. This work provides an atomistic insight into multicomponent interactions in nanochannels and illustrates that such interactions can be manipulated, if needed, to increase the throughput and energy efficiency of nanofluidic systems.

Nanoscale flow cytometry of patient plasma for the detection of prostate cancer-associated extracellular vesicles

Introduction Prostate cancer is the predominant cancer in men, affecting one in seven men during their lifetime. Current tests for prostate cancer include the digital rectal exam and the prostate-specific antigen (PSA) test. Extracellular vesicles (EVs) are submicron particles that participate in intercellular cross-talk by releasing cell mediators such as microRNA, carbohydrates and proteins. While they are known to express the broad tetraspanin family of proteins, i.e. CD9/CD63, prostate cancer-derived EVs have also been found to express PSA and six transmembrane epithelial antigen of the prostate (STEAP1). Traditionally, scientists have purified these EVs through ultracentrifugation. Here we propose a tandem purification of patient plasma, followed by nanoscale flow cytometry (A50+) as a novel method to detect tumour-derived EVs. Materials and Methods Plasma was obtained from healthy volunteers, patients with benign prostatic hyperplasia (BPH), and patients with metastatic prostate cancer. CD9, CD63, PSA and STEAP1 were used as primary antibodies for the purification of EVs from neat plasma. To perform the purification in tandem, Protein G immunoprecipitation using CD9 and PSA was carried out first, followed by immunoaffinity purification with biotinylated CD63 and STEAP1. First and second elutions were collected for the enumeration of dual positive events by A50+. Initial histogram overlays and bivariate plots of neat and purified plasma were computed, then exported as comma-separated values for mathematical modelling by MATLAB. Results Strong dual positive EV populations from patient plasma were optimised, demonstrating that the method enriches tumour-derived EVs from neat samples of patient plasma. This was observed for HVs, patients with benign prostatic hyperplasia, and prostate cancer patients with Gleason 4+4. Enrichment in these purified samples was measured by A50+ and demonstrated by overlaying purified and non-purified histoplots by MATLAB. Additional results show that PSA and STEAP1 can be adapted to detect single or dual positive populations of tumour-associated EVs in prostate cancer patients. Discussions and Conclusions This study suggests that tandem purification of tumour-associated EVs and A50+ analysis from plasma of prostate cancer patients can lead to earlier diagnosis and risk stratification, compared to traditional screening tests and aspiration cytology. Future studies will be directed toward optimizing this detection method for markers of other cancer types to achieve better outcomes in cancer detection and prognosis.

Single-Particle Discrimination of Retroviruses from Extracellular Vesicles by Nanoscale Flow Cytometry

Retroviruses and small EVs overlap in size, buoyant densities, refractive indices and share many cell-derived surface markers making them virtually indistinguishable by standard biochemical methods. This poses a significant challenge when purifying retroviruses for downstream analyses or for phenotypic characterization studies of markers on individual virions given that EVs are a major contaminant of retroviral preparations. Nanoscale flow cytometry (NFC), also called flow virometry, is an adaptation of flow cytometry technology for the analysis of individual nanoparticles such as extracellular vesicles (EVs) and retroviruses. In this study we systematically optimized NFC parameters for the detection of retroviral particles in the range of 115–130 nm, including viral production, sample labeling, laser power and voltage settings. By using the retroviral envelope glycoprotein as a selection marker, and evaluating a number of fluorescent dyes and labeling methods, we demonstrate that it is possible to confidently distinguish retroviruses from small EVs by NFC. Our findings make it now possible to individually phenotype genetically modified retroviral particles that express a fluorescent envelope glycoprotein without removing EV contaminants from the sample.

Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic Landscape of Oligodendrocytes.

Oligodendrocytes are a type of neuroglia that provide trophic support and insulation to axons in the central nervous system. The genesis and maturation of oligodendrocytes are essential processes for myelination and the course of CNS development. Using ion mobility-enhanced, data-independent acquisitions and 2D-nanoUPLC fractionation operating at nanoscale flow rates, we established a comprehensive data set of proteins expressed by the human oligodendroglia cell line MO3.13. The final dataset incorporating all fractions comprised 223 531 identified peptides assigned to 10 390 protein hits, an improvement of 4.5 times on identified proteins described previously by our group using the same cell line. Identified proteins play pivotal roles in many biological processes such as cell growth and development and energy metabolism, providing a rich resource for future studies on oligodendrocyte development, myelination, axonal support, and the regulation of such process. Our results can help further studies that use MO3.13 cells as a tool of investigation, not only in relation to oligodendrocyte maturation, but also to diseases that have oligodendrocytes as key players. All MS data have been deposited in the ProteomeXchange with identifier PXD004696.

A model for electromigration induced flow in liquid metals

Electromigration in liquid metals can be used for mass transport over a considerable length with micro- and nano-scale flow features. Exploitation of this phenomenon, however, requires a sound understanding of the liquid metal flow under an applied electric field. Depending on the sign of the effective charge number, Z*, liquid metals flow along a set direction under the applied electric field. A few liquid metals, e.g. Ga, Sn, etc, flow in the direction of the electric field, while a few others, e.g. Pb, flow in the opposite direction. Here, we propose a new model for predicting the direction of the aforementioned flow for a given liquid metal. Our model incorporates Lennard-Jones potential into the cell model of liquids in order to calculate the value of Z* as a function of temperature. We then carry out experiments on a few metals to validate the model and show that it indeed correctly predicts the ensuing flow.

Fluid-driven metamorphism of the continental crust governed by nanoscale fluid flow.

The transport of fluids through the Earth's crust controls the redistribution of elements to form mineral and hydrocarbon deposits, the release and sequestration of greenhouse gases, and facilitates metamorphic reactions that influence lithospheric rheology. In permeable systems with a well-connected porosity, fluid transport is largely driven by fluid pressure gradients. In less permeable rocks, deformation may induce permeability by creating interconnected heterogeneities, but without these perturbations, mass transport is limited along grain boundaries or relies on transformation processes that self-generate transient fluid pathways. The latter can facilitate large-scale fluid and mass transport in nominally impermeable rocks without large-scale fluid transport pathways. Here, we show that pervasive, fluid-driven metamorphism of crustal igneous rocks is directly coupled to the production of nanoscale porosity. Using multi-dimensional nano-imaging and molecular dynamics simulations, we demonstrate that in feldspar, the most abundant mineral family in the Earth's crust, electrokinetic transport through reaction-induced nanopores (10-100 nm) can potentially be significant. This suggests that metamorphic fluid flow and fluid-mediated mineral transformation reactions can be considerably influenced by nanofluidic transport phenomena.

The slip effect of micro-droplets in Rankine vortex

The method of moments with interphase slip is simplified to numerically study the interaction between nanoscale droplets and gas flow in a Rankine vortex. In the method, the flow of gas phase and the moments of the droplets size distribution are calculated respectively and the transfers of momentum and heat between the gas and the droplets which are expressed by the moments are introduced into the governing equations as the source terms. In this way, the velocity slip between the gas phase and the droplet phase is captured by the present method. Then, the method is used to simulate the flow of Rankine vortex where the water droplets with constant radius are injected into the vortex core. The results show that the vortex is disturbed and the droplets move outward due to the effect of the velocity slip between the phases. The larger the droplet radius, the stronger the velocity slip effect. When the radius of the injected droplets is small, the vortex keeps stable and the droplets aggregate as a ring outside the core of the vortex. When the droplets radii are large enough, the vortex is not stable any more due to the strong slip effect and negative vorticity is induced in the core of the vortex. The droplets form a swing arm and spiral out of the vortex. At last, the effects of the growth of droplets on the vortex evolution and interphase slip are also investigated. The grown droplets spiral out and the position of maximum mean radius also moves outward with time. In the vortex core, condensation stops after a short time because no more vapor is supplied. With the growing process, more momentum is transferred from the gas phase to the droplets and the slip velocity between droplets and gas vanishes more quickly.

Effects of density on flow in a nano channel using a molecular-continuum hybrid method

A molecular-continuum hybrid method was developed to simulate micro- and nano-scale fluid flows that cannot be predicted using continuum fluidics. Molecular dynamics simulation was used near stationary solid surfaces, and Navier-Stokes equations were used in other regions. We carried out Couette flow simulation using this hybrid method and validated the results by comparing them with the analytical solution. We also studied the dependence of the velocity slip and slip length on the surface energy, liquid density, and roughness for a liquid channel flow with and without nano-structures on the solid surface. The behavior of the liquid near the solid wall changed with the surface energy as well as the liquid density. The variation of the velocity slip and slip length according to the surface energy also depended on the liquid density as well as the surface roughness. We compared the required computational time obtained from the molecular-continuum hybrid method with that obtained from full molecular dynamics simulation under the same computational condition, giving much shorter computational time for the case using the molecular-continuum hybrid method than that for full molecular dynamics simulation.

Modeling Water Flow Through Carbon Nanotube Membranes with Entrance/Exit Effects

ABSTRACTCarbon nanotube–based membranes have gained significant attention due to their transport efficiency and wide range of applications, including molecular sieving and sensing. Recently, in order to attain high transport rates, many studies have focused on reducing membrane thickness. A reduction in membrane thickness results in the dominance of entrance/exit effects over surface effects, particularly for carbon nanotubes (CNTs), due to their hydrophobicity. However, experimentally obtained nanoscale flow rate data span a wide range, and entrance/exit effects are often neglected when analyzing these data. In this study, we modeled the water flow rate through various lengths and radii of CNTs using molecular dynamics simulations while also taking entrance/exit effects into consideration. Based on viscosity and slip length calculations, a water flow model is proposed that covers various lengths and radii of CNTs. Moreover, the enhancement factor of CNT membranes is reassessed using entrance/exit effects. The results of this study can be used for the optimal design of ultraefficient CNT membranes for potential applications such as water filtration.

Melt-processed P3HT and PE Polymer Nanofiber Thermal Conductivity

ABSTRACT Thermal management is a growing challenge for electronics packaging because of increased heat fluxes and device miniaturization. Thermal interface materials (TIMs) are used in electronic devices to transfer heat between two adjacent surfaces. TIMs need to exhibit high thermal conductivity and must be soft to minimize thermal contact resistance. Polymers, despite their relative softness, suffer from low thermal conductivity (∼0.2 W/m-K). To overcome this challenge, we infiltrate nanoporous anodic aluminum oxide (AAO) templates with molten polymer to fabricate large area arrays of vertically aligned polymer nanofibers. Nanoscale confinement effects and flow induced chain elongation improve polymer chain alignment (measured using polarized Raman spectroscopy) and thermal conductivity (measured using the photoacoustic method) along the fiber’s long axis. Conjugated poly(3-hexylthiophene-2,5-diyl) (P3HT) and non- conjugated polyethylene (PE) of various molecular weights are explored to establish a relationship between polymer structure, nanofiber diameter, and the resulting thermal conductivity. In general, thermal conductivity improves with decreasing fiber diameter and increasing polymer molecular weight. Thermal conductivity of approximately 7 W/m-K was achieved for both the ∼200 nm diameter HDPE fibers and the 100 nm diameter P3HT fibers. These results pave the way for optimization of the processing conditions to produce high thermal conductivity fiber arrays using different polymers, which could potentially be used in thermal interface applications.

Impact of the kinetic boundary condition on porous media flow in the lattice Boltzmann formulation.

To emphasize the importance of the kinetic boundary condition for micro- to nanoscale flow, we present an ad hoc kinetic boundary condition suitable for torturous geological porous media. We found that the kinetic boundary condition is one of the essential features which should be supplemented to the standard lattice Boltzmann scheme in order to obtain accurate continuum observables. The claim is validated using a channel flow setup by showing the agreement of mass flux with analytical value. Further, using a homogeneous porous structure, the importance of the kinetic boundary condition is shown by comparing the permeability correction factor with the analytical value. Finally, the proposed alternate to the kinetic boundary condition is validated by showing its capability to capture the basic feature of the kinetic boundary condition.