Nanofluidic Devices Research Articles

Nanofluidic Lab-On-A-Chip Systems for Biosensing in Healthcare.

Biosensing plays a vital role in healthcare monitoring, disease detection, and treatment planning. In recent years, nanofluidic technology has been increasingly explored to be developed into lab-on-a-chip biosensing systems. Given now the possibility of fabricating geometrically defined nanometric channels that are commensurate with the size of many biomolecules, nanofluidic-based devices are likely to become a key technology for the analysis of various clinical biomarkers, including DNA (deoxyribonucleic acid) and proteins in liquid biopsies. This review summarizes the fundamentals and technological advances of nanofluidics from the purview of single-molecule analysis, detection of low-abundance molecules, and single-cell analysis at the subcellular level. The extreme confinement and dominant surface charge effects in nanochannels provide unique advantages to nanofluidic devices for the manipulation and transport of target biomarkers. When coupled to a microfluidic network to facilitate sample introduction, integrated micro-nanofluidic biosensing devices are proving to be more sensitive and specific in molecular analysis compared to conventional assays in many cases. Based on recent progress in nanofluidics and current clinical trends, the review concludes with a discussion of near-term challenges and future directions for the development of nanofluidic-based biosensing systems toward enabling a new wave of lab-on-a-chip technology for personalized and preventive medicine.

Mechanically Stable PMMA‐Based Large‐Area Nano‐Channels with Sub‐10 nm Depth

AbstractArtificial sub‐microfluidic and nanofluidic devices allow for studying mass or ion transport effects under spatial confinement. It remains challenging to fabricate large‐scale, nanofluidic channels of well‐defined thickness for fundamental studies and practical applications, especially for extreme confinement conditions (e.g., with sub‐10 nm channel height). Here, a strategy is reported to fabricate large‐scale nano‐channels with the channel height down to 5.0 nm. The fabrication is enabled by developing ultra‐flat and ultra‐thin polymethylmethaacrylate (PMMA) layers as the spacer. The ease of scaling up the channel length to a millimeter in the lateral dimensions with high mechanical stability is demonstrated. Furthermore, experimental evidence is provided of the role of the mechanical coupling between the spacer and capping materials in determining the device's mechanical properties, and how controlling the channel width and the top graphite thickness can be employed to tailor the device's mechanical properties. Finally, employing near‐field IR experiments, the decay constant is established for the near‐field absorption intensity of PMMA molecules inside the channel by increasing the top layer thickness. This work develops a novel method for fabricating large‐area, mechanically stable nano‐channels for nanofluidic devices and lays the foundation for further in situ spectroscopic studies of electrochemistry within sub‐10 nm confinement.

Unlocking Nanoprecipitation: A Pathway to High Reversibility in Nanofluidic Memristors.

Solid-state nanochannels have emerged as a promising platform for the development of ionic circuit components with analog properties to their traditional electronic counterparts. In the last years, nanofluidic devices with memristive properties have attracted special interest due to their applicability in, for example, the construction of brain-like computing systems. In this work, an asymmetric track-etched nanofluidic channel with memory-enhanced ion transport is reported. The results illustrate that the formation of nanoprecipitates on the channel walls induces memory effects in ion transport, leading to characteristic hysteresis loops in the current-voltage curves, a hallmark of memristive behavior. Notably, these memristive properties are achievable with a straightforward experimental setup that combines an aqueous solvent and a relatively low-soluble inorganic salt. The various conductance states can be rapidly and reversibly tuned over prolonged time scales. Furthermore, under appropriate measurement conditions, the nanofluidic device can alternate between different iontronic regimes and states, encompassing ion current rectification, ON-OFF states, and memristor-like behavior. These findings provide insights into the design and optimization of nanofluidic devices for bioinspired ionic circuit components.

A penta-hybrid approach for modeling the nanofluid flow in a spatially dependent magnetic field

Abstract The penta-hybrid nanofluid is a nanofluid that contains five different types of nanoparticles. It can achieve higher heat transfer rates than conventional hybrid nanofluids due to the synergistic effects of the nanoparticles. It also has more diverse physical and thermal properties, which make it more adaptable for various applications. Therefore, this research examines the influence of localized magnetic fields on the vortex dynamics in a penta-hybrid nanofluidic flow in a vertical cavity with an aspect ratio of 1:10, driven by a top and bottom lid moving in the opposite direction. The stream-vorticity formulation is used to solve the dimensionless governing partial differential equation. A confined magnetic field in the form of horizontal and vertical strips has been applied instead of a uniform magnetic field throughout the flow domain, which is more realistic. Moreover, MATLAB codes developed by the authors are used to investigate how these parameters affect the flow and thermal properties of the nanofluids. The results suggest that magnetic fields have an impact on how stress, flow patterns, and temperature are distributed. Moreover, the presence of a magnetic field influences the spacing of isotherms, indicating a more even temperature distribution. It has also been observed that stress distribution is affected by the magnetic field, with higher stress levels near walls and regions with velocity-induced stress. However, in certain areas, the magnetic field can decrease shear stress depending on its strength and orientation. These study findings have implications for designing and operating nanofluidic devices. For instance, utilizing a magnetic field can help regulate flow patterns, temperature distribution, and stress distribution within nanofluidic channels. This capability could prove beneficial for a range of applications, such as cell separation, drug delivery, and nanofluidic heat exchange systems.

Relationship between Capillary Wettability, Mass, and Momentum Transfer in Nanoconfined Water: The Case of Water in Nanoslits of Graphite and Hexagonal Boron Nitride.

The flow of water confined in nanosize capillaries is subject of intense research due to its relevance in the fabrication of nanofluidic devices and in the development of theories for fluid transport in porous media. Here, using molecular dynamics simulations carried out on 2D capillaries made up of graphite, hexagonal boron nitride (hBN) and a mix of the two, and of sizes from subnanometer to few nanometers, we investigate the relationship between the wettability of the wall capillary, the water diffusion, and its flow rate. We find that the water diffusion is decoupled from its flow properties as the former is not affected either by the height or chemistry of the capillary (except for the subnanometer slits), while the latter is dependent on both. The capillaries containing hBN show a reduced flow rate compared to those that are purely graphitic, likely due to the high friction coefficient between water and hBN. Such resistance to the flow is, however, at its maximum in the smallest capillary and lower for larger ones. Finally, we show that the flow rate values obtained from the Hagen-Poiseuille theory are almost always smaller than those obtained from simulations, indicating that either the slip length or the viscosity of nanoconfined water could be substantially different from the bulk values.

Role of Underlying Substrates on the Interfacial Thermal Transport in Supported Graphene Nanochannels: Implications of Thermal Translucency.

We study the role of underlying substrates on interfacial heat transfer within supported graphene nanochannels. Due to graphene's translucency, the underlying substrate, apart from its known hydrodynamic impact on fluid flow, also influences heat transport. We introduce the term "thermal translucency" to describe this phenomenon in the context of interfacial heat transfer. Our findings reveal that the Kapitza resistance, RK, is dependent on the specific underlying substrate. The specific underlying substrate alters the water-graphene interface potential landscape due to graphene's translucency, leading to a breakdown in the inverse relationship between interfacial water density peaks and RK values, typically observed at water-graphene and water-graphite interfaces. Remarkably, higher interfacial water density peaks correlate with more ordered energy patterns, not necessarily tied to more hydrophilic substrates as the literature commonly suggests for lower RK values. The insights provided have implications for controlling and tuning thermal transport and heat storage in nanofluidic devices.

Water structures in tip-charged carbon nanotubes.

Carbon nanotubes (CNTs) have potential applications in separation membranes and nanofluidic devices. It is well known that the behavior of water molecules confined in CNTs is affected by surface functional groups and external electric fields, leading to structural changes. The understanding of these structural changes of water within various CNTs is crucial, particularly in the context of material separation. While there have been many investigations into the effects of individual specific functional groups, a comprehensive understanding of the effect of these functional groups and the electric fields they generate on water molecules remains elusive. In this study, we investigate the properties of water molecules in tip-charged CNTs of (8,8), (10,10), and (12,12) chiral vectors with positive charges at one tip and negative charges at the other tip. Abstraction of ionized functional groups as tip charges enables a comprehensive understanding that is independent of individual functional groups. The symmetrically arranged tip-charges spontaneously generate a strong and symmetric electric field in the CNTs. However, the strength and directionality of the electric field are non-uniform and complex. In the interiors of (8,8) and (10,10) tip-charged CNTs, helical and square structures, which have disturbances caused by the non-uniformity of the electric field, are observed. The properties of the water molecules differed significantly in the center of the CNTs and near positive and negative charges, despite the electric field symmetry. In (12,12) tip-charged CNTs with 12 charges, a local ring structure is observed in the vicinity of negative charges but not in the vicinity of positive charges. It is concluded that the water structures in tip-charged CNTs have different characteristics from those in plain CNTs under a uniform electric field.

Classification of DNA Mixtures by Nanoelectrokinetic Driftless Preconcentration

Nanofluidic phenomena, particularly Ion Concentration Polarization (ICP), have been actively utilized for advancing various research fields, including chemical analysis and biomedical diagnostics, over the past century. While ICP can be used as effective preconcentration techniques in bio-/chemical analysis, there are few studies to investigate the shape of preconcentration plug, especially perpendicular distribution of analyte in the preconcentration plug. Previously we have reported the theoretical analysis of the distribution so that the types of plug were categorized as dumbbell or plug shape. In this study, we further investigated the classification of real DNAs within micro-/nanofluidic devices by examining the preconcentration dynamics of different DNA types under diverse electrical conditions. Our investigation successfully distinguished distinct preconcentration profiles for Short DNA, Multi-short DNAs, and Equitable DNA with introducing the concept of the Radius of Gyration for Fluorescence (RGF). We provided a quantitative framework to analyze and differentiate preconcentration shapes with reasonable precision. These findings not only deepen our understanding of DNA preconcentration dynamics but also provide implications for genetic diagnostics. As a simpler and more accessible pre-test tool, our research could be utilized as the efficient genetic testing, particularly in diagnosing disorders characterized by variations in DNA length.

Ion current rectification coupled with asymmetric temperature and surface charge in ultrashort conical nanopores

Ion current rectification (ICR) is one of the electrodynamic properties in asymmetric nanochannels, which has been utilized to develop biosensors, heavy metal ion detection, and ion diodes. Previous studies on ICR mainly focused on long nanopores (length >500 nm), and relatively few studies on ion rectification performance in short nanopores. Here, we use a finite element numerical solution to simulate the effect of coupling asymmetric temperature and surface charge distribution on the ion rectification performance of ultrashort conical nanopores (length = 100 nm). The results show that the ion rectification performance is significantly improved when the inner and outer surfaces of the nanopore are charged non-uniformly, which is more than three times that when the inner surface of the nanopore is charged non-uniformly or the outer surface is charged non-uniformly. In addition, the positive temperature difference enhances the ion enrichment and dissipation and improves the ion rectification performance of nanopores. On the contrary, negative temperature difference inhibits ion enrichment and dissipation in pores, which is not conducive to improving ion rectification performance. Abnormal behavior is observed for nanopores non-uniform charged only on the outer wall surface, where the negative temperature gradient enhances the accumulation and dissipation of ions within the pores, thereby increasing the rectification ratio. In addition, in order to more clearly understand the ion transport behavior in the ultrashort nanopore under asymmetric temperature conditions, we further investigated the influence of the tip radius of the nanopore, the solution volume concentration, and the charge type of each surface charge distribution on the ion current rectification performance. The results reveal the ion transport mechanism of ultrashort conical nanopores and provide practical guidance for designing and optimizing nanofluidic devices.

Wood Ion Pumps Enabled by Light-Responsive MoS2-Decorated Nanocellulosic Channels.

Light-driven active ion transport discovered in nanomaterials (e.g., graphene, metal-organic framework, and MXene) implicates crucial applications in membrane-based technology and energy conversion systems. However, it remains a challenge to achieve bulk assembly. Herein, we employ the scalable wood as a framework for in situ growth of MoS2 nanosheets to facilitate light-responsive ion transport. Owing to the aligned and negatively charged wood nanochannels, the MoS2-decorated wood exhibits an excellent nanofluidic conductivity of 8.3 × 10-5 S cm-1 in 1 × 10-6 M KCl. Asymmetric light illumination creates the separation of electrons and holes in MoS2 nanosheets, enabling ions to move uphill against a wide range of concentration gradients. As a result, the MoS2-decorated wood can pump ions uphill against a 20-fold concentration gradient at a light intensity of 300 mW cm-2. When the illumination is applied to the opposite side, the osmotic current along the 20-fold concentration gradient can be enhanced to 75.1 nA, and the corresponding osmotic energy conversion power density increases to more than 12.6 times that of the nonilluminated state. Based on the light-responsive behaviors, we are extending the use of MoS2-decorated wood as the ionic elements for nanofluidic circuits, such as ion switches, ion diodes, and ion transistors. This work provides a facile and scalable strategy for fabricating light-controlled nanofluidic devices from biomass materials.

Light-Powered Directional Ion Transport via PFN-Br/MoS2 Heterogeneous Membranes: Band Alignment and Activation Energy Barrier Engineering.

Biological photoresponsive ion transport systems consistently attract researchers' attention owing to their remarkable functions of harvesting energy from nature and participating in visual perception systems. Designing and constructing artificial light-driven ion transport devices to mimic biological counterparts remains a challenge owing to fabrication limitations in nanoconfined spaces. Herein, a typical conjugated polyelectrolyte (PFN-Br) was assembled onto a laminated MoS2M using simple solution-processing vacuum filtration, resulting in a heterogeneous three- and two-dimensional nanoporous membrane. The designed band alignment between PFN-Br and MoS2 enables effective directional ion transport under irradiation in an equilibrium solution, even against a 30-fold concentration gradient. The staggered energy structure of PFN-Br and MoS2 enhances charge separation and establishes a photogenerated potential as the driving force for ion transport. Additionally, the activation energy barrier for ion transport across the heterogeneous membrane decreased by 60% after light irradiation, considerably improving ion transport flux. The easy fabrication and high performance of the membrane in light-powered ion transport provide promising approaches for designing nanofluidic devices with possible applications in energy conversion, light-enhanced biosensing, and photoresponsive ionic devices.

Integrated In-Plane Nanofluidic Devices for Resistive-Pulse Sensing.

Single-particle (or digital) measurements enhance sensitivity (10- to 100-fold improvement) and uncover heterogeneity within a population (one event in 100 to 10,000). Many biological systems are significantly influenced by rare or infrequent events, and determining what species is present, in what quantity, and the role of that species is critically important to unraveling many questions. To develop these measurement systems, resistive-pulse sensing is used as a label-free, single-particle detection technique and can be combined with a range of functional elements, e.g., mixers, reactors, filters, separators, and pores. Virtually, any two-dimensional layout of the micro- and nanofluidic conduits can be envisioned, designed, and fabricated in the plane of the device. Multiple nanopores in series lead to higher-precision measurements of particle size, shape, and charge, and reactions coupled directly with the particle-size measurements improve temporal response. Moreover, other detection techniques, e.g., fluorescence, are highly compatible with the in-plane format. These integrated in-plane nanofluidic devices expand the toolbox of what is possible with single-particle measurements.

Potentiometric Studies on Ion-Transport Selectivity in Charged Gold Nanotubes.

Under ideal conditions, nanotubes with a fixed negative tube-wall charge will reject anions and transport-only cations. Because many proposed nanofluidic devices are optimized in this ideally cation-permselective state, it is important to know the experimental conditions that produce ideal responses. A parameter called Ccrit, the highest salt concentration in a contacting solution that still produces ideal cation permselectivity, is of particular importance. Pioneering potentiometric studies on gold nanotubes were interpreted using an electrostatic model that states that Ccrit should occur when the Debye length in the contacting salt solution becomes equivalent to the tube radius. Since this "double-layer overlap model" (DLOM), treats all same-charge ions as identical point charges, it predicts that all same-charged cations should produce the same Ccrit. However, the effect of cation on Ccrit in gold nanotubes was never investigated. This knowledge gap has become important because recent studies with a polymeric cation-permselective nanopore membrane showed that DLOM failed for every cation studied. To resolve this issue, we conducted potentiometric studies on the effect of salt cation on Ccrit for a 10 nm diameter gold nanotube membrane. Ccrit for all cations studied were, within experimental error, the same and identical, with values predicted by DLOM. The reason DLOM prevailed for the gold nanotubes but failed for the polymeric nanopores stems from the chemical difference between the fixed negative charges of these two membranes.

Advanced ion-selective wood membranes: Leveraging aligned cellulose nanofibers for enhanced osmotic energy conversion

Nanofluidic reverse electrodialysis (RED) is widely recognized as an exceptionally effective method for harvesting osmotic energy. Nevertheless, its progress has been impeded by the high costs and intricate fabrication processes associated with the required ion exchange membranes. The ion-selective wood membranes (ISWM) are derived directly from natural wood through a meticulously designed two-step chemical modification and densification process. The obtained ISWM with a highly charged surface effectively preserves the alignment of nanochannels from the cellulose fibers sourced in natural wood. Moreover, the laminated structure consisting of oriented nanofibers enhances ion conductivity by a factor of 4 compared to natural wood birch under low KCl concentrations. The charged and aligned nanochannels serve as nanofluidic conduits, facilitating selective ion transport. This, in turn, engenders efficient charge separation and the generation of an electrochemical potential difference. In energy harvesting systems such as ISWM-RED, the synergistic interplay between the electrochemical potential difference and ionic flux manifests in a remarkable output power density, reaching up to 658 mW m−2 to a salinity gradient of KCl at a magnitude of 50-fold. ISWM is an outstanding nanofluidic material that provides a cost-effective and easy-to-prepare solution for producing natural nanofluidic materials. Our investigation delineates a promising trajectory for developing high-performance nanofluidic RED devices tailored for efficient osmotic energy harvesting from renewable and abundant natural resources.

Local nano-electrode fabrication utilizing nanofluidic and nano-electrochemical control.

Miniaturized systems have attracted much attention with the recent advances in microfluidics and nanofluidics. From the capillary electrophoresis, the development of glass-based microfluidic and nanofluidic technologies has supported advances in microfluidics and nanofluidics. Most microfluidic systems, especially nanofluidic systems, are still simple, such as systems constructed with simple straight nanochannels and bulk-scale electrodes. One of the bottlenecks to the development of more complicated and sophisticated systems is to develop the locally integrated nano-electrodes. However, there are still issues with integrating nano-electrodes into nanofluidic devices because it is difficult to fit the nano-electrode size into a nanofluidic channel at the nanometer level. In this study, we propose a new method for the fabrication of local nano-electrodes in nanofluidic devices with nanofluidic and nano-electrochemistry-based experiments. An electroplating solution was introduced to a nanochannel with control of the flow and the electroplating reaction, by which nano-electrodes were successfully fabricated. In addition, a nanofluidic device was available for nanofluidic experiments with the application of 200kPa. This method can be applied to any electroplating material such as gold and copper. The local nano-electrode will make a significant contribution to the development of more complicated and sophisticated nanofluidic electrophoresis systems and to local electric detection methods for various nanofluidic devices.

A nanofluidic spiking synapse

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

The synergistic effects of salinity and pressure gradients on sustainable energy conversion in nanofluidics

In recent years, osmotic energy conversion and electrokinetic energy conversion within nanochannels have received widespread attention. In this work, we propose four kinds of energy conversion models in nanochannels, including pressure-driven power generation, salinity-driven power generation, the positive combination of pressure gradient and salinity gradient and the negative combination. The changes in ion transport behavior and energy conversion characteristics are analyzed. The results show that the combination of salinity gradient and pressure gradient is not a simple superposition. Compared to the power of the single drive mode before optimization, the power under positive combination (PC) can reach 1.02 pW, and the power enhancement ratio is as high as 1.6. The negative combination has a certain optimization potential under a large concentration ratio and small pressure gradient condition. The higher the surface charge density, the greater the output power, but the optimization effect worsens. On the contrary, a larger channel length corresponds to a smaller output power, but the optimization effect becomes better. The reasonable choice of surface charge density and channel length needs to be weighed. These studies provide valuable guidance for the design of future nanofluidic energy conversion devices.

Stimuli-Responsive Delivery of Ions through Layered Materials-Based Triangular Nanofluidic Device.

The elegance and accuracy of biological ion channels inspire the fabrication of artificial devices with similar properties. Here, we report the fabrication of iontronic devices capable of delivering ions at the nanomolar (nmol) level of accuracy. The triangular nanofluidic device prepared with reconstructed vanadium pentoxide (VO) membranes of thickness 45 ± 5.5 μm can continuously deliver K+, Na+, and Ca2+ ions at the rate of 0.44 ± 0.24, 0.35 ± 0.06, and 0.03 nmol/min, respectively. The ionic flow rate can be further tuned by modulating the membrane thickness and salt concentration at the source reservoir. The triangular VO device can also deliver ions in minuscule doses (∼132 ± 9.7 nmol) by electrothermally heating (33 °C) with a nichrome wire (NW) or applying light of specific intensities. The simplicity of the fabrication process of reconstructed layered material-based nanofluidic devices allows the design of complicated iontronic devices such as the three-terminal-Ni-VO (3T-Ni-VO) devices.

Stimuli-Responsive Ion Transport Regulation in Nanochannels by Adhesion-Induced Functionalization of Macroscopic Outer Surface.

Responsive regulation of ion transport through nanochannels is crucial in the design of smart nanofluidic devices for sequencing, sensing, and water-energy nexus. Functionalization of the inner wall of the nanochannel enhances interaction with ions and fluid but restricts versatile chemical approaches and accurate characterizations of fluidic interfaces. Herein, we reveal a responsive regulating mechanism of ion transport through nanochannels by polydopamine (PDA)-induced functionalization on the macroscopic outer surface of nanochannels. Responsive molecules were codeposited with PDA on the outer surface of nanochannels and formed a valve of nanometer thickness to manually manipulate ion transport by changing its gap spacing, surface charge, and wettability under external stimulus. The response ratio can be up to 100-fold by maximizing the proportion of responsive molecules on the outer surface. Laminating the codepositions of different responsive molecules with PDA on the channel's outer surface produces multiple responses. A nearly universal adhesion of PDA with responsive molecules on the open outer surface induces nanochannels responsive to different external stimuli with variable response ratios and arbitrary combinations. The results challenge the primary role of functionalization on the nanoconfined interface of nanofluidics and open opportunities for developing new-style nanofluidic devices through the functionalization of macroscopic interface.

Unveiling the impact of atomic-scale defects and surface roughness on interfacial properties in hexagonal boron nitride

Atomic-scale defects are ubiquitous in two-dimensional (2D) materials, yet their impact on interfacial properties remains insufficiently understood. Hexagonal boron nitride (hBN) is a 2D inorganic material with potential applications in nanofluidic devices and desalination. Here, we show that specific vacancy defects, in conjunction with monolayer roughness, can be used to manipulate the wetting and frictional behavior of hBN. Using combined first principles and classical modeling, we compute water contact angles and slip lengths on realistic hBN surfaces. Our findings demonstrate a significant alignment with experimental results. The combined effect of vacancy defects and surface roughness, known as exposed edges, provides a compelling explanation for the water contact angle (WCA) of 66° on pristine, uncontaminated hBN. Furthermore, this suggests that specific vacancy defects contribute to an enhanced hydrophilicity of hBN surfaces. The combined approach not only achieves high predictive accuracy but also predicts water slip length on hBN of roughly 1 nm, in agreement with the experiments. The findings emphasize the significance of incorporating vacancy defects and surface roughness in molecular simulations when modeling nanomaterial–water interfaces. This work will open up new avenues to understanding water flow through nanochannels and membranes, paving the way for revolutionary advancements in water purification and desalination.