Nanofluidic Networks Research Articles

Single-Pore Nanofluidic Logic Memristor with Reconfigurable Synaptic Functions and Designable Combinations.

The biological neural network is a highly efficient in-memory computing system that integrates memory and logical computing functions within synapses. Moreover, reconfiguration by environmental chemical signals endows biological neural networks with dynamic multifunctions and enhanced efficiency. Nanofluidic memristors have emerged as promising candidates for mimicking synaptic functions, owing to their similarity to synapses in the underlying mechanisms of ion signaling in ion channels. However, realizing chemical signal-modulated logic functions in nanofluidic memristors, which is the basis for brain-like computing applications, remains unachieved. Here, we report a single-pore nanofluidic logic memristor with reconfigurable logic functions. Based on the different degrees of protonation and deprotonation of functional groups on the inner surface of the single pore, the modulation of the memristors and the reconfiguration of logic functions are realized. More noteworthy, this single-pore nanofluidic memristor can not only avoid the average effects in multipore but also act as a fundamental component in constructing complex neural networks through series and parallel circuits, which lays the groundwork for future artificial nanofluidic neural networks. The implementation of dynamic synaptic functions, modulation of logic gates by chemical signals, and diverse combinations in single-pore nanofluidic memristors opens up new possibilities for their applications in brain-inspired computing.

Scalability of nanopore osmotic energy conversion

AbstractArtificial nanofluidic networks are emerging systems for blue energy conversion that leverages surface charge‐derived permselectivity to induce voltage from diffusive ion transport under salinity difference. Here the pivotal significance of electrostatic inter‐channel couplings in multi‐nanopore membranes, which impose constraints on porosity and subsequently influence the generation of large osmotic power outputs, is illustrated. Constructive interference is observed between two 20 nm nanopores of 30 nm spacing that renders enhanced permselectivity to osmotic power output via the recovered electroneutrality. On contrary, the interference is revealed as destructive in two‐dimensional arrays causing significant deteriorations of the ion selectivity even for the nanopores sparsely distributed at an order of magnitude larger spacing than the Dukhin length. Most importantly, a scaling law is provided for deducing the maximal membrane area and porosity to avoid the selectivity loss via the inter‐pore electrostatic coupling. As the electric crosstalk is inevitable in any fluidic network, the present findings can be a useful guide to design nanoporous membranes for scalable osmotic power generations.

Modifying surface charge density of thermoplastic nanofluidic biosensors by multivalent cations within the slip plane of the electric double layer

Thermoplastic nanofluidic devices are promising platforms for sensing single biomolecules due to their mass fabrication capability. When the molecules are driven electrokinetically through nanofluidic networks, surface charges play a significant role in the molecular capture and transportation, especially when the thickness of the electrical double layer is close to the dimensions of the nanostructures in the device. Here, we used multivalent cations to alter the surface charge density of thermoplastic nanofluidic devices. The surface charge alteration was done by filling the device with a multivalent ionic solution, followed by withdrawal of the solution and replacing it with KCl for conductance measurement. A systematic study was performed using ionic solutions containing Mg2+ and Al3+ for nanochannels made of three polymers: poly(ethylene glycol) diacrylate (PEGDA), poly(methyl methacrylate) (PMMA) and cyclic olefin copolymer (COC). Overall, multivalent cations within the slip plane decreased the effective surface charge density of the device surface and the reduction rate increased with the cation valency, cation concentration and the surface charge density of thermoplastic substrates. We demonstrated that a 10-nm diameter in-plane nanopore formed in COC allowed translocation of λ-DNA molecules after Al3+ modification, which is attributed to the deceased viscous drag force in the nanopore by the decreased surface charge density. This work provides a general method to manipulate surface charge density of nanofluidic devices for biomolecule resistive pulse sensing. Additionally, the experimental results support ion-ion correlations as the origin of charge inversion over specific chemical adsorption.

Electrokinetic identification of ribonucleotide monophosphates (rNMPs) using thermoplastic nanochannels

With advances in the design and fabrication of nanofluidic devices during the last decade, there have been a few reports on nucleic acid analysis using nanoscale electrophoresis. The attractive nature of nanofluidics is the unique phenomena associated with this length scale that are not observed using microchip electrophoresis. Many of these effects are surface-related and include electrostatics, surface roughness, van der Waals interactions, hydrogen bonding, and the electric double layer. The majority of reports related to nanoscale electrophoresis have utilized glass-based devices, which are not suitable for broad dissemination into the separation community because of the sophisticated, time consuming, and high-cost fabrication methods required to produce the relevant devices. In this study, we report the use of thermoplastic nanochannels (110 nm x 110 nm, depth x width) for the free solution electrokinetic analysis of ribonucleotide monophosphates (rNMPs). Thermoplastic devices with micro- and nanofluidic networks were fabricated using nanoimprint lithography (NIL) with the structures enclosed via thermal fusion bonding of a cover plate to the fluidic substrate. Unique to this report is that we fabricated devices in cyclic olefin copolymer (COC) that was thermally fusion bonded to a COC cover plate. Results using COC/COC devices were compared to poly(methyl methacrylate), PMMA, devices with a COC cover plate. Our results indicated that at pH = 7.9, the electrophoresis in free solution resulted in an average resolution of the rNMPs >4 (COC/COC device range = 1.94 – 8.88; PMMA/COC device range = 1.4 – 7.8) with some of the rNMPs showing field-dependent electrophoretic mobilities. Baseline separation of the rNMPs was not possible using PMMA- or COC-based microchip electrophoresis. We also found that COC/COC devices could be assembled and UV/O3 activated after device assembly with the dose of the UV/O3 affecting the magnitude of the electroosmotic flow, EOF. In addition, the bond strength between the substrate and cover plate of unmodified COC/COC devices was higher compared to PMMA/COC devices. The large differences in the electrophoretic mobilities of the rNMPs afforded by nanoscale electrophoresis will enable a new single-molecule sequencing platform we envision, which uses molecular-dependent electrophoretic mobilities to identify the constituent rNMPs generated from an intact RNA molecule using a processive exonuclease. With optimized nanoscale electrophoresis, the rNMPs could be identified via mobility matching at an accuracy >99% in both COC/COC and PMMA/COC devices.

Nanoplumbing with 2D Metamaterials.

Complex manipulations of DNA in a nanofluidic device require channels with branches and junctions. However, the dynamic response of DNA in such nanofluidic networks is relatively unexplored. Here, the transport of DNA in a 2D metamaterial made by arrays of nanochannel junctions is investigated. The mechanism of transport is explained as Brownian motion through an energy landscape formed by the combination of the confinement free energy of DNA and the effective potential of hydrodynamic flow, which both can be tuned independently within the device. For the quantitative understanding of DNA transport, a dynamic mean-field model of DNA at a nanochannel junction is proposed. It is shown that the dynamics of DNA in a nanofluidic device with branched channels and junctions is well described by the model.

Multiscale simulation of nanofluidic networks of arbitrary complexity

We present a hybrid molecular-continuum method for the simulation of general nanofluidic networks of long and narrow channels. This builds on the multiscale method of Borg et al. (Microfluid Nanofluid 15(4):541–557, 2013; J Comput Phys 233:400–413, 2013) for systems with a high aspect ratio in three main ways: (a) the method has been generalised to accurately model any nanofluidic network of connected channels, regardless of size or complexity; (b) a versatile density correction procedure enables the modelling of compressible fluids; (c) the method can be utilised as a design tool by applying mass-flow-rate boundary conditions (and then inlet/outlet pressures are the output of the simulation). The method decomposes the network into smaller components that are simulated individually using, in the cases in this paper, molecular dynamics micro-elements that are linked together by simple mass conservation and pressure continuity relations. Computational savings are primarily achieved by exploiting length-scale separation, i.e. modelling long channels as hydrodynamically equivalent shorter channel sections. In addition, these small micro-elements reach steady state much quicker than a full simulation of the network does. We test our multiscale method on several steady, isothermal network flow cases and show that it converges quickly (within three iterations) to good agreement with full molecular simulations of the same cases.

Motor-Driven Assembly of Dynamic, Self-Healing Lipid Nanotube Networks

Interconnected and highly reticulated lipid organelles such as the endoplasmic reticulum play important roles in wide range of physiological processes. While these structures provide a matrix for organizing membrane constituents, the lumen represents a continuous nanofluidic network for the transport of proteins and small molecules throughout the cells. Here, we describe a system in which synthetic interconnected, millimeter-scale nanofluidic networks were formed from the cooperative interaction between phospholipid vesicles and motor protein-based transport. In this system, the energy-driven transport of microtubule filaments by kinesin motors provides a pulling force that acts on multilamellar liposomes, connected via biotin-streptavidin bonds, and results in the formation of highly bifurcated networks of lipid nanotubes. Moreover, the processing of microtubules by the motors enables self-healing within this system in which nanotubes are continuously elongating and collapsing while maintaining the overall network morphology. The size/shape of the networks can be further modulated by regulating microtubule surface density, as well as total amount and physical properties of the lipid. Once formed, we characterized the diffusivity of the lipids and the ability of these networks to support materials transport. Attachment of quantum dots to lipids within the networks suggests that the lipids remain highly fluid, and that particle transport closely follows a one-dimensional process when the particle density is low, and a single-file, one-dimensional process when particle density is high. Current work is focused on characterizing the connectivity of multi-vesicle networks and interstitial materials transport as a model system for studying biomolecular transport and communication.Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

A Continuous Network of Lipid Nanotubes Fabricated from the Gliding Motility of Kinesin Powered Microtubule Filaments

Synthetic interconnected lipid nanotube networks were fabricated on the millimeter scale based on the simple, cooperative interaction between phospholipid vesicles and kinesin-microtubule (MT) transport systems. More specifically, taxol-stabilized MTs, in constant 2D motion via surface absorbed kinesin, extracted and extended lipid nanotube networks from large Lα phase multilamellar liposomes (5-25 μm). Based on the properties of the inverted motility geometry, the total size of these nanofluidic networks was limited by MT surface density, molecular motor energy source (ATP), and total amount and physical properties of lipid source material. Interactions between MTs and extended lipid nanotubes resulted in bifurcation of the nanotubes and ultimately the generation of highly branched networks of fluidically connected nanotubes. The network bifurcation was easily tuned by changing the density of microtubules on the surface to increase or decrease the frequency of branching. The ability of these networks to capture nanomaterials at the membrane surface with high fidelity was subsequently demonstrated using quantum dots as a model system. The diffusive transport of quantum dots was also characterized with respect to using these nanotube networks for mass transport applications.

Wafer-Scale Fabrication of Nanofluidic Arrays and Networks Using Nanoimprint Lithography and Lithographically Patterned Nanowire Electrodeposition Gold Nanowire Masters

Wafer scale (cm(2)) arrays and networks of nanochannels were created in polydimethylsiloxane (PDMS) from a surface pattern of electrodeposited gold nanowires in a master-replica process and characterized with scanning electron microscopy (SEM), atomic force microscopy (AFM), and fluorescence imaging measurements. Patterns of gold nanowires with cross-sectional dimensions as small as 50 nm in height and 100 nm in width were prepared on silica substrates using the process of lithographically patterned nanowire electrodeposition (LPNE). These nanowire patterns were then employed as masters for the fabrication of inverse replica nanochannels in a special formulation of PDMS. SEM and AFM measurements verified a linear correlation between the widths and heights of the nanowires and nanochannels over a range of 50 to 500 nm. The PDMS replica was then oxygen plasma-bonded to a glass substrate in order to create a linear array of nanofluidic channels (up to 1 mm in length) filled with solutions of either fluorescent dye or 20 nm diameter fluorescent polymer nanoparticles. Nanochannel continuity and a 99% fill success rate was determined from the fluorescence imaging measurements, and the electrophoretic injection of both dye and nanoparticles in the nanochannel arrays was also demonstrated. Employing a double LPNE fabrication method, this master-replica process was also used to create a large two-dimensional network of crossed nanofluidic channels.

Nanotube-interconnected liposome networks

Tunneling phospholipid nanotubes between animal cells have recently been identified as a major building block in an important fundamental mechanism of cell-to-cell communication. In order to gain deeper understanding of this interaction and other micro- and nanoscale phenomena connected to material transport and communication in the living world, cell-sized biomimetic devices are required, which need to be structurally or functionally sufficiently close to the living cell. Networks of liposomes and lipid nanotubes are suitable model systems, as they are functionally versatile and structurally highly flexible biomimetic membrane compartments, which allow an effective approach to investigations of chemical synthesis and material transport at the length scale of a biological cell. They are an excellent foundation for detailed studies of cell-to-cell communication, chemical reaction dynamics in confined spaces, macromolecular crowding, exocytosis and other processes critically important for the function of biological cells. In this article we give an overview over the past years of research on nanotube–vesicle networks, introduce briefly fundamental physical and chemical principles, basic and sophisticated experimental techniques of network generation and manipulation, and show application examples and modern approaches to nanofluidic networks that constitute potential future research directions.

A new method of UV-patternable hydrophobization of micro- and nanofluidic networks

This work reports a new method to hydrophobize glass-based micro- and nanofluidic networks. Conventional methods of hydrophobizing glass surfaces often create particulate debris causing clogging especially in shallow nanochannels or require skilful handling. Our novel method employs oxygen plasma, silicone oil and ultraviolet (UV) light. The contact angle of the modified bare glass surface can reach 100° whilst the inner channels after treatment facilitate stable and durable water-in-oil droplet generation. This modified surface was found to be stable for more than three weeks. The use of UV in principle enables in-channel hydrophobic patterning.

Nanofluidic networks created and controlled by light

Nanofluidic networks have been fabricated in an oil-in-water emulsion. Micron-sized oil drops with ultralow interfacial tensions are connected by stable oil threads a few nm across. Lasers are used both to construct the nanofluidic network and to transport the fluid from one drop to another. These networks form a platform for chemistry on the attolitre scale.

Sound and light: acoustics play an unexpected role during laser machining

The ultimate aim of microand nanofluidics is to construct micro total-analysis systems (μTAS), in which complex analytic processes are performed on a chip for simplified application, decreased costs, and minimal sample volumes. To realize this goal, complex microand nanofluidic networks must be integrated into a single chip. Moreover, achieving appropriate interconnection among components and high device density usually require 3D geometries. Thus, the advantages of conventional 2D planar lithography-etch-bond processes are offset by the difficulty of achieving true 3D geometries. Laser machining using femtosecond pulses constitutes a promising method of 3D nanofabrication: far-field optical ablation allows true 3D (rather than multilayer) geometries, while submicron feature sizes are still attainable using tightly-focused laser pulses operating in the optics-in-critical-intensity regime. This takes advantage of the deterministic character of femtosecond laser machining4 to achieve precise and reproducible ablation of nanofeatures inside and on the surface of glass or other transparent materials. If machining is performed in liquids, it is possible to form long, open channels in a single step since debris is cleared from the channels by expanding bubbles produced during laser ablation.3, 5, 6 However, like other, more conventional microdrilling methods, optical machining is limited in terms of the attainable aspect ratio (AR) of subsurface channels: debris extrusion becomes difficult as the machining progresses far into the material.7 Similar to conventional microdrilling methods, femtosecond laser machining has been limited to AR < 100.8 By optimizing the machining protocols we were able to extend the AR somewhat, but found that the effectiveness drops precipitously at around AR = 300. This initially was ascribed to increased resistance to flow in longer channels, which predictably inhibits clearing of debris, and thus ultimately must limit reasonably attainable AR. However, repeated scans of the laser over AR = 300 abruptly and unexpectedly recovered machining effectiveness, thus enabling further lengthening of the channel. Moreover, even though the end of the channel resumed growing, the poor machining region around AR = 300 initially remained clogged with glass debris, and the channel appeared to be divided into two parts. With further scans of the laser, these two parts united, achieving a continuous longer channel. Closer examination shows the localized regions of poor machining to be associated with dramatically changed bubble dynamics. When the AR is smaller than 300, vigorous bubble expansion effectively extrudes water-entrained debris out of the channel. However, as AR approaches 300, machining becomes inefficient, with both bubble expansion and debris extrusion becoming severely attenuated. Interestingly, a second region of poor machining is encountered when the channel becomes twice as long, suggesting harmonic phenomena. And indeed, we find evidence for a (to the best of our knowledge) hitherto unidentified form of acoustic node that presents an alternative acoustic pathway for the dissipation of absorbed laser energy, and consequently decreases the energy available for bubble expansion. The acoustic AR barrier at 300 can be delayed either by using degassed water to assist femtosecond laser machining or by varying the ambient pressure during machining. This is predicted from a physical model in which acoustic nodes form when an internal two-phase (gas and water) flow forms a stable resonant structure. The impedance of the water and gas structures becomes matched, allowing deposited energy to readily dissipate across the fluid-gas interface, thus causing fluid circulation to fail due to a precipitous decrease in bubble expansion. The bubbles may even completely vanish, despite persisting for hundreds of milliseconds only a few microns away, where

Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates.

Microfluidic and nanofluidic technologies have long sought a fast, reliable method to overcome the creative limitations of planar fabrication methods, the resolution limits of lithography, and the materials limitations for fast prototyping. In the present work, we demonstrate direct 3D machining of submicrometer diameter, subsurface fluidic channels in glass, via optical breakdown near critical intensity, using a femtosecond pulsed laser. No postexposure etching or bonding is required; the channel network (or almost any arbitrary-shaped cavity below the surface) is produced directly from "art-to-part". The key to this approach is to use very low energy, highly focused, pulses in the presence of liquid. Microbubbles that result from laser energy deposition gently expand and extrude machining debris from the channels. These bubbles are in a highly damped, low Reynolds number regime, implying that surface spalling due to bubble collapse is unimportant. We demonstrate rapid prototyping of three-dimensional "jumpers", mixers, and other key components of complex 3D microscale analysis systems in glass substrates.

Dynamics of Membrane Nanotubulation and DNA Self-Assembly

A localized point-like force applied perpendicular to a vesicular membrane layer, using an optical tweezer, leads to membrane nanotubulation beyond a threshold force. Below the threshold, the force-extension curve shows an elastic response with a fine structure (serrations). Above the threshold the tubulation process exhibits a new reversible flow phase for the multilamellar membrane, which responds viscoelastically. Furthermore, with an oscillatory force applied during tubulation, broad but well-resolved resonances occur in the flow phase, presumably matching the time scales associated with the vesicle-nanotubule coupled system. These nanotubules, anchored to the optical tweezer also provide, for the first time, a direct probe of the real-time dynamics of DNA self-assembly on membranes. Our studies are a step in the direction of analyzing the dynamics of membrane self-assembly and artificial nanofluidic membrane networks.

Nanofluidic networks based on surfactant membrane technology.

We explore possibilities to construct nanoscale analytical devices based on lipid membrane technology. As a step toward this goal, we present nanotube-vesicle networks with fluidic control, where the nanotube segments reside at, or very close (<2 microm) to optically transparent surfaces. These nanofluidic systems allow controlled transport as well as LIF detection of single nanoparticles. In the weak-adhesion regime, immobilized vesicles can be approximated as perfect spheres with nanotubes attached at half the height of the vesicle in the axial (z) dimension. In the strong-adhesion regime (relative contact area, Sr* approximately 0.3), nanotubes can be adsorbed to the surface with a distance to the interior of the nanotubes defined by the membrane thickness of approximately 5 nm. Strong surface adsorption restricts nanotube self-organization, enabling networks of nanotubes with arbitrary geometries. We demonstrate LIF detection of single nanoparticles (30-nm-diameter fluorescent beads) inside single nanotubes. Transport of nanoparticles was induced by a surface tension differential applied across nanotubes using a hydrodynamic injection protocol. Controlled transport in nanotubes together with LIF detection enables construction of nanoscale fluidic devices with potential to operate with single molecules. This opens up possibilities to construct analytical platforms with characteristic length scales and volume orders of magnitudes smaller than employed in traditional microfluidic devices.