Detection of Individual Molecules and Ions by Carbon Nanotube‐Based Differential Resistive Pulse Sensor

This paper presents a new method of sensing single molecules and cations by a carbon nanotube (CNT)‐based differential resistive pulse sensing (RPS) technique on a nanofluidic chip. A mathematical model for multichannel RPS systems is developed to evaluate the CNT‐based RPS signals. Individual cations, rhodamine B dye molecules, and ssDNAs are detected successfully with high resolution and high signal‐to‐noise ratio. Differentiating ssDNAs with 15 and 30 nucleotides are achieved. The experimental results also show that translocation of negatively charged ssDNAs through a CNT decreases the electrical resistance of the CNT channel, while translocation of positively charged cations and rhodamine B molecules increases the electrical resistance of the CNT. The CNT‐based nanofluidic device developed in this work provides a new avenue for single‐molecule/ion detection and offers a potential strategy for DNA sequencing.     

Zero‐Depth Interfacial Nanopore Capillaries

High‐fidelity analysis of translocating biomolecules through nanopores demands shortening the nanocapillary length to a minimal value. Existing nanopores and capillaries, however, inherit a finite length from the parent membranes. Here, nanocapillaries of zero depth are formed by dissolving two superimposed and crossing metallic nanorods, molded in polymeric slabs. In an electrolyte, the interface shared by the crossing fluidic channels is mathematically of zero thickness and defines the narrowest constriction in the stream of ions through the nanopore device. This novel architecture provides the possibility to design nanopore fluidic channels, particularly with a robust 3D architecture maintaining the ultimate zero thickness geometry independently of the thickness of the fluidic channels. With orders of magnitude reduced biomolecule translocation speed, and lowered electronic and ionic noise compared to nanopores in 2D materials, the findings establish interfacial nanopores as a scalable platform for realizing nanofluidic systems, capable of single‐molecule detection.     

An All‐Plastic Field‐Effect Nanofluidic Diode Gated by a Conducting Polymer Layer

The design of an all‐plastic field‐effect nanofluidic diode is proposed, which allows precise nanofluidic operations to be performed. The fabrication process involves the chemical synthesis of a conductive poly(3,4‐ethylenedioxythiophene) (PEDOT) layer over a previously fabricated solid‐state nanopore. The conducting layer acts as gate electrode by changing its electrochemical state upon the application of different voltages, ultimately changing the surface charge of the nanopore. A PEDOT‐based nanopore is able to discriminate the ionic species passing through it in a quantitative and qualitative manner, as PEDOT nanopores display three well‐defined voltage‐controlled transport regimes: cation‐rectifying, non‐rectifying, and anion rectifying regimes. This work illustrates the potential and versatility of PEDOT as a key enabler to achieve electrochemically addressable solid‐state nanopores. The synergism arising from the combination of highly functional conducting polymers and the remarkable physical characteristics of asymmetric nanopores is believed to offer a promising framework to explore new design concepts in nanofluidic devices.     

Freeform,Reconfigurable Embedded Printing of All‐Aqueous 3D Architectures

Aqueous microstructures are challenging to create, handle, and preserve since their surfaces tend to shrink into spherical shapes with minimum surface areas. The creation of freeform aqueous architectures will significantly advance the bioprinting of complex tissue‐like constructs, such as arteries, urinary catheters, and tracheae. The generation of complex, freeform, three‐dimensional (3D) all‐liquid architectures using formulated aqueous two‐phase systems (ATPSs) is demonstrated. These all‐liquid microconstructs are formed by printing aqueous bioinks in an immiscible aqueous environment, which functions as a biocompatible support and pregel solution. By exploiting the hydrogen bonding interaction between polymers in ATPS, the printed aqueous‐in‐aqueous reconfigurable 3D architectures can be stabilized for weeks by the noncovalent membrane at the interface. Different cells can be separately combined with compartmentalized bioinks and matrices to obtain tailor‐designed microconstructs with perfusable vascular networks. The freeform, reconfigurable embedded printing of all‐liquid architectures by ATPSs offers unique opportunities and powerful tools since limitless formulations can be designed from among a breadth of natural and synthetic hydrophilic polymers to mimic tissues. This printing approach may be useful to engineer biomimetic, dynamic tissue‐like constructs for potential applications in drug screening, in vitro tissue models, and regenerative medicine.     

Single-molecule spectroscopy using nanoporous membranes

We describe a novel approach for optically detecting DNA translocation events through an array of solid-state nanopores that potentially allows for ultra high-throughput, parallel detection at the single-molecule level. The approach functions by electrokinetically driving DNA strands through sub micrometer-sized holes on an aluminum/silicon nitride membrane. During the translocation process, the molecules are confined to the walls of the nanofluidic channels, allowing 100% detection efficiency. Importantly, the opaque aluminum layer acts as an optical barrier between the illuminated region and the analyte reservoir. In these conditions, high-contrast imaging of single-molecule events can be performed. To demonstrate the efficiency of the approach, a 10 pM fluorescently labeled lambda-DNA solution was used as a model system to detect simultaneous translocation events using electron multiplying CCD imaging. Single-pore translocation events are also successfully detected using single-point confocal spectroscopy.     

Nanoparticle conjugation increases protein partitioning in aqueous two-phase systems

We describe the effect of bioconjugation to colloidal Au nanoparticles on protein partitioning in poly(ethylene glycol) (PEG)/dextran aqueous two-phase systems (ATPS). Horseradish peroxidase (HRP) was conjugated to colloidal Au nanoparticles by direct adsorption. Although HRP alone had very little phase preference, HRP/Au nanoparticle conjugates typically partitioned to the PEG-rich phase, up to a factor of 150:1 for conjugates of 15-nm colloidal Au. Other protein/Au nanoparticle conjugates exhibited partitioning of greater than 2000:1 to the dextran-rich phase, as compared with approximately 5:1 for the free protein. The degree of partitioning was dependent on polymer concentration and molecular weight, nanoparticle diameter, and in some instances, nanoparticle concentration in the ATPS. The substantial improvements in protein partitioning achievable by conjugation to Au nanoparticles appear to result largely from increased surface area of the conjugates and require neither chemical modification of the proteins or polymers with affinity ligands, increased polymer concentrations, nor addition of high concentrations of salts. Adsorption to colloidal particles thus provides an attractive route for increased partitioning of enzymes and other proteins in ATPS. Furthermore, these results point to ATPS partitioning as a powerful means of purification for biomolecule/nanoparticle conjugates, which are increasingly used in diagnostics and materials applications.     

Nanoparticle transport in conical-shaped nanopores

This report presents a fundamental study of nanoparticle transport phenomena in conical-shaped pores contained within glass membranes. The electrophoretic translocation of charged polystyrene (PS) nanoparticles (80- and 160-nm-radius) was investigated using the Coulter counter principle (or "resistive-pulse" method) in which the time-dependent nanopore current is recorded as the nanoparticle is driven across the membrane. Particle translocation through the conical-shaped nanopore results in a direction-dependent and asymmetric triangular-shaped resistive pulse. Because the sensing zone of conical-shaped nanopores is localized at the orifice, the translocation of nanoparticles through this zone is very rapid, resulting in pulse widths of ~200 μs for the nanopores used in this study. A linear dependence between translocation rate and nanoparticle concentration was observed from 10(7) to 10(11) particles/mL for both 80- and 160-nm-radius particles, and the magnitude of the resistive pulse scaled approximately in proportion to the particle volume. A finite-element simulation based on continuum theory to compute ion fluxes was combined with a dynamic electric force-based nanoparticle trajectory calculation to compute the position- and time-dependent nanoparticle velocity as the nanoparticle translocates through the conical-shaped nanopore. The computational results were used to compute the resistive pulse current-time response for conical-shaped pores, allowing comparison between experimental and simulated pulse heights and translocation times. The simulation and experimental results indicate that nanoparticle size can be differentiated based on pulse height, and to a lesser extent based on translocation time.     

Local electrical potential detection of DNA by nanowire-nanopore sensors

Nanopores could potentially be used to perform single-molecule DNA sequencing at low cost and with high throughput. Although single base resolution and differentiation have been demonstrated with nanopores using ionic current measurements, direct sequencing has not been achieved because of the difficulties in recording very small (～pA) ionic currents at a bandwidth consistent with fast translocation speeds. Here, we show that solid-state nanopores can be combined with silicon nanowire field-effect transistors to create sensors in which detection is localized and self-aligned at the nanopore. Well-defined field-effect transistor signals associated with DNA translocation are recorded when an ionic strength gradient is imposed across the nanopores. Measurements and modelling show that field-effect transistor signals are generated by highly localized changes in the electrical potential during DNA translocation, and that nanowire-nanopore sensors could enable large-scale integration with a high intrinsic bandwidth.     

Microfluidic Generation of All‐Aqueous Double and Triple Emulsions

Higher order emulsions are used in a variety of different applications in biomedicine, biological studies, cosmetics, and the food industry. Conventional droplet generation platforms for making higher order emulsions use organic solvents as the continuous phase, which is not biocompatible and as a result, further washing steps are required to remove the toxic continuous phase. Recently, droplet generation based on aqueous two‐phase systems (ATPS) has emerged in the field of droplet microfluidics due to their intrinsic biocompatibility. Here, a platform to generate all‐aqueous double and triple emulsions by introducing pressure‐driven flows inside a microfluidic hybrid device is presented. This system uses a conventional microfluidic flow‐focusing geometry coupled with a coaxial microneedle and a glass capillary embedded in flow‐focusing junctions. The configuration of the hybrid device enables the focusing of two coaxial two‐phase streams, which helps to avoid commonly observed channel‐wetting problems. It is shown that this approach achieves the fabrication of higher‐order emulsions in a poly(dimethylsiloxane)‐based microfluidic device, and controls the structure of the all‐aqueous emulsions. This hybrid microfluidic approach allows for facile higher‐order biocompatible emulsion formation, and it is anticipated that this platform will find utility for generating biocompatible materials for various biotechnological applications.     

Molecular Design of Solid‐State Nanopores: Fundamental Concepts and Applications

Solid‐state nanopores are fascinating objects that enable the development of specific and efficient chemical and biological sensors, as well as the investigation of the physicochemical principles ruling the behavior of biological channels. The great variety of biological nanopores that nature provides regulates not only the most critical processes in the human body, including neuronal communication and sensory perception, but also the most important bioenergetic process on earth: photosynthesis. This makes them an exhaustless source of inspiration toward the development of more efficient, selective, and sophisticated nanopore‐based nanofluidic devices. The key point responsible for the vibrant and exciting advance of solid nanopore research in the last decade has been the simultaneous combination of advanced fabrication nanotechnologies to tailor the size, geometry, and application of novel and creative approaches to confer the nanopore surface specific functionalities and responsiveness. Here, the state of the art is described in the following critical areas: i) theory, ii) nanofabrication techniques, iii) (bio)chemical functionalization, iv) construction of nanofluidic actuators, v) nanopore (bio)sensors, and vi) commercial aspects. The plethora of potential applications once envisioned for solid‐state nanochannels is progressively and quickly materializing into new technologies that hold promise to revolutionize the everyday life.     

Concentration and size separation of DNA samples at liquid-liquid interfaces

This report introduces a new analytical concept utilizing the mass transfer resistance of a liquid-liquid interface to concentrate and separate DNA samples. DNA molecules can be electrophoretically accumulated at a liquid-liquid interface of an aqueous two-phase system (ATPS) of poly(ethylene glycol) (PEG) and dextran, two polymers that form two immiscible phases in aqueous electrolyte solutions. The detachment of DNA from the interface into the other phase can be triggered by increasing the applied electric field. We experimentally study the size dependence of the detachment process for a broad spectrum of DNA fragments. In a regime where the coiling of the chains does not play a significant role, the process shows a linear dependence on the diffusion coefficient, with shorter DNA chains detaching at lower electric field strengths than larger ones. The concept may enable novel separation protocols for preparative and analytical purposes.     

多角度动态光散射法的纳米颗粒精确测量

基于动态光散射原理,采用自主研发的多角度动态光散射装置,对纳米及亚微米颗粒粒径准确测量方法进行了探究。自研装置采用带有光阑组的精密入射光路设计,以及匹配液池及Beam-stop设计,极大提高了信噪比;同时避免了测量角度的互补方向上,由于样品池与空气界面折射率不同导致的反射光信号对有效信号的干扰。在此基础上,对不同浓度、粒径的聚苯乙烯(PS)颗粒溶液进行了测定及不确定度分析。结果表明,对同一粒径的PS颗粒,增加颗粒浓度时,多重散射首先发生于大、小测量角度,越接近90°,发生多重散射的浓度越高;随着粒径增大,受不可忽略的颗粒间相互作用的影响,粒径测量结果表现出了强烈的角度依赖性,甚至波动性。     

Micro‐/Nanofluidics for Liquid‐Mediated Patterning of Hybrid‐Scale Material Structures

Various materials are fabricated to form specific structures/patterns at the micro‐/nanoscale, which exhibit additional functions and performance. Recent liquid‐mediated fabrication methods utilizing bottom‐up approaches benefit from micro‐/nanofluidic technologies that provide a high controllability for manipulating fluids containing various solutes, suspensions, and building blocks at the microscale and/or nanoscale. Here, the state‐of‐the‐art micro‐/nanofluidic approaches are discussed, which facilitate the liquid‐mediated patterning of various hybrid‐scale material structures, thereby showing many additional advantages in cost, labor, resolution, and throughput. Such systems are categorized here according to three representative forms defined by the degree of the free‐fluid–fluid interface: free, semiconfined, and fully confined forms. The micro‐/nanofluidic methods for each form are discussed, followed by recent examples of their applications. To close, the remaining issues and potential applications are summarized.     

Interfacially Polymerized Particles with Heterostructured Nanopores for Glycopeptide Separation

Porous polymer materials are extensively used for biomolecule separation. However, conventional homogeneous porous polymer materials cannot efficiently separate specific low‐abundance biomolecules from complex samples. Here, particles fabricated by emulsion interfacial polymerization featuring heterostructured nanopores with tunable size are reported, which can be used to realize low‐abundance glycopeptide (GP) separation from complex biofluids. The heterostructured surface inside the nanopores allows solvent‐dependent local adsorption of biomolecules onto hydrophilic or hydrophobic regions. Low‐abundance hydrophilic GPs in complex biofluids can be efficiently separated via the hydrophilic region of nanopores in low‐polarity solvent after the hydrophobic region removes high‐abundance hydrophobic proteins and non‐glycopeptides in high‐polarity solvent. It is expected that these particles with heterostructured nanopores can be used for separation of nucleic acids, saccharides, and proteins, and downstream clinical diagnosis.     

Reactive self-tracking solar concentrators: concept, design, and initial materials characterization

étendue limits angular acceptance of high-concentration photovoltaic systems and imposes precise two-axis mechanical tracking. We show how a planar micro-optic solar concentrator incorporating a waveguide cladding with a nonlinear optical response to sunlight can reduce mechanical tracking requirements. Optical system designs quantify the required response: a large, slow, and localized increase in index of refraction. We describe one candidate materials system: a suspension of high-index particles in a low-index fluid combined with a localized space-charge field to increase particle density and average index. Preliminary experiments demonstrate an index change of aqueous polystyrene nanoparticles in response to a low voltage signal and imply larger responses with optimized nanofluidic materials.     

Competitive adsorption of surfactant foaming agents to nanoclays added to cement foams for enhanced strength

The adsorption affinity of a surfactant foaming agent (SFA), α-olefin sulphonate (AOS)—used for generation of foam for low density concrete—to organically-modified montmorillonite (OMMT) has been investigated. OMMT has been proposed as an additive to cement and concrete for improved strength and durability. Similar thermodynamic processes are involved in the generation and stabilisation of foam and in the compatibilisation and stabilisation of organic particles in aqueous environments, so interaction between SFA and OMMT particles is likely. Association of foaming agent molecules with organoclay may lead to poor foaming performance and potential instability of the nanoparticles due to displacement of dispersants from the particle surface by foaming agent. Adsorption isotherms determined using a combination of ion-pair reverse phase high performance liquid chromatography (RP-HPLC) and gravimetric methods revealed that there is a relatively high affinity of AOS for the organoclay particles. This is a dynamic process, with smaller molecules adsorbing quickly but being displaced by larger molecules at higher surfactant loading. From the adsorption isotherm it was possible to calculate the minimum AOS addition that will ensure the full foaming performance in the cement formulation. Relative adsorption affinity and competitive adsorption at the particle surface of AOS with non-ionic and anionic surfactants commonly used as wetting and dispersing agents, was studied. The dispersants displayed considerably higher relative adsorption onto the organoclay than AOS, particularly in the case of the anionic species. There is evidence that some AOS adsorption takes place in particle systems stabilised by non-ionic dispersants; displacement of high adsorption affinity dispersants by the lower affinity AOS from the OMMT particle surface was not observed.     

Interaction mechanism of in-situ nano-TiN-AlN particles and solid/liquid interface during solidification

This paper deals with the interaction mechanism between in situ nanometer-grade TiN-AlN particles and the solid/liquid (S/L) interface during the solidification of an in situ TiN-AlN/Al composite. According to the setting of a force balance for the particles in front of the S/L interface during solidification, F = F(buoyant) + F(repulsive) + F(viscous). We obtained the relationship between the critical cooling velocity of the liquid composite, Vr, and the size of the ceramic particle, rp. By this relationship formula, we can know that the S/L interface engulfs particles or pushes them to the crystal grain boundary during the solidification of a TiN-AlN/Al composite. It is found that Vr is proportional to the radius of ceramic particles by transmission electron microscope (TEM) observation. The TEM test indicates that the smaller the particle is, the more easily the S/L interface engulfs particles.     

Highly efficient and ultra-small volume separation by pressure-driven liquid chromatography in extended nanochannels

The rapidly developing interest in nanofluidic analysis, which is used to examine liquids ranging in amounts from the attoliter to the femtoliter scale, correlates with the recent interest in decreased sample amounts, such as in the field of single-cell analysis. For general nanofluidic analysis, the fact that a pressure-driven flow does not limit the choice of solvents (aqueous or organic) is important. This study shows the first pressure-driven liquid chromatography technique that enables separation of atto- to femtoliter sample volumes, with a high separation efficiency within a few seconds. The apparent diffusion coefficient measurement of the unretentive sample suggests that there is no increase in the viscosity of toluene in the extended nanospace, unlike in aqueous solvents. Evaluation of the normal phase separation, therefore, should involve only the examination of the effect of the small size of the extended nanospace. Compared to a conventionally packed high-performance liquid chromatography column, the separation here results in a faster separation (4 s) by 2 orders of magnitude, a smaller injection volume (10(0) fL) by 9 orders, and a higher separation efficiency (440,000 plates/m) by 1 order. Moreover, the separation behavior agrees with the theory showing that this high efficiency was due to the small and controlled size of the separation channel, where the diffusion through the channel depth direction is fast enough to be neglected. Our chip-based platform should allow direct and real-time analysis or screening of ultralow volume of sample.     

Directing substrate morphology via self-assembly: ligand-mediated scission of gallium-indium microspheres to the nanoscale

We have developed a facile method for the construction of liquid-phase eutectic gallium-indium (EGaIn) alloy nanoparticles. Particle formation is directed by molecular self-assembly and assisted by sonication. As the bulk liquid alloy is ultrasonically dispersed, fast thiolate self-assembly at the EGaIn interface protects the material against oxidation. The choice of self-assembled monolayer ligand directs the ultimate size reduction in the material; strongly interacting molecules induce surface strain and assist particle cleavage to the nanoscale. Transmission electron microscopy images and diffraction analyses reveal that the nanoscale particles are in an amorphous or liquid phase, with no observed faceting. The particles exhibit strong absorption in the ultraviolet (～200 nm), consistent with the gallium surface plasmon resonance, but dependent on the nature of the particle ligand shell.