Design and Optical Trapping of a Biocompatible Propeller-like Nanoscale Hybrid

Designing nanoscale objects with the potential to perform externally controlled motion in biological environments is one of the most sought-after objectives in nanotechnology. Different types of chemically and physically powered motors have been prepared at the macro- and microscale. However, the preparation of nanoscale objects with a complex morphology, and the potential for light-driven motion has remained elusive to date. Here, we go a step forward by designing a nanoscale hybrid with a propeller-resembling shape, which can be controlled by focused light under biological conditions. Our hybrid, hereafter "Au@DNA-origami", consists of a spherical gold nanoparticle with self-assembled, biocompatible, two-dimensional (2D) DNA sheets on its surface. As a first step toward the potential utilization of these nanoscale objects as light-driven assemblies in biological environments, we show that they can be optically trapped, and hence translated and deposited on-demand, and that under realistic trapping conditions the thermally induced dehybridization of the DNA sheets can be avoided.     

The use of magnetic nanoparticles in thermal therapy monitoring and screening: Localization and imaging (invited)

Magnetic nanoparticles have many diagnostic and therapeutic applications. A method termed magnetic spectroscopy of nanoparticle Brownian motion (MSB) was developed to interrogate in vivo the microscopic environment surrounding magnetic nanoparticles. We can monitor several effects that are important in thermal therapy and screening including temperature measurement and the bound state distribution. Here we report on simulations of nanoparticle localization. Measuring the spatial distribution of nanoparticles would allow us to identify ovarian cancer much earlier when it is still curable or monitor thermal therapies more accurately. We demonstrate that with well-designed equipment superior signal to noise ratio (SNR) can be achieved using only two harmonics rather than using all the harmonics containing signal. Alternatively, smaller magnetic field amplitudes can be used to achieve the same SNR. The SNR is improved using fewer harmonics because the noise is limited.     

Multibuilding Block Janus Synthesized by Seed‐Mediated Self‐Assembly for Enhanced Photothermal Effects and Colored Brownian Motion in an Optical Trap

The asymmetrical features and unique properties of multibuilding block Janus nanostructures (JNSs) provide superior functions for biomedical applications. However, their production process is very challenging. This problem has hampered the progress of JNS research and the exploration of their applications. In this study, an asymmetrical multibuilding block gold/iron oxide JNS has been generated to enhance photothermal effects and display colored Brownian motion in an optical trap. JNS is formed by seed‐mediated self‐assembly of nanoparticle‐loaded thermocleavable micelles, where the hydrophobic backbones of the polymer are disrupted at high temperatures, resulting in secondary self‐assembly and structural rearrangement. The JNS significantly enhances photothermal effects compared to their homogeneous counterpart after near‐infrared (NIR) light irradiation. The asymmetrical distribution of gold and iron oxide within JNS also generates uneven thermophoretic force to display active colored Brownian rotational motion in a single‐beam gradient optical trap. These properties indicate that the asymmetrical JNS could be employed as a strong photothermal therapy mediator and a fuel‐free nanoscale Janus motor under NIR light.     

Modeling particle shape-dependent dynamics in nanomedicine

One of the major challenges in nanomedicine is to improve nanoparticle cell selectivity and adhesion efficiency through designing functionalized nanoparticles of controlled sizes, shapes, and material compositions. Recent data on cylindrically shaped filomicelles are beginning to show that non-spherical particles remarkably improved the biological properties over spherical counterpart. Despite these exciting advances, non-spherical particles have not been widely used in nanomedicine applications due to the lack of fundamental understanding of shape effect on targeting efficiency. This paper intends to investigate the shape-dependent adhesion kinetics of non-spherical nanoparticles through computational modeling. The ligand-receptor binding kinetics is coupled with Brownian dynamics to study the dynamic delivery process of nanorods under various vascular flow conditions. The influences of nanoparticle shape, ligand density, and shear rate on adhesion probability are studied. Nanorods are observed to contact and adhere to the wall much easier than their spherical counterparts under the same configuration due to their tumbling motion. The binding probability of a nanorod under a shear rate of 8 s(-1) is found to be three times higher than that of a nanosphere with the same volume. The particle binding probability decreases with increased flow shear rate and channel height. The Brownian motion is found to largely enhance nanoparticle binding. Results from this study contribute to the fundamental understanding and knowledge on how particle shape affects the transport and targeting efficiency of nanocarriers, which will provide mechanistic insights on the design of shape-specific nanomedicine for targeted drug delivery applications.     

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.     

Carbon nanotubes as electrodes for dielectrophoresis of DNA

Dielectrophoresis can potentially be used as an efficient trapping tool in the fabrication of molecular devices. For nanoscale objects, however, the Brownian motion poses a challenge. We show that the use of carbon nanotube electrodes makes it possible to apply relatively low trapping voltages and still achieve high enough field gradients for trapping nanoscale objects, e.g., single molecules. We compare the efficiency and other characteristics of dielectrophoresis between carbon nanotube electrodes and lithographically fabricated metallic electrodes, in the case of trapping nanoscale DNA molecules. The results are analyzed using finite element method simulations and reveal information about the frequency-dependent polarizability of DNA.     

Real-time template-assisted manipulation of nanoparticles in a multilayer nanofluidic chip

The ability to control dynamically the flow and placement of nanoscale particles and biomolecules in a biocompatible, aqueous environment will have profound impact in advancing the fields of nanoplasmonics, nanophotonics, and medicine. Here, an approach based on electrokinetic forces is demonstrated that enables dynamically controlled placement of nanoparticles into a predefined pattern. The technique uses an applied voltage to manipulate nanoparticles in a multilayer nanofluidic chip architecture. Simulations of the nanoparticles' motion in the nanofluidic chip validate the approach and are confirmed by experimental demonstration to produce uniform 200-nm-diameter spherical nanoparticle arrays. The results are important as they provide a new method that is capable of dynamically capturing and releasing nanoscale particles and biomolecules in an aqueous environment, which could lead to the creation of reconfigurable nanostructure patterns for nanoplasmonic, nanophotonic, biological sensing, and drug-delivery applications.     

Coherent light scattering on nanofluids: computer simulation results

If coherent light is incident on a suspension containing nanoparticles, they act as scattering centers and the result of the far-field interference is a "speckled" image. The scattering centers have a complex movement of both sedimentation and Brownian motion. Consequently the speckle image is not static but presents time fluctuations. A computer code to simulate the dynamics of the coherent light scattering on nanofluids was written, tested, and used to calculate the far-field intensity variation for nanofluids having different particle size. The results are discussed and an alternative experimental method for fast nanoparticle size assessing is suggested as a possible application.     

Real-time observation of Brownian motion and cluster movement of ferro- and non-magnetic particles in magnetic fluids

Cluster movements of ferro- and non-magnetic particles in magnetic fluids were investigated using optical microscope system and image processing system. Real-time visualizations of the Brownian motion of particles and the chain-like cluster movement of both types of particle were performed under a magnetic field. The principal objectives of this study were to clarify the applicability of the optical microscope system and image processing system, and to analyze the growth process of the cluster under magnetic field. The analysis of particle image was done using Particle Tracking Velocimetry (PTV). The results clarified that the real-time observation of Brownian motion and cluster movement of ferro- and non-magnetic particles in magnetic fluids can be carried out using the optical microscope system and the PTV image measurement. Independent continuous measurements with changing positions and velocity of the minute particle were made possible. The study concluded that the system can obtain satisfactory results on growth process measurement of cluster under a magnetic field.     

Real-time observation of Brownian motion and cluster movement of ferro- and non-magnetic particles in magnetic fluids

Cluster movements of ferro- and non-magnetic particles in magnetic fluids were investigated using optical microscope system and image processing system. Real-time visualizations of the Brownian motion of particles and the chain-like cluster movement of both types of particle were performed under a magnetic field. The principal objectives of this study were to clarify the applicability of the optical microscope system and image processing system, and to analyze the growth process of the cluster under magnetic field. The analysis of particle image was done using Particle Tracking Velocimetry (PTV). The results clarified that the real-time observation of Brownian motion and cluster movement of ferro- and non-magnetic particles in magnetic fluids can be carried out using the optical microscope system and the PTV image measurement. Independent continuous measurements with changing positions and velocity of the minute particle were made possible. The study concluded that the system can obtain satisfactory results on growth process measurement of cluster under a magnetic field.     

High‐Throughput Continuous Flow Production of Nanoscale Liposomes by Microfluidic Vertical Flow Focusing

Liposomes represent a leading class of nanoparticles for drug delivery. While a variety of techniques for liposome synthesis have been reported that take advantage of microfluidic flow elements to achieve precise control over the size and polydispersity of nanoscale liposomes, with important implications for nanomedicine applications, these methods suffer from extremely limited throughput, making them impractical for large‐scale nanoparticle synthesis. High aspect ratio microfluidic vertical flow focusing is investigated here as a new approach to overcoming the throughput limits of established microfluidic nanoparticle synthesis techniques. Here the vertical flow focusing technique is utilized to generate populations of small, unilamellar, and nearly monodisperse liposomal nanoparticles with exceptionally high production rates and remarkable sample homogeneity. By leveraging this platform, liposomes with modal diameters ranging from 80 to 200 nm are prepared at production rates as high as 1.6 mg min⁻¹ in a simple flow‐through process.     

Simultaneous quantification of multiple magnetic nanoparticles

Distinct magnetic nanoparticle designs can have unique spectral responses to an AC magnetic field in a technique called the magnetic spectroscopy of Brownian motion (MSB). The spectra of the particles have been measured using desktop spectrometers and in vivo measurements. If multiple particle types are present in a region of interest, the unique spectral signatures allow for the simultaneous quantification of the various particles. We demonstrate such a potential experimentally with up to three particle types. This ability to concurrently detect multiple particles will enable new biomedical applications.     

Elevation performance of 1.25D and 1.5D transducer arrays

Present 1D phased array probes have outstanding lateral and axial resolution, but their elevation performance is determined by a fixed aperture focused at a fixed range. Multi-row array transducers can provide significantly improved elevation performance in return for “modest” increases in probe and system complexity. Time domain simulations of elevation beam profiles are used to compare several types of multi-row probes. The elevation aperture of a 1.25D probe increases with range, but the elevation focusing of that aperture is static and determined principally by a mechanical lens with a fixed focus (or foci). 1.25D probes can provide substantially better near- and far-field slice thickness performance than 1D probes and require no additional system beamformer channels. 1.5D, probes use additional beamformer channels to provide dynamic focusing and apodization in elevation. 1.5D probes can provide detail resolution comparable to, and contrast resolution substantially better than, 1.25D probes, particularly in the mid- and far-field. Further increases in system channel count allow the use of 1.75D and 2D arrays for adaptive acoustics and two-dimensional beam steering. Significant improvements in clinical image quality can be expected as multi-row probes become increasingly available in the marketplace     

Structure and properties of nano-hydroxypatite scaffolds for bone tissue engineering with a selective laser sintering system

In this study, nano-hydroxypatite (n-HAP) bone scaffolds are prepared by a homemade selective laser sintering (SLS) system based on rapid prototyping (RP) technology. The SLS system consists of a precise three-axis motion platform and a laser with its optical focusing device. The implementation of arbitrary complex movements based on the non-uniform rational B-Spline (NURBS) theory is realized in this system. The effects of the sintering processing parameters on the microstructure of n-HAP are tested with x-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The particles of n-HAP grow gradually and tend to become spherical-like from the initial needle-like shape, but still maintain a nanoscale structure at scanning speeds between 200 and 300 mm min(-1) when the laser power is 50 W, the light spot diameter 4 mm, and the layer thickness 0.3 mm. In addition, these changes do not result in decomposition of the n-HAP during the sintering process. The results suggest that the newly developed n-HAP scaffolds have the potential to serve as an excellent substrate in bone tissue engineering.     

Nanofluidic preconcentration and detection of nanoparticles

The fast detection and characterization of nanoparticles, such as viruses or environmental pollutants, are important in fields ranging from biosensing to quality control. However, most existing techniques have practical throughput limitations, which significantly limit their applicability to low analyte concentrations. Here, we present an integrated nanofluidic scheme for preconcentration and subsequent detection of nanoparticle samples within a continuous flow-through system. Using a Brownian ratchet mechanism, we increase the nanoparticle concentration ～27-fold. Single nanoparticles are subsequently detected and characterized by optical heterodyne interferometry. A wide range of potential applications can be foreseen, including real-time analysis of clinically relevant virus samples and contamination control of processing fluids used in the semiconductor industry.     

What Have We Learnt About the Mechanisms of Rapid Water Transport,Ion Rejection and Selectivity in Nanopores from Molecular Simulation?

Nanopores have demonstrated an extraordinary ability to allow water molecules to pass through their interiors at rates far exceeding expectations based on continuum theory. Moreover, simulation studies suggest that particular nanoscale pores have the potential to discriminate between water and salts as well as to distinguish between a range of different ion types. Some of the unusual features of transport in these nanopores have been elucidated with molecular dynamics simulation, specifically the spontaneous filling and rapid transport of water, the rejection of ions and the selection between ions. The main focus of this review, however, is the physical mechanisms which act to produce such remarkable behaviour at this scale, drawing on the many studies that have been conducted in the last decade. Since molecular dynamics simulations allow the motion of individual atoms to be followed over time, they have the potential to provide fundamental insight into the reasons why transport in nanoscale pores differs from expectations based on macroscopic theory. Gaining an understanding of the mechanisms of transport in these tiny pores should guide future experiments in this area aimed at developing novel technologies and improving existing membrane separation techniques.     

A Monte Carlo solution of transport equations

A local method is developed for solving partial differential transport equations. The method is local in the sense that the value of the unknown solution of these equations can be calculated at arbitrary space and time coordinates directly rather than extracting its value from the field solution as done when using current numerical methods for solution. The proposed method is based on an analogy between the partial differential operator of transport equations and the infinitesimal generator of Itô processes, the Itô formula, the Dynkin formula, and Monte Carlo simulation. The method can be applied to solve transport problems with Dirichlet and Neumann boundary conditions. The solution of transport problems with Neumann boundary conditions is less simple because it requires the use of reflected Brownian motion and Itô processes.     

Effect of aggregation kinetics on the thermal conductivity of nanoscale colloidal solutions (nanofluid)

The thermal conductivity, k, of nanoscale colloidal suspensions (also known as nanofluid), consisting of nanoparticles suspended in a base liquid, is much higher than the thermal conductivity of the base liquid at very small volume fractions of the nanoparticles. However, experimental results from various groups all across the world have shown various anomalies such as a peak in the enhancement of k with respect to nanoparticle size, an increase as well as a decrease in the ratio of k of these colloidal solutions with the k of the base fluid with increasing temperature, and a dependence of k on pH and time. In this paper, the aggregation kinetics of nanoscale colloidal solutions are combined with the physics of thermal transport to capture the effects of aggregation on k. Results show that the observed anomalies reported in experimental work can be well described by taking aggregation kinetics into account. Finally, we show that colloidal chemistry plays a significant role in deciding the k of colloidal nanosuspensions.     

Liquid‐Phase Transmission Electron Microscopy for Studying Colloidal Inorganic Nanoparticles

For the past few decades, nanoparticles of various sizes, shapes, and compositions have been synthesized and utilized in many different applications. However, due to a lack of analytical tools that can characterize structural changes at the nanoscale level, many of their growth and transformation processes are not yet well understood. The recently developed technique of liquid‐phase transmission electron microscopy (TEM) has gained much attention as a new tool to directly observe chemical reactions that occur in solution. Due to its high spatial and temporal resolution, this technique is widely employed to reveal fundamental mechanisms of nanoparticle growth and transformation. Here, the technical developments for liquid‐phase TEM together with their application to the study of solution‐phase nanoparticle chemistry are summarized. Two types of liquid cells that can be used in the high‐vacuum conditions required by TEM are discussed, followed by recent in situ TEM studies of chemical reactions of colloidal nanoparticles. New findings on the growth mechanism, transformation, and motion of nanoparticles are subsequently discussed in detail.