Magnetically Selective Versatile Transport of Microrobotic Carriers.

Field-driven transport systems offer great promise for use as biofunctionalized carriers in microrobotics, biomedicine, and cell delivery applications. Despite the construction of artificial microtubules using several micromagnets, which provide a promising transport pathway for the synchronous delivery of microrobotic carriers to the targeted location inside microvascular networks, the selective transport of different microrobotic carriers remains an unexplored challenge. This study demonstrated the selective manipulation and transport of microrobotics along a patterned micromagnet using applied magnetic fields. Owing to varied field strengths, the magnetic beads used as the microrobotic carriers with different sizes revealed varied locomotion, including all of them moving along the same direction, selective rotation, bidirectional locomotion, and all of them moving in a reversed direction. Furthermore, cells immobilized with magnetic beads and nanoparticles also revealed varied locomotion. It is expected that such steering strategies of microrobotic carriers can be used in microvascular channels for the targeted delivery of drugs or cells in an organized manner.

Magnetic Lateral Ladder for Unidirectional Transport of Microrobots: Design Principles and Potential Applications of Cells-on-Chip.

Functionalized microrobots, which are directionally manipulated in a controlled and precise manner for specific tasks, face challenges. However, magnetic field-based controls constrain all microrobots to move in a coordinated manner, limiting their functions and independent behaviors. This article presents a design principle for achieving unidirectional microrobot transport using an asymmetric magnetic texture in the shape of a lateral ladder, which the authors call the "railway track." An asymmetric magnetic energy distribution along the axis allows for the continuous movement of microrobots in a fixed direction regardless of the direction of the magnetic field rotation. The authors demonstrated precise control and simple utilization of this method. Specifically, by placing magnetic textures with different directionalities, an integrated cell/particle collector can collect microrobots distributed in a large area and move them along a complex trajectory to a predetermined location.  The authors can leverage the versatile capabilities offered by this texture concept, including hierarchical isolation, switchable collection, programmable pairing, selective drug-response test, and local fluid mixing for target objects. The results demonstrate the importance of microrobot directionality in achieving complex individual control. This novel concept represents significant advancement over conventional magnetic field-based control technology and paves the way for further research in biofunctionalized microrobotics.

Tailoring matter orbitals mediated using a nanoscale topographic interface for versatile colloidal current devices.

Conventional micro-particle manipulation technologies have been used for various biomedical applications using dynamics on a plane without vertical movement. In this case, irregular topographic structures on surfaces could be a factor that causes the failure of the intended control. Here, we demonstrated a novel colloidal particle manipulation mediated by the topographic effect generated by the "micro hill" and "surface gradient" around a micro-magnet. The magnetic landscape, matter orbital, created by periodically arranged circular micro-magnets, induces a symmetric orbit of magnetic particle flow under a rotating magnetic field. The topographic effect can break this symmetry of the energy distribution by controlling the distance between the source of the driving force and target particles by several nanometers on the surface morphology. The origin symmetric orbit of colloidal flow can be distorted by modifying the symmetry in the energy landscape at the switching point without changing the driving force. The enhancement of the magnetic effect of the micro-magnet array can lead to the recovery of the symmetry of the orbit. Also, this effect on the surfaces of on-chip-based devices configured by symmetry control was demonstrated for selective manipulation, trapping, recovery, and altering the direction using a time-dependent magnetic field. Hence, the developed technique could be used in various precise lab-on-a-chip applications, including where the topographic effect is required as an additional variable without affecting the existing control method.

Magnetophoretic Micro-Distributor for Controlled Clustering of Cells.

Cell clustering techniques are important to produce artificial cell clusters for in vitro models of intercellular mechanisms at the single-cell level. The analyses considering physical variables such as the shape and size of cells have been very limited. In addition, the precise manipulation of cells and control of the physical variables are still challenging. In this paper, a magnetophoretic device consisting of a trampoline micromagnet and active elements that enable the control of individual selective jumping motion and positioning of a micro-object is proposed. Based on a numerical simulation under various conditions, automatic separation or selective clustering of micro-objects according to their sizes is performed by parallel control and programmable manipulation. This method provides efficient control of the physical variables of cells and grouping of cells with the desired size and number, which can be a milestone for a better understanding of the intercellular dynamics between clustered cells at the single-cell level for future cell-on-chip applications.

Magnetophoretic Decoupler for Disaggregation and Interparticle Distance Control.

The manipulation of superparamagnetic beads has attracted various lab on a chip and magnetic tweezer platforms for separating, sorting, and labeling cells and bioentities, but the irreversible aggregation of beads owing to magnetic interactions has limited its actual functionality. Here, an efficient solution is developed for the disaggregation of magnetic beads and interparticle distance control with a magnetophoretic decoupler using an external rotating magnetic field. A unique magnetic potential energy distribution in the form of an asymmetric magnetic thin film around the gap is created and tuned in a controlled manner, regulated by the size ratio of the bead with a magnetic pattern. Hence, the aggregated beads are detached into single beads and transported in one direction in an array pattern. Furthermore, the simultaneous and accurate spacing control of multiple magnetic bead pairs is performed by adjusting the angle of the rotating magnetic field, which continuously changes the energy well associated with a specific shape of the magnetic patterns. This technique offers an advanced solution for the disaggregation and controlled manipulation of beads, can allow new possibilities for the enhanced functioning of lab on a chip and magnetic tweezers platforms for biological assays, intercellular interactions, and magnetic biochip systems.

Fabrication of Sn@Al2O3 Core-shell Nanoparticles for Stable Nonvolatile Memory Applications.

Sn@Al2O3 core-shell nanoparticles (NPs) with narrow spatial distributions were synthesized in silicon dioxide (SiO2). These Sn@Al2O3 core-shell NPs were self-assembled by thermally annealing a stacked structure of SiOx/Al/Sn/Al/SiOx sandwiched between two SiO2 layers at low temperatures. The resultant structure provided a well-defined Sn NP floating gate with a SiO2/Al2O3 dielectric stacked tunneling barrier. Capacitance-voltage (C-V) measurements on a metal-oxide-semiconductor (MOS) capacitor with a Sn@Al2O3 core-shell NP floating gate confirmed an ultra-high charge storage stability, and the multiple trapping of electron at the NPs, as expected from low-k/high-k dielectric stacked tunneling layers and metallic NPs, respectively.

Multifarious Transit Gates for Programmable Delivery of Bio-functionalized Matters.

Programmable delivery of biological matter is indispensable for the massive arrays of individual objects in biochemical and biomedical applications. Although a digital manipulation of single cells has been implemented by the integrated circuits of micromagnetophoretic patterns with current wires, the complex fabrication process and multiple current operation steps restrict its practical application for biomolecule arrays. Here, a convenient approach using multifarious transit gates is proposed, for digital manipulation of biofunctionalized microrobotic particles that can pass through the local energy barriers by a time-dependent pulsed magnetic field instead of multiple current wires. The multifarious transit gates including return, delay, and resistance linear gates, as well as dividing, reversed, and rectifying T-junction gates, are investigated theoretically and experimentally for the programmable manipulation of microrobotic particles. The results demonstrate that, a suitable angle of the gating field at a suitable time zone is crucial to implement digital operations at integrated multifarious transit gates along bifurcation paths to trap microrobotic particles in specific apartments, paving the way for flexible on-chip arrays of biomolecules and cells.

Genomic structures of dysplastic nodule and concurrent hepatocellular carcinoma.

Although high-grade dysplastic nodule (HGDN) is a preneoplastic lesion that precedes hepatocellular carcinoma (HCC), the genomic structures of HGDN in conjunction with HCC remain elusive. The objective of this study was to identify genomic alterations of HGDN and its difference from HCC that may drive HGDN progression to HCC. We analyzed 16 regions of paired HGDN and HCC from 6 patients using whole-exome sequencing to find somatic mutation and copy number alteration (CNA) profiles of HGDN and HCC. The numbers of mutations, driver mutations, and CNAs of HGDNs were not significantly different from those of HCCs. We identified that the CNA gain of 1q25.3-1q42.13 was predominant in the HCCs compared with that in the HGDNs. Two cases (one nodule-in-nodule case and another case with closely attached HCC and HGDN) showed several overlapped driver mutations (CTNNB1 and CEBPA) and CNAs (losses of CDKN2A, RB1, and TP53) between HGDNs and HCCs, suggesting their roles in the early HCC development. The other 4 cases with spatially separated HCCs and HGDNs showed few overlapped alterations between the paired HCCs and HGDNs. Mutations in ERBB2 and CCND1, and CNAs (gains of CTNNB1, MET, and SMO and losses of PTEN, TP53, and SETD2) were identified as "HCC predominant," suggesting their roles in the progression of HGDN to HCC. Our data show that HCCs are direct descendants of HGDNs in some cases, but there is no direct evidence of such relationship in spatially separated cases. Genomic features of HGDN identified in this study provide a useful resource for dissecting clues for the genetic diagnosis of HGDN and HCC.

Magnetically Characterized Molecular Lubrication between Biofunctionalized Surfaces.

We demonstrate an efficient approach for quantifying frictional forces (sub-piconewton) at nano-bio interfaces by controlled magnetic forces, which is based on simultaneous measurements of critical frequencies for streptavidin-coupled magnetic particles. The maximum phase angle, being corresponded with the critical frequency, is formulated in terms of magnetic, frictional, and viscous forces of the particles on DNA- and SiO2-functionalized micromagnet arrays. The streptavidin/DNA interface shows lower friction as an enhanced lubrication than the streptavidin/SiO2 interface, which is indicated by the lower transition field of quasi-static motion, the larger ratio of dynamic particles, and also the higher velocity of the particles. The friction coefficients at the streptavidin/DNA and streptavidin/SiO2 interfaces are evaluated numerically as 0.07 and 0.11, respectively, regardless of the vertical force and the velocity. The proposed method would open up new possibilities to study mechanical interactions at biological surfaces.

STADIUM: Species-Specific tRNA Adaptive Index Compendium.

Due to the increasing interest in synonymous codons, several codon bias-related terms were introduced. As one measure of them, the tRNA adaptation index (tAI) was invented about a decade ago. The tAI is a measure of translational efficiency for a gene and is calculated based on the abundance of intracellular tRNA and the binding strength between a codon and a tRNA. The index has been widely used in various fields of molecular evolution, genetics, and pharmacology. Afterwards, an improved version of the index, named specific tRNA adaptation index (stAI), was developed by adapting tRNA copy numbers in species. Although a subsequently developed webserver (stAIcalc) provided tools that calculated stAI values, it was not available to access pre-calculated values. In addition to about 100 species in stAIcalc, we calculated stAI values for whole coding sequences in 148 species. To enable easy access to this index, we constructed a novel web database, named STADIUM (Species-specific tRNA adaptive index compendium). STADIUM provides not only the stAI value of each gene but also statistics based on pathway-based classification. The database is expected to help researchers who have interests in codon optimality and the role of synonymous codons. STADIUM is freely available at http://stadium.pmrc.re.kr.

Structural Analysis of Recombinant Human Preproinsulins by Structure Prediction, Molecular Dynamics, and Protein-Protein Docking.

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.

Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

A novel scheme for nanoparticle steering in blood vessels using a functionalized magnetic field.

Magnetic drug targeting is a drug delivery approach in which therapeutic magnetizable particles are injected, generally into blood vessels, and magnets are then used to guide and concentrate them in the diseased target organ. Although many analytical, simulation, and experimental studies on capturing schemes for drug targeting have been conducted, there are few studies on delivering the nanoparticles to the target region. Furthermore, the sticking phenomenon of particles to vessels walls near the injection point, and far from the target region, has not been addressed sufficiently. In this paper, the sticking issue and its relationship to nanoparticle steering are investigated in detail using numerical simulations. For wide ranges of blood vessel size, blood velocity, particle size, and applied magnetic field, three coefficient numbers are uniquely generalized: vessel elongation, normal exit time, and force rate. With respect these new parameters, we investigated particle distribution trends for a Y-shaped channel and computed ratios of correctly guided particles and particles remaining in the vessel. We found that the sticking of particles to vessels occurred because of low blood flow velocity near the vessel walls, which is the main reason for low targeting efficiency when using a constant magnetic gradient. To reduce the sticking ratio of nanoparticles, we propose a novel field function scheme that uses a simple time-varying function to separate the particles from the walls and guide them to the target point. The capabilities of the proposed scheme were examined by several simulations of both Y-shaped channels and realistic three-dimensional (3-D) model channels extracted from brain vessels. The results showed a significant decrease in particle adherence to walls during the delivery stage and confirmed the effectiveness of the proposed magnetic field function method for steering nanoparticles for targeted drug delivery.

Fabrication of N-doped porous ZnO nanosheets by annealing Zn films at low temperatures.

In this work, the direct growth of nitrogen (N)-doped porous ZnO nanosheets at low temperatures via the conventional plasma-enhanced chemical vapor deposition (PECVD) method is presented. The growth was based on the thermal annealing of a Zn film composed of Zn nanosheets in oxygen and nitrogen vapors produced via PECVD, with N2O as a source gas. The ZnO nanosheets with well-defined crystallinity were found to have been grown at temperatures over 280 degrees C, and to have had N-doped porous structures. The ZnO nanosheets grown at 380 degrees C were shown to have had a mean thickness of about 5 nm, a mean pore diameter of about 13.3 nm, and 6.7% porosity, and exhibited Raman and photoluminescence peaks characteristic of N-doped ZnO. It is suggested that the ZnO nanosheets were likely formed through their direct oxidation.

Synthesis of cobalt-based nanocrystal layer in silicon dioxide for nonvolatile memory applications.

Cobalt silicide (CoSi) nanocrystal (NC) layer distributed within narrow spatial region is synthesized by thermal annealing of a sandwich structure comprised of a thin cobalt (Co) film sandwiched between two silicon-rich oxide (SiO(x)) layers. It is shown that the size of the CoSi NCs can be controlled by varying the Co film thickness, an increase in the size with increasing thickness. Capacitance-voltage (C-V) measurements on a test metal/oxide/semiconductor (MOS) structure with floating gate based on CoSi NCs of 3.8 nm in diameter and 1.4 x 10(12) cm2 in density are shown to have C-V characteristics suitable for nonvolatile memory applications, including a C-V memory window of about 9.5 V for sweep voltages between -15 V and +8, a retention time >10(8) s, and an endurance > 10(6) program/erase cycles.

Modeling of marine litter drift and beaching in the Japan Sea.

Characteristics of drift and beaching of floating marine litter in the Japan Sea are examined numerically using the reanalysis data of the Japan Sea Forecasting System of Kyushu University. The residence time of model marine litter deployed uniformly over the surface of the Japan Sea strongly depends on the buoyancy ratio. However, almost all litter beaches or flows out through straits within 3years. Experiments with inputs of litter imposed at large cities and the Tsushima Straits as well as river basins of the Japan Sea exhibit a good agreement with beach surveys with regard to country ratios of beached litter along the Japanese coast in cases of lighters. In a case of lighter, almost all lighters originating from Japan beach along the Japanese coast, while almost all lighters originating from a country surrounding the Japan Sea except Japan beach along the coast of that country and the Japanese coast.

The changes in particle charge distribution during rapid growth of particles in the plasma reactor.

The changes in particle charging were investigated during the rapid growth of particles in the plasma reactor by the discrete-sectional model and the Gaussian charge distribution function. The particle size distribution becomes bimodal in the plasma reactor and most of the large particles are charged negatively, but some fractions of small particles are in a neutral state or even charged positively. As the particles accumulate in the plasma reactor, the amount of electrons absorbed onto the particles increases, while the electron concentration in the plasma decreases. As the mass generation rate of small particles (monomers) decreases or as the initial electron concentration increases, the electron concentration in the plasmas increases and the particle charge distribution is shifted in the negative direction and the fraction of particles charged negatively and the average number of electrons per particle increase. With the decrease in monomer diameter, the electron concentration decreases in the beginning of plasma discharge, but, later, increases. For high mass generation rate of monomers or for low initial electron concentration or for small monomer diameter, the fraction of particles in a neutral state increases and the particle size distribution becomes broader.