Single Microparticle Research Articles

Tin and zinc microparticle impacts above the critical adhesion velocity

In cold spray, the critical adhesion velocity, or the point at which microparticles start to adhere to the substrate upon impact, defines the lower bound of the velocity window over which deposition can occur. Less information is available on the upper bound of this deposition window, which has previously been connected to both melting and hydrodynamic penetration processes that can lead to erosion. In this study, we examine impacts of tin microparticles on a tin substrate and zinc microparticles on a zinc substrate across a range of velocities above the critical adhesion velocity. We observe a variety of phenomena that occur as impact velocity is increased, including jetting, melting, fragmentation, and hydrodynamic penetration. Using laser scanning confocal microscopy and scanning electron microscopy, we quantify the net amount of material deposited at each impact site for each material. We use these measurements to understand the circumstances under which an erosive condition is met at high velocities, in which net deposition of microparticle material to the substrate no longer occurs. • Impact-induced melting occurs in both tin and zinc single microparticle impacts. • Confocal microscopy can be used to quantify erosion onset at high velocities. • Erosion in cold spray is caused by melting, penetration, and/or fragmentation. • Jetting, fragmentation, melting, & penetration occur at material-specific speeds.

Additional hindrances to metallurgical bonding from impurities during microparticle impact

Successful cold spray processing requires the formation of metallurgical bonds at the interface between particle impact sites and the substrate. While surface contamination on either the particle or substrate can interfere with metallurgical bonding, the details of particle/substrate interface chemistry are usually obscured or lost during the nanoseconds-long particle impact process. To provide a direct, detailed account of particle-substrate interfacial chemistry, we perform post-mortem scanning transmission electron microscopy and spectroscopy of impact sites of single copper microparticles, launched with a laser-induced particle impact tester, on a copper substrate. In addition to native oxides, we find that amorphous carbon and spherical copper oxide dispersoids are also present near/at the interface. Further, these features are found to influence metallurgical bonding. These results offer additional considerations for optimizing the quality of the cold spray deposition process.

Individual Microparticle Manipulation Using Combined Electroosmosis and Dielectrophoresis through a Si3N4 Film with a Single Micropore.

Porous dielectric membranes that perform insulator-based dielectrophoresis or electroosmotic pumping are commonly used in microchip technologies. However, there are few fundamental studies on the electrokinetic flow patterns of single microparticles around a single micropore in a thin dielectric film. Such a study would provide fundamental insights into the electrokinetic phenomena around a micropore, with practical applications regarding the manipulation of single cells and microparticles by focused electric fields. We have fabricated a device around a silicon nitride film with a single micropore (2–4 µm in diameter) which has the ability to locally focus electric fields on the micropore. Single microscale polystyrene beads were used to study the electrokinetic flow patterns. A mathematical model was developed to support the experimental study and evaluate the electric field distribution, fluid motion, and bead trajectories. Good agreement was found between the mathematic model and the experimental data. We show that the combination of electroosmotic flow and dielectrophoretic force induced by direct current through a single micropore can be used to trap, agglomerate, and repel microparticles around a single micropore without an external pump. The scale of our system is practically relevant for the manipulation of single mammalian cells, and we anticipate that our single-micropore approach will be directly employable in applications ranging from fundamental single cell analyses to high-precision single cell electroporation or cell fusion.

High-precision in situ measurements of size and optical properties of single microparticles in an RF plasma

An enhanced, high-precision, in situ method to determine the radii and refractive indices of single microparticles embedded in a plasma is presented. The particles are confined in the plasma sheath and illuminated with laser light that has a well-defined and adjustable state of polarization. Using an out-of-focus imaging setup, the angle- and polarization-resolved scattering intensities are measured and compared to Lorentz–Mie theory. A two-stage data evaluation process is used to obtain the particle size and the complex refractive index of different particle materials as a function of interaction time with the plasma.

Imaging and Manipulating the Conversion from Single Cuprous Oxide Microparticles to Single Metal Hydroxide Microstructures.

The template-assisted route is an effective avenue for the preparation of core-shell and hollow micromaterials. However, the conversion process is usually characterized by ex situ transmission electron microscopy, limiting the comprehensive understanding of the structure evolution. Here, we use dark-field microscopy (DFM) to visually image the chemical conversion process of Cu2O concave microcubes into metal hydroxide (MHs, M = Co, Ni, and Mn) microstructures at the single-particle level. The details of the conversion process such as early steps in the conversion reaction, intermediate states, and final states are successfully tracked in real time. The in situ DFM experiments clarify that the etching of Cu2O predates the generation of MHs, and the conversion reaction shows significant particle-to-particle variation. Meanwhile, the results also show that experimental parameters dominate the conversion of Cu2O concave microcubes, allowing for the precise manipulation of the reaction degree to obtain Cu2O@Co(OH)2 core-shell microstructures with different shell thicknesses and hollow Co(OH)2 microstructures. The present work offers a direct observation and manipulation of the conversion process of Cu2O microparticles, paving the way for rational design and preparation of various core-shell and hollow micromaterials.

Oxide layer delamination: An energy dissipation mechanism during high-velocity microparticle impacts

The break-up of microparticle surface oxides is needed to generate a clean metal-metal contact for metallurgical bonding during impact events such as seen in cold-spray. However, the mechanism by which this occurs is not clear. Using a laser-induced particle impact tester, we conduct site-specific experiment of single Cu microparticle impacts on a polished Cu substrate and characterize the impact sites. We observe that oxide layers on the particles begin to delaminate at velocities high enough to cause jetting of the substrate around the periphery of the impact site. We show that the energy cost of such delamination is ∼30% of the energy needed to slow and stop particle as it bonds to the substrate, with the remainder being associated with the jetting process and bonding itself. At higher velocities, the oxide barrier is broken up to permit metallurgical bonding. Closer to the particle south-pole where hoop strain is low, oxide layers break up with few gaps and thus no metallurgical bonding is observed. Away from the south-pole where larger strains develop, oxide breakup permits intermittent bonding by the extrusion of bare metal into the gaps between oxide islands. These observations provide new insights towards understanding impact-induced metallurgical bonding during cold-spray process.

Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa

The multi-drug resistance of Pseudomonas aeruginosa is an overwhelming cause of terminal and persistent lung infections in cystic fibrosis (CF) patients. Antimicrobial synergy has been shown for colistin and ivacaftor, and our study designed a relatively high drug-loading dry powder inhaler formulation containing nanoparticles of ivacaftor and colistin. The ivacaftor-colistin nanosuspensions (Iva-Col-NPs) were prepared by the anti-solvent method with different stabilizers. Based on the aggregation data, the formulation 7 (F7) with DSPG-PEG-OMe as the stabilizer was selected for further studies. The F7 consisted of ivacaftor, colistin and DSPG-PEG-OMe with a mass ratio of 1:1:1. The F7 powder formulation was developed using the ultrasonic spray-freeze-drying method and exhibited a rough surface with relatively high fine particle fraction values of 61.4 ± 3.4% for ivacaftor and 63.3 ± 3.3% for colistin, as well as superior emitted dose of 97.8 ± 0.3% for ivacaftor and 97.6 ± 0.5% for colistin. The F7 showed very significant dissolution improvement for poorly water soluble ivacaftor than the physical mixture. Incorporating two drugs in a single microparticle with synchronized dissolution and superior aerosol performance will maximize the synergy and bioactivity of those two drugs. Minimal cytotoxicity in Calu-3 human lung epithelial cells and enhanced antimicrobial activity against colistin-resistant P. aeruginosa suggested that our formulation has potential to improve the treatment of CF patients with lung infections.

Detection and Characterization of Single Particles by Electrochemical Impedance Spectroscopy.

We present an electrochemical impedance spectroscopy (EIS) technique that can detect and characterize single particles as they collide with an electrode in solution. This extension of single-particle electrochemistry offers more information than typical amperometric single-entity measurements, as EIS can isolate concurrent capacitive, resistive, and diffusional processes on the basis of their time scales. Using a simple model system, we show that time-resolved EIS can detect individual polystyrene particles that stochastically collide with an electrode. Discrete changes are observed in various equivalent circuit elements, corresponding to the physical properties of the single particles. The advantages of EIS are leveraged to separate kinetic and diffusional processes, enabling enhanced precision in measurements of the size of the particles. In a broader context, the frequency analysis and single-object resolution afforded by this technique can provide valuable insights into single pseudocapacitive microparticles, electrocatalysts, and other energy-relevant materials.

Imaging adsorption of iodide on single Cu2O microparticles reveals the acid activation mechanism

Imaging an adsorption reaction taking place at the single-particle level is a promising avenue for fundamentally understanding the adsorption mechanism. Here, we employ a dark-field microscopy (DFM) method for in situ imaging the adsorption process of I- on single Cu2O microparticles to reveal the acid activation mechanism. Using the time-lapsed DMF imaging, we find that a relatively strong acid is indispensable to trigger the adsorption reaction of I- on single Cu2O microparticle. A hollow microparticle with the increase in size is obtained after the adsorption reaction, causing the enhancement of the scattering intensity. Correlating the change of the scattering light intensity or particle size with adsorption capacity of I-, we quantitatively analyze the selective uptake, slightly heterogeneous adsorption behavior, pH/temperature-dependent adsorption capacity, and adsorption kinetics as well as isotherms of individual Cu2O microparticles for I-. Our observations demonstrate that the acid-initiated Kirkendall effect is responsible for the high-reaction activity of single Cu2O microparticles for adsorption of I- in the acidic environment, through breaking the unfavorable lattice energy between Cu2O and CuI as well as generating high-active hollow intermediate microparticle.

Acoustic aggregation-induced separation for enhanced fluorescence detection of Alzheimer's biomarker

On-chip microparticle-based separation is a significant activity in analytical and biomedical field. Here, we reported an acoustic aggregation-induced microparticle separation for on-chip fluorescence detection of Alzheimer biomarkers. miRNA-101, an Alzheimer-related biomarker, was used as a model target to validate the performance of the acoustic aggregation-induced separation assay. Under the ultrasound filed, the microparticles would move toward the centre of chip by simply adjusting the frequency and voltage. Such particle aggregation further resulted in fluorescence enhancement comparing with single microparticle. This approach integrated acoustic aggregation-induced microparticle separation with fluorescence enhancement, holding great potential application for the development of lab-on-a-chip based trace biomarkers detection in diagnosis field.

Transport and assembling microparticles via Marangoni flows in heating and cooling modes

The processes of the particles transfer in liquid media and the creation of structures of required configurations on substrates are of great importance in such areas as materials science, coatings, optoelectronics and biomedical researches. To control of the transfer of large ensembles of particles and dynamically transform of the particle aggregates the precise and flexible methods are strongly required. In this work, we propose a method for manipulation of microparticles in volatile liquid layers hundreds of microns thick that relies on the control of Marangoni flows by changing a sign of the temperature gradient in the liquid by the local action of the heat source and/or the heat sink. We have clearly demonstrated the applicability of the method to perform of wide range of manipulations with the particle ensembles: particles assembling in the circular patterns on a substrate when heating is applied, transfer of particles away from a heat sink when the substrate is cooled, and creation of ring-like patterns by changing the temperature gradient sign during particle assembling process. We have also studied the influence of the liquid layer thickness on the particle transfer and the size of the resulting pattern. It was found out that when heating the final pattern area on substrate decreases with the layer thickness, while the time of the pattern formation increases with the layer thickness. In the cooling mode, the final cleaned area decreases with the number of particles but the dependence on the layer thickness is ambiguous. The characteristic time decreases with an increase in the number of particles and slightly increases with the layer thickness. It was also revealed that the increase in the layer thickness makes it possible to create the multilayer dense circular assemblies of particles. The proposed method is simple for implementation, flexible and can be applied for manipulation with particles of any physicochemical properties and shapes. The method is applicable for controlling both a single microparticle and a large group of particles.

Self-assembled microcage fabrication for manipulating and selectively capturing microparticles and cells.

Single-cell-scale selective manipulation and targeted capture play a vital role in cell behavior analysis. However, selective microcapture has primarily been performed in specific circumstances to maintain the trapping state, making the subsequent in situ characterization and analysis of specific particles or cells difficult and imprecise. Herein, we propose a novel method that combines femtosecond laser two-photon polymerization (TPP) micromachining technology with the operation of optical tweezers (OTs) to achieve selective and targeted capture of single particles and cells. Diverse ordered microcages with different shapes and dimensions were self-assembled by micropillars fabricated via TPP. The micropillars with high aspect ratios were processed by single exposure, and the parameters of the micropillar arrays were investigated to optimize the capillary-force-driven self-assembly process of the anisotropic microcages. Finally, single microparticles and cells were selectively transported to the desired microcages by manipulating the flexibly of the OTs in a few minutes. The captured microparticles and cells were kept trapped without additional forces.

Single-Particle Imaging of Anion Exchange Reactions in Cuprous Oxide.

Ion exchange is a predominant and flexible route to tailor the composition and crystal structure of various materials. In situ monitoring of the ion exchange process at the single-particle level is critical to better understand the reaction mechanism and engineer high-performance materials. We report herein a dark-field imaging approach to in situ investigate the anion exchange reactions between individual Cu2O microparticles and S2- or Cl- assisted by the hydrolysis of Sn4+, which are visualized by directly observing the color change of single Cu2O microparticles. The variation of the scattering intensity is applied for quantitative analysis of anion exchange kinetics, revealing that this reaction process is dependent on the morphology, size, environmental pH, and reactant concentration. We directly observe that the corners of Cu2O are the preferential exchange sites, and the reaction activity is surface dependent. Moreover, the reaction rate constant and diffusion coefficient are estimated to be 1.1 × 10-2 s-1 and 9.4 × 10-11 cm2/s. Furthermore, a single-particle colorimetric assay is also fabricated for visual detection of S2-.

Arrest in the Progression of Type 1 Diabetes at the Mid-Stage of Insulitic Autoimmunity Using an Autoantigen-Decorated All-trans Retinoic Acid and Transforming Growth Factor Beta-1 Single Microparticle Formulation.

Type 1 diabetes (T1D) is a disorder of impaired glucoregulation due to lymphocyte-driven pancreatic autoimmunity. Mobilizing dendritic cells (DC) in vivo to acquire tolerogenic activity is an attractive therapeutic approach as it results in multiple and overlapping immunosuppressive mechanisms. Delivery of agents that can achieve this, in the form of micro/nanoparticles, has successfully prevented a number of autoimmune conditions in vivo. Most of these formulations, however, do not establish multiple layers of immunoregulation. all-trans retinoic acid (RA) together with transforming growth factor beta 1 (TGFβ1), in contrast, has been shown to promote such mechanisms. When delivered in separate nanoparticle vehicles, they successfully prevent the progression of early-onset T1D autoimmunity in vivo. Herein, we show that the approach can be simplified into a single microparticle formulation of RA + TGFβ1 with surface decoration with the T1D-relevant insulin autoantigen. We show that the onset of hyperglycemia is prevented when administered into non-obese diabetic mice that are at the mid-stage of active islet-selective autoimmunity. Unexpectedly, the preventive effects do not seem to be mediated by increased numbers of regulatory T-lymphocytes inside the pancreatic lymph nodes, at least following acute administration of microparticles. Instead, we observed a mild increase in the frequency of regulatory B-lymphocytes inside the mesenteric lymph nodes. These data suggest additional and potentially-novel mechanisms that RA and TGFβ1 could be modulating to prevent progression of mid-stage autoimmunity to overt T1D. Our data further strengthen the rationale to develop RA+TGFβ1-based micro/nanoparticle “vaccines” as possible treatments of pre-symptomatic and new-onset T1D autoimmunity.

From Nanosecond Photochemistry to Optical Force Chemistry: My Journey.

Laser was invented in 1960 and soon introduced to chemistry research. We started time-resolved spectroscopy and photochemistry and initial trial was focused to nanosecond and then picosecond electronic absorption spectroscopy for studying molecular electronic excited states, charge separation in molecular complexes, and intermolecular electron transfer in solution. We considered that not only time-resolved but also space-resolved chemistry would be important for future laser-based chemistry and combined pulsed lasers with optical microscopes. Spectroscopy, photochemistry, ablation, and spatial arrangement of single microparticles and microdroplets in solution were carried out. Further we shifted from micro to nano and opened a new field covering spectroscopy, ablation, phase transition, crystallization, patterning, and fabrication. The progress is summarized and discussed as time-resolved nano spectroscopy, ablation nano dynamics, and optical force chemistry.

High-velocity micro-projectile impact testing

High-velocity microparticle impacts are relevant to many fields, from space exploration to additive manufacturing, and can be used to help understand the physical and chemical behaviors of materials under extreme dynamic conditions. Recent advances in experimental techniques for single microparticle impacts have allowed fundamental investigations of dynamical responses of wide-ranging samples, including soft materials, nano-composites, and metals, under strain rates up to 108 s−1. Here we review experimental methods for high-velocity impacts spanning 15 orders of magnitude in projectile mass and compare method performances. This review aims to present a comprehensive overview of high-velocity microparticle impact techniques to provide a reference for researchers in different materials testing fields and facilitate experimental design in dynamic testing for a wide range of impactor sizes, geometries, and velocities. Next, we review recent studies using the laser-induced particle impact test platform comprising target, projectile, and synergistic target-particle impact response, hence demonstrating the versatility of the method with applications in impact protection and additive manufacturing. We conclude by presenting the future perspectives in the field of high-velocity impact.

Laser-Induced Single-Molecule Extraction and Detection in Aqueous Poly(N-isopropylacrylamide)/1-Butanol Solutions.

We report photothermal phase separation of aqueous poly(N-isopropylacrylamide) (PNIPAM)/1-butanol (BuOH) solutions by focused 1064 nm laser irradiation and subsequent single microparticle formation in the solution. The single microparticle [diameter = ∼10 μm and volume = ∼picoliter (pL)] produced by laser irradiation was optically trapped by the incident 1064 nm laser beam, and this enabled us in situ Raman/fluorescence microspectroscopies of the particle. Raman spectroscopy demonstrated that the particle produced by laser irradiation was composed of PNIPAM and BuOH. In the presence of rhodamine B (RhB) in the solution, RhB was distributed from the water phase to the PNIPAM/BuOH microparticle produced by laser irradiation, as confirmed by fluorescence microspectroscopy. Laser-induced distribution/extraction of RhB to a single PNIPAM/BuOH microparticle was shown to be possible at the RhB concentration as low as 10-14 mol/dm3, where the RhB fluorescence intensity from the particle showed a step-by-step increase by every ∼3 min laser irradiation. This is the first demonstration of laser-induced simultaneous extraction and detection of single RhB molecules in solution.

Mechanistic explanation of the (up to) 3 release phases of PLGA microparticles: Monolithic dispersions studied at lower temperatures

The aim of this study was to better understand the underlying drug release mechanisms in poly(lactic-co-glycolic acid) (PLGA) microparticles in which the drug is dispersed in the form of tiny particles (“monolithic dispersions”). Differently sized diprophylline-loaded microparticles were prepared using a solid-in-oil-in-water solvent extraction/evaporation technique. The microparticles were characterized before and after exposure to phosphate buffer pH 7.4 at 4, 20 and 37 °C. In vitro drug release was measured from ensembles and single microparticles. GPC, DSC, SEM, gravimetric analysis, drug solubility measurements and optical microscopy were used to elucidate the importance of polymer swelling & degradation, drug dissolution and diffusion. The diprophylline was initially homogeneously distributed throughout the microparticles in the form of tiny crystals. The burst release (1st phase) was strongly temperature-dependent and likely attributable to the dissolution of drug crystals with direct surface access (potentially via tiny pores). The about constant release rate during the 2nd phase also strongly depended on the temperature. It can probably be explained by the dissolution of drug crystals in surface near regions undergoing local swelling. During the observation period, the 3rd (again rapid) drug release phase was only observed at 37 °C, and seems to be caused by substantial PLGA swelling throughout the entire microparticles. This phase starts as soon as a critical polymer molecular weight of about 25 kDa is reached: Significant amounts of water penetrate into the systems, dissolving the remaining diprophylline crystals and substantially increasing the mobility of the dissolved drug molecules. Thus, this study provides additional experimental evidence (obtained at lower temperatures) confirming the hypothesized root causes for drug release from PLGA microparticles containing dispersed drug particles.

Laser manipulation of airborne microparticles behind non-transparent obstacles with the help of circular Airy beams.

An approach for the realization of three-dimensional laser manipulation of agglomerations of carbon nanoparticles behind non-transparent obstacles in the air is proposed and investigated. The approach is based on the use of circular Airy beams (CABs), which are structured laser beams with self-healing and autofocusing properties. The possibility to trap and guide both single and multiple microparticles in the case of a non-distorted CAB and a CAB distorted by an on-axis metal rod is demonstrated. We believe that these results open new possibilities for the control of trapped particles that are out of sight and hidden by different obstacles.

In "Vitro" Lps-Stimulated Sertoli Cells Pre-Loaded With Microparticles: Intracellular Activation Pathways.

Sertoli cells (SC) are immune privileged cells with the capacity of modulating the immune response by expressing several immune-regulatory factors. SC have the capacity to respond to external stimuli through innate phagocytic and antibacterial activities. This evidence evoked a potential role of SC as drug carriers and therapeutic agents. Such stimuli drive SC towards a still unknown evolution, the clinical relevance of which as yet remains undisclosed. This study sought to investigate the effects of external stimuli in the form of polymeric microparticles (MP) and bacteria derived endotoxins, such as lipopolysaccharides (LPS), in order to identify the pathways potentially involved in cell phenotype modifications. Compared to single stimulation, when combined, MP and LPS provoked a significant increase in the gene expression of IDO, PD-L1, FAS-L, TLR-3, TLR-4, MHC-II, ICAM-1, TFGβ1, BDF123, BDF129, BDF3 and pEP2C. Western Blotting analysis demonstrated up-regulation of the ERK 1–2 and NF-kB p65 phosphorylation ratios. Our study, showing the exponential increase of these mediators upon combined MP and LPS stimulation, suggests a “switch” of SC function from typical cells of the blood-testicular barrier to nonprofessional tolerogenic antigen-presenting cells. Further studies should target the clinical and technological implications of such stimuli-induced SC transformation.