In nonphotochemical laser-induced nucleation (NPLIN), an unfocused nanosecond laser pulse with low intensity (≈MW/cm²) triggers nearly instantaneous nucleation in supersaturated solutions, a process that would typically take days or weeks when the solution is left undisturbed. Previous studies have shown that the introduction of nanoparticles into supersaturated solutions enhances the probability of NPLIN measured during a fixed time window, compared to undoped control experiments. However, the precise mechanisms driving this enhancement remain unclear hampering industrial implementation of NPLIN. In this study, we systematically investigate how the properties of doped nanoparticles─specifically their concentration and chemical composition─affect the NPLIN probability in supersaturated urea solutions. We observed that higher laser intensities resulted in elevated NPLIN probabilities at a fixed pegylated gold nanoparticle (AuNP) concentration and supersaturation, while increasing concentrations of AuNPs at a fixed laser intensity and supersaturation interestingly led to higher NPLIN probabilities. Moreover, supersaturated solutions doped with gold nanoparticles exhibited significantly higher NPLIN probabilities compared to silica nanoparticle doped solutions at comparable nanoparticle size and concentration. We interpret these experimental results based on the impurity heating hypothesis as well as recent results highlighting the role of thermocavitation. We furthermore propose a helicopter-view model based on a thermodynamic equilibrium stage sequence. Our findings highlight the significance of nanoparticle properties in the design of heteronucleants optimized for NPLIN applications.

PURPOSE: Platinum-based chemotherapy and immune checkpoint inhibitors are key components of systemic treatment for muscle-invasive and advanced urothelial cancer. The ideal integration of these two treatment modalities remains unclear as clinical trials have led to inconsistent results. Modulation of the tumor-immune microenvironment by chemotherapy is poorly characterized. We aimed to investigate this modulation, focusing on potential clinical implications for immune checkpoint inhibitor response. EXPERIMENTAL DESIGN: We assessed immune cell densities, spatial relations, and tumor/stromal components from 116 patients with urothelial bladder cancer (paired data for 95 patients) before and after platinum-based chemotherapy. RESULTS: Several published biomarkers for immunotherapy response changed upon chemotherapy treatment. The intratumoral CD8+ T-cell percentage increased after treatment and was associated with increased TNFα-via-NF-κB signaling. The percentage of PDL1+ immune cells was higher after chemotherapy. An increase in chemo-induced changes that potentially inhibit an antitumor immune response was also observed, including increased fibroblast-based TGFβ signaling and distances from immune cells to the nearest cancer cell. The latter two parameters correlated significantly in posttreatment samples, suggesting that TGFβ signaling in fibroblasts may play a role in spatially separating immune cells from cancer cells. We examined specific chemotherapy regimens and found that treatment with methotrexate, vinblastine, doxorubicin, and cisplatin was associated with an increase in the macrophage cell percentage. Gemcitabine-containing chemotherapy was associated with upregulation of fibroblast TGFβ signaling. CONCLUSIONS: The opposing effects of platinum-based chemotherapy on the immune cell composition and stromal context of the tumor-immune microenvironment may explain the inconsistent results of clinical trials investigating chemotherapy and immune checkpoint inhibitor combinations in bladder cancer.

In the literature, two different frameworks exist for describing the rheology of solid/liquid suspensions: (1) the “viscous” framework in terms of the relative suspension viscosity, η_r, as a function of the reduced solid volume fraction, f=f_m, with f_m the maximum flowable packing fraction, and (2) the “frictional” framework in terms of a macroscopic friction coefficient, μ, as a function of the viscous number, I_v, defined as the ratio of the viscous shear to the wall-normal particle stress. Our goal is to compare the two different frameworks, focusing on the effect of friction between particles. We have conducted a particle-resolved direct numerical simulation study of a dense non-Brownian suspension of neutrally buoyant spheres in slow plane Couette flow. We varied the bulk solid volume fraction from f_b ¼ 0:1 to 0.6 and considered three different Coulomb friction coefficients: μ_c ¼ 0, 0.2, and 0.39. We find that η_r scales well with f=f_m, with f_m obtained from fitting the Maron–Pierce correlation. We also find that μ scales well with I_v. Furthermore, we find a monotonic relation between f=f_m and I_v, which depends only weakly on μ_c. Since η_r ¼ μ=I_v, we thus find that the two frameworks are largely equivalent and that both account implicitly for Coulomb friction. However, we find that the normal particle stress differences, N₁ and N₂, when normalized with the total shear stress and plotted against either f=f_m or I_v, remain explicitly dependent on μ_c in a manner that is not yet fully understood.

Results from particle-resolved Direct numerical simulations are presented for dense suspensions of frictional non-colloidal spheres in viscous pressure-driven channel flow. The bulk solid volume fraction varies between ϕ_b=0.2 and 0.6, and the Coulomb friction coefficient is either μ_c=0 or 0.5. The main objectives are to unravel the influence of (1) ϕ_b and μ_c on the flow development time and of (2) heterogeneous shear on the steady-state suspension rheology. Starting from an initially homogeneous distribution, the particles show shear-induced migration toward the core until equilibrium is reached. The flow development time decays exponentially with increasing ϕ_b/Φ_R, where Φ_R is a friction-dependent reference bulk concentration beyond which particle contacts cause a rapid increase in the particle stress. The steady-state rheology is studied by means of the ‘viscous’ and ‘frictional’ rheology frameworks. Excluding the central core and wall regions, the data for the local relative suspension viscosity collapse onto a single curve as function of the normalized local concentration ϕ¯/ϕ_m, where ϕ_m is the friction-dependent maximum flowable packing fraction. The frictional rheology shows ‘subyielding’ at low viscous number I_v in the core region, where the macroscopic friction coefficient μ drops below the minimal value found for homogeneous shear flows. A modified frictional rheology model is presented that captures subyielding. Finally, a model is presented for ϕ¯/ϕ_mp as function of I_v, where ϕ_mp is a modified maximum flowable packing fraction. It captures both ‘overcompaction’ in the core beyond ϕ_m at high ϕ_b and maximum core concentrations below ϕ_m at lower ϕ_b.

Non-photochemical laser-induced nucleation (NPLIN) has emerged as a promising primary nucleation control technique offering spatiotemporal control over crystallization with potential for polymorph control. So far, NPLIN was mostly investigated in milliliter vials, through laborious manual counting of the crystallized vials by visual inspection. Microfluidics represents an alternative to acquiring automated and statistically reliable data. Thus we designed a droplet-based microfluidic platform capable of identifying the droplets with crystals emerging upon Nd:YAG laser irradiation using the deep learning method. In our experiments, we used supersaturated solutions of KCl in water, and the effect of laser intensity, wavelength (1064, 532, and 355 nm), solution supersaturation (S), solution filtration, and intentional doping with nanoparticles on the nucleation probability is quantified and compared to control cooling crystallization experiments. Ability of dielectric polarization and the nanoparticle heating mechanisms proposed for NPLIN to explain the acquired results is tested. Solutions with lower supersaturation (S = 1.05) exhibit significantly higher NPLIN probabilities than those in the control experiments for all laser wavelengths above a threshold intensity (50 MW/cm²). At higher supersaturation studied (S = 1.10), irradiation was already effective at lower laser intensities (10 MW/cm²). No significant wavelength effect was observed besides irradiation with 355 nm light at higher laser intensities (≥50 MW/cm²). Solution filtration and intentional doping experiments showed that nanoimpurities might play a significant role in explaining NPLIN phenomena.

Herein, we study the influences of the laser-exposed volume and the irradiation position on the nonphotochemical laser-induced nucleation (NPLIN) of supersaturated potassium chloride solutions in water. The effect of the exposed volume on the NPLIN probability was studied by exposing distinct milliliter-scale volumes of aqueous potassium chloride solutions stored in vials at two different supersaturations (1.034 and 1.050) and laser intensities (10 and 23 MW/cm²). Higher NPLIN probabilities were observed with increasing laser-exposed volume as well as with increasing supersaturation and laser intensity. The measured NPLIN probabilities at different exposed volumes are questioned in the context of the dielectric polarization mechanism and classical nucleation theory. No significant change in the NPLIN probability was observed when samples were irradiated at the bottom, top, or middle of the vial. However, a significant increase in the nucleation probability was observed upon irradiation through the solution meniscus. We discuss these results in terms of mechanisms proposed for NPLIN.

A droplet-based microfluidic platform is presented to study the nucleation kinetics of calcium oxalate monohydrate (COM), the most common constituent of kidney stones, while carefully monitoring the pseudo-polymorphic transitions. The precipitation kinetics of COM is studied as a function of supersaturation and pH as well as in the presence of inhibitors of stone formation, magnesium ions (Mg2+), and osteopontin (OPN). We rationalize the trends observed in the measured nucleation rates leveraging a solution chemistry model validated using isothermal solubility measurements. In equimolar calcium and oxalate ion concentrations with different buffer solutions, dramatically slower kinetics is observed at pH 6.0 compared to pHs 3.6 and 8.6. The addition of both Mg2+ and OPN to the solution slows down kinetics appreciably. Interestingly, complete nucleation inhibition is observed at significantly lower OPN, namely, 3.2 × 10-8 M, than Mg2+ concentrations, 0.875 × 10-4 M. The observed inhibition effect of OPN emphasizes the often-overlooked role of macromolecules on COM nucleation due to their low concentration presence in urine. Moreover, analysis of growth rates calculated from observed lag times suggests that inhibition in the presence of Mg2+ cannot be explained solely on altered supersaturation. The presented study highlights the potential of microfluidics in overcoming a major challenge in nephrolithiasis research, the overwhelming physiochemical complexity of urine.

Nonphotochemical laser-induced nucleation (NPLIN) is a promising primary nucleation control method, yet its underlying mechanism remains elusive. To contribute to the discussion on whether the polarization of laser irradiation in NPLIN experiments influences the polymorphic outcome, we revisit NPLIN experiments with aqueous glycine solutions with supersaturations ranging between S = 1.5 and S = 1.7 irradiated by nanosecond pulses (∼7 ns) of near-infrared wavelength (1064 nm). Systematically altering laser light excitation properties, including the number of pulses and type of polarization, we quantified the nucleation kinetics and characterized the polymorphic form that crystallized upon laser irradiation. Due to the stochasticity of the nucleation process, a large number of samples (>100 per each experimental point) were studied under carefully controlled experimental conditions such as the ambient temperature, cooling rate, and aging period. We observed significant differences among laser-irradiated, spontaneously nucleated, and crash-cooled samples in terms of nucleation kinetics and polymorphic form. This result indicates that laser irradiation provides a different polymorph-forming pathway in comparison to crash-cooling and spontaneous nucleation. However, no clear dependence between the polymorphic form and the polarization of laser irradiation is observed. We discuss our results in the context of previous reports supported thorough quantification of sample heating in NPLIN experiments.

In this comparative study, a solid composite, AN/HTPB-based propellant was prepared by conventional processing in a mechanical mixer and by applying an advanced processing technique relying on resonant acoustic mixing (RAM). After curing of the propellants, cross-sections were prepared and characterized by scanning electron microscopy. Also the density of the propellants was measured and finally the ballistic properties were measured using chimney burner tests. The experimental results clearly showed that the oxidizer particles, the homogeneity of the propellants, the density and the burn rate properties are hardly affected by the processing method. For the propellant studied in this research, resonant acoustic mixing is a very promising, advanced processing technique that can be applied as an alternative to the conventional mechanical mixing of this high solid load propellant composition.

In the domain of energetic nanomaterials, more specifically nano-sized explosives and oxidizers, many small scale production methods have been explored up to now. So far only limited attempts have been made to scale up the production to tens or maximally a few hunderds of grams. This paper provides a review of these small scale production methods as well as characterization techniques for nanometric explosives and oxidizers. As a result of the limited scale-up, the application of energetic nanomaterials in typical propellant and explosive formulations is currently very limited. This might be caused by the fact that a clear and commonly shared view on which energetic nanomaterials and production processes it would be economically beneficial and feasible to invest in is lacking at the moment. Furthermore, a considerable number of technical challenges can be expected regarding the processing of energetic nanomaterials on a composition level. To manage these challenges, this review proposes several technical solutions which may contribute to a better understanding of the benefits, risks and costs involved in the use and scale-up of energetic nanomaterials and, if considered economically feasible, a more widespread application of these nanomaterials in the defense and space domains.

A tensile module system placed within a Scanning Electron Microscope (SEM) was utilized to conduct in-situ tensile testing of propellant samples. The tensile module system allows for real-time in-situ SEM analysis of the samples to determine the failure mechanism of the propellant material under tensile force. The focus of this study was to vary the experimental parameters of the tensile module system and analyze how they affect the failure mechanism of the samples. The experimental parameters varied included strain rate and sample temperature (-54, +25 and +40°C). Stress-strain diagrams were recorded during the in-situ tensile tests, and these results were coupled with the in-situ images and videos of the samples captured with SEM analysis. The experiments conducted at -54°C showed a different failure behavior of the propellant sample due to its rigidity at this low temperature, while experiments conducted at +25 and +40°C displayed a similar failure mechanism. For future testing using this tensile tester, special attention should be given to improved temperature control of the specimen, especially at low temperatures.

An explosive composition, derived from AFX-757, was systematically varied by using three different qualities of Class I RDX. The effect of internal defect structure of the RDX crystal on the shock sensitivity of a polymer bonded explosive is generally accepted (Doherty and Watt, 2008). Here the response to a mechanical non-shock stimulus is studied using an explosion-driven deformation test as well as the ballistic impact chamber. No correlation between RDX crystal quality and deformation sensitivity is observed. The DDT behavior (Deflagration to Detonation Transition) of the three plastic bonded explosives, although similar in composition, is distinct regarding the rate of diameter increase in the explosion-driven deformation test. Recovered polymer bonded explosive from the explosion-driven deformation test responds equally fast or slower in the ballistic impact chamber. Based on our experimental results the shear rate threshold as a single parameter describing mechanical sensitivity is challenged, and preference is given to the development of an ignition criterion based on inter-granular sliding friction under the action of a normal pressure.

When applied to a pure component suspension in an apolar solvent, a strong inhomogeneous electric field induces particle movement, and the particles are collected at the surface of one of the two electrodes. This new phenomenon was used to separately isolate two organic crystalline compounds, phenazine and caffeine, from their suspension in 1,4-dioxane. First, crystals of both compounds were collected at different electrodes under the influence of an electric field. Subsequent cooling crystallization enabled the immobilization and growth of the particles on the electrodes, which were separately collected after the experiment with purities greater than 91%. This method can be further developed into a technique for crystal separation and recovery in complex multicomponent suspensions of industrial processes.

Studying links between triacetone triperoxide (TATP) samples from crime scenes and suspects can assist in criminal investigations. Isotope ratio mass spectrometry (IRMS) and gas chromatography (GC)-IRMS were used to measure the isotopic compositions of TATP and its precursors acetone and hydrogen peroxide. In total, 31 TATP samples were synthesized with different raw material combinations and reaction conditions. For carbon, a good differentiation and a linear relationship were observed for acetone–TATP combinations. The extent of negative (δ¹³C) fractionation depended on the reaction yield. Limited enrichment was observed for the hydrogen isotope (δ²H) values of the TATP samples probably due to a constant exchange of hydrogen atoms in aqueous solution. For oxygen (δ¹⁸O), the small isotopic range and excess of water in hydrogen peroxide resulted in poor differentiation. GC-IRMS and IRMS data were comparable except for one TATP sample prepared with high acid concentration demonstrating the potential of compound-specific isotope analysis. Carbon IRMS has practical use in forensic TATP investigations.