Non-photochemical Laser-induced Nucleation Research Articles

Laser‐Induced Nucleation of Acetaminophen through the Addition of Insoluble Impurities and Acidic Polymers

AbstractThis study investigates the crystallization of acetaminophen (ACET) in ultrapure water and a 10 wt.% aqueous polyacrylic acid (PAA) solution using non‐photochemical laser‐induced nucleation (NPLIN) for the first time. Using a 532 nm nanosecond laser, two distinct crystal morphologies—rhombic and tetragonal plate‐like—are formed in both solvents after adding impurities. Notably, the PAA solution showed a reduced number of crystals and slower growth rates compared to ultrapure water, suggesting that the acidic polymer modulates crystal growth. Interestingly, crystals are not induced by the laser without impurities. However, impurities like copper phthalocyanine (CuPc) or boron carbide (CB4) enabled successful NPLIN, with CB4 showing higher nucleation efficiency than CuPc. The study also explores how laser power affects nucleation probability and identifies potential laser energy thresholds. Experimental data on ACET crystal sizes over time are fitted to derived equations, which accurately represented trends and predicted results. The nanoparticle heating mechanism and the role of acidic polymers in affecting nucleation probability and growth rate are discussed, along with potential mechanisms for changes in crystal morphology.

Effect of acidic polymers on the morphology of non-photochemical laser-induced nucleation of potassium bromide

Non-photochemical laser-induced nucleation (NPLIN) in supersaturated potassium bromide (KBr) solutions with the addition of acidic polymers is reported here for the first time. Upon absorbing the incident laser, crystallites are immediately induced along the laser pathway in the solution, eventually growing into needle-shaped crystals of varying sizes. When comparing induction time, nucleation probability, and crystal habits with spontaneous nucleation, the results suggest that NPLIN creates a distinct morphological pathway, transforming cubic crystals into needle-like structures. Additionally, it improves crystallization probability and growth rate. This paper aims to realize control from crystal nucleation to crystal growth by adding acidic polymers to the process of laser-induced nucleation, potentially influencing crystal morphology modification in NPLIN. With 19 wt% acidic polymers added to the solution as additives, control over both crystal growth and morphological modifications was observed: cubic KBr crystals with square patterns were produced through laser irradiation, and there was a varying reduction in both the number and growth rate of the crystals. The influence of acidic polymers on the solution environment was analyzed to determine the reasons for the variations in crystal quantity and growth speed. The underlying mechanisms responsible for the changes in crystal shape were also discussed.

Effect of Laser-Exposed Volume and Irradiation Position on Nonphotochemical Laser-Induced Nucleation of Potassium Chloride Solutions.

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.

Strong Enhancement of Nucleation Efficiency of Aqueous Ethylenediamine Sulfate Solutions by Nonphotochemical Laser-Induced Nucleation: Investigations on the Role of Solid Impurities in the Mechanism

Strong Enhancement of Nucleation Efficiency of Aqueous Ethylenediamine Sulfate Solutions by Nonphotochemical Laser-Induced Nucleation: Investigations on the Role of Solid Impurities in the Mechanism

Design and Validation of a Droplet-based Microfluidic System To Study Non-Photochemical Laser-Induced Nucleation of Potassium Chloride Solutions.

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.

A Review of Laser-Induced Crystallization from Solution.

Crystallization abounds in nature and industrial practice. A plethora of indispensable products ranging from agrochemicals and pharmaceuticals to battery materials are produced in crystalline form in industrial practice. Yet, our control over the crystallization process across scales, from molecular to macroscopic, is far from complete. This bottleneck not only hinders our ability to engineer the properties of crystalline products essential for maintaining our quality of life but also hampers progress toward a sustainable circular economy in resource recovery. In recent years, approaches leveraging light fields have emerged as promising alternatives to manipulate crystallization. In this review article, we classify laser-induced crystallization approaches where light-material interactions are utilized to influence crystallization phenomena according to proposed underlying mechanisms and experimental setups. We discuss nonphotochemical laser-induced nucleation, high-intensity laser-induced nucleation, laser trapping-induced crystallization, and indirect methods in detail. Throughout the review, we highlight connections among these separately evolving subfields to encourage the interdisciplinary exchange of ideas.

New Cocrystallization Method: Non-photochemical Laser-Induced Nucleation of a Cocrystal of Caffeine–Gallic Acid in Water

This paper reports for the first time the crystallization of cocrystals (caffeine–gallic acid) in water using the non-photochemical laser-induced nucleation (NPLIN) technique. The nucleation temporal control of NPLIN and the induction time reduction (70 times shorter than spontaneous nucleation) allow the obtention of cocrystals on demand, with excellent repeatability. Prior to NPLIN experiments, solubility measurements, metastable zone limit determination, and spontaneous nucleation (SN) are carried out. Supersaturated solutions at three different molarities of caffeine (0.0158, 0.0167, and 0.0179 M) are prepared and dissolved at 338 K. Supersaturated solutions are exposed to a 532 nm-wavelength nanosecond pulsed laser at 296 K. Some hours later, crystals can be filtered. The impact of supersaturation on probability of nucleation has been studied, and the result shows a higher supersaturation, which implies a higher probability of nucleation. Crystalline form characterization has employed a combination of Raman scattering, high-performance liquid chromatography, thermogravimetry, differential scanning calorimetry, and powder X-ray diffraction; the sizes of the cocrystals are too small for a single-crystal X-ray diffraction experiment. Two different cocrystal forms are obtained: a new polymorph of hemihydrate CAFGAL.0.5H2O from spontaneous nucleation by precipitation and a new hydrate form CAFGAL.1.5H2O from NPLIN and from spontaneous nucleation of a supersaturated solution without evaporation. These results open a promising way to crystallize cocrystals in the context of the pharmaceutical industry.

Potassium Sulfate: A New Candidate to Explore Non-Photochemical Laser-Induced Nucleation Mechanisms

In this paper, we report a study on the nucleation behavior of potassium sulfate (K2SO4) from aqueous solutions under the influence of unfocused nanosecond laser pulses. The objective is to contribute to the general understanding of the Non-Photochemical Laser-Induced Nucleation (NPLIN) mechanism. First, the influence of several parameters such as supersaturation as well as laser parameters (pulse energy, number of pulses, and laser polarization) on induction time, probability of nucleation and mean number of crystals in comparison with spontaneous nucleation was investigated. Then, we examined the influence of gas composition (i.e., degassing and gas bubbling (CO2 and N2)) of the supersaturated solutions on the NPLIN kinetics, showing no correlation between gas content (or nature) on the crystallization behavior. Our study questions the role of impurities within the solution regarding the mechanism of laser-induced nucleation.

Analysis of the experimental parameters impacting non-photochemical laser-induced nucleation of glycine in water

Analysis of the experimental parameters impacting non-photochemical laser-induced nucleation of glycine in water

Morphology control of laser-induced dandelion-like crystals of sodium acetate through the addition of acidic polymers

Crystal growth speeds, crystal sizes and the morphology of sodium acetate (CH3COONa) crystals in the presence of polymaleic acid and polyacrylic acid with different concentrations were investigated in supersaturated solutions of sodium acetate. The technique of non-photochemical laser-induced nucleation (NPLIN) was used to produce initial crystallites of anhydrous CH3COONa. The anhydrous CH3COONa crystal growth in solution after laser irradiation resembled the formation of dandelion seed heads. Even though NPLIN could offer temporal–spatial control of crystal nucleation without the addition of acidic polymers, the crystal growth rates were heterogeneous for crystallites along the laser pathway, which led to irregular crystalline sizes and morphologies. Here, a controllable approach from crystal nucleation to crystal growth has been designed through the addition of acidic polymers in the laser-induced growth of anhydrous CH3COONa crystals. In the presence of an acidic polymer, both the crystal growth and the morphological modification were controlled from tuft-shaped crystals to dandelion-like crystals. As bulk solid thicknesses and crystal growth speeds can be modified by different mass fractions of acidic polymer, a mathematical model was established to analyse the dynamics of crystal growth under the effect of acidic polymers. The model reproduces remarkably well the experimental trend and predicts experimental results. The changes in supersaturation and the number of nuclei through the addition of acidic polymers were analysed to investigate the underlying mechanism of morphological difference.

Effect of Acidic Polymers on the Morphology of Laser-Induced Nucleation of Cesium Chloride.

An approach to controlling morphology and size is presented through the combination of laser-induced nucleation and polymer additives. Here, we apply the technique of non-photochemical laser-induced nucleation to irradiate a supersaturated solution (S = 1.15) of cesium chloride (CsCl). The solution immediately responds to laser exposure, and spherical crystallites are produced along the laser pathway. The crystals gradually grow into snowflake-like crystals with different sizes. In this report, two types of acidic polymers including polyepoxysuccinic acid (PESA) and polyaspartic acid (PASA) were individually added in supersaturated CsCl solution to shape its crystalline morphology; we found that a particular property of this control from PESA is uniformity in modification of crystal sizes. Additionally, we observed that both PESA and PASA were able to decrease crystal growth velocity and the quantity of crystals after laser irradiation. With the effect of more than 0.2 wt % PESA in solution, spherical crystallites were initially induced by laser; after that, crystal growth velocities and sizes became slower and smaller with increase in mass fraction of PESA, which led to identical crystal sizes. With the effect of more than 5 wt % PESA, the resulting crystalline morphology obtained by laser was flower-like crystals, whilst cuboid-shaped crystals could be obtained by spontaneous nucleation. Classical nucleation theory, crystal growth rate, and additives as large-size impurities were discussed to analyze the underlying mechanism of the change in morphology.

Influence of Laser Parameters and Experimental Conditions on Nonphotochemical Laser-Induced Nucleation of Glycine Polymorphs

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 pola...

Microfluidic Laser-Induced Nucleation of Supersaturated Aqueous Glycine Solutions

A microfluidic device was designed and fabricated for non-photochemical laser-induced nucleation (NPLIN) in continuous laminar flow, which enabled real-time in situ characterization of crystal size...

Formation of thioglucoside single crystals by coherent molecular vibrational excitation using a 10-fs laser pulse

Compound crystallization is typically achieved from supersaturated solutions over time, through melting, or via sublimation. Here a new method to generate a single crystal of thioglucoside using a sub-10-fs pulse laser is presented. By focusing the laser pulse on a solution in a glass cell, a single crystal is deposited at the edge of the ceiling of the glass cell. This finding contrasts other non-photochemical laser-induced nucleation studies, which report that the nucleation sites are in the solution or at the air-solution interface, implying the present crystallization mechanism is different. Irradiation with the sub-10-fs laser pulse does not heat the solution but excites coherent molecular vibrations that evaporate the solution. Then, the evaporated solution is thought to be deposited on the glass wall. This method can form crystals even from unsaturated solutions, and the formed crystal does not include any solvent, allowing the formation of a pure crystal suitable for structural analysis, even from a minute amount of sample solution.

Non-photochemical laser-induced nucleation.

Non-photochemical laser-induced nucleation (NPLIN) is the formation of a new phase from a metastable phase by the action of light on matter. Using millijoule, nanosecond laser pulses at visible and near-infrared wavelengths, it is possible to form the new phase localized in the volume of the beam. In the case of nucleating molecular solids, the laser polarization may have an effect on the particular polymorph that is formed. Despite the huge potential for applications of NPLIN, there is uncertainty regarding the molecular-scale mechanism, and various possible scenarios may well be relevant to nucleation in general and not just NPLIN. In this Perspective, the discovery and phenomenology of NPLIN are described, putative mechanisms are outlined, and some observations on the broader class of nucleation phenomena are given.

Using optical tweezing to control phase separation and nucleation near a liquid–liquid critical point

About 20 years ago, it was shown that lasers can nucleate crystals in super-saturated solutions and might even be able to select the polymorph that crystallises. However, no theoretical model was found explaining the results and progress was slowed down. Here we show that laser-induced nucleation may be understood in terms of the harnessing of concentration fluctuations near a liquid-liquid critical point using optical tweezing in a process called laser-induced phase separation (LIPS) and LIPS and nucleation (LIPSaN). A theoretical model is presented based on the regular solution model with an added term representing optical tweezing while the dynamics are modelled using a Kramers diffusion equation, and the roles of heat diffusion and thermophoresis are evaluated. LIPS and LIPSaN experiments were carried out on a range of liquid mixtures and the results compared to theory.

Dendritic Growth of Glycine from Nonphotochemical Laser-Induced Nucleation of Supersaturated Aqueous Solutions in Agarose Gels

We have observed two new morphologies of crystalline glycine grown from supersaturated aqueous solutions in agarose gels: tree-branch dendrites that nucleate spontaneously from a solution interface...

Control over phase separation and nucleation using a laser-tweezing potential.

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is stilla poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid-liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter.

Multiparameter Investigation of Laser-Induced Nucleation of Supersaturated Aqueous KCl Solutions

Various mechanisms have been proposed to explain the nonphotochemical laser-induced nucleation (NPLIN). Identifying the dominant mechanism requires addressing a large set of experimental parameters with a statistically significant number of samples, forced by the stochastic nature of nucleation. In this study, with aqueous KCl system, we focus on the nucleation probability as a function of laser wavelength, laser intensity, and sample supersaturation, whereas the influence of filtration and the laser-induced radiation pressure on NPLIN activity is also studied. To account for the nucleation stochasticity, we used 80–100 samples. The NPLIN probability showed an increase with increasing laser intensity. The results are different from the previous report, as a supersaturation independent intensity threshold is not observed. No dependence of the NPLIN probability on the laser wavelength (355, 532, and 1064 nm) was observed. Filtration of samples reduced the nucleation probability suggesting a pronounced role ...

Effects of nanoparticle heating on the structure of a concentrated aqueous salt solution.

The effects of a rapidly heated nanoparticle on the structure of a concentrated aqueous salt solution are studied using molecular dynamics simulations. A diamond-like nanoparticle of radius 20 Å is immersed in a sodium-chloride solution at 20% above the experimental saturation concentration and equilibrated at T = 293 K and P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is observed that after 2-3 ns, the salt ions are depleted far more than water molecules from a proximal zone 15-25 Å from the nanoparticle surface. This leads to a transient reduction in molality in the proximal zone and an increase in ion clustering in the distal zone. At longer times, ions begin to diffuse back into the proximal zone. It is speculated that the formation of proximal and distal zones, and the increase in ion clustering, plays a role in the mechanism of nonphotochemical laser-induced nucleation.