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Laser diffraction analysis

Laser diffraction analysis is a widely used technique for determining the particle size distribution of powders, granules, and suspensions by measuring the angular variation in the intensity of light scattered from a laser beam as it passes through a dispersed sample of particles.^[1] The method relies on the principle that larger particles scatter light at smaller angles while smaller particles scatter at larger angles, with the scattering pattern analyzed using Mie scattering theory to calculate equivalent spherical diameters based on the sample's optical properties, such as refractive index.^[2] For particles larger than approximately 50 μm or those that are opaque, the Fraunhofer approximation can be applied as a simplification, though it is less accurate for smaller or transparent materials.^[1] This technique is standardized under ISO 13320:2020, which provides guidelines for instrument performance, validation, and reporting of results, ensuring reproducibility across wet (liquid dispersion) and dry (aerosol) measurement modes.^[3] Applications span industries including pharmaceuticals for drug formulation control, food processing for quality assurance, chemicals for material characterization, and environmental monitoring for aerosol analysis, accommodating particle sizes from submicron (0.01 μm) to several millimeters with rapid analysis times under one minute.^[4] Key advantages include its broad dynamic range, high throughput without needing calibration standards, and ability to produce volume-weighted distributions like D10, D50, and D90 percentiles, though limitations arise from the need for precise optical parameters and potential inaccuracies due to multiple scattering at high concentrations or agglomeration effects.^[1]

Introduction

Definition and Basic Principle

Laser diffraction analysis (LDA), also known as laser diffraction spectroscopy, is an ensemble technique for determining the particle size distribution (PSD) of a sample by examining the angular pattern of laser light diffracted or scattered by particles suspended in a gas or liquid medium. This method is widely used in industries such as pharmaceuticals, materials science, and food processing due to its ability to provide rapid, non-destructive measurements of polydisperse samples containing thousands to millions of particles simultaneously.^[5] The basic principle relies on the interaction of a coherent laser beam with particles, where diffraction and scattering cause the light to deviate at angles that depend on the particle dimensions. Specifically, larger particles diffract light at smaller angles with higher intensity, while smaller particles produce scattering at wider angles with lower intensity; this inverse relationship allows the intensity distribution across various angles to be inverted mathematically to yield the PSD, typically assuming particles are spherical and non-interacting.^[6] The core diffraction relation can be approximated as \theta \approx \frac{\lambda}{d}, where \theta is the scattering angle, \lambda is the laser wavelength, and d is the particle diameter, providing a conceptual link between observed angles and size without requiring detailed derivation.^[7] These patterns are interpreted using foundational models like Fraunhofer and Mie scattering theories to account for optical effects. LDA is effective for particles ranging from approximately 0.1 \mum to several millimeters, offering measurements in seconds to minutes, which makes it suitable for both laboratory and process control applications.^[8] The technique's broad dynamic range stems from the use of multiple detectors capturing low- to high-angle scattering, ensuring reliable PSD data across this scale without sample alteration.

Historical Development

The roots of laser diffraction analysis trace back to 19th-century experiments on light diffraction and scattering. In 1814, Joseph von Fraunhofer observed and mapped dark lines in the solar spectrum using prisms and slits, contributing to early spectroscopic insights, while his later invention of the diffraction grating in 1821 laid the groundwork for understanding diffraction patterns that would inform particle sizing techniques.^[9] Building on this, Lord Rayleigh published seminal papers in 1871 explaining the scattering of light by small particles, establishing the theoretical basis for how light interacts with matter much smaller than its wavelength, which enabled subsequent applications in particle characterization.^[10] The practical application of diffraction for particle sizing emerged in the 1960s, with initial proposals for using coherent light sources like lasers to measure spray droplets and powders based on angular scattering patterns. Key milestones marked the transition to commercial viability. The first commercial laser diffraction instrument was introduced by the French company CILAS in 1968, initially focused on wet suspensions for industrial applications.^[11] This was followed in 1974 by Leeds & Northrup's MICROTRAC system in the United States, which expanded capabilities to dry powders and received US Patent 3,873,206 for its rotating detector design using a helium-neon laser.^[12] During the 1970s, the adoption of Mie scattering theory gained traction as computing power improved, allowing more accurate modeling beyond the Fraunhofer approximation for smaller particles and refractive index considerations, enhancing precision in size distribution measurements.^[13] Standardization advanced with the publication of ISO 13320 in 1999, providing guidelines for measurement procedures, instrument qualification, and data reporting, which was updated in 2009 and again in 2020 (ISO 13320:2020) to incorporate advancements in optics, software, and protocols for accuracy evaluation.^[3] The evolution of laser diffraction analysis reflects ongoing innovations in hardware and computation. In the 1980s, systems shifted from exclusively wet dispersion to include robust dry powder feeding mechanisms, broadening applicability to pharmaceuticals, minerals, and aerosols, with early examples like the 1975 MICROTRAC Model 7991 demonstrating dry measurement feasibility.^[12] The 1990s saw integration of advanced computational Mie modeling, enabled by personal computers, which permitted full Mie solutions for complex refractive indices and non-spherical effects, improving accuracy for submicron particles.^[14] Post-2010 advancements include hybrid systems combining laser diffraction with dynamic imaging for better handling of non-spherical particles, such as the 2018 Microtrac SYNC analyzer, which merges size and shape analysis to address limitations in traditional diffraction for irregular morphologies; further developments as of 2025 incorporate AI-assisted data processing for enhanced precision.^[12]

Theoretical Foundations

Fraunhofer Approximation

The Fraunhofer approximation provides a simplified model for interpreting the far-field diffraction patterns generated by particles in laser diffraction analysis, particularly suited to larger particles where wave optics effects are dominated by diffraction rather than interference from internal refractions. This approach treats the particle as an opaque circular obstacle that diffracts an incident plane wave, yielding an angular intensity distribution that inversely correlates with particle size—larger particles produce diffraction at smaller angles. It forms the basis for early particle sizing methods and remains computationally efficient for approximate calculations in certain regimes. The approximation is applicable when the particle diameter d is much larger than the light wavelength \lambda, typically d > 10\lambda (e.g., for visible light around 0.5–0.6 \mum, this corresponds to particles larger than about 5–6 \mum), and under far-field conditions where the detector distance r greatly exceeds d^2 / \lambda. These conditions ensure that the observation plane receives effectively plane wavefronts from the diffracted light, and the model neglects refraction, absorption, and phase shifts within the particle, assuming it behaves as a purely diffracting disk.^[15]^[16] The mathematical foundation rests on the Huygens-Fresnel principle, which describes wave propagation as the superposition of secondary spherical wavelets emanating from each point on the incident wavefront obstructed by the particle. In the Fraunhofer limit, the quadratic phase variation across the aperture (Fresnel term) is negligible due to the large distance, simplifying the diffraction integral to a Fourier transform of the particle's projected aperture function—a uniform disk of radius a = d/2. The scattered electric field amplitude E(\theta) at scattering angle \theta (small angles, \sin\theta \approx \theta) is then

E(\theta) = \frac{i A e^{i k r}}{\lambda r} \int_0^{2\pi} \int_0^a \exp\left[i k \rho \theta \cos\phi \right] \rho \, d\rho \, d\phi,

where A = \pi a^2 is the projected area, k = 2\pi / \lambda is the wavenumber, \rho and \phi are polar coordinates over the disk, and the integral assumes unit incident field amplitude. The angular integral yields $2\pi J_0(k a \theta \rho) (Bessel function of order zero), and integrating over \rho gives the closed form E(\theta) = \frac{A e^{i k r}}{\lambda r} \cdot \frac{2 J_1(k a \sin\theta)}{k a \sin\theta}, where J_1 is the first-order Bessel function of the first kind. The scattering amplitude is proportional to the particle circumference because the edge diffraction dominates the far-field pattern, with the transform scaling linearly with the boundary length in the high-frequency limit. The resulting intensity distribution is

I(\theta) = I_0 \frac{A^2}{\lambda^2 r^2} \left[ \frac{2 J_1(k a \sin\theta)}{k a \sin\theta} \right]^2,

with I_0 the incident intensity at the particle; this Airy-like pattern features a central maximum narrowing with increasing a, enabling size estimation from the angular width.^[17]^[18] This model's advantages include its computational simplicity, as the analytical form avoids numerical integration of full wave equations, and it establishes a direct inverse relationship between diffraction angle and particle size (\theta \propto 1/d), facilitating rapid inversion for size distributions in polydisperse samples. It was employed in early laser diffraction instruments developed in the 1970s for applications like spray droplet sizing. However, limitations arise for smaller particles (d \lesssim 10\lambda) where near-field effects or Mie resonances become significant, and for particles with low refractive index contrasts (e.g., transparent materials in similar media), as the model overestimates scattering by ignoring internal refractions.^[15]^[18]^[16]

Mie Scattering Theory

Mie scattering theory provides an exact solution to Maxwell's equations for the scattering of electromagnetic waves by homogeneous, spherical particles of arbitrary size relative to the wavelength.^[14] This model comprehensively accounts for diffraction, refraction, reflection, and absorption effects, making it particularly suitable for laser diffraction analysis (LDA) where particles may be transparent or comparable in size to the laser wavelength.^[19] Unlike approximations, Mie theory requires knowledge of the complex refractive index m = n + i k of the particle material relative to the medium, as well as the incident wavelength, to predict the scattered light intensity accurately.^[16] The mathematical foundation of Mie theory involves expanding the incident, internal, and scattered electric and magnetic fields in series of vector spherical harmonics, leading to boundary conditions that yield the Mie coefficients a_n and b_n for each partial wave of order n.^[20] These coefficients determine the amplitude of the scattered fields. The scattering efficiency Q_\text{sca}, which quantifies the fraction of incident light scattered by a single particle, is given by

Q_\text{sca} = \frac{2}{k^2 a^2} \sum_{n=1}^\infty (2n+1) \left( |a_n|^2 + |b_n|^2 \right),

where k = 2\pi / \lambda is the wavenumber, a is the particle radius, and the sum converges rapidly for most practical size parameters x = k a.^[20] The angular distribution of scattered intensity is derived from the scattering amplitude functions S_1(\theta) and S_2(\theta), expressed as infinite series involving the Mie coefficients and Riccati-Bessel functions; the phase function p(\theta), normalized such that \int_0^\pi p(\theta) \sin\theta \, d\theta = 2, describes the angular scattering pattern I(\theta) \propto |S_1(\theta)|^2 \cos^2\phi + |S_2(\theta)|^2 \sin^2\phi for unpolarized light.^[21] In LDA instrumentation, Mie theory is implemented through numerical software that computes theoretical scattering patterns for an assumed particle size distribution (PSD) by integrating over the contributions from particles of various sizes, weighted by their volume fraction.^[22] Modern systems employ iterative algorithms to fit these modeled patterns to the experimentally measured angular intensity data, enabling accurate PSD retrieval across a wide range (typically 0.01–3000 μm).^[19] This approach significantly improves accuracy over the Fraunhofer approximation—particularly for sub-micron particles—by properly accounting for refractive effects, serving as the limiting case of Mie theory for large, opaque particles (x \gg 1, |m| \gg 1).^[16] Accurate application of Mie theory in LDA demands precise input of the real part n (related to refraction) and imaginary part k (related to absorption) of the refractive index, often obtained from literature or independent measurements.^[23] Sensitivity to these parameters is high; small errors in n can significantly affect the derived particle sizes, especially for particles near 1 μm, underscoring the need for material-specific validation.^[24]

Instrumentation

Optical Configuration

The optical configuration of laser diffraction instruments centers on a coherent laser source that generates a monochromatic beam, typically a helium-neon (He-Ne) laser operating at 633 nm with a power output around 4 mW, to ensure stable and uniform illumination of the sample. This beam is expanded and collimated using spatial filters and lenses to form a parallel, uniform profile with a width of 10-20 mm, minimizing edge effects and providing consistent particle illumination across the measurement zone. The sample cell, positioned at the focal point of the system, introduces the dispersed particles into the beam path; for wet dispersion, it employs a flow-through cell with ultrasonic agitation to maintain suspension in liquid media, while dry dispersion uses a vibratory or compressed air system to aerosolize powders, both ensuring non-agglomerated and representative sampling without altering the optical path.^[23]^[25] Key optical components include a Fourier transform lens, which focuses the scattered light and converts the angular scattering pattern into a spatial intensity distribution on the detector plane, enabling direct correlation between scattering angle and particle size per the Fraunhofer approximation.^[26] A beam splitter is often integrated to divert a portion of the incident beam for real-time alignment monitoring, maintaining beam stability and position. Auto-alignment mechanisms, such as auxiliary lasers and trap detectors, adjust the optics dynamically to compensate for vibrations or drifts, ensuring measurement precision as outlined in ISO 13320:2020 guidelines, including new protocols for instrument qualification.^[3] Instrument variations extend the measurable size range beyond the standard 0.1 µm to 3 mm by employing single-lens systems for routine applications or multiple-lens configurations with converging optics to handle larger particles exceeding 1 mm, where low-angle scattering dominates.^[3]^[23] These adaptations adhere to ISO 13320:2020 standards for optical setup, focusing scattered light efficiently without introducing aberrations, and incorporate updated accuracy evaluation methods.^[3]

Detection and Data Acquisition Systems

In laser diffraction instruments, the detection system captures the spatial intensity pattern of scattered light generated from the interaction of the laser beam with particles, as produced by the upstream optical configuration. The primary detectors are multi-element silicon photodiode arrays, typically consisting of 32 to 126 channels arranged in logarithmic angular segments to cover scattering angles from approximately 0.02° to 35° or more, enabling precise measurement of light intensity across a wide dynamic range.^[3]^[5] These arrays, often positioned in the focal plane of a Fourier lens, use individual photodiodes to detect photocurrents proportional to the scattered light flux at each angular position, with forward-scattering detectors handling small-angle diffraction from larger particles and additional wide-angle or back-scattering elements addressing contributions from finer particles.^[3]^[27] Signal processing begins with the conversion of analog photocurrents from the photodiode arrays into digital signals via high-speed analog-to-digital converters (ADCs), operating at sampling rates in the kHz range to capture transient scattering events.^[5] Real-time averaging of multiple measurement scans—often over 30 to 90 seconds—reduces noise from particle fluctuations and environmental interference, producing a smoothed intensity profile.^[27] This initial processing occurs at the hardware level, ensuring low-latency data handling suitable for both wet and dry dispersion systems. The output from the data acquisition system is a raw scattering pattern represented as intensity versus scattering angle or detector channel, with typical resolutions of 50 to 100 data points per measurement, providing the foundational dataset for subsequent analysis.^[3] These patterns reflect the angular distribution of scattered light, where higher intensities at smaller angles indicate larger particles and vice versa. Calibration of the detection system involves using certified reference materials, such as monodisperse polystyrene spheres, to verify the mapping of detector channels to specific scattering angles and to ensure alignment accuracy within 1-2 microns.^[3] This process adheres to ISO 13320:2020 guidelines, which recommend periodic verification using traceable standards to maintain instrument performance across the 0.1 µm to 3 mm particle size range and include enhanced protocols for accuracy assessment.^[3] Advancements in detection technology include the integration of charge-coupled device (CCD) cameras alongside traditional photodiode arrays, allowing for simultaneous wide-angle capture and optional image-based validation of particle morphology in hybrid systems.^[28] This enhances resolution for complex samples by combining diffraction data with visual inspection, though CCDs are primarily supplementary to the core multi-element arrays.

Measurement Procedure

Sample Preparation and Dispersion

Sample preparation and dispersion are critical steps in laser diffraction analysis to ensure that the particle sample is representative and free from agglomerates, as inadequate dispersion can lead to overestimated particle sizes and unreliable distributions.^[29] The goal is to de-agglomerate particles without fracturing them or altering their morphology, thereby achieving a stable suspension or aerosol that mimics the primary particle state.^[30] Poor preparation often results from insufficient energy input or incompatible dispersants, which can cause multiple scattering events or sedimentation during measurement.^[31] Wet dispersion is commonly used for particles across a broad size range, involving dilution of the sample in a suitable liquid dispersant to form a stable suspension. Typical dispersants include water with added surfactants (e.g., sodium hexametaphosphate at 0.1-0.5% concentration) for aqueous systems or organic solvents like ethanol for hydrophobic materials, selected based on the sample's chemical compatibility to prevent dissolution or flocculation.^[29] Mechanical aids such as stirring (up to 3000 rpm) or ultrasonic baths (operating at 20-40 kHz, often 40 kHz with 50-200 W power for 1-5 minutes) are applied to break aggregates, ensuring low viscosity (<10 cP or mPa·s) for proper circulation in the measurement cell.^[32] The suspension concentration is adjusted to achieve an obscuration of 8-12% (typically 5-10% for particles 1-100 μm), corresponding to a volume fraction of 0.1-1% and a sample volume of 10-50 mL, which optimizes signal-to-noise ratio while avoiding multiple scattering.^[31] Dry dispersion suits non-cohesive powders, particularly for particles larger than 1 μm, where the sample is aerosolized without liquid to avoid potential agglomeration upon drying. Powder is fed via a venturi injector or vibratory rod feeder at rates of 0.1-1 g per measurement, with compressed air (0.5-4 bar pressure) generating shear forces to disperse aggregates without excessive fragmentation.^[33] Optimal pressure is determined by titration, starting low (e.g., 0.5 bar) and increasing until results stabilize, often matching wet dispersion outcomes for validation.^[29] This method is ideal for hygroscopic or heat-sensitive materials but requires careful control to minimize satellite droplets or uneven flow. Key challenges in dispersion include applying sufficient shear to de-agglomerate without breaking fragile particles, especially for cohesive fines below 10 μm, and selecting dispersants that match the material's surface chemistry (e.g., non-polar solvents for organics to reduce adhesion).^[29] Overly aggressive ultrasonication can fracture particles, leading to finer distributions, while insufficient energy leaves clusters that bias results toward larger sizes.^[30] Guidelines from ISO 13320 ensure reproducibility by specifying protocols for sample inspection, dispersant selection, and concentration control, recommending reference materials for method validation and tolerances such as ±3% for D10 repeatability in wet methods. Typical sample amounts are 0.1-1 g for dry powders or 0.1-1% volume fractions in wet suspensions, with documentation of all preparation parameters essential for traceability.^[30]

Scanning and Measurement Process

The scanning and measurement process in laser diffraction analysis begins with the introduction of the prepared sample into the instrument's measurement cell, ensuring it is adequately dispersed to avoid agglomeration or settling. For wet dispersions, the sample is typically loaded into a liquid module where a circulation pump or stirrer initiates flow to maintain homogeneity, while dry powders are introduced via a vibration or dispersion unit to aerosolize the particles into a gas stream. This step relies on prior sample preparation to achieve the appropriate concentration, as undispersed samples can lead to erroneous scattering patterns.^[27]^[34] Prior to scanning, the instrument performs an alignment check to verify the laser beam's positioning relative to the detectors and lenses, often automatically adjusting to within 1-2 microns to ensure accurate light path integrity; any misalignment triggers error flags to prevent invalid data collection. A background measurement is then conducted with no sample present to establish baseline scattering levels. Once aligned, the laser beam illuminates the sample continuously, capturing the angular distribution of scattered light over an integration period of typically 10 to 90 seconds per scan, depending on the system and whether polarization intensity differential scattering (PIDS) is enabled for finer particles.^[27]^[35]^[34] Obscuration, defined as the percentage of incident laser light attenuated by the sample (typically targeted at 8-12% for wet measurements and 4-8% for dry to optimize signal-to-noise ratio), is monitored in real-time; the system may auto-adjust flow rates or prompt dilution/addition if levels fall outside 4-20%, ensuring reliable diffraction patterns without multiple scattering interference. Measurements can operate in single-point mode for rapid concentration checks or full-range mode for comprehensive particle size distribution (PSD) data across 0.1 µm to 3 mm, with wet protocols using liquid dispersants and dry modes employing gas dispersion for powders. To enhance statistical reliability, 3-5 replicate scans are commonly performed and averaged, capturing raw intensity data at multiple detector angles.^[27]^[35]^[34] The entire process per sample, from loading to raw data capture, typically lasts 1-5 minutes, enabling high throughput of over 100 measurements per hour in automated configurations, though exact duration varies with integration time and replicates. This efficiency stems from the continuous laser scanning and rapid detector acquisition, concluding with the storage of unprocessed scattering pattern files for subsequent analysis.^[35]^[27]^[34]

Data Analysis

Particle Size Distribution Derivation

The derivation of particle size distribution (PSD) in laser diffraction analysis involves an inversion process that transforms the measured angular scattering intensity pattern into a volumetric distribution of particle sizes. This is achieved through nonlinear least-squares fitting, where the observed scattering data is compared to theoretical patterns generated using the Mie or Fraunhofer model. The process assumes a log-normal or user-defined PSD form and iteratively optimizes the volume fractions of discrete particle size classes to minimize the residual between measured and predicted intensities.^[36]^[34] Key steps begin with inputting the refractive index of the particles and dispersant, which is essential for accurate Mie theory application as the model for pattern generation. Theoretical scattering patterns are then computed for a series of discrete size bins, typically around 100 bins logarithmically spaced from 0.01 to 3000 μm, forming a model matrix that relates size classes to detector responses. Volume fractions for these bins are optimized via iterative algorithms, such as non-negative least-squares, to solve the inverse problem and fit the experimental data.^[16]^[36]^[34] The output is a volume-weighted PSD, often expressed as \frac{dV}{d(\log d)}, where V is the volume fraction and d is the particle diameter, providing a cumulative or density curve across the size range. Common metrics include percentiles such as D10 (10% undersize), D50 (median), and D90 (90% undersize), along with the span calculated as \frac{D90 - D10}{D50} to quantify distribution width. These metrics are standardized for reporting equivalent spherical diameters.^[34] Proprietary software in commercial systems, such as those from Malvern Panalytical or Beckman Coulter, automates the computation, employing algorithms that ensure convergence when residuals fall below 1%. The method assumes particles are spherical and optically homogeneous, with validation typically performed using monodisperse standards like polystyrene latex spheres to confirm accuracy.^[16]^[37]^[34]

Validation and Quality Assurance

Validation of laser diffraction analysis involves the use of certified reference materials to verify the accuracy of particle size distribution measurements. For instance, NIST Standard Reference Material (SRM) 1004b, consisting of borosilicate glass spheres with certified diameters ranging from 38.5 μm to 148.4 μm, is commonly employed to calibrate instruments and assess performance.^[38] Measured values, such as the median diameter (D50), are compared to certified values, with acceptable tolerances typically within ±1.5% for instrument accuracy and ±2.5% for method repeatability to ensure reliability.^[30] Key quality metrics for ensuring reproducibility and data integrity include relative standard deviation (RSD) for critical parameters like D50, which should be less than 3% across multiple measurements under identical conditions.^[30] Additionally, chi-squared goodness-of-fit tests are applied during data inversion to evaluate how well the scattering model matches the observed diffraction pattern, with values close to 1 indicating a good fit.^[39] Obscuration stability, monitored during measurements to maintain consistent laser attenuation (typically 10-20%), serves as another indicator of measurement quality, preventing artifacts from unstable sample dispersion.^[40] Common error sources in laser diffraction include multiple scattering at high particle concentrations, which distorts the diffraction pattern and overestimates smaller sizes; this is mitigated by sample dilution to achieve optical transmission above 10%.^[41] Non-sphericity of particles introduces bias, as the method assumes spherical shapes, potentially leading to significant errors in reported sizes for highly irregular forms.^[34] Compliance with international standards is essential for robust validation. ISO 13320 (2020 edition) outlines protocols for reporting measurement uncertainty, including contributions from instrument calibration and sample variability, and recommends instrument qualification through Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) to confirm operational integrity.^[3]^[30] Recent practices emphasize software audits to verify algorithmic compliance with standards like 21 CFR Part 11 for data integrity in regulated environments.^[42] Inter-laboratory comparisons, such as those conducted on fine powders, demonstrate reproducibility across instruments, with standard deviations for D50 ranging from 4% to 21% for particles larger than 1 μm.^[43] Hybrid validation combining laser diffraction with microscopy addresses shape-related effects, providing orthogonal confirmation of size distributions.^[44]

Applications

Industrial and Pharmaceutical Uses

In the pharmaceutical industry, laser diffraction analysis is widely employed for particle size distribution (PSD) control during drug formulation to ensure product efficacy and consistency. For inhalers and nasal sprays, it measures aerosol droplet sizes, where a median diameter (D50) of 1-5 μm is critical for optimal lung deposition and bioavailability, as particles in this range effectively reach the respiratory tract without excessive settling or impaction.^[45]^[46] In tablet manufacturing, it assesses active pharmaceutical ingredient (API) PSD to optimize dissolution rates and prevent issues like content non-uniformity during compression.^[29] This technique complies with regulatory standards such as United States Pharmacopeia (USP) General Chapter <429>, which outlines light diffraction methods for accurate PSD measurement in drug products, supporting quality control and batch release.^[47] A key application in tablet production involves monitoring API particle size to mitigate segregation, where differences in particle dimensions cause uneven blending and lead to dosage variability; laser diffraction enables real-time adjustments to maintain homogeneity during direct compression.^[48]^[49] In industrial materials processing, laser diffraction determines aggregate sizing in cement and minerals, influencing concrete strength and workability by quantifying PSD to meet specifications for fineness and uniformity.^[50]^[51] For pigments and coatings, it evaluates particle uniformity to enhance opacity and coverage, as consistent submicron to micron-sized distributions prevent defects like mottling in paints and inks.^[52] The food industry utilizes laser diffraction for emulsion droplet sizing, such as measuring milk fat globules (typically 0.1-10 μm) to assess stability, texture, and flavor release in dairy products like cream and yogurt.^[53]^[54] It also supports powder flowability assessment in milling processes, where PSD data guides optimization to reduce clumping and improve handling of ingredients like flour or sugar.^[55] Process integration benefits from laser diffraction's measurement speed, enabling high-throughput industrial operations through in-line monitoring. In chemical reactors and spray drying, it provides real-time PSD feedback to control crystallization and drying parameters, ensuring product quality without halting production.^[56]^[57]^[58]

Scientific and Environmental Applications

In scientific research, laser diffraction analysis plays a crucial role in characterizing nanomaterials, particularly nanoparticles dispersed in colloidal systems. This technique enables the measurement of particle size distributions (PSDs) across a wide range, from submicron to multimicron scales, which is essential for understanding colloidal stability and behavior in applications such as drug delivery and material synthesis. For instance, studies on multimodal colloidal dispersions have demonstrated that laser diffraction provides accurate PSDs by analyzing light scattering patterns, allowing researchers to resolve overlapping size populations that are challenging for other methods.^[59] Similarly, in aerosol studies for climate modeling, laser diffraction is used to determine the PSD of volcanic ash particles, which influence atmospheric radiative forcing and global temperature variations. Analysis of ash from eruptions like Eyjafjallajökull has shown fine particle fractions (below 10 μm) that can remain suspended for weeks, affecting cloud formation and solar radiation scattering.^[60]^[61] Environmental monitoring leverages laser diffraction for assessing water quality through the analysis of suspended sediments in rivers, where PSDs inform sediment transport dynamics and pollutant binding. In-stream deployments of laser diffraction instruments, such as the LISST series, have quantified sediment concentrations and sizes in rivers in the United States, revealing how fine particles (2-63 μm) contribute to turbidity and habitat degradation during high-flow events.^[62] For air pollution, the method sizes particulate matter fractions like PM2.5 and PM10 in emissions, aiding in source attribution and health risk evaluation. Research on urban aerosols has employed laser diffraction to differentiate emission profiles from industrial sources, showing PM10 distributions dominated by coarse particles (up to 10 μm) that settle rapidly, while PM2.5 persists longer in the atmosphere.^[63] In biological applications, laser diffraction facilitates pollen grain analysis by providing high-throughput PSD measurements, essential for taxonomic studies and aerobiology. For Cedrus atlantica pollen, the technique has quantified grain sizes around 50-60 μm with variability linked to environmental factors, correlating strongly with microscopic observations.^[64] It also supports cell analysis in suspensions, where PSDs help assess aggregate formation in microbial cultures. Soil particle distribution studies using laser diffraction evaluate erosion potential by modeling aggregate stability; repeated measurements during dispersion reveal disintegration kinetics, with finer fractions (<2 μm) indicating higher erosion risk in agricultural fields.^[65]^[66] Advanced in situ applications include oceanographic profiling for plankton sizing via submersible laser diffraction devices, which capture real-time PSDs of marine particles during blooms. In the Northwestern Mediterranean, combined laser diffraction and transmissometry have mapped nanophytoplankton sizes (2-20 μm), linking distributions to primary productivity and carbon flux.^[67] Forensic science employs laser diffraction for particle matching in soil evidence, where PSDs of the <63 μm fraction distinguish provenance based on textural signatures from crime scenes.^[68]

Comparisons

With Dynamic Light Scattering

Laser diffraction analysis (LDA) and dynamic light scattering (DLS) are both optical techniques for particle size characterization, but they differ fundamentally in their measurement principles. LDA relies on the static scattering of laser light, where the angular distribution of diffracted light is analyzed to determine particle size based on the inverse relationship between particle diameter and scattering angle, often using Mie or Fraunhofer theory. In contrast, DLS measures the dynamic fluctuations in scattered light intensity caused by Brownian motion of particles in suspension, deriving size from the diffusion coefficient via the Stokes-Einstein equation.^[39] These principles make LDA suitable for ensemble measurements of static patterns, while DLS captures temporal variations sensitive to particle mobility.^[69] The measurable size ranges of the two techniques also diverge significantly, reflecting their complementary applications. LDA typically covers a broad spectrum from approximately 10 nm to 3.5 mm, excelling in the micron to millimeter regime for polydisperse samples.^[70] DLS, however, is optimized for smaller particles, ranging from 1 nm to about 10 μm, with optimal performance below 1 μm for monodisperse or low-polydispersity systems.^[71] LDA's wider range supports analysis of bulk materials like powders, but it assumes particle sphericity and known optical properties, potentially introducing errors for non-spherical or highly irregular particles. DLS is more sensitive to nanoscale features and aggregation but requires dilute liquid suspensions to avoid multiple scattering and is prone to inaccuracies in polydisperse samples where larger particles dominate the signal.^[69] In terms of strengths, LDA offers faster measurement times and robustness for dry or concentrated dispersions, making it ideal for industrial quality control of bulk powders in pharmaceuticals and materials.^[71] DLS provides higher sensitivity for detecting small contaminants or protein aggregates in solutions, often requiring only microliters of sample, though it demands careful preparation to mitigate sedimentation or viscosity effects.^[70] Regarding accuracy, LDA yields volume-weighted particle size distributions, emphasizing larger particles by mass, whereas DLS produces intensity-weighted distributions, which over-represent larger species due to their stronger scattering; conversions between these weightings are necessary for direct comparisons, and discrepancies of 10-20% are common even for spherical particles.^[39] Overall, the techniques are often used complementarily: DLS for nanoscale and solution-based analyses (e.g., nanoparticles or biologics), and LDA for micrometer-scale powders (e.g., excipients in drug formulation), enabling comprehensive characterization across size scales.

With Sedimentation and Sieving Methods

Laser diffraction analysis (LDA) differs fundamentally from sedimentation and sieving methods in its measurement principles. LDA is an optical technique that assesses particle size by analyzing the diffraction pattern produced when a laser beam interacts with the entire ensemble of particles in a sample, providing a volume-based particle size distribution without physical separation.^[5] In contrast, sedimentation relies on gravitational settling governed by Stokes' law, where particle size is inferred from the velocity at which particles of known density settle through a liquid medium, typically measuring cumulative mass distributions.^[72] Sieving, a mechanical method, determines particle size through physical screening via stacked meshes of varying aperture sizes, yielding a mass-based distribution for discrete fractions.^[73] The applicable size ranges for these techniques vary significantly, influencing their suitability for different materials. LDA covers a broad spectrum from approximately 0.1 μm to 3 mm, enabling analysis of both fine and coarse particles in a single measurement.^[3] Sedimentation is effective for particles between 0.5 μm and 100 μm but becomes inefficient for finer sizes due to prolonged settling times and for coarser particles due to rapid sedimentation.^[72] Sieving excels with coarser materials, typically from 20 μm to 10 cm, but lacks precision below 20 μm where particles may pass through apertures irregularly or clog meshes.^[74] Each method offers distinct strengths and weaknesses relative to LDA. LDA provides rapid, non-destructive analysis of the whole sample but can be sensitive to particle shape, as it assumes spherical equivalents that may overestimate sizes for irregular forms.^[73] Sedimentation delivers high accuracy for particles with significant density contrasts to the suspending fluid, making it reliable for density-based separations, though it is time-consuming—often requiring hours or days—and limited to dilute suspensions to avoid interactions.^[75] Sieving is straightforward, cost-effective, and requires minimal sample preparation, ideal for bulk coarse materials, but it is labor-intensive, prone to operator variability, and imprecise for fine particles due to agglomeration or incomplete separation.^[76] In practice, these methods serve complementary use cases, with LDA often supplanting others for efficiency. LDA is preferred for quick quality control in industries handling polydisperse powders, such as pharmaceuticals and chemicals, where real-time feedback is essential.^[5] Sedimentation remains valuable for analyzing fine clays and soils in geotechnical applications, where precise density-driven fractionation is needed.^[77] Sieving suits aggregate characterization in construction and mining, providing robust data for large samples of gravel or sand.^[73] LDA frequently validates sieving results for coarser fractions in hybrid workflows, enhancing overall accuracy without full replacement.^[78] Correlations between LDA and these methods are generally strong for particles larger than 10 μm, where volume-based LDA outputs align well with mass-based sedimentation or sieving distributions, often showing R² values exceeding 0.9 in comparative studies.^[79] However, discrepancies arise below 10 μm, attributed to LDA's diffraction bias toward larger apparent sizes for non-spherical fines, leading to underestimation of clay content compared to sedimentation.^[80] Sieving-LDA agreement holds for spherical or semi-spherical particles above 50 μm but diverges for irregular shapes due to differing equivalent diameter definitions.^[73]

Limitations

Theoretical Assumptions and Errors

Laser diffraction analysis relies on several foundational assumptions that underpin the Mie and Fraunhofer scattering theories used to interpret diffraction patterns and derive particle size distributions (PSDs). A primary assumption is that particles are spherical, which simplifies the mathematical modeling of light scattering but introduces systematic bias when applied to non-spherical morphologies such as rods or fibers, where reported sizes can result in up to 20% overestimation due to orientation effects and altered scattering patterns.^[81] Another key assumption is isotropic scattering, implying uniform light interaction regardless of particle orientation, which holds reasonably for random suspensions but fails for anisotropic particles, exacerbating size estimation errors. Additionally, the theory assumes single scattering events, where light interacts with only one particle before detection; violations occur at high concentrations, leading to multiple scattering errors when obscuration exceeds 15%, resulting in underestimation of particle sizes by distorting the forward-scattering profile.^[82]^[83] Refractive index (RI) assumptions further compound potential inaccuracies, as Mie theory—the preferred model for broad size ranges—requires precise knowledge of the complex RI (real and imaginary parts) for both particles and the dispersing medium. Unknown or complex RIs, common in heterogeneous or absorbing materials, can propagate to 5-15% errors in PSDs, particularly for particles below 10 µm, because mismatched values alter the inversion of scattering data to size equivalents.^[84] For opaque particles with significant absorption (non-zero imaginary RI), this leads to additional deviations, as the theory overemphasizes diffraction over refraction and reflection, skewing fine-particle fractions. Absorption effects are especially pronounced in pigmented or metallic samples, where even small RI uncertainties amplify size biases.^[81] Theory-specific limitations highlight further vulnerabilities. The Fraunhofer approximation, valid for large particles (>25-50 µm) where diffraction dominates, underestimates small-particle fractions by up to 20-35% in the sub-micron range, as it neglects wave optics and refraction, treating particles as opaque disks without RI input.^[16]^[85] In contrast, Mie theory, while more comprehensive for particles across 0.1-1000 µm, over-relies on accurate RI values; deviations here can shift Dv50, particularly when absorption is unaccounted for, as the full electromagnetic solution becomes sensitive to optical parameters.^[86] Error quantification in laser diffraction involves uncertainty propagation from input parameters like RI, concentration, and model choice, often assessed via ISO 13320 guidelines for validated systems. Typical PSD errors range from 5-10% for Dv50 in well-characterized spherical samples, but can exceed 15% with non-spherical shapes or multiple scattering, where propagation models show sensitivity coefficients amplifying RI errors by factors of 2-5 for fine fractions.^[3]^[81] For instance, obscuration beyond 20% introduces multiple scattering biases that propagate to 5% or greater size underestimation, while spherical assumption violations yield bimodal artifacts in PSDs for fibrous materials.^[83] Mitigation strategies address these assumptions through software and empirical adjustments. Modern instruments incorporate shape factors, such as sphericity ratios (surface area of particle to equivalent sphere), to correct Mie inversions for known morphologies, reducing bias by 10-30% for mildly non-spherical particles like aggregates.^[81] Empirical corrections, derived from calibration with shape-specific standards, further refine PSDs for rods or fibers by applying orientation-averaged models, though full accuracy requires complementary techniques like microscopy for validation.^[27] Optimal obscuration (8-12%) and RI sensitivity analyses in software help propagate uncertainties transparently, ensuring errors remain below 10% for routine applications.^[86]

Practical Challenges and Instrument Variability

One major practical challenge in laser diffraction analysis arises from dispersion issues, where incomplete de-agglomeration of particle clusters can lead to artificial bimodal distributions in the measured size profile, misrepresenting the true primary particle sizes.^[87] This occurs particularly in dry dispersion modes, as insufficient energy input during sample preparation fails to break down agglomerates effectively, while excessive shear forces can cause breakage in fragile materials like certain pharmaceutical powders or biological samples, resulting in overly fine size fractions.^[29] To mitigate these, optimized dispersion protocols, such as controlled ultrasonic or mechanical agitation, are essential, though they require material-specific tuning to balance de-agglomeration without inducing damage.^[88] Sample-related problems further complicate measurements, as high-density particles, such as metal oxides or dense minerals, can settle rapidly in the flow cell, leading to uneven sampling and biased results toward larger sizes.^[89] Similarly, sticky or cohesive particles, common in organic or polymer-based materials, often clog the measurement cell or tubing, interrupting the analysis and necessitating frequent cleaning or dilution adjustments.^[41] Low sample concentrations exacerbate signal-to-noise ratios, producing noisy data with poor obscuration levels below 5-10%, while overly high concentrations trigger multiple scattering events that distort the diffraction pattern and overestimate finer fractions.^[41] Instrument variability introduces additional inconsistencies across devices from different manufacturers, primarily due to differences in optical configurations, such as lens array designs that influence angular resolution and the minimum detectable particle size.^[90] For instance, systems with wider-angle detectors may better resolve sub-micron particles but exhibit reduced sensitivity for larger ones compared to narrower-field designs. Calibration drift over time, caused by laser source degradation or detector alignment shifts, necessitates annual requalification using certified reference materials to maintain accuracy within ISO-specified tolerances.^[44] Environmental factors also impact instrument performance, with fluctuations in temperature and humidity altering laser stability and refractive index assumptions in the dispersion medium, potentially shifting measured size distributions by up to 5-10% in sensitive setups.^[91] Portable units are particularly susceptible to vibrations from ambient sources, which can introduce artifacts in the scattering pattern, emphasizing the need for stable mounting or isolation in field applications.^[92] Recent critiques highlight inter-laboratory reproducibility challenges, where ISO 13320:2020 targets repeatability below 5% coefficient of variation for key metrics like D50, due to inconsistent dispersion pressures in dry modes compared to more stable wet modes.^[30] Post-2020 updates to the standard have prompted calls for enhanced standardized reporting, including detailed dispersion parameters and environmental controls, to improve comparability across labs and reduce method-induced discrepancies.^[3]

References

[1]
None
### Summary of Laser Diffraction Particle Size Analysis
[2]
[PDF] Particle Size Analysis by Laser Diffraction Spectrometry:Application ...
In the wet method, the powder sample must first be dispersed into a non-reactive liquid carrier such as alcohol. This can be achieved by various chemical and/or ...
[3]
[PDF] Principles, Methods, and Application of Particle Size Analysis
✓ Zeta potential is measured using a forward angle of detection; therefore, the laser beam must pass through the entire sample. ✓ Too high a concentration and ...Missing: definition | Show results with:definition
[4]
Laser Diffraction for Particle Size Analysis - Beckman Coulter
Laser diffraction measurements capture information about particle size distribution by measuring scattering intensity as a function of the scattering angle, ...
[5]
Laser diffraction for particle sizing - Anton Paar Wiki
It is based on the observation that the angle of (laser) light diffracted by a particle corresponds to the size of the particle.
[6]
A Guide to Understanding Laser Diffraction Principles + Theory
Aug 19, 2019 · Laser diffraction is highly effective for particle size analysis. Learn how it works, the key theories, and the best scientific instruments ...
[7]
Particle Size Analysis - An Explanation - Malvern Panalytical
Size range: 0.01 - 3500µm · Laser diffraction.
[8]
Joseph von Fraunhofer (1787–1826) | High Altitude Observatory
Well versed in the mathematical wave theory of light, Fraunhofer used his diffraction grating to actually measure the wavelength of specific colors and dark ...
[9]
Lord Rayleigh: A Scientific Life - Optics & Photonics News
In his papers on light scattering from small particles (1871), his equations used Cartesian coordinates; thus, he wrote separate equations for the x, y and z ...
[10]
[PDF] Laser-diffraction-size-analysis.pdf - ResearchGate
This work led to a first generation of commercial laser diffraction siz- ers from CILAS (France), Leeds and Northrup. (USA), and Malvem Instruments (UK). Sub ...
[11]
Celebrating 50 Years of Laser Diffraction - Microtrac
In 1974 Leeds and Northrup delivered the first instrument to use Laser Diffraction to measure Particle Size Distributions. ... Particle Size & Shape Analysis ...
[12]
[PDF] Mie theory the first 100 years - ATA Scientific
In the late 1970's, when laser diffraction systems were first introduced, limited computing power made it difficult, and impractical, to rigorously apply Mie ...
[13]
ISO 13320:2009 - Particle size analysis — Laser diffraction methods
ISO 13320:2009 provides guidance on instrument qualification and size distribution measurement of particles in many two-phase systems.
[14]
What are the Mie scattering and Fraunhofer diffraction theories?
Jul 14, 2023 · Computers in the 1970s were only powerful enough to compute diffraction data with the simpler Fraunhofer approximation. Mie has been widely used ...
[15]
Fraunhofer Diffraction Theory and Mie Scattering Theory - Shimadzu
The particle size is relatively large (at least, 10 times the laser wavelength); The scattering angle is small (30° or less). In a range in which these ...
[16]
Mie, Fraunhofer Diffraction Theories - Beckman Coulter
The theory predicts the relative intensity of scattered light as a function of particle size, angle of observation, and wavelength and polarization of the ...
[17]
[PDF] Today in Physics 218: diffraction by a circular aperture or obstacle
Apr 2, 2004 · The Bessel function of the first kind, of order m, can be represented by the integral. Bessel functions of different order are related by the.
[18]
A laser diagnostic technique for the measurement of droplet and ...
A laser diagnostic technique for the measurement of droplet and particle size distribution. J. SWITHENBANK,; J. BEER,; D. TAYLOR,; D. ABBOT and; G. MCCREATH.
[19]
Mie Theory and Mie Scattering - Malvern Panalytical
Jan 8, 2010 · Mie theory uses the refractive index difference between the particle and the dispersing medium to predict the intensity of the scattered light.
[20]
[PDF] Absorption and Scattering of Light by Small Particles
Accordingly, this book is divided into three parts. Part 1, Chapters 1 through 8, is primarily scattering theory. After an introduction there is a chapter on ...
[21]
Mie Scattering & Mie Theory: Particle Analysis - Microtrac
Mie Scattering & Mie Theory are used in Microtrac's laser diffraction particle size analyzers. Learn more about the technology and working mechanisms here!
[22]
Static Light Scattering (SLS) / Laser Diffraction Particle ... - HORIBA
The LA-960V2 particle size analyzer represents the tenth generation laser diffraction instrument designed by HORIBA. Hundreds of refinements to the basic ...Missing: 1974 Leeds Northrup
[23]
Particle Size Analysis with Laser Diffraction - Sympatec
Laser diffraction is the established and most efficient light scattering method for particle size analysis covering a wide range from submicron to millimetre ...
[24]
Principles and Applications of Laser Diffraction Technology - AZoM
Jun 14, 2018 · The principle of laser diffraction is the relationship that exists between light scattering (its angle and intensity) and particle size.
[25]
Choosing between wet and dry dispersion - Malvern Panalytical
Mar 30, 2011 · Two methods are available – wet dispersion and dry dispersion. Both methods have their own strengths, and both should be applied with care and consideration.Missing: optical | Show results with:optical
[26]
Laser Diffraction (LD): Particle Size Analyzers - Microtrac
MICROTRAC particle analyzers for laser diffraction, an efficient method for particle size determination ✓ high quality ✓ reliable measurement ➤ Learn more.Missing: 1974 Leeds Northrup
[27]
ISO 13320:2020 - Particle size analysis — Laser diffraction methods
In stock 2–5 day deliveryISO 13320:2020 provides guidance for particle size analysis using laser diffraction, covering sizes from 0.1 µm to 3 mm, for various two-phase systems.
[28]
[PDF] LS 13 320 Laser Diffraction Particle Size Analyzer
The method involves the analysis (deconvolution) of the patterns of scattered light produced when particles of different sizes are exposed to a beam of light.
[29]
Laser Diffraction Analysis | Particle Size Measurement - Bettersize
Measurement range: 0.01 - 3,500μm (Laser System). Measurement ... DeepSizer 300. Your Essential Tool for Sediment Insight. Particle size range: 0.1 - 2000 μm.
[30]
Method Development for Laser-Diffraction Particle-Size Analysis
During recent decades, the unique attributes of laser-diffraction analysis have positioned it as the particle-sizing technique of choice for the resulting ...
[31]
[PDF] Accuracy and Repeatability of Laser Diffraction Analysis According ...
ISO 13320:2020 defines the requirements for particle size analysis using laser diffraction. This standard describes the theory, instrument design principles, ...
[32]
Laser Diffraction for Particle Sizing - Sample Concentration/Dilution (1)
May 11, 2021 · Sample concentration is key; too high concentration causes light interaction with multiple particles, while too low causes poor signal-to-noise ...Missing: ADC rate
[33]
https://www.malvernpanalytical.com/en/products/product-range/mastersizer-range/accessories/aero-m
[34]
Aero M - Dry Powder Dispersion Unit - Malvern Panalytical
Dispersion pressure range, 0 - 4 bar. Pressure setting precision, +/- 0.1 bar. Pressure setting accuracy, +/- 0.03 bar. Feed rate range, 0 - 58ms-2 (expressed ...
[35]
[PDF] INTERNATIONAL STANDARD ISO 13320
Jan 3, 2021 · ISO 13320 is about particle size analysis using laser diffraction methods, and is the second edition from 2020.
[36]
Laser Diffraction Particle Size Analysis | Malvern Panalytical
Laser diffraction is a particle sizing technique measuring size by analyzing light scattering angles, using Mie theory, with a wide dynamic range.
[37]
[PDF] Laser diffraction particle sizing in STRESS YC AGRAWAL* and HC ...
McCAVE and J. B. RILEY (1991) Laser diffraction size analysis. In: Principles, methods and applications of particle size analysis, J. P. M. SYVITSK1, editor ...
[38]
https://tsapps.nist.gov/srmext/certificates/archives/1004b.pdf
[39]
[PDF] Certificate - National Institute of Standards and Technology
A unit of. SRM 1004b consists of a single bottle containing approximately 43 g of solid spherical borosilicate glass beads. Certified Values: A NIST certified ...
[40]
[PDF] Particle Size Analysis Overview | Entegris
The Gaussian result indicates a high Chi Squared value ... 4 From ISO 13320-1, Particle size analysis – Laser Diffraction. Methods, Part 1: General Principles.
[41]
Considerations for Stable, Consistent Results Using Laser Diffraction
Mar 14, 2023 · Laser diffraction is an analysis technique that can detect particle size by measuring the angle at which particles scatter light. In a liquid ...
[42]
[PDF] Top 10 errors in particle analysis and how to avoid them - Microtrac
In laser diffraction, too high a particle concentration can lead to multiple scattering, and if too little sample is used, the signal-to-noise ratio is poor.
[43]
[PDF] Assessment of Multiple Scattering Errors of Laser Diffraction ... - DTIC
Mar 17, 2003 · Swithenbank, J., Beer, J. M. and Taylor, D. S., "A Laser Diagnostic Technique for the Measurement of. Droplet and Particle Size Distribution", ...
[44]
[PDF] Interpreting Laser Diffraction Results for Non-Spherical Particles
Dec 10, 2019 · Particle shape is often overlooked in Laser Diffraction measurements, but it affects the diffraction pattern used to determine particle size.
[45]
Inter‐laboratory Study of Particle Size Distribution Measurements by ...
Sep 6, 2012 · Presented are results of an inter-laboratory study (ILS) for measurements of the particle size distribution of fine powders in wet ...
[46]
System Verification Resources - HORIBA
Laser diffraction analyzers are often verified using standards with a known distribution of particles. Both ISO13320 and USP<429> suggest using polydisperse ...
[47]
[PDF] Bioavailability and Bioequivalence Studies for Nasal Aerosols ... - FDA
(PSD) in aerosols and sprays (Sections V.B.3, 4). Drug PSD in suspension formulations. 151 has the potential to influence the rate and extent of drug ...Missing: tablets | Show results with:tablets
[48]
In Vitro and In Vivo Performance of Dry Powder Inhalation ...
For pulmonary drug delivery, the optimum particle size is 1–5 μm (53). In ... laser diffraction following aerosol generation from the Miat® monodose inhaler.
[49]
[PDF] 429 Light Diffraction Measurement of Particle Size
Nov 23, 2016 · Moreover, sufficient information must be documented about the sample, the sample preparation, the dispersion conditions, and the cell type.
[50]
Segregation of formulated powders in direct compression process ...
Nov 25, 2023 · In this study, powder segregation in a direct compression process is investigated as a typical example for evaluation of segregation intensity in a process ...
[51]
Particle size distributions measured using laser diffraction.
The uniform distribution of APIs is essential in tablet formulations, particularly in direct compression, where powder blending is the only means of ensuring ...
[52]
Critical Particle Size Distribution for Cement using Laser Diffraction
Laser diffraction has emerged as the preferred sizing method in cement industry due to its simplicity and accuracy as compared to the more traditional methods.
[53]
Particle size distribution of cement using laser diffraction
Jun 24, 2009 · The particle size distributions of the various cement samples have been measured by laser diffraction using a Mastersizer.
[54]
Sizing Pigment Particles by Laser Diffraction - tridentequipments
Apr 21, 2022 · A novel technique for enhancing submicron sizing in standard laser diffraction systems. The technique is called PIDS, for Polarization Intensity Differential ...<|separator|>
[55]
Particle Size in the Food Industry - Anton Paar Wiki
They were determined by laser diffraction using the Litesizer DIF liquid mode. For ELS milk a monomodal particle size distribution is shown with a peak size ...
[56]
Using Laser Diffraction to Measure Dairy and Food Emulsions - AZoM
Mar 4, 2016 · Laser diffraction measures fat droplet size in food emulsions, which is vital for stability, flavor, and mouthfeel, and helps understand ...Missing: industry globules flowability milling
[57]
(PDF) Laser diffraction and light scattering techniques for the ...
Apr 21, 2015 · Laser diffraction and light scattering techniques for the analysis of food matrices. Authors: Rosita Primavera, Renato Carlo Barbacane, Marco Congia, Marcello ...
[58]
Automated Continuous Crystallization Platform with Real-Time ...
Jul 9, 2024 · The system combines automated crystallization, sample preparation, and immediate crystal size analysis via online laser diffraction (LD)
[59]
Insitec Dry | On-line Particle Size Analyzer | Malvern Panalytical
Insitec Dry is a robust particle size analyzer using laser diffraction to measure particles from 0.1 to 2500 µm, providing real-time monitoring and control.Missing: reactors crystallization
[60]
Application to Particle Sizing in Spray Drying - ResearchGate
Aug 6, 2025 · For example, an in-line laser diffraction instrument has been applied as a process analytical technology (PAT) tool to measure the particle size ...Missing: reactors | Show results with:reactors
[61]
Measurement of the Size Distribution of Multimodal Colloidal ...
May 25, 2021 · In this study, we assessed the accuracy of LD for the measurement of the modal diameter of both single and mixed populations of polystyrene particles.
[62]
Atmospheric and Environmental Impacts of Volcanic Particulates
Aug 1, 2010 · Laser diffraction analysis of particle size is commonly used to give ... size (radius) distribution of airborne ash particles.
[63]
Assessment of the potential respiratory hazard of volcanic ash from ...
Sep 11, 2017 · Particle size analysis. Particle size data were collected by laser diffraction using a Malvern Mastersizer 2000 with Hydro MU attachment at ...
[64]
In-Stream Laser Diffraction for Measuring Suspended Sediment ...
This study evaluates the laser in situ scattering and transmissometry (LISST) instrument LISST-SL2, a laser diffraction instrument for suspended sediment ...
[65]
Ecological Assessment of Particulate Material (PM5 and PM10) in ...
May 28, 2020 · We tested the suitability of tree leaves (Common Lime) to assess PM 5 and PM 10 deposition in the three summer months of 2018 in Debrecen city, Hungary.
[66]
Cedrus atlantica pollen morphology and investigation of grain size ...
Aug 10, 2017 · The morphology and size variability of pollen grains of Cedrus atlantica were investigated using a novel approach employing laser diffraction granulometry.
[67]
Laser Diffractometry in the Measurements of Soil and Sediment ...
Laser diffraction analysis is a fast, reliable and automated method that provides detailed and highly resolved soil and sediment particle size distribution. In ...
[68]
Laser diffraction analysis of aggregate stability and disintegration in ...
Soil aggregate behavior assessed using repeated laser diffraction measurements. •. Dynamics of aggregate disintegration can be modeled as first-order processes.
[69]
Combining laser diffraction, flow cytometry and optical microscopy to ...
During April 2013, about 90 continuous profiles of PSD quantified through in situ laser diffraction ... Plankton is a key compartment of marine ecosystems.
[70]
Particle size distribution analysis of soils using laser diffraction
The use of laser diffraction for the particle size distribution analysis of the sub-63 μm fraction of soil samples is described.
[71]
Particle Detection and Characterization for Biopharmaceutical ...
... particle size distributions (PSD), polydispersity, viscosity, color, or ... laser diffraction (LD); dynamic light scattering (DLS). MALS and SLS ...
[72]
Choosing Laser Diffraction or Dynamic Light Scattering - HORIBA
Dynamic light scattering can be used with samples that have much smaller particle sizes than laser diffraction. Therefore, a significant fraction of very small ...
[73]
Particle size analysis methods: Dynamic light scattering vs. laser ...
Laser diffraction is more suitable for analyzing samples that have large particles (>10 µm). The intensity signal is stronger and results are related to the ...Missing: ADC | Show results with:ADC
[74]
Particle Analysis Techniques Compared :: Microtrac.com
With static laser light scattering (SLS) analysis, also called laser diffraction, particle size is measured indirectly by detecting intensity distributions of ...<|control11|><|separator|>
[75]
A Review of Different Particle Sizing Methods - Anton Paar Wiki
Laser diffraction measures solid and liquid particle sizes from the upper nano- to lower millimeter range. The measurement is based on the diffraction of laser ...Missing: detectors | Show results with:detectors
[76]
Laser diffraction vs. Sieving comparison - Malvern Panalytical
Feb 8, 2011 · Laser diffraction and sieving can provide similar results when characterising spherical or semi-spherical particles. However, it is not unusual ...
[77]
Sieving methods of sieve analysis - RETSCH
Larger particles, from a size of about 40 mm, are usually measured by hand or on the basis of photos, while sieving is often used for the particle size analysis ...
[78]
[PDF] Basic principles of particle size analysis - ATA Scientific
Figure 6 shows the expected differences between a sedimentation and laser diffraction results. ... laser beam and diffraction is obtained from all the particles.
[79]
10 Differences Between Laser Diffraction and Sieving - AZoM
Mar 11, 2014 · 10 Differences Between Laser Diffraction and Sieving for Routine Particle Size Analysis · Smaller Sample · Faster Experiments · Repeatability and ...
[80]
Soil texture analysis by laser diffraction and sedimentation and ...
Jun 22, 2023 · Purpose: Laser diffraction (LD) for determination of particle size distribution (PSD) of the fine earth fraction appeared in the 1990s, partly ...Abstract · Introduction · Materials and methods · Results
[81]
Particle size analysis: A comparison of laboratory-based techniques ...
Apr 15, 2024 · This study aims to assess and compare laboratory-based methods of particle size analysis that are commonly used in the field of sedimentology.
[82]
Determination of Particle Size Distribution: Comparison of Standard ...
Feb 8, 2024 · Laser diffraction analysis is an alternative to standard sedimentation methods designed to determine particle size distribution.
[83]
Adequacy of laser diffraction for soil particle size analysis | PLOS One
In this study, the sedimentation based sieve plummet balance method and the laser diffraction method were used to measure the particle size distribution of 22 ...
[84]
[PDF] NIST recommended practice guide : particle size characterization
This guide addresses issues in particle size analysis, addressing practical issues and guiding non-experts, but is not exhaustive.
[85]
[PDF] Introduction to Laser Diffraction - HORIBA
Feb 24, 2022 · Assumptions: a) all particles are much larger than the light ... ISO-13320:2020, A.5: For small particles, match is poor. Use Mie ...
[86]
Evaluation and correction of laser scattering-based particle size ...
May 9, 2024 · For an obscuration up to 0.2, the particle size inversion errors remain below 5%, indicating a weak influence of multiple scattering. However, ...
[87]
Quantified Effects of Particle Refractive Index Assumptions on Laser ...
May 1, 2019 · Core Ideas Particle refractive index (RI) assumptions are evaluated across the fine earth fraction of diverse soils.
[88]
[PDF] Choosing the most Suitable Theory in Laser Diffraction Mie or ...
The choice of the Fraunhofer theory for the small particles leads to a significant error of around 35% on the D50 value. An estimation of the refractive.<|separator|>
[89]
Top tips for avoiding particle sizing failures with your laser diffraction ...
Jun 7, 2016 · For the sample containing larger particles, particle size is stable over a much wider obscuration range. Larger particles scatter light at ...
[90]
[PDF] Improving the consistency of particle size measurement
The principles of laser diffraction for particle sizing are comprehensively summarised in the international standard ISO/DIS 13320 and the NIST Recommended ...
[91]
Wet Analysis Method Using Laser Diffraction | Malvern Panalytical
Nov 11, 2013 · The particle analysis method using wet analysis is currently the most widely used method to obtain reproducible results in laser diffraction ...
[92]
[PDF] Size Analysis with a Laboratory Laser-Diffraction Analyzer - USGS.gov
May 21, 2018 · All three materials met the ISO requirements for use as an accuracy verification material for laser- diffraction analysis (ISO 13320:2009 6.5).
[93]
Why Instrument Variety Matters in Laser Diffraction Testing
Jun 23, 2025 · The Beckman Coulter LS13 320 utilizes a similar wide size range to the Malvern Panalytical Mastersizer 3000, generally spanning from 40 nm to ...
[94]
Effects of Temperature and Humidity on Laser Diffraction ... - NIH
Environmental conditions such as temperature and humidity not only may influence variability of the aerosol generation but also may influence PSD during the ...
[95]
[PDF] PARTICLE SIZE ANALYSIS BY LASER LIGHT DIFFRACTION
Laser light diffraction analyzes the diffraction pattern of particles exposed to light. The scattered light pattern is measured using a multi-element detector.