Advanced Particle Sizing

Dynamic Light Scattering (DLS)

- The technique resolves the issue of determining size for submicron particles and macromolecules, which are too small for traditional microscopy, by analyzing the rapid, random fluctuations in scattered light intensity resulting from Brownian motion.

- The raw signal is processed using a digital correlator to generate an autocorrelation function, whose decay rate is inversely proportional to the particle’s diffusion speed, allowing for accurate size calculation via the Stokes-Einstein equation.

- DLS systems typically require only microliter volumes of sample suspension, mitigating the financial and resource constraints associated with characterizing expensive or precious materials where sample availability is limited.

- The measurement yields the Z-Average size, an intensity-weighted harmonic mean diameter, which is a highly robust and repeatable metric for monitoring the average size of narrow-distribution colloidal systems over time.

- The instrumentation can operate in a high backscatter angle configuration (e.g., 173°), effectively minimizing the influence of high concentrations or large contaminants by reducing the overall light path and maximizing the signal from the small particles closest to the detector.

- Specialized analysis algorithms can interpret the autocorrelation function in terms of cumulants for moderately polydisperse samples, providing an index of distribution width to quantify the degree of particle size variation.

- The DLS principle is fundamentally suited for aqueous and organic solvents, requiring only the knowledge of the suspending fluid’s viscosity and temperature to calculate the particle's hydrodynamic diameter accurately.

- Its rapid measurement speed makes it an efficient tool for routine quality control checks where fast confirmation of colloidal stability or macromolecular integrity is necessary to maintain production throughput.

Static Light Scattering (SLS) / Laser Diffraction

- Laser Diffraction is fundamentally effective for characterizing particle sizes across an extremely broad range, from nanometers up to thousands of micrometers, addressing the need for a single instrument capable of monitoring both fine powder ingredients and coarse abrasive materials.

- The technology determines particle size based on the inverse relationship between particle size and the angle of scattered light, utilizing a highly engineered array of photodetectors to capture the diffraction pattern across a vast angular range (e.g., 0-170 degrees).

- For particles smaller than approximately 20 micrometers, the analysis leverages Mie scattering theory, requiring accurate input of the material’s refractive and absorption indices to precisely model the refracted and absorbed light components, thereby eliminating calculation inaccuracy.

- The optical system employs multiple light sources at different wavelengths, ensuring that the scattering phenomenon is optimally measured across the entire size range, from the smallest particles requiring short wavelengths to the largest particles measured by low-angle diffraction.

- An automatic laser alignment system, controlled by the instrument's software, ensures that the optical path is perfectly maintained in seconds, removing the manual intervention and potential operator-induced error that compromises measurement precision.

- Integrated, software-controlled wet circulation systems include features like ultrasonic probes and dispersant pumps, ensuring that agglomerated particles are fully separated and uniformly presented to the measurement cell in a highly reproducible manner.

- The measurement is compliant with international standards, such as ISO 13320, providing guaranteed accuracy and precision when certifying materials against D10, D50, and D90 specifications for regulatory reporting and commercial agreement.

- A sealed, maintenance-free optical bench design, often featuring post-less cast aluminum mountings, delivers long-term stability and immunity to environmental dust or vibration, ensuring superior instrument-to-instrument precision regardless of operational environment.

Molecular Weight

- Molecular Weight determination often utilizes Static Light Scattering (SLS) principles, where measurements of scattered light intensity are taken at multiple sample concentrations to extrapolate data to the theoretical condition of zero concentration.

- The SLS method enables the calculation of the weight-average molecular weight ($M_w$) using a Debye plot, providing a well-defined value that is independent of empirical correlation factors, a common source of uncertainty in polymer analysis.

- The technique simultaneously allows for the calculation of the second virial coefficient ($A_2$) from the slope of the Debye plot, which is an essential thermodynamic parameter for assessing the solvent interaction and stability of macromolecules in solution.

- Alternatively, the rapid Dynamic Light Scattering (DLS) approach can estimate molecular weight using the empirical Mark-Houwink-Sakurada equation, which relies on pre-determined constants specific to the polymer/solvent system.

- While the SLS method is time-consuming and requires highly accurate sample preparation and concentration data, the DLS method is advantageous when polymer concentration is not precisely known or when extremely fast characterization is required.

- For small macromolecules (with a Radius of Gyration less than 20 nm), the system simplifies the SLS requirement by allowing data to be collected at a single angle (90°), avoiding the complex process of multi-angle measurements and extrapolation to zero angle.

- The reliance of the DLS-based calculation on literature-derived empirical constants introduces a known systematic challenge, which must be managed by ensuring the constants used are appropriate for the exact solvent, temperature, and polymer type being studied.

- The molecular weight determination is critical for characterizing synthetic polymers, proteins, and dendrimers, providing a key quality metric that directly affects the functional performance and viscosity of these materials in final products.

Zeta Potential

- Zeta potential quantifies the electrokinetic potential at the shear plane of a particle, serving as the definitive measure for predicting the electrostatic stability of colloidal suspensions and mitigating aggregation.

- The measurement utilizes Electrophoretic Light Scattering (ELS), where an electric field is applied across the sample cell, causing charged particles to move; the Doppler shift in the scattered light is then measured to calculate the electrophoretic mobility.

- A large magnitude of zeta potential (typically above |25 mV|) is directly correlated with a high degree of electrostatic stabilization, resolving the critical problem of formulating stable liquid products or controlling particle interactions.

- The system facilitates the automated determination of the Isoelectric Point (IEP)—the pH value where the zeta potential is zero—using an integrated autotitrator to systematically adjust the suspension pH, thereby guiding formulation chemists to the optimal stability conditions.

- Precision dosing with burettes and a molecular sieve treatment for incoming air ensure that titrant reagents are delivered precisely without air bubbles and that atmospheric carbon dioxide contamination is prevented, maintaining the accuracy of pH adjustments.

- The analysis is sensitive to the surrounding medium, as the concentration of dissolved salts or specific ions can shield the surface charge, allowing researchers to accurately model the effect of ionic strength on particle interactions.

- Specialized, reusable graphite electrode cells are designed to ensure electrical conductivity and minimize fouling during repeated measurements, addressing the issue of consumable costs and potential drift associated with single-use cells.

- While the technique is crucial for nanoparticles, the instrumentation must account for the physical constraint of gravitational settling in larger particles (above 1 µm), which interferes with the measurement of electrophoretic mobility and requires careful sample handling to produce reliable data.

Image Analysis of Particles

- Image analysis fundamentally overcomes the limitation of light scattering techniques by directly measuring a particle's true physical dimensions and shape parameters, rather than relying on an equivalent spherical diameter model.

- The process involves sophisticated software algorithms that perform object detection to separate touching or agglomerated particles in an image, ensuring that the size and shape distribution is not skewed by false representations of particle clusters.

- The technology facilitates the generation of shape-based distributions, quantifying metrics such as aspect ratio, circularity, and elongation, which are vital quality indicators for non-spherical materials like fibers, platelets, and crystalline powders.

- Acquisition requires features like bright, uniform illumination and high-quality optics to ensure high-contrast images, resolving the issue of poor boundary definition which often limits the accuracy of automated measurement.

- Dynamic Image Analysis involves passing particles in flow across the camera’s optics, allowing for the rapid measurement of tens of thousands of individual particles to achieve statistically significant and representative distributions.

- The instrumentation can be implemented in an in-line configuration, integrating directly into a process pipe or reaction vessel, allowing for real-time monitoring of particle dimension changes without the delay or bias of manual sampling.

- By comparing images of particles with known defects or morphological inconsistencies, manufacturers can establish precise quality control parameters based on visual characteristics, enhancing product consistency beyond simple size specifications.

- The method is particularly advantageous for large particles (over approximately 0.5 µm) where visible light microscopy is preferred, offering a cost-effective, high-resolution alternative to electron microscopy, which requires complex and destructive sample preparation.

Nanoparticle Tracking Analysis (NTA)

- NTA provides an absolute counting methodology by visualizing and tracking the Brownian motion of individual nanoparticles in a liquid sample, delivering accurate concentration data ($particles/mL$) essential for dosing and yield optimization.

- The core innovation is the use of multispectral illumination (e.g., multiple lasers at different power levels) to create a light sheet, ensuring that highly polydisperse samples—from weakly scattering small particles to intensely scattering large contaminants—are all accurately tracked simultaneously.

- The system resolves the critical challenge of scattered light intensity disparity, where typical scattering instruments are overwhelmed by the signal from larger particles, obscuring the detection of smaller, critical nanoparticles in a mixture.

- By capturing a video over time, the software calculates the diffusion coefficient for each tracked particle individually, enabling the generation of a high-resolution size distribution that is far less susceptible to averaging errors than ensemble techniques.

- The technology allows for the real-time visualization of kinetic processes, such as protein aggregation or dissolution, providing direct, qualitative evidence to support quantitative size and concentration measurements for formulation stability studies.

- NTA is a highly effective tool for characterizing complex biological samples like extracellular vesicles, viruses, and nanobubbles, providing the necessary size and concentration metrics for vaccine development and advanced therapeutic research.

- The measurement is an elegant and absolute method that does not require pre-calibration standards or prior knowledge of the particle's refractive index or density, streamlining the analytical workflow and reducing method development time.

- The ability to accurately quantify size and concentration across a wide range (e.g., 10 nm to 15 µm) in a single test ensures that analysts can reliably monitor both product particles and larger foreign material contamination simultaneously.

Centrifugal Sedimentation

- Centrifugal Sedimentation provides high-resolution Particle Size Distribution (PSD) measurement for samples ranging from 10 nm to 40 µm by classifying particles based on their sedimentation speed under high centrifugal force.

- The method uniquely resolves mixtures of particles that have the same size but different material densities, as the sedimentation rate is directly proportional to density, enabling the separated analysis of multi-material systems like complex slurries.

- The system generates an extreme centrifugal force (up to 30,000 G), which is necessary to induce measurable sedimentation of tiny nanoparticles within a reasonable analysis time, overcoming the sluggish diffusion that governs their movement under gravity alone.

- Precision measurement is achieved using two distinct techniques: the Line-start mode, where a thin layer of sample is injected onto the surface of a homogeneous fluid column, and the Homogeneous mode, providing flexibility based on sample properties.

- An integrated temperature control and cooling function is vital for stabilizing the sample chamber and rotor, preventing temperature fluctuation that would otherwise alter the fluid's viscosity and corrupt the accuracy of the sedimentation time measurement.

- Its high resolution makes it highly effective at detecting and quantifying small populations of foreign particles or agglomerates that might be missed by lower-resolution methods, ensuring tighter quality control over trace contaminants.

- The method is highly valuable for slurry applications, such as in semiconductor manufacturing (CMP slurries), where it can detect differences in particle size in the single nanometer level and assess the dispersibility of the stock solution.

- The cuvette-type cell design simplifies cleaning and replacement, effectively reducing the risk of sample carryover or cross-contamination between high-purity or chemically sensitive materials.

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