Understanding the Coulter Principle

Written by Sophie Lindsey on March 6, 2025. Posted in How to….

Understanding the Coulter Principle: The Science Behind the Beckman Coulter Multisizer 4e

Introduction

Particle size analysis is a critical aspect of numerous scientific and industrial applications, from pharmaceutical development to food processing and materials science. One of the most widely used and precise methods for particle characterisation is the Coulter Principle, which forms the foundation of the Beckman Coulter Multisizer 4e. This advanced instrument has revolutionised the way researchers and manufacturers measure particle size and concentration, offering high resolution and accuracy across a wide range of applications.

The Coulter Principle Explained

The Coulter Principle, also known as the Electrical Sensing Zone (ESZ) method, was developed by Wallace H. Coulter in the 1950s. This principle states that when particles suspended in an electrolyte solution pass through a small aperture between two electrodes, they cause a temporary change in electrical resistance proportional to their volume. Each particle displaces a specific amount of electrolyte, generating an electrical pulse that is directly correlated to the particle’s size.

The Coulter Principle offers several advantages over optical and laser-based methods, including:

High accuracy: Direct measurement of volume ensures precise sizing.
Wide dynamic range: Capable of detecting particles from sub-micron to hundreds of microns.
Independent of particle refractive index: Unlike laser diffraction, the method does not rely on light scattering, making it ideal for opaque or irregularly shaped particles.
Absolute counting: Unlike ensemble methods, the Coulter Principle enables individual particle counting and size distribution analysis.

The Beckman Coulter Multisizer 4e: Advancing Particle Analysis

The Beckman Coulter Multisizer 4e is a state-of-the-art instrument that utilizes the Coulter Principle to provide high-resolution particle size distribution analysis with unparalleled precision. It is widely used in industries such as pharmaceuticals, biotechnology, food and beverage, and materials science.

Key Features and Advantages

Broad Measurement Range: The Multisizer 4e can measure particles ranging from 0.2 to 1,600 microns, making it suitable for diverse sample types.
High Resolution and Accuracy: The ability to measure individual particles provides detailed distribution profiles, allowing detection of subtle differences in particle populations.
Advanced Aperture Technology: The system utilizes multiple aperture sizes to optimise analysis for specific sample types.
Robust Data Analysis and Reporting: Integrated software offers detailed statistical analysis, real-time monitoring, and customisable reporting for enhanced usability.
Versatility Across Industries: The instrument is widely used for applications such as blood cell analysis, battery materials research, protein aggregation studies, and more.

Applications of the Multisizer 4e

The versatility of the Multisizer 4e makes it a valuable tool across multiple disciplines:

Pharmaceuticals: Ensures uniformity in drug formulations and stability of suspensions.
Biotechnology: Used for analysing cell size distributions and monitoring cell cultures.
Batteries and Materials Science: Evaluates particle distribution in battery electrodes for optimal performance.
Food and Beverage: Determines particle size in emulsions and powders to ensure product consistency.
Cosmetics: Assesses particle size in creams and lotions for texture and stability control.

Conclusion

The Coulter Principle remains one of the most reliable and precise methods for particle size analysis, and the Beckman Coulter Multisizer 4e exemplifies its power and versatility. By offering high-resolution data, absolute particle counting, and broad application potential, the Multisizer 4e is an essential tool for researchers and industry professionals seeking accurate and reproducible particle characterisation.

Whether in pharmaceuticals, biotechnology, or materials science, the Coulter Principle continues to drive advancements in particle analysis, helping scientists and engineers develop better products and technologies for the future.

What is Flow Imaging Microscopy (FIM)?

Written by Sophie Lindsey on February 17, 2025. Posted in How to….

What is Flow Imaging Microscopy (FIM)?

Flow Imaging Microscopy is a fast and automated method to see highly-resolved digital images of microscopic particles in a flowing liquid.

Using FlowCam, you can very quickly learn about the size, count, shape, and identity of the particles in your sample.

Flow Imaging Microscopy began as a novel concept when the first flow imaging microscope—FlowCam—was developed at Bigelow Laboratory for Ocean Sciences in Boothbay Harbour, Maine. The then-available tools, a microscope for plankton identification and a flow cytometer for counting, were time-consuming and labour-intensive, so the scientists at Bigelow sought to develop a better method.

FlowCam 8400 collage of diatoms collected in Casco Bay

Their FlowCam design combined the benefits of a flow cytometer and a microscope in a single instrument. A sample of ocean water could be introduced into the system, and particles would be automatically, digitally imaged and analysed.

Today, FlowCam is an essential tool in particle characterisation labs in a broad array of biologics and materials applications that care about the size, shape, and morphology of particles in solution:

Aquatic: the study of microbial life in the world’s marine and freshwater bodies to understand key processes driving these ecosystems
Biopharma: characterization of biopharmaceutical aggregates and other subvisible particles in parenteral drugs to evaluate the stability of formulations
Cell and gene therapy: analysis of cells, aggregates of drug carriers, and drug delivery vehicles
Food and beverage: quality control of food ingredients where particle shape can affect taste and texture
Materials: formulation development, process troubleshooting, and QA/QC testing for microspheres, emulsions, encapsulated materials, fibres, and polymers.

How Does Flow Imaging Particle Analysis Work?

The flow imaging particle analysis workflow is streamlined with FlowCam! A sample containing particles is injected into a flow cell, where it flows through a path positioned between a light source and a magnifying objective in front of a digital camera. As the sample passes by, the camera automatically captures images of up to 50,000 particles per minute.

In real-time, VisualSpreadsheet software extracts single particle images from the camera images. It compiles a variety of basic measurements such as particle count, diameter, volume, and aspect ratio, as well as more advanced morphology measurements like circularity, elongation, and perimeter. Other particle characteristics include intensity, transparency, and colour. Using VisualSpreadsheet, you can readily sort, filter, classify, and display your data analysis in various formats.

Direct Particle Measurements

One of the key advantages of flow imaging microscopy with FlowCam is that particle measurements are calculated directly from an image of the particle. Since flow imaging microscopy is designed with fixed optics at known magnifications, distance measurements on the image can be directly converted to real distance measurements on the object. Flow imaging systems do not have to make any assumptions about a particle’s size and shape because they measure multiple particle properties directly from an image.

Other particle analysis systems, such as light obscuration, laser diffraction, and light scattering, need to make assumptions about the particle’s physical dimensions. These techniques measure a signal proportional to a physical dimension and convert that signal to a value representing the number of particles and corresponding particle size distribution in the sample. In addition, many of these analytical techniques only measure ensemble (bulk) properties, i.e., the properties of the overall population distribution.

The ultimate benefit of performing flow imaging microscopy with a FlowCam imaging system is that you can visualize single particles and calculate desired sample properties based directly on individual particle images.

What is Surface Plasmon Resonance

Written by Sophie Lindsey on February 11, 2025. Posted in How to….

What is Surface Plasmon Resonance?

SPR picture.png

Surface plasmon resonance (SPR) is an optical, surface-sensitive technique used to study the label-free interaction of biomolecules in a complex environment in real-time. In a typical SPR experiment, ligands are immobilised on a SPR sensor surface which is exposed to a flowing solution of analytes in a microfluidic channel. The sensor surface is generally a glass prism covered with a thin metal layer, like gold or silver. A plane-polarized, monochromatic incident light is directed onto the sensor to which the ligands are attached, creating charged oscillations, called surface plasmons, at the metal surface. When analytes become bound to surface-immobilised ligands, the surface plasmon resonance conditions change, resulting in a change in the reflected angle or wavelength of the light, depending on the interrogation used. This change is captured and plotted vs. time to generate a sensorgram.

Sensograms

Sensorgrams are used to extract affinity and kinetic data of the interactions between the ligand and analyte. They can also reveal any specificity and concentration information through the magnitude of the SPR signal. In general, a sensorgram has five phases:

Baseline: The initial phase is the baseline. A running or flow buffer is used to condition the sensor surface and check for any sensor system instability.

Association: The second phase is where analytes begin to bind to immobilized ligands. It is indicated by the initial sharp rise of the SPR signal in the sensorgram and it is ideally a single exponential curve.

Steady state: This phase occurs at the top flat portion of the sensorgram where the net rate of bound analytes is zero.

Dissociation: This phase begins when the analyte solution is replaced by a wash buffer, which causes the specific interactions between the analytes and ligands to break

Regeneration: Finally, a low pH buffer such as glycine is flowed to reset the SPR baseline signal as the beginning of the experiment

How do I measure Particle Size?

Written by Sophie Lindsey on December 2, 2024. Posted in How to….

Beckman Coulter LS 13 320 XR Laser Diffraction Particle Size Analyser 21 CFR Part 11

How do I measure Particle Size?

Particle size analysis is crucial across most industries, impacting product performance in pharmaceuticals, food production, paints and pigments as well as many other industries.

One versatile instrument for this purpose is the Beckman Coulter LS13320XR, which utilises laser diffraction for accurate particle size measurement.

This advanced system accommodates both wet and dry analysis, making it ideal for a broad range of applications.

$Beckman Coulter LS 13 320 XR Laser Diffraction Particle Size Analyser 21 CFR Part 11$

This image gives you an idea of the size of many particles we are familiar with in day to day life.

The LS13320XR has the capability to measure particles from 10 nm – 3,500 µm making it a really versatile instrument for analysing almost any particle.

Dry Analysis with the Tornado Module

For dry powders or granular samples, the Tornado Module provides an efficient, contamination-free solution.

Dry analysis is especially useful for larger particles and materials incompatible with liquid dispersion.

Wet Analysis with the Universal Liquids Module (ULM)

The Universal Liquids Module (ULM) is designed for wet dispersion, ideal for materials dispersed in liquids such as emulsions, suspensions, or fine powders requiring stabilisation.

Wet analysis using the LS13320XR is a simple, easy to use technique and is highly effective for particles down to the nanometer scale, offering detailed insights into fine particle systems.

By offering robust solutions for both wet and dry methods, the Beckman Coulter LS13320XR enables accurate, reproducible particle size measurements tailored to specific sample requirements. Whether optimising formulations or ensuring quality control, this system delivers exceptional flexibility and precision.

How to measure particle size – Dry

How to measure particle size – Wet

Particle World: 3P Instruments 24th Application Magazine

Written by Sophie Lindsey on August 7, 2024. Posted in How to….

Particle World magazine 24 particle characterisation news

The 24th edition of our application magazine “Particle World” is released!

Our “Particle World 24” has just been published. Read about the characterisation of particles, powders, and pores of various materials in pure or dispersed form. New measurement possibilities and recommendations for their implementation, experiences in carrying out analyses and evaluation are presented on 32 pages.

A highlight is the technical article on the new BeNano instrument series: now with autotitrator and DLS microrheology option! The BeNano series is the latest generation of optical measuring instruments for the comprehensive characterisation of particles in the size range 0.3 nm to 15 µm. The flagship BeNano 180 Zeta Pro combines the methods of dynamic light scattering (DLS), electrophoretic light scattering (ELS) and static light scattering (SLS). This allows particle size, rheology parameters, zeta potential and molecular weight to be determined in one system. In the article starting on page 9, the new autotitrator for automatic, time-saving pH-dependent determination of the zeta potential is presented using a sample measurement with bovine serum albumin (BSA). In addition, the new microrheology option is clearly explained step by step and it is shown which statements can be derived with it about the viscoelastic properties of the materials to be examined.

Other topics in the latest “Particle World” include:

Bettersizer line: New small-volume dispersion units for special particle size measurements
Powder characterisation – methods and equipment at a glance
How isothermal is an isotherm?
The influence of the sorption method sensitivity factor (SMSF) to gas sorption measurements
Invitation to the Adsorption event series and review of our Adsorption Week 2023
New cooperation with Rubolab: magnetic suspension balance and high-pressure adsorption analyser now in our portfolio
New Altamira series for catalyst characterisation
Extract from our range of contract measurements

We hope you enjoy reading it! Do you have questions about one of the articles or would you like to write your own article in the next issue? Do you wish to receive the print version free of charge?

Please contact us:

Particle Characterisation Specialists — info@meritics.com (01582)704807

Revolution Measurements for Additive Manufacturing

Written by Sophie Lindsey on August 5, 2024. Posted in How to….

Revolution Measurements for Additive Manufacturing

Rotating drum rheometers have been widely used to study powders for Additive Manufacturing applications for over 15 years [1-8] and powders in general for roughly 40 years. The concept of studying powder flow behaviour in a rotating cylinder or “drum” was presented in Kaye et al [9,10] in 1995. Powder was placed in a clear cylinder with a light source in front of it. An array of photocells was places behind the cylinder. The cylinder or drum was rotated, and the sample powder would prevent or allow light from light source to reach the photocells. In this way, the avalanching behaviour of the powder could be studied. This concept was commercialised under the name Aero-Flow in 1996 by Amherst Process Instruments. As a result of this detection method, the Aero-Flow could only measure the time between avalanches.

The Revolution

The best detection method to study powder in a rotating drum is naturally a digital imaging device. However, in the 1990’s digital imaging devices and processing systems were expensive, and the time required to analyse a single image was roughly 20 to 30 seconds. This situation changed rapidly at the end of the 1990’s with increases in computer processing speed and development of inexpensive digital imaging devices. A commercial instrument using a digital camera to image the powder in the drum was developed by Mercury Scientific Inc. in 2002 and was commercialised under the name Revolution Powder Analyser.

Download the full Bulletin from the Mercury Scientific website

4 Applications of Enhanced Laser Diffraction Analysis

Written by Sophie Lindsey on July 5, 2024. Posted in How to…, News.

4 Applications of Enhanced Laser Diffraction Analysis

Particles diffract light through a specific angle depending upon their size, creating a diffraction pattern of light and dark circles. Measuring the intensity of light over a wide range of angles enables analysts to determine a particle size distribution. Laser diffraction analysis operates on this general principle.

Mie and Fraunhofer Diffraction Theories

Gustav Mie’s theory of diffraction is used in an array of light scattering applications, including laser diffraction analysis. It requires some knowledge of the particle and suspending fluid’s optical properties to acquire accurate data. An approximation of the Mie theory by Fraunhofer was developed for applications where the size of a particle is larger than the wavelength of light being diffracted. This eliminated the need for prior knowledge of the optical properties as they have minimal effects on data.

Fraunhofer’s approximation of Mie theory is typically used to measure particles of up to 30µm. To provide reliable and accurate particle size distribution measurements, good resolution of the angular pattern of the diffracted light is required, alongside a large number of detectors (>100).

As particle size decreases, the angle through which light is diffracted gets bigger and the intensity smaller, which makes detection of the actual angle of diffraction difficult. Below 1µm, it becomes virtually impossible to distinguish light from different particle sizes, and impossible below 0.4µm. Using more than one wavelength of light helps to quantify this but only marginally and some instruments use curve fitting type routines to estimate data below the measuring limits.

Overcoming the difficulties of measuring sub micron particles

Sub-micron particles scatter polarised light differentially depending on the polarisation and wavelength. Enhanced laser diffraction analysis uses this property to provide real measured size distributions rather than estimates down to 10nm (0.01µm). It measures the intensity of polarised light at 3 additional wavelengths. The difference in intensity between the vertically polarised and horizontally polarised light (Polarisation Intensity Differential Scattering – PIDS) provides information on the quantity and sizes of particles in this region. This can be integrated into the Mie theory calculation for quantifiable size distribution measurements.

This enhanced measurement range provides the basis for dynamic materials characterisation and particle measuring for a broad range of industrial, academic, and commercial sectors.

This blog post will explore four common applications of enhanced laser diffraction analysis.

- 1. Soil Studies
  The enhanced laser diffraction particle size analyser is used to measure particle or grain size of soil and sediment samples, a property that can be indicative of how a soil has formed.

- 2. Pigment Sizing
  Laser diffraction analysis enabled with polarisation intensity differential scattering (PIDS) can measure particles down to the nanometer scale (nm) by sequentially illuminating a sample with wavelengths of alternately polarised light. This method has been used to reliably size pigment particles as small as 10 nm.

- 3. Quality Control of Chemical Compounds
  Enhanced laser diffraction analysis is uniquely suited to quality control (QC) applications with a superior resolution and unmatched dynamic range compared to conventional laser diffraction techniques. It provides a rapid assessment of the particle size distributions in powder or liquid samples, with well over 100 light detectors enabling the resolution of subtle differences in particle size.

- 4. Research and Development
  Laser diffraction analysis for R&D purposes can be complex as some instruments require prior knowledge of a sample’s particle size characteristics, such as whether a single peak of particles is expected or if they may be more than one population of particles such as aggregates. The LS 13320 XR enhanced laser diffraction analyser does not require this information. The software carries out complex and comprehensive analysis of the diffraction patterns to provide an accurate particle size distribution without any need for the operator having to guess at the expected result.

Enhanced Laser Diffraction Analysis with Meritics

Meritics is the UK’s leading supplier of particle analysis instrumentation for an extensive range of applications. We work with cutting-edge technology manufacturers to provide the most advanced measurement systems available.

The LS 13 320 XR is our most enhanced laser diffraction analysis tool. It is capable of performing in all the aforementioned applications and more. If you would like any more information, please do not hesitate to contact us.

The importance of Multi-Flow Testing?

Written by Sophie Lindsey on July 4, 2024. Posted in How to….

The importance of Multi-Flow Testing?

Revolution Multi-Flow Test

Test Type: Instantaneous Dynamic

Measures: Micro-Structure

Powders can behave very differently depending on the amount of energy they are subjected to as they move through handling equipment. One powder may flow more evenly as it is subjected to more mechanical energy while another powder may become erratic. This behaviour can be studied using the Revolution Multi-Flow Test Method. In the multi-flow method, the sample drum speed is increased gradually over time and the sample powder’s behaviour is measured.

“The Mercury Scientific Revolution Powder Analyser excels in powder analysis, offering exceptional accuracy and efficiency. Its advanced design makes it essential for researchers and manufacturers seeking superior quality control and processing.”

More information on the Revolution

The Multi-Flow Analysis studies how a powder or granular material transitions from avalanching to continually flowing as it is subjected to faster speeds. By gradually increasing the rotation speed in the Multi-Flow Analysis, the user can evaluate the speed at which their powder is no longer avalanching in their process but flowing continuously. This data can be used to predict how powders will behave in high speed equipment.

The Revolution is available in the UK exclusively from Meritics Ltd.

Why do we need to measure Particle Concentration?

Written by Sophie Lindsey on June 21, 2024. Posted in How to….

Why do we measure Particle Concentration?

Determining the particle characteristics of various products and biological materials is increasingly reliant on the measurement of particle concentration, alongside particle size. It is a crucial metric in a range of industries and academic studies, where products are manufactured to microscopic parameters or where quality assurance – or research – must be maintained and carried out at a molecular level.

The process of measuring particle concentration is important to researchers and engineers in biopharmaceuticals, protein aggregation studies, nanomaterial characterization, and more..

This article will explore in more detail the various industries and schools of research which measure particle concentration:.

Nanomaterials are commonly referred to as a material with particles of nanoscale dimensions of between 1 – 1000 nanometers (nm). In 2011, the European Commission clarified that definition to include specific requirements of particle concentration for a material to be categorically defined as nanomaterial. It describes a nanomaterial as: “A natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm – 100 nm.”.

Precise measurement of particle concentration is required to ensure that any new materials are correctly identified and regulated accordingly. This is a crucial metric for materials scientists in a range of fields to consider..

Pharmaceutical

Studying the particle concentration of cell biology allows scientists and researchers to accurately assess drug delivery and optimize biological responses to drug administering by measuring the particle concentration of the delivery vector. It can also help industry leaders to understand drug stability under a range of environmental factors such as temperature and humidity, influencing best practice on how to manufacture and administer a wide range of pharmaceuticals..

Laboratory tests that measure the particle concentration and size of antibodies, white and red blood cells, and platelets in a blood sample are commonly performed in the development and manufacture of vaccines, particularly in the assessment of vaccine dosages and their subsequent performances. It is a crucial factor in the evaluation of immunization success and the analysis of perceived biological resistances.

Despite innovations in emergent materials for use in a range of commercial and emergency service sectors, natural sediments and soils are still a primary material for the implementation of flood protection, foundation-laying for construction, and of course, agriculture. Measuring the particle concentration of soil helps to characterize the applications of various soil samples, for example in the distinction of soil types ideal for drainage and aeration from those that are highly compatible with various crops.

Water Treatment

Specialists in the water treatment sector are required to perform consistent and precise assessments of the cleanliness of drinking water for human consumption. Dedicated metric hardware that analyses the particle concentration of drinking water can quickly determine that samples are free of contaminants, including solids and bacteria, ensuring that water treatment is carried out to stringent industry standards.

Particle Analysis Solutions from Meritics

Meritics is the UK’s leading supplier of particle characterization instruments and laboratory services, with a range of accurate and reliable equipment that is applicable to many disparate fields. These include:

FlowCam Flow Imaging Microscopy (FIM), which can distinguish particles such as protein aggregates from other contaminants from 3μm to several hundred microns, with the provision for accurate particle shape analysis;
The Multisizer 4e, which is the most broadly applied particle counting and sizing instrument, providing high resolution and excellent statistical accuracy, with a sizing range of 0.2µm – 1600µm.

If you would like any more information on the applications of the particle concentration analyzers we supply, please do not hesitate to get in touch.

Particle Size: An Important Factor in Many Applications

Written by amanda-meritics on August 18, 2023. Posted in How to…. No Comments on Particle Size: An Important Factor in Many Applications

Nanoparticle size and concentration analysis

Particle Size: An Important Factor in Many Applications

Particle size is the physical property that describes the size of individual particles in a material. It is an important factor in many applications and industries, ranging from pharmaceuticals, cosmetics, and food production to chemical processing and construction. In this blog post, we will dive into the importance of particle size and how it can impact various applications.

What is Particle Size?

Particle size refers to the size of individual particles that make up a material. The size of these particles can vary greatly, from nanometers to millimeters. The most common way to measure particle size is through the use of a particle size analyser.

Importance of Particle Size

Particle size is an important factor in many fields and industries. In the pharmaceutical industry, for example, the size of drug particles can impact their absorption rate by the body. The smaller the particles, the greater the surface area, which leads to faster absorption. In cosmetics, particle size affects the texture and feel of the product. For instance, in sunscreens, smaller particle sizes are used to allow for easier and more even application, while still providing the UV protection.

In food production, particle size plays an important role in texture and taste. For example, in baking, the particle size of flour can impact the final texture of the baked goods. Particle size also affects the solubility and flow of powders, which is important in the chemical industry. The size of particles in paint can affect its appearance and the ease of application.

The Impact of Particle Size on Properties

Not only does particle size affect the properties of a product or material, but it can also be used to control those properties. For example, in the production of catalysts, the size of the particles can affect their reactivity. By controlling the particle size, researchers can tune the catalytic activity of the material. In the development of drug delivery systems, particle size can be used to control release rates and the stability of the particles.

Conclusion

Overall, particle size is a crucial factor to consider in many applications. The size of individual particles can impact the properties and performance of a material or product. By understanding particle size and its effects, researchers and manufacturers can optimize their products and improve their efficiency.