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Particle Imaging Techniques

What is particle imaging used for?

Where particle size analysis is used to produce a distribution curve showing how large the majority of particles in a given solution are, particle imaging also provides the ability quantify morphological (ie. shape) characteristics of particles.

Determining particle shape parameters

When reporting particle size, we try to report just one single number for each particle; the equivalent spherical size. In image analysis reports, this is often termed the CE diameter (or Circular Equivalent diameter). However, when it comes to reporting particle shape, there are many numerical descriptions that can be used, including: length/width, aspect ratio, circularity, compactness, roughness, convexity and elongation. Most image analysis system also report parameters such as lightness/darkness, opacity and intensity. All of these parameters help differentiate one type of particle to another, which is one of the real strengths of image analysis.

Where particle sizing can only report a size distribution, image analysis can be used to quantify subtle differences in shape or optical properties. New image analysis systems also provide powerful software packages that enable classification of particles into different groups. This in turn enables users to quantify different types of materials in the one sample.

How FlowCAM works

FlowCAM is one of the more popular of the new age particle imaging systems. This system counts, sizes and images particles in a sample. The FlowCAM also provides the option of colour analysis and detection of living organisms by means of fluorescence. The measurement process is as follows:

  • Particles are suspended in water
  • The water is pumped through a flow cell
  • Optics and a CCD camera magnify and capture an image of each particle, measuring its shape and size
  • The results are displayed as a scattergram.
  • The user selects distributions to display, and regions in the scattergram of particular interest can be selected and displayed in more detail.
  • A library of information is housed in the system for screening future samples, if necessary.

Real life applications

In real life, particle size and shape determining technologies like those FlowCAM incorporates are used in applications like:

  • Water analysis for environmental purposes, measuring things like plankton, algal blooms and levels of sedimentation
  • Biotechnological settings, where quantification of enzymes or fermentation processes is needed
  • Process monitoring, which covers most industrial applications – monitoring emulsions and dispersions, and in the polymer and pharmaceutical industries.
  • Formulation monitoring, used for solid substances like topical cosmetics, flavour carriers, inks or pigments.

Find an imaging instrument

If you want to undertake particle imaging, the first step is to get the right instrument for the job. ATA Scientific carries a range of quality scientific instruments suited to your needs. Contact us to find out which instrument you need for particle imaging today.

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Different Methods of Particle Size Measurement

Particle size analysis can seem a complex and intricate area. The thought of attempting to measure and draw conclusions about microscopically small particles can seem incredibly confusing and the techniques used to measure particles can perhaps seem daunting. Particle size analysers are of great use in achieving such measurements and techniques such as laser diffraction assist us to understand more about the properties of materials.

However, in order to understand some of the higher level concepts related to this area, it is necessary to have a sound grasp of the concepts that inform results.

Mean, median and mode

These three terms are too often confused and thought to mean the same thing. Far from being one and the same, these terms require definition:

Mean – Mean relates to the arithmetic average of the data.

Median – When concerned with particles, median is the value of the particle size that precisely divides the population into two halves. This means that there is 50% of the population above and 50% of the population below the value.

Mode – Mode defines the most common value in a frequency distribution. This also corresponds to the highest point of the frequency curve.

Common methods of particle size measurement

Because different dimensions of the particle are measured when different techniques are used, different results are obtained. Of the different methods of measurement, each has its own advantages and disadvantages.

Sieves

While this is an old technique, it has the advantage of being cheap and particularly useful for the measurement of large particles. In industries such as mining, this can be particularly useful.

The main disadvantages associated with this technique include: it is not possible to measure sprays or emulsions and measurement of dry powders is also difficult when particles become small. Wet sieving can help to overcome this problem, but it is then very difficult to reproduce results. Materials such as clay, which are cohesive and agglomerated, are also difficult to measure.

As particles tend to orientate themselves through the sieve, operating methods and measurement times need to be standardised if accurate and meaningful results are to be obtained.

Sedimentation

This has been a common method used (historically) in clay and ceramics industries.

There are two main problems with this process: the density of the material is needed and so it is not useful for determining particle size of emulsions where the material does not settle or for dense materials where the material settles quickly. Samples containing components of mixed density can not be accurately resolved. Measurement of small particles is very slow and therefore the process of repeating testing can be tedious.

Electrozone testing

This technique is very good for measuring red blood cells, but for real, industrial materials there are quite a few problems. It is very difficult to measure emulsions and dry powders and it is impossible to measure sprays. It is necessary to measure in an electrolyte and the required calibration standards are expensive.

Laser Diffraction

This is an often favoured technique that is considered to be one of the most accurate and reliable. It has a number of important advantages:

  • It is very flexible and can measure all types of particles (powders, emulsions, suspensions and sprays)
  • It is very rapid (answers can be produced in less than sixty seconds)
  • It offers an absolute method of particle analysis that is grounded in scientific principles and makes it possible for measurements to be taken without the need to calibrate any instrument against the standard
  • The technique provides a very wide and dynamic range
  • It is possible to measure an entire sample
  • The technique is highly repeatable.

Combine technique with instrument

The technique used to measure particle size will depend on the material being analysed, and the instrument used should be one of the highest quality. ATA Scientific is a trusted brand selling a range of scientific instruments suited to measuring particle size. Contact us today to find the right instrument for you.

Looking for the perfect analytics instrument for YOUR next big discovery?

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Using Laser Diffraction for Semisolid Formulations

Because they provide a solution to issues of bioavailability often seen in new drug candidates, semisolid drug formulations are becoming more and more common. These days, they make up a significant proportion of pharmaceutical dosage. When it comes to semisolid drug production, particle size is an undeniably crucial parameter. For this reason, finding an appropriate particle size analyser is of the utmost importance.

In this article, we’ll look at laser diffraction, a widely used method of particle size analysis that can be used for semisolid formulations at elevated temperature.

Why semisolids?

Something like 40 per cent of new chemical entities are challenging to modern drug delivery systems because of their poor aqueous solubility and low bioavailability. Semisolid formulations offer an answer to this problem. Additionally, patient compliance is improved, as semisolid products can be delivered painlessly and with minimal side effects.

Some examples of semisolid drugs include topical creams used for localised skin layer action (eg. Antiseptics and anaesthetics); as well as transdermal drugs that enter the body percutaneously. Semisolids have gained particular traction in transdermal delivery thanks to advances in delivery technology, such as slow release patches. When a transdermal patch is applied to the skin, the drug will enter the blood either through sweat ducts, hair follicles or the stratum corneum (the outer layer of the epidermis). However, the potential of the transdermal drugs to deliver the active ingredient is reliant on the semisolid’s rheological properties.

What makes a good semisolid?

The efficacy and safety of semisolid compounds are largely down to particle size and size distribution. These can have profound effects on bioavailability, dose uniformity and more. The relationship between product performance and particle size can be examined with data generated from the laser diffraction method of particle size analysis, which rests on the idea that particles that move through a laser beam will scatter light at an angle proportional to their size.

By applying stringent techniques in designing its particle size, the local efficacy of a drug’s entry can be maximised, and adverse reactions can be prevented. However, if settling or sedimentation occurs, efficacy will often be compromised due to irregular delivery.

Some of the methods of particle size analysis that have been used over the years include X-ray tomography, confocal imaging and scanning electron microscopy. However, these can usually only be applied while the product is being developed, and usually only with a small amount of material, which can cause problems when trying to characterise larger samples.

Laser diffraction: Why it’s the way forward

Laser diffraction, on the other hand, allows for very rapid measurement, accurate analysis, a broader measurement range, and the capability of looking at many sample types. One of its best properties is its sensitivity to changes in coarse particle fraction which makes it great for studying the instability that results from sedimentation or agglomeration. Additionally, the latest laser diffraction systems are completely automated and user-friendly.

One of the problems with using laser diffraction for semi-solids, however, is that samples are not liquid at room temperature. To deal with this, the laser diffraction system can be equipped with a dispersion cell and water bath, elevating the temperature to make more detailed particle size measurements.

Find the right particle size analyser

It’s important that you not only use the best method for analysing semisolid formulations at elevated temperature, but also use the best instrument. ATS Scientific is a trusted brand that offers a range of quality particle size analysers. Contact us today for more information.

Looking for the perfect analytics instrument for YOUR next big discovery?

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Particle Size Analysis: A Glossary of Terms

In the fascinating world of particle size analysis, there are many difficult terms that you may need to get to grips with. Here we’ve provided a glossary of terms from Agglomeration through to Zeta Potential — it’s truly an A to Z of particle size analysis.

Agglomeration

A jumbled collection or mass of particles that have collected together; furthermore, the collection of these particles is known as “agglomeration”.

Aqueous solubility

Measured by weight, this refers to the maximum percentage of a substance that dissolves in a unit volume of water.

Bioavailability

The extent to which a living organism is able to absorb a drug into its systemic circulation. Bioavailability is important in ensuring drugs have their desired effect in the body.

Chromatography

A method of separating a mixture of compounds by passing them through a medium in which the components progress at different rates.

Coarse particle fraction

The percentage of a material which is composed of large particles.

Dose uniformity

The extent to which the active material within a sample of dosage units remains uniform. It is usually expressed as a percentage of the average content.

Hydrodynamic volume

The overall volume of a polymer when it is situated within a solution. The hydrodynamic volume can be measured by the way the polymer behaves in that solution.

Laser diffraction

A technique for measuring particle size which is predicated on the idea that particles moving through a laser beam will scatter light at an angle directly proportional to their own size. Laser diffraction is one of the most effective methods of particle size analysis.

Milling

The grinding of materials into smaller particles.

Oligomer

A molecule that consists of just a few repeating units, or monomers, which bind together chemically.

Particulate

Small subdivisions of matter that can be found suspended in a gas or liquid.

Percutaneous

Anything which is administered or absorbed through the skin, such as an injection or transdermal drug.

Polydisperity

The state of having a broad range of particle sizes within a semisolid; this stands in opposition to monodispersity, where the particles are all of the same size. Polydispersed materials tend to pack better than monidspersed materials.

Polymer

A large molecule composed of many repeating units, or monomers, which bind together chemically.

Rheology

The study of the deformation and flow of matter, usually in reference to the flow of liquids but also sometimes to semisolids.

Sedimentation

A naturally-occurring process whereby solid particles settle out of the fluid carrying them and come to rest against a barrier.

Semisolid drug

Otherwise referred to as simply a ‘semisolid’, it’s a pharmaceutical product that has some properties of solids and some properties of liquids. Common examples include creams, ointments or gels.

Shear rate

The rate that contiguous fluid layers move in relation to each other.

Size Exclusion Chromatography

A form of chromatography whereby molecules in a solution are separated based on their varying hydrodynamic volume.

Transdermal patch

A patch which is applied to the body in order to administer a certain amount of drugs through the skin and, subsequently, into the bloodstream.

Viscosity

The resistance that a liquid shows to being deformed by sheer stress.

Zeta potential

The effective charge on a particle that is immersed in a liquid.  This can have a significant effect on the stability of particles in suspension.

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The Methods of Gel Permeation Chromatography

In this particle size analysis article, we’ll take a look at two brilliant new methods of gel permeation chromatography (shortened to GPC). Specifically, we’ll look at the benefits of using light scattering detectors and viscosity detectors, as well as how these methods can be combined with more traditional GPC methods such as refractive index detection in order to get the best results.

What is GPC?

In its traditional form, gel permeation chromatography (GPC) is a proven and effective method for determining average molecular weight of polymers and small molecules. It also enables us to ascertain the overall molecular weight distribution. However, conventional GPC does have its limitations. For example, the molecular masses provided by conventional GPC are all relative. In GPC molecules are separated according to hydrodynamic volume, not molecular weigh.  Molecular weights and molecular weight distributions are determined by comparing retention times with molecular weight standards. A calibration curve is utilised in order to achieve this.

Since this really depends on the polymer that is being used, true molecular masses can only be determined if the samples are precisely the same structure. This shortcoming can lead to large deviations occurring in branched samples, as their molecular density is significantly higher than that of linear chains.

The most common detectors used in conventional GPC are:

  • Refractive Index (RI)
  • Ultraviolet (UV)

However, their signals rely on concentration only, not on polymer size or molecular weight. As we’ve already mentioned earlier in this article, light scattering detectors and viscosity detectors have been shown to fix the problems that have for a long time been associated with conventional GPC.

Light scattering detectors

The signals that are provided by static light scattering detectors are directly proportional to the molecular weight of the polymer, as well as concentration of molecules and their refractive index. So the advantage of using static light scattering detectors in GPC is that molecular weight can be gleaned without the need to create a calibration curve.

Viscosity detectors

The signal provided by viscosity detection is relative to intrinsic viscosity and polymer concentration. Intrinsic viscosity is inverse to molecular density, so measurement of intrinsic viscosity gives a good indication of molecular structure.

The famous Mark-Houwink plot shows the double logarithmic plot of molecular weight against intrinsic viscosity. It’s an important plot when it comes to polymer structure analysis, as it mirrors structural changes in the polymer (such as chain rigidity).

By their powers combined

By using the advantages of refractive index detectors, light scattering detectors and viscosity detectors, triple detection can be achieved. Light scattering enables accurate molecular weights to be determined; intrinsic viscosity provides structure information; and concentration gives quantitative ratios of different species. It also enables the differentiation of monomers, dimers, trimers and aggregates.

ATA Scientific offers scientific instruments that can be used for GPC and other associated processes. Contact us today for more information on how we can help you find the right instrument.

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Understanding and Choosing a Particle Size Analyser

Research today would not be so advanced and precise were it not for the existence of Particle Size Analysers. Without these pieces of equipment, much research would be incredibly different to carry out and benefits realised through science may not be known.

What are the Benefits of Particle Size Analysers?

There are a range of benefits from using a Particle Size Analyser, including:

  • Accurate and effective results are delivered in the form of readouts.
  • In a particular sample, particle size analysers identify the size and allocation of particles.
  • The size and shape of particles can be determined from various states of matter – this enables laboratories to examine and analyse many different types of samples and means that research is not limited or likely to omit important features.

Important things to know about Particle Size Analysers

There are a few key things to know about Particle Sizer Analysers that you may not already be aware of, including:

  • Not all Particle Size Analysers are the same. As different pieces of equipment are developed in different ways, some pieces will be better suited for particular purposes and use in different contexts. For example, particular models will be best suited to analysis of specific materials and samples.
  • Different models of Particle Size Analysers are likely to produce different results. This is influenced by whether the device being used is appropriate for analysis of the sample being studied. It is necessary to match devices with samples.
  • As a result of integrity within the industry, significantly flawed and problematic models are not generally available. Having said this, machinery is always subject to malfunction and occasionally devices may have defects. Sometimes, transportation of devices can cause some damage. To counter this, it is important and good practice to carefully inspect all models when they are delivered.

Deciding on a Particle Size Analyser

Because Particle Size Analysers are such a vital piece of equipment for any laboratory and necessary for determining the size and shape of particles, the decision of which one to choose to best meet needs should not be made lightly.

Modern and best quality Particle Size Analysers can today include features such as a short optical bench and intuitive software. Added to this, some devices are capable of analysing both wet and dry materials. An automated microscope and high resolution camera are also features of some state of the art devices. In best quality systems, these features are streamlined and integrated to form an imaging workstation.

Particle Size Analysers are highly specialised pieces of equipment that fulfil an important need; they are unique and so respected for their capacity to determine particle size and shape. Versatile and able to be used to enhance practice and processes in a variety of industries, Particle Size Analysers assist companies to avoid costly errors, damage to machinery and reduced productivity. When companies and industries have greater intelligence about the materials being used, the most effective methods of working can be applied.

Of course, companies should consider such an important investment carefully. Time and research should be prioritised to ensure that a Particle Size Analyser is chosen to best meet the needs of the business. Advances made in research today illuminate the benefits of these devices and the potential they have for enhancing processes and ultimately, the quality of final products.

Choose ATA Scientific

ATA Scientific is a trusted supplier of scientific instruments, offering a range of instruments suited to your needs. Browse our product range today to find the right Particle Size Analyser.

Looking for the perfect analytics instrument for YOUR next big discovery?

Speak with the ATA Scientific team today to get expert advice on the right instruments for your research

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The Benefits of the Zetasizer

In order to be effective, topical oil-based products, or ‘semisolid’ drugs, need to be able to penetrate the skin in a manner that allows them to be delivered to the body’s circulation. Whether it’s for beauty, medicine or any other purpose, the challenge of delivering semisolids into the body is crucial to the success of any given semisolid product.

Measuring the size of particles within these semisolids is the key to ensuring the product is delivered in the most effective manner. Various methods of particle size measurement or analysis are used to measure these materials, including laser diffraction and dynamic light scattering. Further to this, by using an instrument called the Zetasizer, scientists can also understand the variable effects of pH and temperature on the delivery system.

Dynamic light scattering

In order to guarantee the size of the nanoparticles remains consistent at the pH and temperature that will be found on the human body, the process of dynamic light scattering (DLS) can be used. DLS measures the intensity of scattered light from particles suspended under Brownian motion, before analysing fluctuations. DLS is so sensitive that it can track changes in particle size to less than 1nm across, making it very nicely suited to examining potential particle size shifts in the human body.

pH and temperature changes

By studying the effect of pH changes on the nanoparticles, we can finely tune the molecular change that may result when being applied to the human body. For example, when pH values are low, the diameter of the particles increases; if the pH level is raised again, then it will be restored to its former size. Using this technique allows us to control the size of the nanoparticles in the body. Alternatively, we can also use temperature instead of pH; higher temperatures make nanoparticles more hydrophobic, resulting in larger particle sizes.

An example

Take, for example, the Lipodisq delivery system, which copies the way naturally-occurring HDLs [high-density lipoproteins] bind cholesterol in the body. The nanoparticles of the Lipodisq system are able to find a way through the skin while still carrying the pharmaceutical agents with them to be delivered into the bloodstream – but they need to be exactly the right size. In fact, the suitable size range is very small; if the nanoparticles are larger than 50nm (nanometres) in size, they will not be able to breach the outer layer of the skin. If they’re less than 5-10nm, they will be too unstable to properly transport the required ingredients. Therefore, these nanoparticles must fall somewhere between 10nm and 50nm in order to be effective.

Using the Zetasizer

Particle size analysis technology is already having dramatic benefits to the pharmaceutical industry as the ability for executing controlled releases of semisolids into the body is increased. Any method that achieves particle size measurement can go a long way to aiding in this regard, but the fact that the Zetasizer is capable of taking into account variables such as pH and temperature make it an outstanding tool and one that will undoubtedly be used on a more regular basis.

ATS Scientific offers a range of Zetasizer instruments, so browse our product range today to find the right one for you.

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Using Dynamic Imaging Particle Analysis to Characterise Biologics

In recent years we have seen an increase in the role of biologics in medicine. Biologics are medicinal products that are created by biologic processes instead of chemical synthesis; these include products such as blood, vaccines, gene therapy, allergenics or somatic cells. Because of the increased role of biologics, the need to characterise particulate matter within those biologics has increased as well. In this article, we’ll take a look at how dynamic imaging particle size analysis is being used to characterise particulates in biologics, as well as some of the factors that need to be considered when using the technology.

The early days: Light Obscuration

In the early days of particle analysis in biologics, analysts used light obscuration techniques to attempt characterisation, but this method meant they faced a few hurdles. These were as follows:

The transparency of aggregated proteins

Biologics are subject to protein aggregation — that is, the formation of larger particles from a combination of smaller ones. Because aggregated proteins are transparent or “soft”, they are much tougher to detect than opaque particles, and light obscuration technology was not always able to detect them.

The amorphousness of aggregated proteins

The shape of the aggregates vary from circular to strand-like shapes. Light obscuration devices are capable of measuring size, but they assume that the particles are spherical in shape. Because aggregates could be absolutely any shape, many measurements were inaccurate.

The biologics are delivered through pre-filled syringes

This could result in silicone droplets being present, and might also result in inflated particle counts.

The introduction of Dynamic Imaging

A dynamic imaging particle size analyser, on the other hand, is capable of making various measurements even if the particle is transparent. It works by capturing digital microscopic images of biologic particles as they make their way through a flow cell. The result is a more detailed description of the particle and its shape, which also allows for analysts to recognise the difference between aggregates and silicone droplets.

Dynamic Imaging limitations

It would seem, then, that dynamic imaging has solved the problem of characterising biologics — but that’s not to say that the technology is perfect. In particular, there are three factors that analysts must consider whenever characterising biologics with the use of dynamic imaging. These are:

Resolution

Digital images don’t show the real world in the same way that the human eye does. Instead, images are pixelated, which means dynamic imaging systems can only count particles that are no smaller than 1µm, and can only differentiate shape for particles larger than 2-3µm. Electron microscopy is needed to measure particles smaller than these limits, but such a technique has many shortcomings of its own.

Colour threshold

Images are not only limited in size; they are also limited in their colour scale. Because imaging systems are backlit, particles in the optical path reduce the light that passes through to the camera sensor and, as such, the incoming pixel intensity becomes darker. This works fine for opaque particles, but not so well for the transparent protein aggregates. Additionally, the amorphous nature of the aggregates causes light to bend awkwardly around the structure, creating further confusion.

Image quality and sharpness

This great effects on the precision of particle measurements. The less sharp the image, the lower the accuracy when attempting biologic characterisation.

Finding a particle size analyser

Particle size analysers play a key role in biologics, so it’s important that you one you use is of a high quality and from a trusted supplier. ATA Scientific offers a range of quality particle size analysers perfect for characterising particulates in biologics. Contact us today for more information.

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How to Choose a Scientific Equipment Supplier

When you’re investing money in scientific equipment, such as a laser diffraction particle size analyser, it’s important to investigate your options before making a final decision. These days getting value for money is just one of the important considerations you need to make.

Naturally, the complexity of scientific equipment means that it is important not only to choose the equipment itself but also the supplier as well. After all, equipment of such high sensitivity and precision will undoubtedly require the backup of a supplier capable of continued support long after the deal is sealed.

That’s why it’s important to look at the supplier with a critical eye to make sure you are going to get value for money and also professional backup when you need it. Whilst it is true that all manufacturers have a legal responsibility when it comes to supplying any piece of equipment, it will be of little comfort to an aggrieved purchaser if the supplier only wants to perform its legal requirements.

What you need is reassurance that your supplying company will stand beside you over the long term and be capable of providing any assistance necessary to keep your equipment in prime operating condition.

Criteria for choosing a supplier

With this in mind, let’s take a look at some of the criteria against which you should assess your scientific equipment supplier.

Testing

In the first place, you should be looking for the equipment to receive pre-sales testing to ensure that it is properly certified and that the manufacturers requirements are being met. This is often the first sign of a quality supplier and it should be offered upfront at no cost.

Training

Don’t underestimate the training requirements. New pieces of equipment often require some time to get used to, that’s why it’s important to anticipate any training needs that will be necessary to bring your staff up to speed with the new purchase. It is at this point that you need to reassure yourself that the supplier can also provide the on-site training you will need.

Maintenance

All equipment needs to be maintained in accordance with the manufacturer’s specifications and with any regulatory requirements that are in place. Make sure your scientific equipment supplier is in a position to offer this.

Repairs

There will be times when equipment needs to be repaired so it is imperative to ensure that your supplier is in a position to do this. Every quality supplier should have a well equipped workshop and also be flexible enough to provide you with an on-site repair service.

Stock

If your equipment requires the regular supply of consumables, make sure your supplier is able to provide these for you ex-stock. There is nothing more frustrating than waiting for supplies to be imported not to mention the costly downtime you will experience.

Choose ATA Scientific as your supplier

These simple steps make it easier to purchase something like a particle size analyser by choosing a competent scientific equipment supplier which gives you the peace of mind that you need when making such a significant investment. ATA Scientific is a trusted supplier of scientific instruments, so contact us today to find out how we can help you find the instrument you need.

Looking for the perfect analytics instrument for YOUR next big discovery?

Speak with the ATA Scientific team today to get expert advice on the right instruments for your research

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