kromasil_classic_silica_3.5_micrometers kromasil_classic_silica_10_micrometers
In figures 1 and 2, the SEM photographs of Kromasil 3.5 μm and 10 μm are shown.

This is Kromasil

  • high surface area
  • mechanical strength
  • chemical stability
  • chemical purity
  • optimized surface properties
  • well-defined pore structure

The Kromasil Classic silica matrix

Kromasil Classic silica packings are designed to meet the highest demand in HPLC, SFC and SMB from analytical to process scale. The uniqueness of Kromasil Classic high performance spherical silica is the combination of:

  • high surface area
  • mechanical strength
  • chemical stability
  • chemical purity
  • optimized surface properties
  • well-defined pore structure

Kromasil HPLC silica consists of perfectly spherical, totally porous particles. Kromasil is produced in pore sizes 60 Å, 100 Å, and 300 Å.

Kromasil 60 Å is the choice for small, organic molecules when a large, accessible surface area, and thus loadability and capacity, is required. Kromasil 100 Å is used for molecules up to about 10,000 in molecular weight, and Kromasil 300 Å for larger proteins or biomolecules.

Particle sizes available are 1.8, 2.5, 3.5, 5, 7, 10, 13 and 16 μm (larger particles can be produced upon request), all with a narrow particle size distribution for high efficiency, low pressure drop, and best total economy in chromatographic purifications. Surface chemistries include SIL (bare silica), C4, C8, C18, Phenyl, NH2, Diol, and CN.

kromasil_classic_silica_3.5_micrometers kromasil_classic_silica_10_micrometers
In figures 1 and 2, the SEM photographs of Kromasil 3.5 μm and 10 μm are shown.

Of silica particles and analytical HPLC

There are several important properties to be taken into account in the development of a silica matrix for analytical HPLC. The following will have a fundamental impact on the overall performance in analytical HPLC:

Due to the number of properties, as well as superimposed effects of them, it is of utmost importance for us to be able to manufacture a silica with extremely high batch to batch reproducibility. Kromasil silica is the perfect choice for your normal phase (NP) applications but also the ideal platform for derivatization of our new stationary phases.

Kromasil 3.5 μm
Figure 1 | FE-SEM image of Kromasil 100 Å, 3.5 μm particles.

Particle shape

Having perfectly spherical silica particles, like the Kromasil silica shown in figure 1, is not enough.

At least not for us! Several silicas on the market are almost spherical, but have cracks and rough surfaces. As you can see on the FE-SEM image the Kromasil silica has a smooth surface. Combining perfectly spherical silica with a very smooth surface is a great combination when you are looking for a silica with a long lifetime and ideal packing properties.

Pore size and pore volume

What is the perfect pore size? It all depends on the size of the molecule you are trying to separate. Today, Kromasil offers the following pore sizes:

60 Å, 100 Å, and 300 Å.

The pore volume is optimized to give the highest available surface area without loosing mechanical strength. This combination is achieved by optimization of several different manufacturing steps.

Particle size and particle size distribution

particle size distribution
Figure 2 | Particle size distribution showing the dv90/dv10 ratio.

A narrow and above all consistent particle size distribution leads to a column with maximum efficiency and bed stability. By having a narrow particle size distribution you automatically avoid high back pressure due to a low bed porosity. In order to define and secure a narrow particle particle size distribution we use the dv90/dv10 ratio in our quality control (QC) procedure, figure 2.

Particle size and particle size distribution are measured by the electrical sensing zone method. In order to obtain the true particle size, mass calibration is used to compensate for the porosity of the particles. It is essential to understand this ratio and how it is calculated since it is an important factor for the overall HPLC performance. In the market place today several different definitions occur. In order to conceal a wide particle size distribution, quite often the dv90/dv40 ratio is used. Always ask the manufacturer how the particle size distribution is measured and how they calculate it!

Surface properties

The Kromasil surface is topographically smooth and completely free from micro cavities. The surface silanol groups are evenly distributed and relatively neutral in their nature. These factors combined with the high reproducibility of the Kromasil silica surface is the foundation for a reproducible bonding process and derivatized product.

Metal impurities

metalic ions in silica matrix
Figure 3 | The effect of metal ions in the silica matrix and in the silica surface layer.

Strongly bound metal ions present in the silica bulk and in the surface layers are in most cases the outcome from the silica manufacturing process. These metal ion species should be distinguished from adsorbed metal ion species, introduced in the final product due to use of metal ion containing solvents, chemicals etc. Adsorbed metal ion species are often possible to remove during a regeneration process, in contrast to the “built-in”, strongly bound, metal ions, which are part of the final product.

It is well known that strongly electronegative metal ions (e.g. bivalent iron and trivalent aluminum), in the silica matrix, have the ability to enhance the acidity of silanols in their close proximity, figure 3. 

Increased acidity of silanols provides a higher possibility for ion-exchange interactions at any given pH. Moreover, metal ions present in the silica surface layer are able to interact directly with analytes having Lewis-base properties, figure 3. The direct metal-analyte interaction is most pronounced for chelating substances, but it also affects the chromatographic behavior of acids, alcohols, amines etc. Kromasil uses a proprietary manufacturing process. The metal content in all reagents and raw materials are minimized due to a rigorous QC procedure.

Superior loadability and lifetime

The superior loadability and lifetime mean you can reduce the cost for solvent and other parts, and increase productivity.

Kromasil’s business idea since its introduction in 1988 is to offer you the lowest possible total separation cost by providing the highest quality silica-based HPLC, SMB and SFC packing material available. The superior loadability and lifetime mean you can reduce the cost for solvent and other parts, and increase productivity. The packing material is at the heart, and the single most important factor that determines the performance of your processes.

  • High available
    surface area
  • High loadability
  • Improved productivity
    /reduced costs
  • Excellent mechanical
    and chemical stability
  • Long lifetime
  • Improved productivity
    /reduced costs

High loading capacity is key

cost_distribution
The figure shows a real life separation of a chiral compound, with a typical cost distribution between solvent, lost crude, labor, system and packing cost. The solvent normally dominates, making up 50–80% of the total cost. An increase in loadability and productivity will create big savings in this sector.

High loading capacity is key to high productivity and the best total economy in your industrial scale HPLC, SMB or SFC.

The kromasil paradox

A high surface area can be obtained by increasing the pore volume. However, this will normally result in a very weak material, with low mechanical strength.

Kromasil combines a high pore volume, result- ing in a high surface area, with extremely high mechanical strength. This is unique among silica-based packing materials.

In addition, the pore size distribution is very small, resulting in a high available surface area. For every application you have, there is an optimal pore size that will maximize the loading capacity.

Surface chemistry and selectivity

In reversed phase hplc, the type and density of the ligands will determine how much you can load onto the column. Kromasil’s well-defined chemistry, with a high density of adsorption sites, ensures that the peaks will remain narrow even under high loading. At the end of the day, this is what gives you a cost-effective hplc process.

High mechanical strength is crucial

To ensure a problem-free process, with no breakdown of the particles, high mechanical strength is crucial.

Why high mechanical strength?

The primary reason is to withstand mechanical stress in the column. A silica packing is also often exposed to high mechanical stress when unpacked and packed again in production.

Frequent packing and unpacking requires a very stable packing material where no fines creation can be tolerated. If fines are formed in any part of the process this will result in an increasing back-pressure. Eventually the pressure limit for the system is reached, and the column has to be repacked with new material.

The factors behind a stable material

The Kromasil particles are essentially perfectly spherical. In addition, the pore shape and struc- ture is more regular than other materials. The result is mechanical strength that allows extremely high piston pressure in your column.

Many Kromasil customers perform Cleaning In Place (CIP) using highly alkaline conditions to remove adsorbed polypeptide impurities, especially in insulin purification. Such conditions will quickly break down less stable materials mechanically. But with Kromasil, you can apply CIP over and over again.

Chemical stability

A purification process of a pharmaceutical or a biopolymer can consist of steps at very low or very high pH — for the chromatography and for the cleaning procedure.

The secret of the bonded phase

At low pH the bonded phase can be hydrolyzed, resulting in a less hydrophobic surface and reduced retention times for lipophilic compounds. Kromasil’s high ligand coating density, with an efficient end- capping, will ensure a low degree of hydrolysis. For high pH conditions, Kromasil’s extensive coating will ensure that the alkaline mobile phase to a large extent will be kept away from the silica surface.

A stable silica matrix

The Kromasil silica matrix is produced using a sol-gel technology, resulting in a very regular structure. After the gelling, the particles are subjected to several further steps to improve both the chemical and mechanical stability. The result is a superior silica matrix. So even if the silica surface is attacked by an alkaline mobile phase, the matrix itself will be extremely resistant.

All in all, the result is the long lifetime of Kromasil packing material.

Scalable and back-integrated

The beauty of Kromasil is that you always get the same high performance regardless of column size.

With you all the way ...

With Kromasil you always experience the same high performance, regardless of column size.

MAN_SYST_CERT_ISO9001_ISO14001_COL
ISO 9001 and 14001 certifications.

The secret is that we produce a large silica batch and then fractionate it. This way, we can offer the entire range of available particle sizes in any amount.

Whether you choose to purchase a small col- umn, or hundreds of kilos for large-scale produc- tion, the silica will come from the same batch. This means that properties such as particle size distribution, selectivity and loadability are identi- cal, making it easy to scale up.

... And back again

Kromasil is back-integrated from the silica raw material to the finished bonded silica-based packing material. Less than a handful of suppliers worldwide control the entire manufacturing process as well as Kromasil, or come even close to the multi-ton per year production capacity of Kromasil.

Technical support

Kromasil not only supplies the packing material itself, but is also a leader in the field of developing and optimizing methods for the separation.

The Kromasil team has accumulated a wealth of know-how over the years, and is always on hand to help you with questions or problems that arise. With broad experience of separating complex substances around the world, our chemists and chemical engineers can usually pinpoint any problem simply through a dialog with the customer.

Our applications group can also perform a method development for your application, and optimize the running parameters to give you the most economical separation process possible.

In addition, the application guide can help you find suitable conditions for listed or similar compounds.

A global network for support

Kromasil has a global network of dedicated distributors for pre-packed columns and smaller amounts of bulk packings.

The Kromasil Classic products are available packed in columns, from 2.1 mm ID up to 50 mm ID, or as bulk, from gram quantities up to several metric tons. The Kromasil manufacturing plant has probably the largest capacity for producing high quality spherical HPLC packing material in the world. Kromasil products are in-house developed and manufactured in order to be the perfect choice from analytical to process scale liquid chromatography.

Phase availability overview

Silane for Kromasil SIL

Kromasil SIL

Pore sizes: 60 Å, 100 Å and 300 Å

Particle sizes: 1.8, 2.5, 3.5, 5, 7, 10, 13 and 16 μm

Silane for Kromasil CN

Kromasil CN

Pore sizes: 60 Å

Particle sizes: 5, 10 and 16 μm

Silane for Kromasil C4

Kromasil C4

Pore sizes: 100 Å and 300 Å

Particle sizes: 1.8, 2.5, 3.5, 5, 7, 10, 13 and 16 μm

Silane for Kromasil Diol

Kromasil Diol

Pore sizes: 60 Å

Particle sizes: 5 and 10 μm

Silane for Kromasil C8

Kromasil C8

Pore sizes: 100 Å and 300 Å

Particle sizes: 1.8, 2.5, 3.5, 5, 7, 10, 13 and 16 μm

Silane for Kromasil NH2

Kromasil NH2

Pore sizes: 100 Å

Particle sizes: 3.5, 5, 7, 10, 13 and 16 μm

Silane for Kromasil C18

Kromasil C18

Pore sizes: 100 Å and 300 Å

Particle sizes: 1.8, 2.5, 3.5, 5, 7, 10, 13 and 16 μm

Silane for Kromasil Phenyl

Kromasil Phenyl

Pore sizes: 100 Å

Particle sizes: 5, 10 and 16 μm

Silane for Kromasil HILIC-D

Kromasil HILIC-D

Pore sizes: 60 Å

Particle sizes: 5 and 10 μm

Kromasil Eternity

 

Product overview

Kromasil Chiral

 

Product overview

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