No thanks! I would like to know more about CHROMacademy

 Over 3000 E-Learning topics / 5000 Articles & Applications
 

thermo The CHROMacademy Essential Guide:
Core Shell Particles – Present and Future

30th April 2013 11am EST / 4pm GMT

In this session, Dr Fabrice Gritti and Scott Fletcher (Technical Manager, Crawford Scientific) highlight
the benefits of core-shell particle technology and the reasons behind their surprisingly high efficiency.

They will also discuss where core-shell particles fit against other efficiency improving measures such as the use of sub 2μm particles with high pressures and also narrow bore HPLC columns. They will discuss the benefits of using larger and smaller particle size core-shell particles and how particle size and particle morphology might be used to achieve separation requirements. The interesting topic of core to shell thickness ratio will be investigated which will in turn lead to a discussion of current limitations and future possibilities with core-shell technology.

core shell particlesTopics covered include:

  • What are the practical benefits of core-shell particles
  • What’s the real secret behind their high efficiency
  • Will core shell’s high efficiency lead to a reduction in the number of stationary phases required?
  • Why can’t we realise the true benefits of core-shell’s in narrow columns
  • Practical limitations of core-shell particles and core to shell thickness ratio
  • Sub-2μm core-shell particles – what’s the real benefit?
  • Core-shell’s for preparative chromatography
  • The future – what can we expect from these particles?

Who Should Attend:

  • Anyone working with HPLC
  • Anyone interested in current and future developments in HPLC column technology

Find out more about this Month's Essential Guide Webcast »

The Camtasia Studio video content presented here requires JavaScript to be enabled and the latest version of the Adobe Flash Player. If you are using a browser with JavaScript disabled please enable it now. Otherwise, please update your version of the free Adobe Flash Player by downloading here.

 

If you have any more questions on this or any other topic - please post them on our forum >>

The CHROMacademy Essential Guide Tutorial
Core Shell Particles – Present and Future
- Available late April 2013

In this session, Dr Fabrice Gritti and Scott Fletcher (Technical Manager, Crawford Scientific) highlight
the benefits of core-shell particle technology and the reasons behind their surprisingly high efficiency.

They will also discuss where core-shell particles fit against other efficiency improving measures such as the use of sub 2μm particles with high pressures and also narrow bore HPLC columns. They will discuss the benefits of using larger and smaller particle size core-shell particles and how particle size and particle morphology might be used to achieve separation requirements. The interesting topic of core to shell thickness ratio will be investigated which will in turn lead to a discussion of current limitations and future possibilities with core-shell technology.

  ask the CHROMacademy experts

Share this tutorial

World renowned expert Dr Fabrice Gritti and Scott Fletcher take a detailed look at modern core-shell particles.  They start of by reviewing and practically positioning chromatographic efficiency and then trace the history of core-shell particles, in their many guises, right through from their inception in the late 1960’s to the modern particles available today. 

They examine the morphology of modern core-shell particles and review the increased efficiency these particles offer as compared to their traditional fully porous equivalents. They then move on to explain the real reason why modern core-shell particles enjoy the efficiencies they do and examine how they are affected by reducing the column internal diameter.  Latterly they look at their limitations and discuss whether core-shell particles will ever make their way into preparative columns. 

Finally they look to what the future holds for these particles in terms of pH and pressure stability and optimization of particle size and core-to-particle ratio.

 
 

High Efficiency Separations – Benefits and Plate Theory

There are two main benefits associated with high efficiency separations;

  • Increased resolution of complex mixtures
  • Higher throughput via faster separations (i.e. the required resolution is achieved in a shorter timeframe)

The efficiency of a chromatographic peak is a measure of the dispersion of the analyte band as it travels through the HPLC system and column. In an ideal world, chromatographic peaks would be pencil thin lines – however, due to dispersion effects the peaks take on their familiar ‘Gaussian’ shape (or often slightly tailing shape in my case!).

The plate number (N) is a measure of the peak dispersion within the HPLC system and HPLC column, and reflects the column performance. N is derived from an analogy of Martyn and Synge who likened column efficiency to fractional distillation, where the column is divided into ‘Theoretical Plates’.  Each plate is the distance over which the sample components achieve one equilibration between the stationary and mobile phase within the column. Therefore, the more (‘theoretical’) plates available within a column, the more equilibrations possible and the better quality the separation.  The method of calculating column efficiency is shown below in Figure 1. A typical plate number for a 4.6 X 100 mm column with 5 µm particles is between 5000 and 8000.   Of course from a practical perspective, for a given column length, higher plate counts dictate higher efficiency, narrower peaks and an increased chance of achieving the required minimum resolution.

Higher values for the Plate Number (N) are expected for each successive peak within a chromatogram.  Later eluting peaks that look broad in comparison to early eluters may have a higher plate count – remember that efficiency is a measure of band broadening as a function of time

If each successive peak within your chromatogram does not have an increasing value for the plate count (N) then your system contains a large extra-column dead volume, which is dictating the overall system efficiency!

Determination of Efficiency

Determination of Efficiency

Figure 1. Determination of efficiency.

 
 

Factional Distillation Model of Efficiency Theory

When ‘cracking hydrocarbon fractions, more ‘Plates’ there are – the narrower the distribution of carbon numbers from each trap (or plate) within a fractional distillation tower (see the animations in Figures 2 & 3).  Therefore – the higher the number of plates (N) the narrower the ‘peak’ obtained from that trap – this can be directly related to the peak ‘efficiency’ in HPLC where a column with a high number of plates gives narrower (more efficient) peaks.

 

Figure 2. High efficiency distillation process with many plates.

Figure 3. Low efficiency distillation process with only a few plates.

 

Similarly – for a fractionating tower of a given length (L), the higher the number of plates, the lower the distance between each plate, shown as plate height in Figure 2.  Therefore, for high efficiency separations, the plate number (N) should be high and the plate height (H) low.  Note that plate height is often called – ‘Height Equivalent to a Theoretical Plate (HETP)’ These two terms are related through the expression:  H = L / N   (1)

Another important expression which is becoming increasingly popular is that of reduced plate height, as introduced by Giddings. [1]

Reduced plate height (h) is a dimensionless term is calculated by dividing the plate height by the mean particle diameter (dp): h = H / dp

 
 

High Efficiency Separations – Practical Uses

HETP (H) is more convenient term for us to use because if we increase (N) (through the use of new high efficiency particle technology) but the column length (L) remains constant, a decrease in H will be observed. The benefit of this approach is that although analysis time, solvent usage etc. will remain the same, the resolution will be increased, so increasing the number of components which can be separated using the column. Traditionally efficiency (N) has been increased by increasing the column length – this approach is limited however in that longitudinal molecular diffusion (peak dispersion) becomes the limiting factor as retention of the analyte increases as the column length increases.

The alternative use of high efficiency packing materials is to reduce the column dimensions (length and / or internal diameter) until comparable resolution is obtained to the original separation – the advantage being that a similar separation is achieved in a much shorter time, using much less solvent etc.

 

Practical interpretation of the van Deemter Equation

In order to appreciate how we can practically reduce plate height we need to understand the van Deemter equation and corresponding plots. The van Deemter curve shows height equivalent of a theoretical plate (HETP, H) (y-axis) against the eluent linear velocity (u) which is a function of eluent flow rate (F) and column internal diameter (dc) (increasing flow rate will increase linear velocity for a given column internal diameter) and can be calculated using the following equations u = F / dc.

Please note that the dimensionless term reduced linear velocity can also be applied and this is calculated by multiplying the linear velocity (u) by the mean particle diameter (dp) and dividing it by the diffusion coefficient of the solute in the mobile phase (DM): v = u x dp/DM This curve is a composite of curves made up from three individual effects which contribute to band broadening – Eddy Diffusion (A-Term), Longitudinal Molecular Diffusion (B-Term) and Mass Transfer Effects (C-Term).

From the resulting composite curve a ‘theoretical optimum’ linear velocity (area shaded green in Figure 5) can be determined, and hence a flow rate chosen, in order to generate the narrowest, most efficient peaks. As HETP decreases, plate number (N) increases and chromatographic resolution should increase. Efficiency loss is considerable at very low (dictated by the B-Term) or very high (dictated by the C-Term) eluent flow rates, with an optimum practical minimum value lying somewhere in-between.

 

When the goal is to decrease analysis time (whilst maintaining the required resolution), the challenge is to find a set of HPLC conditions and hardware whose optimum HETP values occur at higher flow rates without the usual loss in efficiency. We should be mindful here that increasing eluent linear velocity (flow rate) will increase the pressure drop across the column and increase the observed system back pressure). For those of you who have generated van Deemter curves for your analysis you will most likely find you are operating slightly post-minimum in the ‘practical optimum’ linear velocity (area shaded yellow in Figure 5). Here we sacrifice a small amount of plate height (efficiency), but markedly reduce analysis time by operating at higher flow rates. As we will see, the use of sub 2μm and superficially porous materials permit this.

In order to adjust the composite curve such that the minimum is at increasingly higher linear velocity, we must first identify the A, B and C-Terms and understand how their individual contributions to the composite curve can be reduced.

  • The A term is related to eddy diffusion and is near constant over a range of linear velocities
  • The B term is related to longitudinal molecular diffusion and decreases approximately exponentially with increasing eluent linear velocity – it is the predominant cause of loss in efficiency at lower flow rates.  At high flow rates the B-Term contribution to efficiency loss can be negligible.
  • The C term is related to the mass transfer process and increases linearly with increasing eluent flow rate – it is the predominant cause of loss of efficiency at higher flow rates.  At low flow rates the C-Term contribution to efficiency loss can be negligible.

Figure 4 – Van Deemter composite curve

Figure 4. Van Deemter composite curve.


Figure 5 – Van Deemter composite curve with optimum velocities indicated

Figure 5. Van Deemter composite curve
with optimum velocities indicate.

 
 

Eddy Diffusion (The A term)
The A term in the van Deemter equation is often used to describe variations in mobile phase flow or analyte path within the chromatographic column.
Eddy diffusion itself relates to the fact that an analyte molecule can take one of many possible paths through the column. These multiple paths arise due to inhomogeneities in column packing and variations in the particle size / shape of the packing material. In fact, the Eddy diffusion in the van Deemter equation is often called the “packing” term as it reflects the quality (homogeneity) of the column packing.
Eddy diffusion can be minimized by:

  • Selecting well packed columns
  • Using reduced diameter packing materials
  • Choosing packing material with a narrow particle size distribution

Important considerations for high efficiency HPLC:

  • Analyte molecules move through different paths within the column packing material – leading to reduction in efficiency
  • Larger differences in path-length occur, and hence loss in efficiency, with larger particles and with larger particle size distributions


Figure 6. Animations illustrating the relative contributions of eddy diffusion to analyte band broadening when using packing materials of varying diameter.

 
 

Longitudinal Diffusion (The B Term)
A band of analytes contained in the injection solvent plug will tend to disperse in every direction (both axially and longitudinally) due to the concentration gradient at the outer edges of the analyte band.
The B term in the van Deemter equation is related to the dispersion experienced by analyte molecules due to these concentration gradients. This phenomenon is known as ‘Longitudinal Molecular Diffusion’ because inside the column, the greatest scope for broadening is along the axis of flow. Longitudinal diffusion will occur within all system tubing but will be most pronounced in the column.
Longitudinal diffusion occurs whenever the HPLC system contains internal volumes that are larger than necessary:

  • Tubing length too long and /or too high internal diameter
  • Incorrectly connected or non-zero dead volume fittings
  • Incorrect column nuts and ferrules
  • Detector flow cell which is too large for the required analytical sensitivity

Longitudinal diffusion has a much larger effect at low mobile phase velocities (flow rates); therefore it is reduced when using high linear velocities. However these effects still need to be bourn in mind when designing and using high efficiency HPLC equipment as gains in efficiency can be easily mitigated by small, but additive, extra column system volumes.  This is especially true when using reduced internal diameter (3mm i.d. and below) columns
The plot below depicts the loss of efficiency / increase in plate height associated with the B-Term by running at very low eluent velocities (green peak) as opposed to the much more efficient peak shapes associated by running at higher eluent linear velocities (blue peak).


Figure 7. Peak shape differences at high and low eluent velocities considering the contribution from Longitudinal Molecular diffusion.


 

 
 

Mass Transfer (The C Term)
The C term in the Van Deemter equation is related to analyte ‘mass transfer’ and accounts not only for the dispersive convection in the mobile phase between and within the packing material pores but also for sorption and desorption of the analyte from the stationary phase.
Rather than having a unique residence time in the stationary phase, analyte molecules show a spread of residence times. As analyte molecules move through the stagnant mobile phase within the pores of the stationary phase support material they do so by diffusion only (i.e. the mobile phase is not moving with the eluent flow but is ‘trapped’ within the pore). Analyte molecules will be sorbed onto the stationary phase surface at different depths within the pore. As the diffusion process into and out of the pore is a fixed rate process, this will cause analytes to elute from the pore at different times depending upon the ‘depth’ at which they sorbed onto the analyte surface – broadening the band of analytes as they travel through the column and resulting in loss of efficiency / increased plate height.

Mass transfer effects can be minimized by:

  • using smaller diameter stationary phase particles
  • using low mobile phase flow rates (low linear velocities)
  • increasing column temperature (at high temperatures the diffusion processes speed up and the differences in elution time from the particle are reduced)

When smaller particle are employed the much shallower pore depth / length of through pores and the distance between pores ensure the analyte band stays much tighter and yields high efficiencies with small plate heights


Figure 8. Loss of efficiency associated with
differing penetration depths of deep pores  (C-Term).

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

The concept of solid particles covered with a thin skin or film (pellicular) coated with stationary phase was first described by Hovarth et al in the late 1960’s [2]. They consisted of a solid spherical glass bead onto which a thin film, in the region of a few µm, of styrene divinylbenzene and benzoyl peroxide was coated. Either a strong cation exchanger, sulfonic acid, or strong anion exchanger, quaternary ammonium, was bound onto this layer as the stationary phase. These new particle morphologies were specifically designed for macromolecules such as biochemicals. There were two distinctive advantages expected of these pellicular particles [3];

  1. Increased loading capacity arising from the large saturation capacity of the ion-exchange resins
  2. Low solid-liquid mass transfer kinetics (C term from the above van Deemter equation) due to thin stationary phase film

Anion-exchange particles  were packed into a long  1.9m x 0.11mm internal diameter column and analysis was conducted using a  mobile phase of ammonium formate at a velocity  of 1cm/s, producing an inlet pressure of ca. 35bar.  The results generated were impressive for the time with an efficiency of around 250 – 300 theoretical plates reported, generating a H value of 0.35cm a reduced plate height (h) of around 70.  An example chromatogram of the analysis of ribonucleosides  obtained using the above parameters is shown in Figure 9 below.

 

Figure 9. Chromatogram of a mixture of ribonucleosides on a 193×0.1cm column packed with 50_mparticles superficially coated with a film of an anion exchanger. Gradient elution, 0.04–1.5M ammonium formate (pH = 4.35) at 1 cm/s hence v  = 5000 (=1100 vopt, h = 80, N= 250 plates; peak capacity ¡15.).

 
 

However, in spite of the promising separations described, this type of stationary phase did not prove to be too popular due the limitation of ion-exchange retention mechanisms being specific to ions.

The next phase in development of pellicular particles incorporated a stationary liquid phase. In GC, solid stationary phases produced poor results and much greater results could be achieved when employing a liquid as the stationary phase – gas-liquid chromatography. In the late 1960’s and early 1970’s, the pioneers behind driving HPLC forward had garnered experience, concepts and ideas from the forbearer, gas chromatography. The concept of employing a liquid stationary phase was the favoured route and most of the work around this time focussed on liquid-liquid chromatography rather than the liquid-solid chromatography that we widely enjoy today. In the 1970’s a number of pellicular phases were commercialized and these included Coarsil I and II (Waters Associates, 1970), Zipax (Dupont de Nemours, 1972) and Pellicosil (Macherey-Nagel, 1975). They were typically referred to as superficially porous or Controlled Surface Porosity (CSP) particles. The solid spherical glass bead at the core was in the region of 40 – 50μm and they were then coated with a fine layer (ca. 1μm) of fine silica particles. This thin porous layer was then impregnated with liquid stationary phase such as β, β’-oxydipropionitrile[3].

Although these early particles produced very impressive results with reduced plate heights (h) of around 2.0 – 2.5 not uncommon – good by even today’s standards – they met with only moderate success and soon fell out of favour [3]. There were two major factors why the early commercialized pellicular particles were unsuccessful;

  1. It proved to be very difficult in finding two liquids which are insoluble in one another between which a sample can equilibrate with a rate partition constant different form either zero or infinity.
  2. It was shortly after this time the purer and finer brands of silica became available

There was a reincarnation of pellicular particles with experimental particles available in 1992 and the first commercial particles available from 2000. These columns were specifically intended for protein and peptide analysis and were a direct result of the pharmaceutical company’s interests in biochemcials. The initial experimental particles consisted of a 5μm solid spherical silica core with a porous 1μm layer created by duplicate coatings of a 0.5μm layer of colloidal silica sols.

The commercialized particles consisted of a 4.5μm solid spherical silica core coated with a 0.25μm porous layer created by a single step coacervation process. The advantage of these pellicular particles was once again the hindered mass transfer kinetics (C term) which blighted macromolecules resulting in broad, inefficient peaks. Also, contribution of the A term was reduced and B term was diminished by almost half due to the lesser internal porosity [3]. They met with only limited success although they produced reduced plate heights (h) of 2.6 as compared with 3.2 for their fully porous equivalents.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

The latest generation core-shell particles were introduced in 2006 and these particles were 2.6 – 2.7μm in diameter. Please note that whilst many names have been used to describe these particles since their original inception almost fifty years ago including, superficially porous, pellicular and controlled porosity material, we tend to refer to the modern incarnation as core-shell or simply shell particles. We will use the terminology core-shell particles when referring to these particles throughout this article.

They once again consist of a solid spherical silica core but in the main they are 1.7 – 1.9μm in diameter – please note the size differences are manufacturer specific. A (relatively) thick porous shell is then coated onto the particles which is either 0.5μm thick for the 1.7μm core giving an over all particle size of 2.7μm, or 0.35μm for the 1.9μm core producing an overall particle diameter of 2.6μm. This porous shell can be added by either aggregating silica nanograins in a layering approach or by a single step coacervation process, again manufacturer specific.

A typical example can be observed in Figure 10 which zooms in around a core-shell particle and takes a cross-sectional slice to reveal the solid core and porous shell.

 
 

An additional example of core-shell particles can be seen in Figure 11 which shows SEM photographs of these particles at various magnifications and also shows a typical cross-section of a particle, again under various magnifications [4].

Please note that the layer approach used to create this specific shell can be clearly observed in the bottom right image.

 

Figure 11. SEM images of core-shell particles under various magnifications including a cross-sectional cut clearly showing the solid core with porous shell and the layered approach used to construct the porous shell.

 
 

A main aspect which separates core-shell particles from their fully porous equivalents is their associated particle size distribution (PSD). Due to the fact that the cores are solid, an almost monodisperse distribution can be achieved [5]. The shell is often grown around this core to give the desired thickness. As this shell is much shallower and can be controlled to larger extent, the PSD of core-shells is often in the region of 3 – 6% RSD, this is much tighter as compared to 10 - 30% RSD as is observed for fully porous particles [6].

This is presented below in Figure 12.

 

 Figure 12. Particle size distribution for a 3.0µm full porous and a 2.7µm core-shell particle.

 
 

Another interesting fact about core-shell, as compared to fully porous, particles is the enhanced surface roughness of the core-shell [3]. Given the different process used to prepare each particle, sol-gel process for the fully porous and coacervation of colloidal particles or step-by-step templating around solid core for core-shell, this is perhaps not unsurprising.

The differences are shown below in Figure 13 and this enhanced roughness may go some way to explain the increased efficiency of core-shell particles due the increase in shear stresses between particles to reduce the radial strain from the centre to the column wall and therefore, to provide a more homogenous interstitial velocity.

 

Figure 13. SEM images demonstrating the difference in surface nature of the smooth is fully porous (left) and rough core-shell particle (right).

 

It is also worth pointing out that whilst 2.6 – 2.7μm core-shell particles were the first of the latest generation, and the most popular currently, additional particle diameters are currently available in, 1.3μm, 1.7μm, 4μm, 4.6μm and 5μm and the relative merits of these smaller and larger core-shell particles will be discussed later in the Future of Core-Shell Particles section. As the central core of the core-shell particle is impenetrable and impermeable to analytes the capacity of these types of particle is lower as compared to similarly sized fully porous equivalents.

However, the volume fraction is not significantly lower and the vast majority of the particle is still accessible. The volume fraction can be calculated using equation 1 where the diameter of the solid (di) is divided by the diameter of the particle (de) with the product being raised to the third power and finally subtracted from 1 [3].

 

Equation 1 – Volume fraction determination

Using the above equation and the particle geometries outlined previously, it can therefore be calculated that the volume fraction for the 2.7μm core-shell is 75% and the 2.6μm core-shell is 63% of a fully porous equivalent.  Thereby demonstrating the majority of the particle is still available for analyte interaction.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

The huge advantage that core-shell particle offer over traditional fully porous particles is much increased efficiency for similar particle sizes. Reduced plate heights (h) are shown in Figure 14 for a 2.7μm core-shell compared with a 3.0μm fully porous and Figure 15 for a 5μm core-shell compared with a similar sized fully porous particle (plate height H). [6] [7]

 

Figure 14. Reduced plate height comparisons for 2.7μm core-shell and a 3.0μm fully porous particle for two analytes.

 
 

Figure 15. Plate height comparisons for 5.0μm core-shell and a 5.0μm fully porous particle for two analytes.

 
 

Reduced plate heights (h) of 1.2 - 1.5 are observed for 2.7μm and the more recent 4 - 5μm core-shell particles, this is significantly lower than the values of 2.0 associated with traditional fully porous sub 2μm and 5.0μm particles.

Given the increased efficiencies experienced for core-shell particles, the obvious advantage they offer can be gleaned by comparing them not with similar sized, but with smaller fully porous particles. In Figure 16 we compare the performance of a 2.7μm core-shell to that of a 1.8μm fully porous particle [8]. Note the very similar high plate count (~25,000) for both columns but the 1.8μm fully porous column operates at a 50% increase in back pressure, 456bar as compared to 300bar for the 2.7μm core-shell packed column.

 

Figure 16. Mobile Phase: 65% A: 0.2% Formic Acid: 35% B: Methanol Isocratic, Flow Rate 0.5 mL/min 1μL injection 26 °C Sig = 220, 4 nm, Ref = OffSample:
1. Saccharin 2. Caffeine 3. p-hydroxybenzoic acid 4. Aspartame 5. Dehydroacetic acid 6. Benzoic acid

 

Given the fact that similar efficiencies can be generated to those for sub 2μm fully porous packed columns, but at a much reduced operating back pressures, this has meant that 2.6 – 2.7μm core-shell packed columns can offer UHPLC performance on standard HPLC instrumentation. 

One important caveat is that these highly efficient separations require the system to be operating in a highly efficient and optimised manor as band broadening is not just experienced in the column, but in every connective union and all capillary tubing that the sample comes into contact with. 

This is known as extra column volume (VEC) and will be discussed later in this Essential Guide and the interested reader can find a larger review of band broadening and instrument optimization in the previous CHROMacademy webcast and Essential Guide:
The CHROMacademy Essential Guide Tutorial to High Efficiency HPLC separations

 
 

Another important advantage is that the tight particle size distribution and larger particle size of core-shell particles facilitates the use of the conventional 2μm frit incorporated on the standard HPLC column. Sub 2μm columns requires a 0.2 – 0.5μm frit which can necessitate extra sample clean-up steps in order to ensure that the reduced porosity frit does not become blocked. A partially blocked column inlet frit often manifests itself with shouldering peaks as shown in Figure 17 [9].

 

Figure 17. Peak shouldering resulting from a partially blocked column inlet frit.

 
 

An increasingly popular method for visually comparing column performance is using kinetic plots, in particular Poppe plots. A kinetic plot allows the comparison of column supports with different morphologies and/or sizes, as well as systems using different mobile phases. Poppe plots are a kind of kinetic plot that provide a means to describe the performance limits of HPLC separation systems.

The effects and limitations of particle size and pressure drop are factors that can be explored using such plots. Poppe plots can also be used to compare the performance of different chromatographic systems. [10]   The two factors that feature on the axes of a Poppe plot are the number of theoretical plates (N) and the time required to realize one theoretical plate (the “plate time”, tp). The parameter tp describes the speed of the separation, fast separations result in lower tp values.

The “plate time” (tp) can be related to the plate height (H) and the interstitial mobile-phase velocity (u0), or to the un-retained time (t0) and the plate count:

Equation 2 – Plate time determination.
 
 

Fast separations have a short “plate time” (small tp values) and are located towards the bottom of the figure. High-resolution separations (high numbers of theoretical plates) are located towards the right in the Poppe plot.

The Poppe plot shown in Figure 18 contrasts the performance of fully porous, core-shell and monolithic columns, please note the lower ‘plate time’ for the core-shell column [4].

Figure 18. A Poppe plot contrasting the performance of 2.7μm core-shell with sub 2μm fully porous and monolithic C18 packed columns.

 
 

Another significant benefit of core-shell particles is their superior performance at higher flow rates or eluent velocities.  

Elevated temperatures can occur in the column due to frictional heating effects.  Under any HPLC conditions, when a high velocity stream of mobile phase percolates through a chromatographic column, the bed cannot remain isothermal. Due to the mobile phase decompression, heat is generated along the column. Longitudinal and radial temperature gradients take place along and across its bed, as demonstrated below if Figure 19. [11]

 

Figure 19. Oversimplified temperature profile in a HPLC column with no temperature control.  The temperature increases in the flow direction (left to right); each temperature zone is identified with a different colour.

 

In ultrahigh pressure HPLC (UHPLC), the eluent system experiences increased frictional forces that increase its temperature – this is known as frictional heating. These frictional forces are related to the speed of the eluent system, the applied pressure, the eluent viscosity and the particle size of the packing material. [12], [13]

 
 

The particle size of the packing material is crucial not only in determining the column back-pressure but it is the dominant factor responsible for frictional heating. In essence, if the particle size of the packing material is reduced, then frictional heating will be increased. This has limited the performance of highly efficient fully porous sub 2μm particles, especially at higher velocities.

The C-term of the classical Van Deemter equation increases with increasing column pressure drop. This effect is particularly important with large diameter columns (0.46 cm). The efficiency loss is due to the combination of the radial heterogeneity of the flow profile (faster in the column center, slower along its wall) and of the radial profile of retention factors (lower in the column center, higher close to its wall).

The effects of the radial flow and retention factor distribution add up, causing a progressive increase of the slope of the C-branch of the Van Deemter curve. It is not possible to carry out very fast and efficient separations using conventional columns packed with small particles at high pressures. The columns would need to be thermally insulated and the separation factor to be independent of temperature. Instrument manufacturers have taken measures to prevent the effects of frictional heating, such as very accurate column oven temperature control and small volume ovens, however it remains the case that frictional heating effects are less prevalent with smaller internal diameter columns.  Heat transfer properties of stainless steel columns, power dissipation and temperature control are more efficient with small I.D. columns, so in order to minimize the effects of frictional heating, the use of smaller diameter columns (1 - 2.1 mm) in conjunction with temperature control is recommended. 

It has been demonstrated that core shell type particles have improved heat dissipation properties compared to their fully porous counterparts. [14], [15]

The reason for the superior core-shell performance at higher flow rates, or velocities, is due to the increased heat dissipation of the solid core. Figures 20 and 21 below illustrate the decrease of the column efficiency with increasing flow rate. This definitely shows that narrow-bore columns packed with totally porous particles are more affected by heat friction than those packed with core-shell particles because their heat conductivity is smaller.

 

Figure 20. The temperature effects on reduced plate height due to frictional heating for both a fully porous and a core-shell packed column.

 
 
 
Figure 21. The temperature effects on column efficiency due to frictional heating for both a fully porous and a core-shell packed column.
 
 

It also noteworthy that frictional heating not only deleteriously affect efficiency, or (reduced) plate height, but also can affect analyte selectivity.

Figure 22 depicts how analyte selectivity can be affected by temperature, ionised analytes tend to be affected to the greatest extent [16].

 

Figure 22. Analyte selectivity affected by temperature.  Analytes and conditions proprietary.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

As we previously explored, column efficiency is dependent on the summation of the three factors, the A, B and C Terms. It is important to point out however that all terms do not have the contribution to the overall plate height value (H) and this in turn changes with mobile phase velocity. Taking the optimum mobile phase velocity (uOPT) the typical contribution of the A, B and C terms to plate height (H) could be ordered as A = 75%, B = 20% and C = 5% [17]. Core-shell columns have led to a reduction in the overall plate height by reducing the individual terms by 40%, 30% and 50% respectively. By decreasing order of importance, the low minimum reduced plate heights of columns packed with 2.6 - 27μm core-shell particles is due to the small values of the terms A (80%), B (15%), and C (5%).

Please do note how this contradicts a lot of manufacturer promotional literature that claims that the main benefit of core-shell particles arises from the reduction in the C term due to the thin porous layer. This was the case with the original superficially porous particles and is STILL the case with modern core-shell particles designed for analysing larger biomolecules.

However, for analytes smaller than 500Da the C term is negligible for 2.6 – 2.7μm particles. In fact, when analysing analytes smaller than 500Da and using any column packed with particles smaller than 3µm in diameter, irrespective whether core-shell or fully porous, the contribution from the C term is negligible. The individual contribution of each of the 3 terms to overall reduced plate heights, at various reduced velocities, is shown in Figure 23. [18]

 

Figure 23. Contributions of the longitudinal diffusion (green), eddy dispersion (red), and solid–liquid mass transfer resistance (blue) terms to the overall reduced plate height of 100 mm × 4.6 mm columns packed with 2.5-μm fully porous particles (left) and 2.6-μm core–shell particles (right). Analyte: naphthalene; mobile phase: 65:35 (v/v) acetonitrile–water; temperature = 297 K.

 
 

The contribution from the B term is much less for columns packed with core-shell as compared with fully porous particles.  However, as can be clearly observed in Figure 24, it is the main contributor to reduced plate height, the A term, which is constant at higher reduced velocities but is significantly lower for core-shell (h = 2.0) as compared to totally porous particles (h=2.5). 

The impact of the ratio of the solid core and particle diameter (ρ) on values of the B Term as measured for different ratios of shell diffusivity (Dshell) to bulk diffusion (Dm) – Ω – is shown in Figure 24. [18]

 

Figure 24. Experimental reduced longitudinal diffusion coefficients (B) plotted as a function of the ratio Ω of the sample diffusivity in the porous particle to that in the bulk. Comparison between core–shell and fully porous particles. Both curves are converging toward twice the external obstruction factor (~2 × 0.65 = 1.3 as expected for nonporous particles) when Ω tends towards zero. Most importantly, note the large impact of the ratio of the core-to-particle diameter, ρ, to the diminution of the B coefficient at constant values of Ω.

 

As can be seen in Figure 24, the B term is smallest for non-porous, largest for fully porous and intermediate for core-shell particles.  At a typical shell diffusivity to bulk diffusion ratio (Ω) value of 1.25, the B term can be seen increasing from 4.2 for core-shell to 6.5 for fully porous particles.  This equates to a 35% reduction in B term for core-shell type particles.

 
 

As previously discussed, the majority of column band broadening is due eddy dispersion, the A term, and for core-shell particles the contribution is dramatically reduced as compared to fully porous particles.

This is evidently shown below in Figure 25, where the reduced A term is plotted at various velocities for Acetophenone, for both a fully porous and a core-shell packed column [19].

 

Figure 25. Measurement of the eddy diffusion term by using the subtraction method for a moderately retained compound, Acetophenone. Comparison between fully porous and core-shell particles.  Note the clearly smaller A term of columns packed with shell particles at reduced velocity around the minimum HETP and beyond.

 
 

The reduction in A term of 0.5 h unit, or 40%, for core-shell particles as compared with their fully porous equivalents clearly demonstrates that the exceptional performance of core-shell particles is due to the remarkably low eddy dispersion or A term. Now we need in examine why the A term is so dramatically reduced as compared to fully porous particles.

An often touted reason behind the significant reduction in contribution of the A term is the much tighter particle size distribution enjoyed by core-shell particles and previously described. [20]

 

Figure 26.  The particle size distribution of core-shell and fully porous particles and computer modelled images of their simulated packing.

 

However, the small relative standard deviation (%RSD) in particle size distribution has been shown NOT to significantly reduce the A term. A recent study compared the A term contribution to reduced plate height at various velocities for columns packed with non-porous, core-shell and totally porous particles at extremes of bed porosities (εe). The %RSD of particle size distribution for the non-porous particles was 0%, core-shell particles 5% and fully porous particles 20%. [20]

 

Figure 27.  Reduced plate height contribution of the A term at various velocities for non-porous, core-shell and fully porous particles at extremes of bed porosities (εe).

 

Figure 27 clearly displays that particle size distribution has only a negligible effect on the eddy dispersion, A term.  This indicates that the reduction in A term observed is not due to short-range eddy dispersion, between particles or over a few particle diameters, and therefore must arise from long-range (trans-column) effects, over the entire column.

 
 

The comparison of the eddy dispersion data for six columns packed with the same core-shell particles is plotted in Figure 28 along with calculated trans-channel and inter-channel (short-range) data generated from computer modelled bulk packing’s [21].

This appears to confirm that the difference in reduced plate height contribution of the A term, heddy, must be coming from long-range and not short-range effects.

 

Figure 28.  Comparison between the eddy dispersion data measured on six 4.6 mm × 100 mm columns packed with the same batch of 2.7 μm core-shell particles and the eddy dispersion data calculated for the infinite diameter column. Dispersion through the infinite diameter column is controlled only by trans-channel and short-range inter-channel dispersion since this virtual column has no wall and no border. The mobile phase is a mixture of acetonitrile and water (65/35, v/v), room temperature. Note the weak impact of eddy dispersion through the bulk packing on the total eddy dispersion data recorded with real columns.

 

Even for core-shell columns, which exhibit very low eddy dispersion, the overall value is nearly three times larger than the infinite diameter column.  The inference from this is that the exceptional performance of these columns, arising from the significant lowering of the main contributor, the A term, is governed by wall and/or border (frits and fittings) column effects.  Please note that further work is currently on-going to prove this theory but it is one of the most likely and plausible explanations for core-shell packed columns remarkable efficiencies.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

Contrary to widespread belief, the performance of columns packed with core-shell particles is actually improved with increasing column diameter. The reduced plate height contribution of the A term has been determined for identical core-shell particles packed into columns possessing internal diameters of 0.5mm, 2.1mm and 4.6mm, whilst maintaining liner velocity. Computer simulated data for an infinite diameter column is also shown in Figure 29 [21].

 

Figure 29.  Reduced plate height of naphthalene recorded for 14 different columns packed with 2.7 μm core-shell C18 particles. Two columns have dimensions of 0.5 mm × 50 mm, 94 six columns have dimensions of 2.1 mm × 100 mm, the last six columns have dimensions of 4.6 mm × 100 mm. The mobile phase is a mixture of acetonitrile and water (65/35, v/v). T = 295 K.

 

It is clearly visible that of the experimental columns tested, the 0.5mm internal diameter column has the largest effect of the reduced plate highest contribution of eddy dispersion, the 4.6mm internal diameter column has the smallest and the 2.1mm an intermediate effect. In order to understand why this is the case we must examine inside the column, paying particular attention to the packing arrangements observed. An SEM photograph of a cross-section of core-shell particles packed into a typical column internal diameter is shown in Figure 30. [22]

 
Figure 30.  Core-shell packing arrangements at the column wall and in the center section of the column.
 

A much more highly ordered packing arrangement is observed at the columns walls, as compared to the much more random ordering observed in the center of the column. Any analytes encountering the differing packing arrangements experience differences in eddy dispersion and will therefore increase the overall contribution to reduced plate height.
Analytes are much more likely to experience the differing packing arrangements in reduced internal diameter columns due to greater relative contribution of wall to center region. When introduced into larger internal diameter columns, the majority of analyte molecules will only encounter the more random ordered packing in the center of the column as this region occupies a much larger area in the column, as compared to reduced internal diameter columns.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

Core-shell particles are manufactured using the same grade of silica as used for traditional fully porous particles and the surface is modified with the same types of stationary phase and in the same manner. Therefore, core-shell particles have the same physicochemical limitations as fully porous particles. The main limitations being that the stationary phase can be acidically hydrolysed and bled from the column at low pH, typically less than 2 but this varies depending on the side substituents employed and the length of the modifying ligand. The support material itself can suffer dissolution via basic hydrolysis under highly basic conditions, typically at pH greater than 9 but this varies from manufacturer to manufacturer and again on the length of the stationary phase. The particles that we have discussed in the main during this presentation, the most popular 2.6 – 2.7μm particle size, have an upper operating pressure limit of 600 bar. This is analogues to similar sized fully porous particles. It is worth pointing out that sub 2μm core-shell particles currently available can tolerate pressure of 1000bar, once again similar to those that fully porous particles are comparable of operating at.

It is however worth emphasising that the efficiency of core-shell particles, and highly efficient sub 2μm fully porous particles too, relies on the extra column volume on the chromatograph being employed to be minimized.

An example of the effect on peak shape by increased extra column volume is demonstrated in Figure 31 [23].

 

Figure 31.  Extra column volume (Vec) effects on peak shape.

 
 

A schematic of a typical liquid chromatograph is depicted in Figure 32 with the potential sources of extra column effects highlighted that will lead to an increase in peak width. [24]

 

Figure 32.   The extra column volume (VEC) contribution of the modern HPLC system.

 

Unfortunately a full review of extra column effects and causes is outside the scope of this article but the interested reader is directed to the Fast LC and the Troubleshooting Autosampler, Column and Detector Essential Guides referenced below.

Essential Guide: High Efficiency HPLC Separations Essential Guide

HPLC Troubleshooting Autosampler Column Detector Issues Essential Guide

 
 

The ratio of the solid-core to the overall particle diameter (ρ) is of practical importance and the optimum value is also dependant on analyte size. As discussed when tracing the origins of core-shell particles, most of the first incarnations of these pellicular particles were geared towards analysing large biochemicals. The combination of the hindered mass transfer kinetics (C term) of these large molecules and the thin film of stationary phase produced superior results as compared to fully porous counterparts. The relative resolution for a range of molecule sizes incorporating; small (<500Da), mid-sized (500 – 2000Da), moderately large ( 5,000Da) and very large (60,000Da) is plotted at high velocity (4 x uopt) for varying values of ρ in Figure 33. [19]

 

Figure 33.  Ratio of the theoretical peak resolution with columns packed with shell particles to that of columns packed with fully porous particles as a function of the parameter ρ. In the calculation, the velocity was fixed at four times the optimal velocity, the Henry’s constants of the pair of compounds was set at Kshell,1 = 3.5 and Kshell,2 = 4.0, the same A term was assumed for both types of particles, and the external film mass transfer coefficient was estimated from the Wilson & Geankoplis correlation.
Note the negligible impact of the shorter diffusion path for the resolution of small molecules and the desired range 0.8 < ρ < 0.9 for the optimum resolution of large proteins.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

Preparative chromatography typically involves the separation of only a few compounds, most commonly for purification purposes.  This therefore dictates that selectivity and sample loading (capacity) are of paramount importance. 

Without question, the increased efficiency afforded by core-shell particles would improve resolution but the relative gain may not be worth it and the capacity, or amount of sample that can be loaded, needs to be carefully considered.  The use of preparative columns for very large proteins and other biochemical may be an option but this will need to explored further.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

An area which has improved significantly over the last few years has been the proliferation of stationary phases available to analyse hydrophobic and hydrophilic analytes. This will be a continued source of improvement as even more stationary phases are made available and the needs of the analyst will be continually met. There has been an increase in the use of core-shell columns for Hydrophilic Interaction LIquid Chromatography (HILIC) in very recent times and it will be interesting to see what benefit core-shell particles offer over fully porous particles. There has also been an increase in mixed-mode chromatography over the last decade, as discussed in last month’s Essential Guide [25], and one would expect to see experimental core-shell mixed mode columns available in the near future.

The preparation of high pH stable particles will be of particular interest given the popularity of hybrid (inorganic / organic)totally porous conventional particles.

The ability of the standard 2.6 – 2.7μm particles to be operated at UHPLC pressure (1000bar) would also be beneficial and would extend their applicability.

Looking a little further ahead, the production of sub 1μm core-shell particles would be beneficial but this will require additional – system – modifications. For starters the back pressure that these columns would generate to enjoy the most efficient separations would be well above the 1200bar pressure ceiling of even the most advanced UHPLC systems currently on the market. There is also the issue of extra column volume effects and the fact that, once again, the extra column volumes of even the most advanced systems currently available would be sufficient to negate the extreme efficiencies generated by these particles. Core-shell particles of these diameters may require complete instrument overhauls and all standard column coupling and hardware revisited before they could be practically employed and enjoyed.

Lastly, as discussed above, the solid-core to overall particle diameter ratio (ρ) has not been fully explored in terms of applicability for a wide range of analytes sizes and additional work is foreseen to fully understand this and produce particles that satisfy as wide a range of analytes as possible.

 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 
  1. J.C. Giddings. Dynamics of Chromatography. Dekker, New York, NY, 1965, Chap. 2.

  2. C.G. Horváth, B.A. Preiss, S.R. Lipsky, Anal. Chem. 39 (1967) 1422

  3. Fabrice Gritti, Georges Guiochon, Journal of Chromatography A, Volume 1218, 2011, Pages 1915-1938

  4. Fabrice Gritti, Georges Guiochon, Journal of Chromatography A, Volume 1228, 2012, Pages 2-19

  5. W. Stober, A. Fink, E. Bohn, J. Colloid Interface Sci. 26 (1968) 62.

  6. Fabrice Gritti,  Alberto Cavazzini,  Nicola Marchetti,  Georges Guiochon, Journal of Chromatography A Volume 1157, 2007, Pages 289–303

  7. Joseph J. DeStefano, Stephanie A. Schuster, Jason M. Lawhorn, Joseph J. Kirkland, Journal of Chromatography A, Volume 1258, 2012, Pages 76-83

  8. The CHROMacademy Essential Guide Tutorial to High Efficiency HPLC separations - Tutorial

  9. The CHROMacademy Essential Guide to HPLC Troubleshooting - Autosampler, Column & Detector Issues -Tutorial

  10. H. Poppe. Journal of Chromatography A, 778 (1997) 3-21

  11. CHROMacademy, HPLC, Theory of HPLC, Fast HPLC, 32. Thermal Considerations

  12. André de Villiers, Henk Lauer, Roman Szucs, Stuart Goodall, Pat Sandra. Journal of Chromatography A, 1113 (2006) 84–91

  13. Fabrice Gritti, Michel Martin and Georges Guiochon.  Analytical Chemistry.  2009, 81, 3365–3384

  14. Fabrice Gritti, Georges Guiochon, Journal of Chromatography A, Volume 1217, 2010, Pages 5069-5083

  15. Fabrice Gritti, Georges Guiochon, Journal of Chem. Eng. Sci. Volume 65, 2010, Pages 6310-6319

  16. Adrian Clarke, John Nightingale, Partha Mukherjee and Patrik Petersson.   Chromatography Today, Volume 3, Issue 2, 4

  17. Fabrice Gritti, Georges Guiochon, Journal of Chromatography A, Volume 1252, 2012, Pages 56-66

  18. Fabrice Gritti, Georges Guiochon, LC-GC North America, Volume 30, Issue 7, 586

  19. Fabrice Gritti, Georges Guiochon, Journal of Chromatography A, Volume 1217, 2010, Pages 8167-8180

  20. A. Daneyko, A. Holtzel, S. Khirevich, U. Tallarek, Anal. Chem. 83 (2011) 3903

  21. Fabrice Gritti and Georges Guiochon Anal. Chem., 2013, 85 (6), pp 3017–3035

  22. K. Patel et al, Anal. Chem., 76 (2004) 5777

  23. The CHROMacademy Essential guide to Translating and Transferring HPLC Method - Tutorial

  24. Fabrice Gritti, Carl A. Sanchez, Tivadar Farkas, Georges Guiochon, Journal of Chromatography A, Volume 1217, 2010, Pages 3000-3012

  25. The CHROMacademy Essential Guide Tutorial Mixed Mode Chromatography – the answer to everything? - Tutorial
 
 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now
 
 

Learn chromatography from the experts

Whether you work in a lab or manage a lab, you will benefit from being a member of CHROMacademy.

As a member of CHROMacademy, you will get access to our vast e-Learning archive full of great interactive content and animations.
All our Essential Guide Webcasts and tutorials and LCGCs archive of magazine articles and webcasts from your favourite authors - John Dolan, John Hinshaw, Mike Balough, and Ron Majors. Plus vendor application notes, electronic laboratory tools and calculators and with our 'Ask the Expert' function - help is always at hand.

 

Analytical Chemists

  • I feel empowered to fix things
  • I can troubleshoot effectively
  • I know where to go for help
  • I understand my analyses
  • I know where to get applications
  • I’m up to date
  • I’m more employable
  • My career is progressing
 

Laboratory Managers

  • Improved equipment utilization
  • Faster method development/problem solving
  • Flexible workforce with a common standard
  • Better quality data
  • Get up to speed quicker
  • Lower T&E
  • Less reliant on me
  • I spend less time on training
 

Subscribe for $399 per/year and access:

  • The entire e-Learning archive
  • All Essential Guide Webcasts and Tutorials
  • LCGCs archive of articles and webcasts
  • Expert troubleshooting advice when needed
subscribe now

 


Like CHROMacademy on Facebook and keep up-to-date with the latest webcast, tutorial and eLearning release schedules.

 

Facebook

loading data
loading data
loading data
loading data
loading data
Home | About UsContact Us | SubscribeTerms and Conditions | Advertise | Privacy Policy |

loading data

loading data

loading data

 

loading data


loading data

In this session, Dr Fabrice Gritti and Scott Fletcher (Technical Manager, Crawford Scientific) highlight the benefits of core-shell particle technology and the reasons behind their surprisingly high efficiency. They will also discuss where core-shell particles fit against other efficiency improving measures such as the use of sub 2μm particles with high pressures and also narrow bore HPLC columns. They will discuss the benefits of using larger and smaller particle size core-shell particles and how particle size and particle morphology might be used to achieve separation requirements. The interesting topic of core to shell thickness ratio will be investigated which will in turn lead to a discussion of current limitations and future possibilities with core-shell technology.

Dr Fabrice Gritti
Research Scientist
Department of Chemistry
University of Tennessee at Knoxvill

Scott Fletcher
Technical Manager
Crawford Scientific

Key Learning Objectives:

  • What are the benefits of core-shell particles and how these benefits are derived
  • The practical use of core shell particles and why smaller and larger particle diameter core-shell particles are being introduced
  • Debate whether improving efficiency in HPLC may lead to a reduction in the number of stationary phase chemistries required
  • Current limitations of core-shell technology
  • What the future holds for core-shell particle technology