WO2006082431A1

WO2006082431A1 - Method and apparatus for solids phase chromatography

Info

Publication number: WO2006082431A1
Application number: PCT/GB2006/000395
Authority: WO
Inventors: Yulong Ding
Original assignee: University Of Leeds
Priority date: 2005-02-03
Filing date: 2006-02-03
Publication date: 2006-08-10
Also published as: GB0502229D0

Abstract

The invention provides an apparatus and method for the characterisation and classification of particles, the apparatus comprising means for differentiation of the particles according to their physical or physico-chemical properties, such as particle size, shape, surface roughness, internal structure, density and crystal structure, in addition to thermal and electrical properties, such as thermal or electrical conductivity, acoustic properties, and magnetic properties. The method is known as solids phase chromatography (SPC), and provides a technique for the characterisation and classification of particulate solids of nanometer to millimetre size ranges under both dry and wet conditions.

Description

METHOD AND APPARATUS FOR SOLIDS PHASE CHROMATOGRAPHY

Field of the Invention

The present invention is concerned with the separation and characterisation of particulate solids and provides a method and apparatus which facilitates the handling of solids of nanometre to millimetre size ranges under both wet and dry conditions.

Background to the Invention

Several techniques for the classification of particles are known in the prior art. Most particularly, these include methods such as sieving, centrifugation by means of cyclones, electrostatic precipitation, and various inertial based methods. However, whilst these methods are well suited to the classification of relatively large particles, they are of very limited value for handling particles in the submicron and nano-size ranges. Similarly, many techniques for the characterisation of particles are available, based on the use of well established devices which include, for example, rheometers, zeta-potential analysers, and various size analysers. These methods can be used for the characterisation of both micron and sub-micron particles under certain assumptions, but their capability for characterising particles in terms of parameters such as size and shape in the nano-size range, particularly over the quantum bridge, is very limited. Also, these techniques are applicable to wet systems, wherein the particles are dispersed in a liquid medium.

More recently, there has been disclosed, in US-A-5089126, a method and apparatus which facilitates the complete fractionation of submicron particles according to size by capillary hydrodynamic fractionation. This technique requires the use of small diameter capillaries, and involves the introduction of a minor fraction of a liquid dispersion of particles to be separated into at least one capillary to produce a distribution of particles of differing size exiting the capillary at different times, introducing the separated dispersion into a liquid diluent stream as it exits the capillary, and collecting the diluted, separated liquid dispersion and measuring the particle size distribution thereof. Whilst the technique of US-A-5089126 is well suited to the rapid analytical separation of diverse media such as, for example, rigid colloidal particles and soft latexes, there are limitations in its general applicability. Thus, for example, capillary hydrodynamic fractionation may only be applied to a liquid-solid system, and is not able to handle gaseous particulate mixtures. In addition, the technique is only able to separate particles by size, and is not concerned with other features, such as shape, density or physico-chemical properties; it requires the use of a UV-visible spectrophotometer and, therefore, cannot be used in connection with nanoparticles smaller than the wavelength of light, unless other special means are incorporated, such as the use of fluorescent particles; and, since the technique was developed mainly for use with polymeric particles, its capability in handling metal and metal oxide particles is very limited, with the consequence that it is rarely used for such purposes.

Hence, there is still a requirement for a technique which facilitates the separation, classification and characterisation of, inter alia, nanoparticles and gaseous particulate mixtures, and the present invention seeks to address these deficiencies in the current state of the art. The present inventors have now succeeded in the application of chromatographic principles for the development of a method and apparatus which is particularly suited to the separation, classification and characterisation of particles dispersed in gaseous or liquid phases. The method of the invention shows sufficient versatility to be able to handle particles across a range of sizes from nanosize to millimetre scale, and is equally adept in dealing with solid-gas and solid-liquid systems. The method of the invention is applicable to very small samples, and the samples are retained during testing, so that no waste is generated.

Statements of Invention

Thus, according to a first aspect of the present invention there is provided an apparatus for the characterisation and classification- of particles, said apparatus - comprising means for differentiation of said particles according to the physical or physico-chemical properties of said particles. Specifically, the physical or physico-chemical properties of the particles include size, shape, surface roughness, internal structure, density and crystal structure, in addition to thermal and electrical properties, such as thermal or electrical conductivity, mechanical properties, such as speed of sound, and magnetic properties.

The first aspect of the invention also envisages an apparatus for the characterisation and classification of particles, wherein said apparatus comprises means for the differentiation of said particles according to the size dependence of their physico- chemical properties.

Preferably, said means for the differentiation of said particles according to the physical or physico-chemical properties of said particles comprises at least one column or channel. Said at least one column or channel may have any suitable cross- section but, typically, said cross-section is circular, elliptical, square, rectangular or annular, with cross-sectional dimensions being selected according to purpose and falling in the broad range of nanometres to metres. The at least one column or channel is straight, curved or patterned, or arranged in a 3-dimensional manner.

The dimensions of the at least one column or channel are dependent on whether the said column or channel is to be used for the purposes of particle characterisation or particle classification. Thus, for particle characterisation, the cross-sectional dimensions of the at least one column or channel generally fall in the range of 100 nm to 100 mm, preferably 500 nm to 50 mm, most preferably 1 μm to 10 mm, whereas, in the case of particle classification, typical cross-sectional dimensions are in the range of 1 μm to 5 m, preferably 5 μm to 1 m, most preferably 10 μm to 0.5 m. The length of the at least one column or channel is typically in the range of 1 to 10 ,4 times the cross-sectional dimension, preferably 10 to 1000 times the cross-sectional dimension.

The surface of the at least one column or channel may optionally be fully or partially coated with at least one coating material. Said at least one coating material may be chosen from any of a wide variety of materials, which may be adapted to, for example, enhance the hydrophobicity or hydrophilicity of the surface of the at least one column or channel, or to confer anti-electrostatic properties on said surface. The particular choice of material is dependent on the specific application and, most particularly, on whether the system to be evaluated comprises a dry solid system or a fluid/solid system.

Suitable materials from which said at least one column or channel may be constructed include various metals, metal oxides, semi-conductors, polymers, carbon materials, glasses, and composites thereof, but the preferred materials are stainless steel, aluminium, copper, silicon, carbon composite materials, Pyrex^® glass and Perspex^® glass.

Optionally, said at least one column or channel may contain packing material. Suitable packing materials are chosen according to the proposed application, and include metals, metal oxides, semiconductors, carbon materials and polymers, or their combinations or composites.

Advantageously, the apparatus comprises measurement means. Typically, said measurement means are adapted to facilitate the determination of the pressure profile within said differentiation means. In the preferred embodiment, this involves providing means for the measurement of the pressure profile along the at least one column or channel. Particularly preferred measurement means comprise pressure transducers.

Preferably, said differentiation means is situated in an environment-controlled location, preferably comprising an environment-controlled chamber, wherein conditions such as temperature, pressure and humidity can be closely controlled.

In operation, a sample comprising particles is introduced into said means for differentiation of said particles according to the physical or physico-chemical properties of said particles. Said sample may comprise a solid or a fluid-solid two- phase mixture, wherein said fluid may comprise a liquid or a gas and said particles are comprised in said fluid. Thus, said apparatus preferably comprises at least one means for the introduction of said sample into said means for differentiation of said particles. Typically, said means for the introduction of said sample comprises a suitable unit for fluid-solid or dry solids injection. Said means for the introduction of said sample is located at an end of said means for differentiation of said particles.

The apparatus according to the first aspect of the invention additionally comprises at least one means for the detection of different particles according to their different physical or physico-chemical properties, and typically comprises more than one such means, said means facilitating the identification of different particles comprised within a sample. Said detection means are adapted to identify the particles according to one or more of the aforementioned physical or physico-chemical properties. Thus, said detection means typically comprise at least one of a thermal conductivity detector, an electrical conductivity or capacitance detector, a magnetic detector, an acoustic detector, and an optical detector.

Said detection means are particularly suited to the present invention when a fluid- solid two-phase mixture is under investigation since, for a given carrier fluid, the thermal conductivity, electrical conductivity, electrical capacitance, magnetic response, speed of sound, and optical properties of a fluid-solid two-phase mixture depend not only on the solids concentration, but also on particle physical properties such as crystallisation structure, density and size. Such properties form the basis of particle classification and characterisation using the apparatus of the present invention.

Furthermore, it has been established that pressure profiles along the column are also a function øf- particle- -size. -Consequently, -pressure response -provides an "additional means of particle classification and characterisation using the apparatus of the present invention, and pressure profiles generated by the measurement means comprised in the preferred apparatus of the invention may be used for this purpose. Selection of appropriate detection means for particular samples is of particular importance. Thus, in the case of large particles, the thermal and electrical properties may not be affected by particle size or shape and, consequently, optical and/or magnetic detectors should be used. Conversely, with particles smaller than about 100 nm, identification of the particles with optical detectors is not possible, and such detectors are, therefore, of no value in determining particle size; however, thermal, mechanical and electrical properties change with particle size and shape and, therefore, thermal, acoustic and electrical detectors should be used in such circumstances.

The apparatus of the present invention also comprises at least one means for sample collection, said means being located at an end of said means for differentiation of said particles which is remote from or close to the end wherein is located the means for the introduction of the sample into said differentiation means. Thus, in the preferred embodiment wherein said means for differentiation of said particles comprises at least one column or channel, said means for introduction and means for collection are located at opposite ends, or at the same end, of the at least one column or channel.

Preferably, the apparatus according to the first aspect of the invention additionally comprises at least one of control means and data-logging means, typically comprising a central control unit for automating the procedures and at least one recording device, allowing results to be automatically recorded and displayed.

The present invention also provides a method associated with the use of the apparatus of the invention. Thus, according to a second aspect of the present invention there is provided a method-for-the characterisation and-classification ofηparticles,-said -method^" comprising: (a) introducing a sample of said particles into an apparatus according to the first aspect of the invention;

(b) operating the said apparatus;

(c) collecting samples exiting the said apparatus; and (d) analysing data provided by said apparatus.

The sample is typically introduced into the apparatus according to the first aspect of the invention by use of means for the introduction of the sample into the means for differentiation of the particles according to the physical or physico-chemical properties of said particles, as previously discussed. Thereafter, as also detailed in the earlier discussion, collection of samples exiting the apparatus is most conveniently achieved by use of means for sample collection, and analysis of data is generally provided by data-logging means which allow results to be automatically recorded and displayed.

Description of the Invention

The method according to the second aspect of the invention is described as solids phase chromatography (SPC), and provides a technique for the classification and characterisation of particulate solids of nanometer to millimetre size ranges under both dry and wet conditions. The method relies on the effects of a) the interaction of particles with column wall and/or packing, b) the interaction between fluid and particles, and c) the dependence of thermal properties (e.g. thermal conductivity), electrical properties (e.g. electrical conductivity), acoustic properties, and magnetic properties on the particles and/or the particle-fluid mixture. Typically, apparatus according to the first aspect of the invention comprises at least one column or channel, a unit for fluid-solids or dry solids injection, a measurement device for pressure profile along the at least one column or channel, an environment controlled chamber for the at least one column or channel, a detection unit, a samples collection

-unit at -the exit-of the- at- least-one column- or charmel,~and-axentral-coτitrol^~and^~data- ^' logging unit. In operation, injection of a small amount of solids particles into the column or channel causes the pressure profile to show at least one peak, said at least one peak travelling to the downstream direction with the pulse of particles. The at least one peak is broadened while travelling and eventually disappears after all injected particles are elutriated from the column or channel. For a given column, and packing if used, the peak height and width at the exit, and the residence time, are dependent on the particle size, density and shape, as well as the properties and flow rate of the injection fluid and from these data, characterisation of the particles is possible. Pressure and pressure drop measurements are conducted by using pressure transducers, micron-manometers or other means installed along the column. Other measurements are performed, according to particular circumstances, via the use of one or more detectors chosen from such as thermal conductivity detectors (TCD), electrical conductivity or capacitance detectors (ECD), magnetic detectors (MD), acoustic detectors (AD) and optical detectors (OD).

The success of the technique in achieving the characterisation and classification of particles is based on the fact that, for a given carrier fluid, the thermal conductivity, electrical conductivity, electrical capacitance, magnetic response, speed of sound, and optical properties of a fluid-solid two-phase mixture are dependent not only on the solids concentration, but also on particle physical properties, such as crystallisation structure, density and size. For particles smaller than about 100 nm, size dependence of particle physical and chemical properties has been observed. Thus, for example, the effective thermal conductivity of a nanoparticle decreases with decreasing particle size when the size is smaller than the mean free path of the energy carriers, said energy carriers principally comprising phonons for dielectric and semiconductor materials, and electrons for metals.

These principles form the basis of particle characterisation and classification using

-the-SP-C technique. Ηowever; the-correct strategic-selection- of^~detectoτs^~fbr specific applications is crucial to the success of the technique. Thus, for example, for large particles, wherein the thermal and electrical properties may not be affected by particle size or shape, optical, electrical or magnetic detectors are required to be used whereas, for particles smaller than around 100 nm, optical detectors are of less value, since they are unable to recognise the particles directly; in such cases, where thermal, mechanical and electrical properties change with particle size (the so-called size effect) and shape, the use of thermal, acoustic and electrical detectors is necessary.

Separation of particles is achieved since particles with different physical properties will come out of the at least one column or channel at different times, and it is this principle that forms the basis for the characterisation and classification of the particles. By the use of two or more columns, it is possible to achieve continuous characterisation and/or classification of particles. Optionally, a degree of control over residence time may be achieved by the application of external fields, such as magnetic and/or electrical fields, to the apparatus of the invention.

The at least one column or channel comprised in the preferred embodiment of the apparatus according to the first aspect of the present invention is preferably round, square, rectangular, elliptical or annular in cross-section, with dimensions in the nanometer to metre range. The at least one column or channel may be unpacked or packed with particles of various shapes. The system shows great versatility in that it can be made very small to be used as a laboratory analytical device, or it may be much larger, and adapted for use in the industrial scale characterisation and classification of particulate solids. Optionally, the at least one column or channel is arranged in 3-dimensional manner and is provided with a multiplicity of entrance and exit ports, to allow for the greatest flexibility of operations.

The apparatus and method of the present invention thereby provide an effective facility for the characterisation and characterisation of particles, the technique being based on differences in residence time, peak characteristics, and the like, these parameters being -funetion-of-particle physical-properties; column^~l^"en^"gth7^"aHd carrier properties, as well as interaction between particles and the inner surface of the column. The apparatus and method find application in the purification of particulate products, the characterisation of samples which are only available in small quantities and, most particularly, in the characterisation and classification of particles at the millimetre, micrometer and submicron scale, especially nanoparticles, for which there is no effective technique available according to the prior art. The apparatus and method are suitable for quality control applications in various industrial sectors, may be applied to both dry and wet systems, and provide dynamic characterisation and the potential for in-line and on-line applications. Specifically, the apparatus may, for example, replace the cascade impactor currently used in relation to inhalation technologies in the pharmaceutical industry. The apparatus of the invention is compact and convenient, and shows high ease of operation.

Thus, the apparatus and method of the invention find potential use in a wide variety of different applications including, for example, the pharmaceutical and general chemical industries, including such as the manufacture of pigments and detergents, nanomanufacturing, food production, biotechnology, and the nuclear industry.

Description of the Drawings

A better understanding of the principles surrounding the apparatus and method of the present invention, and of their practical applications, may be gleaned from the accompanying drawings, wherein

Figure 1 illustrates the principal features of an apparatus according to the present invention;

Figure 2 shows a schematic representation of an apparatus for characterisation of powders under both dry and wet conditions;

Figure 3 shows a schematic representation of an apparatus for continuous separation ^~antl/σr^~^ia^sifeatiOn^~of^~p^~a^^ — sample— inj ection^~with— a^~ corresponding multi-loop switch at the exit; Figure 4 shows a schematic representation of an apparatus having an arrangement of columns or channels in one layer. The inset in Figure 4 shows a schematic representation of a cross-sectional view taken across the line A-A of the main figure, illustrating an apparatus having multiple layers;

Figure 5 shows the configuration of an apparatus according to the invention adapted for the characterisation and classification of particles of varying particle sizes;

Figure 6 illustrates the particle size distributions of the samples of glass beads under investigation in an apparatus of the invention;

Figures 7 and 8 show the volume percentages of particles detected over time (the so- called breakthrough curve) according to the method of the invention for a sample of glass beads in the size range of 106-125 μm at gas velocity ranges of 1.5 and 1.9 m/s;

Figures 9 and 10 illustrate comparative data for the volume percentages of particles detected over time (breakthrough curve) according to the method of the invention for samples of glass beads in the size ranges (sieve cuts) of 38-45 μm, 53-63 μm, and 106-125 μm at gas velocity ranges of 1.5 and 1.8 m/s;

Figure 11 shows the pressure changes detected over time by the method of the invention for sample of glass beads in the size ranges (sieve cuts) of 38-45 μm, 53-63 μm, 75-90 μm and 106-125 μm at a gas velocity of 1.8 m/s;

Figure 12 illustrates the particle size distributions of samples of Micro Crystalline Cellulose under investigation in an apparatus of the invention;

Figure 13 shows the weight percentages of particles detected over time (breakthrough curve)-aGGording-to the-method-Of-the-invention-for^^{^} Cellulose in the size range of 53-65 μm at gas velocity ranges of 1.5, 1.7, 1.8 and 1.9 m/s; Figure 14 illustrates comparative data for the weight percentages of particles detected over time (breakthrough curve) according to the method of the invention for samples of Micro Crystalline Cellulose in the size ranges (sieve cuts) of 53-63 μm, 75-90 μm, and 150-180 μm at a gas velocity range of 1.5 m/s; and

Figure 15 shows the pressure changes detected over time by the method of the invention for sample of Micro Crystalline Cellulose in the size ranges (sieve cuts) of 53-63 μm, 75-90 μm, 106-125 μm and 150-180 μm at a gas velocity of 1.8 m/s.

Referring firstly to Figure 1, there is shown an illustration of a simple apparatus according to the invention comprising a single column, showing the basic principles of the technique of solids phase chromatography.

Turning to Figure 2, there is shown an apparatus according to the invention comprising elutriation and reference columns located in a temperature-controlled environment, and equipped with injection and discharge ports and detectors selected from thermal conductivity detectors (TCD), electrical conductivity or capacitance detectors (ECD), magnetic detectors (MD), acoustic detectors (AD) and optical detectors (OD). The pressure distribution along the columns and pressure drop (ΔP) across the columns may be monitored by means of pressure transducers; typically, up to around 100 such transducers may be present in at least one of columns 1 and 2.

Figure 3 shows an apparatus comprising a multiplicity of columns equipped with a coupled multi-loop injection unit and multi-loop exit switch, which is suitable for the continuous separation and/or classification of particles.

In Figure 4 there is illustrated an apparatus comprising packed or unpacked small channels, injection means comprising a particle feed or injection unit, a fluid feed -and-additionahfluid4njectionφortS7sample-collectiOn-means-comprismg-aτnulti^lOoρ^~ valve for sample collection, detection means and data logging means, the channels being located within a compartment within which an external field may be applied to the channels and material passing therethrough.

Figure 5 shows an apparatus according to the invention which comprises a separation channel 1, access to which is controlled by means of mass flow controllers 10 and injection valve 8. Said separation channel 1 is connected via cyclones 3 to sampler 4, which is in turn activated by stepper motor 5. Operation of the mass flow controllers . 10 and injection valve 8 is achieved by the computer 7 via DAQ 6. Said computer 7 is loaded with a software package (for example, Labview^® or other suitable package) for control and data-logging purposes. In operation, a sample under investigation is introduced via injector 9 and injection valve 8, and is carried through the separation channel 1 by the carrier gas admitted via the needle valves 11 and mass flow controllers 10. Separation of the sample is achieved through the separation channel 1 and the separated fractions are then passed via the cyclones 3 to be collected by the sampler 4 and further analysed thereafter, Sampler 4 comprises between 1 and 100 containers, it is attached via a shaft to stepper motor 5, and its rotation is controlled by computer 7, such that different fractions are collected in different containers. Pressure transducers 2 are installed along the column and generate pressure profiles which are stored by computer 7. In the figure, five such transducers are illustrated but, in practice, the number in use may be anywhere between 2 and around 100.

Figures 6-11 illustrate the results obtained by the use of the apparatus of the invention in performance of the method of the invention in relation to samples of glass beads, and the data presented are discussed in more detail in Example 4.

Figures 12-15 illustrate the results obtained by the use of the apparatus of the invention in performance of the method of the invention in relation to samples of Micro Crystalline Cellulose, and the data presented are discussed in more detail in ^■Example 5~ Thus, the invention will now be further illustrated, though without limitation, by reference to the following examples:

EXAMPLES

Example 1

A series of 8 tests was carried out using a 100 mm inner diameter and 1000 mm long column packed with 10 mm spherical particles, the column being operated at room temperature and 1.05 bar pressure. Compressed air was used as the carrier gas, and the superficial gas velocity was 1 m/s. Glass beads of 55 μm (from 40-70 μm sieve cut) and 112.5 μm (from 75-150 μm sieve cut) were tested. Despite the column having a small aspect ratio (length/diameter) of only 10, and containing large packed particles, separation of small and larger particles was achieved, with over 70% particles smaller than 75 μm being collected in the first 10 seconds, and with only 20% of particles larger than 75 μm being collected over the same period.

Example 2

A series of 5 tests was carried out using a 50 mm inner diameter and 1000 mm long column packed with 10 mm spherical particles, the column being operated at room temperature and about 1.1 bar pressure. Air was used as the carrier gas, and the superficial gas velocity was 1-1.6 m/s. Both resin beads of 215 μm (from 180-250 μm sieve cut) and glass particles of 112.5 μm (from 75-150 μm sieve cut) were tested. The results showed that most particles took a route close to the column wall, which indicated that the use of an annular packed bed was more effective.

Example 3

A series of 6 tests was carried out using a 50 mm inner diameter and 1000 mm long column packed with a monolith with 3 mm by 3 mm square openings, the column being-Operated-at-roonrtemperature and abouHr.l bar-pressure; Air^"was^~αsed ^"asthe^" carrier gas, and the superficial gas velocity was 1.1 m/s. A mixture of resin beads of 215 μm (from 180-250 μm sieve cut) and glass particles of 112.5 μm (from 75-150 μm sieve cut) was tested. The solids concentration of the mixture was 0.025% by volume. The results showed that the residence time distribution of resin beads differed from that of glass particles at the exit of the column.

Example 4

A series of 80 tests was carried out using a 9.5 mm inner diameter and 2000 mm long column packed with 2 mm spherical particles, the column being operated at room temperature and about 1.01 bar pressure at the column exit. Air was used as the carrier gas, and the superficial gas velocity was 1.5-1.9 m/s. Glass beads of various size ranges were tested. Some of the data obtained are presented in Figures 6-11.

From Figure 6, there may be gleaned the particle size distributions of samples of glass beads in the particle size ranges (sieve cuts) of 38-45 μm, 53-63 μm, 75-90 μm and 106-125 μm which were investigated using the apparatus of the invention for obtaining the breakthrough curves and pressure profiles. In each case, the curves illustrate a normal distribution of particles.

Figures 7 and 8 show comparative data for the breakthrough curves obtained according to the method of the invention for a sample of glass beads in the size range (sieve cut) of 106-125 μm using different gas velocities of 1.5 and 1.9 m/s, respectively. It can be seen that a gas velocity of 1.9 m/s allows for a better reproducibility of results, and the method of the invention can, indeed, facilitate margins of accuracy of better than 4% by the correct choice and control of gas velocity.

The comparative data illustrated in Figures 9 and 10 show the breakthrough curves obtained according to the method of the invention for samples of glass beads in the size ranges (sieve cuts) of 38-45 μm, 53-63 μm, and 106-125 μm at gas velocity ranges-o-f--l-.-5-and.-l-.8- m/s_r respectively-- These -data-show- that- small-particles -are- passed through the apparatus more slowly than larger particles, and also indicate that small particles produce a more diffusive front. The relationship between the residence time and the particle size thus obtained can be used to prepare calibration curves as a means for characterisation of the particles.

Finally, from Figure 11 can be seen the pressure changes detected over time by the method of the invention for samples of glass beads in the size ranges (sieve cuts) of

38-45 μm, 53-63 μm, 75-90 μm and 106-125 μm at a gas velocity of 1.8 m/s. From a study of the pressure signals obtained, it can be discerned that pressure profiles are affected more quickly by smaller particles than by larger particles. The relationship between the peak time/shape and particle size thus generated provides another means for characterisation of the particles .

Example 5

A series of 80 tests was carried out using a 9.5 mm inner diameter and 2000 mm long column packed with 2 mm spherical particles, the column being operated at room temperature and about 1.01 bar pressure at the column exit. Air was used as the carrier gas, and the superficial gas velocity was 1.5-1.9 m/s. Powdered samples of the pharmaceutical excipient Micro Crystalline Cellulose (MCC) of various size ranges were tested. Some of the data obtained are presented in Figures 12-15.

From Figure 12, there may be gleaned the particle size distributions of samples of Micro Crystalline Cellulose in the particle size ranges (sieve cuts) of 53-63 μm, 75- 90 μm, 106-125 μm and 150-180 μm which were investigated using the apparatus of the invention for obtaining the breakthrough curves and pressure profiles. In each case, the curves illustrate a normal distribution of particles.

Figure 13 shows the comparative breakthrough curves obtained according to the method of the invention for a sample of Micro Crystalline Cellulose in the size range (sieve cut) of 53-63 μm using different gas velocities of 1.5, 1.7, 1.8 and 1.9 m/s, respectivelyr Not -suφrisingly;- it is- seen -that a gas velocity-of 1.9 m/s- causes the particles to pass through the apparatus more rapidly. The data illustrated in Figure 14 show the comparative breakthrough curves obtained according to the method of the invention for samples of Micro Crystalline Cellulose in the size ranges (sieve cuts) of 53-63 μm, 75-90 μm, and 150-180 μm at a gas velocity range of 1.5 m/s. These data show that small particles are passed through the apparatus more slowly than larger particles. The relationship between the residence time and the particle size thus obtained can be used to prepare calibration curves as a means for characterisation of the particles.

Finally, from Figure 15 can be seen the pressure changes detected over time by the method of the invention for samples of Micro Crystalline Cellulose in the size ranges

(sieve cuts) of 53-63 μm, 75-90 μm, 106-125 μm and 150-180 μm at a gas velocity of

1.8 m/s. From a study of the pressure signals obtained, it can be discerned that pressure profiles are affected more quickly by smaller particles than by larger particles. The relationship between the peak time/shape and particle size thus generated provides another means for characterisation of the particles.

Thus, the inventors have shown that the solids phase chromatography (SPC) techniques according to the invention may be used for the non-destructive classification and characterisation of particles.

Claims

1. An apparatus for the characterisation and classification of particles, said apparatus comprising means for differentiation of said particles according to the physical or physico-chemical properties of said particles.

2. An apparatus as claimed in claim 1 wherein said apparatus comprises means for the differentiation of said particles according to the size dependence of said physico-chemical properties.

3. An apparatus as claimed in claim 1 or 2 wherein the physical or physico- chemical properties of the particles comprise at least one of size, shape, surface roughness, internal structure, density, crystal structure, thermal properties, electrical properties, mechanical properties or magnetic properties.

4. An apparatus as claimed in claim 3 wherein said thermal or electrical properties comprises thermal or electrical conductivity.

5. An apparatus as claimed in claim 3 wherein said mechanical properties comprise speed of sound.

6. An apparatus as claimed in any one of claims 1 to 5 wherein said means for the differentiation of said particles according to the physical or physico- chemical properties of said particles comprises at least one column or channel.

7. An apparatus as claimed in claim 6 wherein said at least one column or channel may has a cross-section which is circular, elliptical, square, rectangular- or-annular.

8. An apparatus as claimed in claim 6 or 7 wherein said at least one column or channel is straight, curved or patterned, or arranged in a 3 -dimensional manner.

9. An apparatus as claimed in claim 6, 7 or 8 for the characterisation of particles wherein the cross-sectional dimensions of the at least one column or channel fall in the range of 100 nm to 100 mm.

10. An apparatus as claimed in claim 9 wherein said cross-sectional dimensions fall in the range of 500 nm to 50 mm.

11. An apparatus as claimed in claim 10 wherein said cross-sectional dimensions fall in the range of 1 μm to 10 mm.

12. An apparatus as claimed in claim 6, 7 or 8 for the classification of particles wherein the cross-sectional dimensions of the at least one column or channel fall in the range of 1 μm to 5 m.

13. An apparatus as claimed in claim 12 wherein said cross-sectional dimensions fall in the range of 5 μm to 1 m.

14. An apparatus as claimed in claim 13 wherein said cross-sectional dimensions fall in the range of 10 μm to 0.5 m.

15. An apparatus as claimed in any one of claims 6 to 14 wherein the length of said at least one column or channel is in the range of 1 to 10⁴ times the cross- sectional dimension of said at least one column or channel.

-1-6- --An apparatus- as-claimed -in claim 1-5-wherein-said-length is-in-the-range-of IO- to 1000 times said cross-sectional dimension.

17. An apparatus as claimed in any one of claims 6 to 16 wherein the surface of said at least one column or channel is fully or partially coated with at least one coating material.

18. An apparatus as claimed in claim 17 wherein said at least one coating material comprises a material adapted to enhance the hydrophobicity or hydrophilicity of the surface of the at least one column or channel or to confer anti-electrostatic properties on said surface.

19. An apparatus as claimed in any one of claims 6 to 18 wherein said at least one column or channel is constructed from a material selected from metals, metal oxides, semi-conductors, polymers, carbon materials, glasses and composites thereof.

20. An apparatus as claimed in claim 19 wherein said material is selected from stainless steel, aluminium, copper, silicon, carbon composite materials, Pyrex^® glass and Perspex^® glass.

21. An apparatus as claimed in any one of claims 6 to 20 wherein said at least one column or channel contains packing material.

22. An apparatus as claimed in claim 21 wherein said packing material comprises a material selected from metals, metal oxides, semiconductors and polymers, or their combinations or composites.

23. An apparatus as claimed in any one of claims 6 to 22 wherein said at least one column or channel is arranged in 3-dimensional manner and is provided with a multiplicity of entrance and exit ports.

24. An apparatus as claimed in any one of claims 1 to 23 which additionally comprises measurement means.

25. An apparatus as claimed in claim 24 wherein said measurement means is adapted to facilitate the determination of the pressure profile within said differentiation means.

26. An apparatus as claimed in claim 24 or 25 wherein said measurement means comprises at least one pressure transducer.

27. An apparatus as claimed in any preceding claim wherein said differentiation means is situated in an environment-controlled location.

28. An apparatus as claimed in any preceding claim which additionally comprises at least one means for the introduction of a sample into said means for differentiation of said particles.

29. An apparatus as claimed in claim 28 wherein said means for the introduction of said sample comprises a suitable unit for fluid-solid or dry solids injection.

30. An apparatus as claimed in claim 28 or 29 wherein said means for the introduction of said sample is located at an end of said means for differentiation of said particles.

31. An apparatus as claimed in any preceding claim which additionally comprises at least one means for the detection of different particles according to their different physical or physico-chemical properties.

32. An apparatus as claimed in claim 30 wherein said means for the detection of different particles according to their different physical or physico-chemical properties comprise at least one of a thermal conductivity detector, an electrical- conductivity or capacitance detector, a_^.magnetic detector, an acoustic detector and an optical detector.

33. An apparatus as claimed in any preceding claim which additionally comprises at least one means for sample collection, said means being located at an end of said means for differentiation of said particles which is remote from or close to the end wherein is located the means for the introduction of the sample into said differentiation means.

34. An apparatus as claimed in any preceding claim which additionally comprises at least one of control means and data-logging means.

35. An apparatus as claimed in any preceding claim which additionally comprises at least one means for the application of an external field.

36. An apparatus as claimed in claim 35 wherein said external field comprises at least one of a magnetic field or an electrical field.

37. An apparatus as claimed in any preceding claim which comprises:

(a) at least one column or channel;

(b) a unit for fluid-solids or dry solids injection; (c) a measurement device for pressure profile along the at least one column or channel;

(d) an environment controlled chamber for the at least one column or channel;

(e) a detection unit; (f) a samples collection unit at the exit of the at least one column or channel;

(g) a central control unit; and (h) a data-logging unit.

38. A method for the characterisation and classification of particles, said method comprising: (a) introducing a sample of said particles into an apparatus as claimed in any one of claims 1 to 37;

(b) operating the said apparatus;

39. A method as claimed in claim 38 for the characterisation and classification of particles at the millimetre, micrometer or submicron scale.

40. A method as claimed in claim 39 wherein said particles comprise nanoparticles.

41. A method as claimed in any one of claims 38 to 40 for the separation and classification of particles in dry systems.

42. A method as claimed in any one of claims 38 to 40 for the separation and classification of particles in wet systems.

43. A method as claimed in any one of claims 38 to 42 for use in in-line or on- line applications.

44. A method as claimed in any one of claims 38 to 43 for use in the pharmaceutical and general chemical industries, the manufacture of pigments and detergents, nanomanufacturing, food production, biotechnology, or the nuclear industry.

45. A method as claimed in claim 44 for use in connection with inhalation technology in the pharmaceutical industry.

46. A method as claimed in any one of claims 38 to 45 comprising determining the relationship between pressure response and particle size.

47. The use of an apparatus as claimed in any one of claims 1 to 37 for the characterisation of particles.

48. The use of an apparatus as claimed in any one of claims 1 to 37 for the classification of particles.