CHROMATOGRIMS

Description

FIELD OF INVENTION

[0001] The invention relates to a chromatographic column containing a porous stationary phase CONTEXT OF THE INVENTION

[0002] Chromatography is generally carried out on a porous packing consisting of beds of fine particles of a few micrometers or tens of micrometers in diameter. These packings have a high pressure drop in operation, from several tens to several hundred bars, and low productivity.

[0003] These characteristics prevent them from being used for extensive industrial purposes as a separation process.

[0004] PCT patent US2004 / 032958 by Belov et al. provides an example of an embodiment attempting to solve this problem through the use of a multi-capillary packing material, consisting of a set of parallel capillary tubes. However, the optimal operating conditions of a production process are not mentioned anywhere. The products offered in the examples are not characterized. No chromatographic separation is described.

[0005] The paper "Multicapillary column gas chromatography with element-selective detection", R. Lobinski et al., Trends in analytical chemistry, vol. 18, no. 7, describes the use of multicapillary packings in gas chromatography.

[0006] Parmentier's French patent 14 59175 presents a new solution to the problems posed by these packings, characterized in that the walls separating the channels are made porous. This configuration allows for very high yields. However, for a more rustic application with less demanding yields, it may be more economical to create packings with solid and mechanically very resistant walls.

[0007] The invention provides a composite packing for chromatography, comprising at least one capillary pipe made of at least one first glassy material, each pipe passing through the packing between an upstream face through which the mobile phase enters the packing and a downstream face through which the mobile phase leaves the packing, in which: each pipe comprises, on at least a portion of the inner wall thereof, at least one secondary material consisting of an organic gel or a mineral which is porous in the solvent state, the thickness of the secondary material defines, inside the pipe, at least one tubular channel empty of solid material, the channel being open in order to allow the mobile phase to enter and extending continuously between the upstream and downstream faces of the capillary pipe, BRIEF DESCRIPTION OF THE INVENTION

[0008] The invention provides a material exchange process, in which a gaseous, liquid or supercritical mobile phase containing separate species is circulated through a packing comprising a stationary phase, the product being characterized in that: the packing comprises a plurality of capillary conduits formed from at least one first material, the conduits passing through the packing between an upstream face through which the mobile phase enters the packing and a downstream face through which the mobile phase leaves the packing coating, each conduit comprising, on at least a portion of the inner wall thereof, at least one porous secondary material which is made of an organic gel or a porous mineral, the thickness of the secondary material defining, within the conduit, at least one tubular channel empty of solid material, the channel being open to allow the mobile phase to enter and extend continuously between the upstream and downstream faces of the capillary conduit; the secondary material has a thickness between 0.05 times and 0.5 times the diameter of the channel material characterized in that the process is carried out on a column whose pipes have a thickness of porous secondary material of between 0.01 times and 0.15 times the diameter of the channel, at an elution rate between 5 times and 50 times the optimum rate of the mobile phase defined by the minimum of the Van Deemter curve of the major compound separating out, under the process conditions The cumulative volume of the capillary conduit is greater than 15% of the total packing volume.

[0009] Advantageously, the method according to the invention is characterized in that the exchange of materials is carried out in such a way as to achieve a chromatographic separation.

[0010] Advantageously, the method according to the invention is characterized in that the separation of a charge is carried out in a plurality of cycles

[0011] Advantageously, the method according to the invention is characterized in that the method is carried out with a cycle time of less than 600 seconds, more advantageously less than 180 seconds and even more advantageously less than 30 seconds.

[0012] Advantageously, the method according to the invention is characterized in that the porous secondary material has a thickness between 0.05 times and 0.25 times the diameter of the channel.

[0013] Advantageously, the process according to the invention is characterized in that it is carried out on a column whose pipes contain a thickness of porous materials between 0.01 times and 0.15 times the diameter of the channel, at an elution rate of between 5 times and 25 times the optimum mobile phase velocity defined by the minimum of the Van Deemter curve of the majority compound separating, under the process conditions.

[0014] Advantageously, the method according to the invention is characterized in that the thickness of secondary material is supported on a non-porous capillary wall of between 0.01 times and 0.15 times the diameter of the channel, at an elution speed of between 5 times and 25 times the optimal mobile phase speed defined by the minimum of the Van Deemter curve of the compound to be separated which is predominant under the process conditions.

[0015] Advantageously, the method according to the invention is characterized in that the thickness of secondary material is carried on a non-porous wall of the capillary.

[0016] Advantageously, the method according to the invention is characterized in that the diameter of the channels is less than 150 micrometers, preferably less than 50 micrometers, and even more preferably less than 15 micrometers.

[0017] Advantageously, the method according to the invention is characterized in that the secondary material is a silica gel.

[0018] Advantageously, the method according to the invention is characterized in that the porous material is a polymeric gel.

[0019] According to a preferred method of carrying out the invention, the porous secondary material is a copolymer of styrene and divinylbenzene comprising sulfonic, carboxylic, amine or quaternary ammonium radicals.

[0020] Advantageously, the porous secondary material supports a liquid stationary phase.

[0021] Advantageously, the chromatographic process is carried out in a simulated moving bed.

[0022] Advantageously, the chromatographic process is carried out on a continuous annular rotating apparatus. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] -- there figure 1is a sectional view of a principle view of a cylindrical multicapillary packing in a direction parallel to its major axis. -- the figure 2 is a sectional view of a principle view of a cylindrical multicapillary packing in a direction perpendicular to its major axis. there figure 3 schematically describes the structure of an example of a lining duct. figures 4 And 5 explain two variants of carrying out a chromatographic process. There figure 6 shows the Van Deemter curves of multicapillary packings. figure 7 shows the comparative productivity of multicapillary packings and particulate packings. The figure 8 shows the comparative productivity of multicapillary packings and particulate packings over a wide operating range. DETAILED DESCRIPTION OF THE INVENTION

[0024] The invention proposes a material exchange method in which a gaseous, liquid or supercritical mobile phase containing species to be separated is circulated through a packing comprising a stationary phase, said method being characterized in that: - the packing comprises a plurality of capillary conduits made of at least a first material, conduits passing through the packing between a so-called upstream face through which the mobile phase enters the packing and a so-called downstream face through which the mobile phase leaves the packing, - each conduit comprises on at least part of its inner wall at least a second material consisting of a porous organic or mineral gel - the thickness of said second material defines inside the conduit at least one tubular channel empty of solid material and open to the passage of the mobile phase, said channel extending continuously between the upstream and downstream faces of said capillary conduit, - the average diameter of the channels is less than 250 micrometers - said thickness of porous secondary material has a thickness of between 0.05 times and 0.5 times the diameter of the channel - this method is carried out with a mobile phase speed of between 5.0 times and 50 times the optimal mobile phase velocity defined by the minimum of the Van Deemter curve of the compound to be separated predominantly under the process conditions.

[0025] Advantageously, the cumulative volume of the capillary conduits represents more than 15% of the total volume of the packing.

[0026] In order to increase the number of theoretical plates in a packing for chromatography, we seek to reduce the resistance to material transfer, and therefore the diffusion lengths. We therefore seek to work with thin layers of porous material, and to work at a low elution speed.

[0027] To increase the hourly productivity of a chromatographic packing in preparative application; or capacity, we seek on the contrary, according to the state of the art, to increase the quantity of stationary phase and to work at high elution speed.

[0028] An optimization carried out on the capillary packings according to the invention has on the contrary shown that, by reducing the thickness of the porous stationary phase layer, the gain in transfer resistance largely outweighs the loss in capacity, making it possible to maintain high efficiencies at very high mobile phase flow rates.

[0029] This unexpected result is the basis of the present invention.

[0030] This is possible with capillary packings, because the thickness of the stationary phase can be controlled independently of the channel diameter with such materials, which is not the case with particulate packings. The latter are limited to a single void fraction, of the order of 35 to 40%.

[0031] On the other hand, the capillary packing allowing high permeability, the pressures necessary to obtain high flow rates of mobile phase remain in the state of the art at reasonable costs.

[0032] These data come in particular from the study carried out figure 7 .

[0033] On the other hand, beyond a speed equal to 50 times the optimal speed of the Van Deemter curve, the pressure losses of the bed become prohibitive.

[0034] Advantageously, this process is characterized in that the exchange of material is carried out in such a way as to achieve a chromatographic separation.

[0035] Advantageously, all the conduits are straight, pass through the lining from one side to the other and open out on its upstream and downstream faces.

[0036] Advantageously, the layer of porous secondary material is deposited in the form of a layer separate from the first material and is carried on the inner periphery of said first material.

[0037] In such a lining, the capillary conduits comprise a part substantially empty of solid material, releasing a continuous channel extending from the upstream face to the downstream face of the lining, described in this text as the part of the conduits open to the passage of the fluid or channel.

[0038] The secondary material deposited on the wall of the ducts is porous.

[0039] In particular, at least the wall of the conduits has a continuous network of pores, said pores being open to the conduits.

[0040] Capillary ducts are advantageously straight, although it is not excluded that the ducts have bends or angles.

[0041] According to the invention, this thickness of porous secondary material has a thickness of between 0.05 times and 0.25 times the diameter of the capillary open to the passage of the fluid or channel.

[0042] Advantageously, the chromatographic process is carried out on a column whose conduits comprise a thickness of porous materials of between 0.01 times and 0.15 times the diameter of the conduit open to the passage of the fluid or channel, at an elution speed of between 5 times and 25 times the optimal mobile phase speed defined by the minimum of the Van Deemter curve.

[0043] Advantageously, the diameter of the conduit open to the passage of the fluid or channel is less than 250 micrometers, preferably less than 150 micrometers, even more preferably less than 50 micrometers and even more preferably less than 15 micrometers.

[0044] When the porous secondary material has areas of different thicknesses, the thickness of this material will be calculated as its surface average over the part of the conduit surface that it covers.

[0045] Advantageously, the multicapillary packing according to the invention will be produced with a diameter greater than 10 mm, preferably greater than 25 mm and even more preferably greater than 50 mm.

[0046] Advantageously, the multicapillary packing according to the invention will be produced with a section greater than 1 cm 2<, preferably greater than 5 cm 2< and even more preferably greater than 20 cm 2< so as to be able to be used for preparative purposes.

[0047] Advantageously, the length of the conduits is greater than 10 millimeters, preferably greater than 50 millimeters, and even more preferably greater than 200 millimeters.

[0048] In fact, its manufacture is simple and can be extended to any desired diameter, several decimeters or several meters.

[0049] This important point constitutes one of the aspects of the invention.

[0050] In fact, material exchange packings could not be produced to date with channel diameters less than 250 microns in large dimensions.

[0051] By diameter of the capillary conduit open to the passage of the fluid or channel, we mean the diameter or hydraulic diameter of the conduit empty of material in which the fluid constituted by the mobile phase can flow freely convectively.

[0052] Due to the thinness of the porous secondary material layer, diffusive phenomena can occur very quickly. As a result, the packing becomes very efficient and can accept much higher mobile phase flow rates. These two factors together considerably increase its productivity per unit volume.

[0053] On the other hand, a multicapillary packing has a pressure drop in operation 10 times lower than that of a particulate packing. This makes it possible to considerably reduce the volume of the packing for a given separation.

[0054] Finally, the extremely short cycle time of such packing preferably leads to splitting a load into a plurality of loads processed in sequence. The accumulation of these factors constitutes the present invention.

[0055] These characteristics allow the packings of the present invention to be used in preparative chromatography, when it is desired to separate quantities of material freed from impurities.

[0056] These quantities of material will advantageously be greater than 10 milligrams per hour, preferably greater than 1 gram per hour, and even more preferably greater than 100 grams per hour.

[0057] Advantageously, these quantities are separated into a large number of very rapid injections for a discontinuous process.

[0058] Indeed, we can see in the table below (see figure 7 ) that the cycle times of a chromatographic process according to the invention are extremely short, compared to those of a particulate packing (see the line Elution time Capillary bed / particulate bed). This constitutes one of the aspects of the invention.

[0059] Advantageously, the load to be purified will be separated by a plurality of cycles.

[0060] According to a first implementation method, a cycle will last less than 3600 seconds. This will be particularly the case for ion exchange devices.

[0061] Advantageously for a chromatography process, each of these cycles will last less than 600 seconds, preferably less than 150 seconds, and more advantageously less than 30 seconds.

[0062] Advantageously, each of these cycles will last more than 3 seconds, preferably more than 10 seconds. This helps to extend the life of the control components.

[0063] In the case of a cyclic process, the cycle time is the time between two charge injections.

[0064] In the case of a process carried out on a continuous annular chromatograph, the cycle time will represent the time taken by one revolution of the packing.

[0065] In the case of a simulated moving bed, the cycle time will be taken as the residence time of the mobile phase in the sum of the elementary packings constituting the process.

[0066] These fillings will have a volume advantageously greater than 1 cm 3< , preferably greater than 100 cm 3< , and even more preferably greater than 1 liter.

[0067] In the case of the present invention, the Van Deemter curve will be measured under conditions of high dilution, in order to be as much as possible in the domain of linear chromatography.

[0068] Advantageously, the dilution of the species on which the Van Deemter curve will be measured will have a concentration in the sample to be separated of less than 5% by mole, more advantageously less than 5 parts per thousand by mole, and even more advantageously less than 500 parts per million by mole.

[0069] Advantageously, to determine the Van Deemter curve, the majority species in molar fraction among the species to be separated will be taken.

[0070] By process conditions we mean that the Van Deemter curve is measured with the same stationary phase, at the same temperature and with the same elution solvents as the process, possibly with the same elution gradients of the mobile phase, and the same temperature gradients for the column, on a column having the same length as that of the process.

[0071] Advantageously, the VanDeemter curve can be measured on a standard column of 4.6 mm diameter.

[0072] We know in fact that the performance in terms of the number of theoretical plates of the chromatographic process varies little with the diameter of the column in the current state of the art.

[0073] We can therefore extrapolate to a larger diameter column the performances obtained on a column of analytical diameter, which is easier to produce and operate.

[0074] Advantageously, the porous secondary material has a pore volume of between 0.15 and 0.95 cm 3 < / cm 3 < of material.

[0075] More preferably, the porous secondary material has a pore volume of between 0.3 and 0.80 cm 3 < / cm 3 < of material.

[0076] Advantageously, the chromatographic process is carried out on a column comprising a thickness of porous secondary material of between 0.01 times and 0.25 times the diameter of the capillary open to the passage of the fluid or channel, at an elution speed of between 2 times and 25 times the optimal mobile phase speed defined by the minimum of the Van Deemter curve.

[0077] Preferably, the chromatographic process is carried out on a column comprising a thickness of porous secondary material between 0.01 times and 0.15 times the diameter of the capillary open to the passage of the fluid or channel, at an elution speed between 5 times and 25 times the optimal mobile phase speed defined by the minimum of the Van Deemter curve.

[0078] More preferably, the chromatographic process is carried out on a column comprising a thickness of porous secondary material between 0.01 times and 0.10 times the diameter of the capillary open to the passage of the fluid or channel, at an elution speed between 5 times and 50 times the optimal mobile phase speed defined by the minimum of the Van Deemter curve.

[0079] Advantageously, the thickness of porous secondary material is carried on a wall of the capillary in the first non-porous material.

[0080] According to another embodiment, the thickness of secondary porous material is carried on a wall of the capillary in the first porous material.

[0081] Advantageously, the diameter of the conduits open to the passage of the fluid or channels is less than 500 micrometers, preferably less than 250 micrometers, even more preferably less than 50 micrometers.

[0082] According to a preferred method of implementation, the diameter of the conduits open to the passage of fluid or channels is less than 15 micrometers.

[0083] According to a preferred method of carrying out the invention, the porous secondary material is a silica gel for chromatography.

[0084] Advantageously, the specific surface area of ​​the porous secondary material is between 50 and 800 m 2 < / g, and preferably between 70 and 600 m 2 < / g.

[0085] Advantageously, the specific surface area will be measured by adsorption of nitrogen on the porous material.

[0086] The mobile phase velocity is defined as the empty barrel velocity or superficial velocity, that is, the velocity that the fluid would have if it flowed regularly over the entire section of the packing.

[0087] Capillary ducts are advantageously straight, although it is not excluded that the ducts have bends or angles.

[0088] The capillary ducts have a uniform cross-section relative to each other and along their length.

[0089] The variability of the cross-section of the ducts will be conveniently defined by a relative standard deviation. This relative standard deviation represents the ratio of the standard deviation of the diameter of the ducts to the average diameter of the ducts, expressed as a percentage. Advantageously, the ducts present in the first material have an average diameter that is substantially constant from one duct to another, such that the standard deviation of the diameter on the sample of ducts of the lining does not exceed 10% of the average diameter, preferably does not exceed 2% of the average diameter, and even more preferably does not exceed 1.0% of the average diameter. In this text, the term average of a set of values ​​of a variable X means its arithmetic mean E[X]. The standard deviation is defined as the square root of the arithmetic mean of ( X -E[ X ]) 2< . By distribution, we mean in this text a set of values ​​of the variable X.

[0090] Advantageously, the diameter of the conduit does not vary by more than 10% over the length of the same conduit.

[0091] Advantageously, this diameter preferably does not vary by more than 2% over the length of the same conduit. Even more advantageously, the diameter does not vary by more than 1% over the length of the same conduit.

[0092] Advantageously, the diameter of the conduits open to the passage of the fluid or channels have a substantially constant average diameter from one conduit to another, such that the standard deviation of the diameter on the sample of conduits of the lining does not exceed 10% of the average diameter, preferably does not exceed 2% of the average diameter, and even more preferably does not exceed 1.0% of the average diameter.

[0093] Advantageously, the conduits pass right through the packing, thus minimizing the pressure drop within the packing during the chromatographic separation process.

[0094] Advantageously, the cumulative volume of the conduits open to the passage of the fluid or channels represents more than 5% of the total volume of the packing, preferably more than 15% of said total volume and even more preferably more than 50% of the total volume of the packing. In this text, the term "total volume of the packing" means the volume occupied by the packing, including its porosity and its conduits; said total volume can therefore be calculated from the external dimensions of said packing. The volume of the channels is measured in the following manner: number of channels x average section of a conduit open to the passage of the fluid or channel x average length of a channel.

[0095] The volume of secondary material is calculated by the formula: number of conduits x average section of the stationary phase in a conduit x average length of a conduit.

[0096] Advantageously, the volume of the capillary conduits represents more than 5% of the total volume of the packing, preferably more than 15% of said total volume and even more preferably more than 50% of the total volume of the packing. The volume of the conduits is measured as follows: number of channels x average section of a conduit x average length of a conduit. By conduit is meant the conduit comprising the channel and the porous secondary material.

[0097] Advantageously, the volume occupied by the porous secondary material in the packing is greater than 2% of the volume of the packing excluding the conduits, preferably greater than 5% of said volume and more preferably greater than 10% of said volume. By "volume of the packing excluding the conduits" is meant the difference between the total volume of the packing and the volume of the part of the capillary conduits open to the passage of the fluid or channels.

[0098] The conduits may have a cross-section of any suitable shape, for example circular, square, rectangular, hexagonal, star-shaped, slot-shaped, etc. Where the conduits have a non-circular cross-section, the term "diameter" of the said conduits means their hydraulic diameter.

[0099] In particular, the ducts have a circular cross-section.

[0100] In particular, the ducts have a regular hexagonal section.

[0101] In particular, the ducts have a flat or slotted shape delimited by two parallel planes.

[0102] Advantageously, the conduits have a hydraulic diameter less than or equal to 250 µm. According to one embodiment, the hydraulic diameter of the conduits is less than or equal to 50 µm, or even less than or equal to 15 µm. The hydraulic diameter is conventionally calculated as equal to four times the cross-section of a conduit (in m 2 < ) divided by the perimeter of said conduit wetted by the mobile phase (in m).

[0103] Finally, the relative standard deviation of the thickness of porous secondary material on a section of the lining is preferably less than 10%, even more preferably less than 5%, and even more preferably less than 2.0%. In this case, the relative standard deviation characterizes the ratio between the standard deviation of the thickness of porous material and its average, expressed in %.

[0104] The porosity of the material can be advantageously defined in chromatography in three ways: 1. The porosity of an organic gel may come from the swelling of a crosslinked gel in an organic, mineral or aqueous solvent, swelling advantageously representing more than 2% of its volume, and preferably more than 10% of its volume. 2. It may come from a porosity of the material in the unsolvated state. 3. It may come from the porosity of a support on which a gel is deposited in the form of a thin layer

[0105] According to the invention, the pore volume comprises the cumulative volume of micropores, mesopores and macropores.

[0106] By porosity of the material we mean the porosity of the secondary material excluding the volume of the conduits open to the passage of the fluid or channels.

[0107] Advantageously, the porosity of the secondary material will be measured in the dry, desolventized state.

[0108] Mesopores are pores with a diameter between 2 and 50 nanometers; macropores are pores with a diameter greater than 50 nanometers; micropores are pores with a diameter less than 2 nanometers.

[0109] The pore sizes mentioned in this text are measured using two different techniques depending on the nature of the material tested: when it is a mineral material and in particular silica, the technique used is mercury porosimetry for macro and mesoporosity, and nitrogen adsorption for microporosity; when it is a polymeric material or based on mineral matrices covered with organic gels, mercury porosimetry is used for macroporosity and nitrogen adsorption porosimetry for mesoporosity and microporosity.

[0110] The invention is described in more detail in the drawings described below.

[0111] In the example illustrated on the figure 1 , the capillary conduits are straight, parallel, and spaced regularly. The different conduits have morphologies and diameters as identical as possible. Each conduit passes through the packing from one side to the other, that is to say that it advantageously has its ends open on each side 4 and 5 of the packing, allowing the circulation of the fluid from the inlet side 4 to the outlet side 5.

[0112] Such packing can therefore be used in a chromatographic column.

[0113] There figure 2 is a top view of face 5 of the lining of the figure 1 seen along direction 6. The openings of the individual capillary conduits 1 can be seen in the mass 2 of organic gel.

[0114] According to one embodiment, the wall of the conduits 10 is made of a solid continuum made of a first material supporting the porous secondary material 11 ( figure 3) on its internal periphery. The part of the conduits open to the passage of a fluid is constituted by the central passage of the capillary 12 or channel. The conduit can be of circular or hexagonal section.

[0115] According to this embodiment, the wall of the conduits may be made of a first non-porous material, said material being chosen from: -glass -silica -a silicoaluminate such as cordierite -stainless steel -an organic polymer such as polypropylene, polyethylene, PEEK, polytetrafluoroethylene or PTFE, polyvinylidene fluoride or PVDF.

[0116] According to another embodiment, the wall of the conduits is made of one of the materials from this list to which porosity is given.

[0117] Advantageously the gel constituting the stationary phase is the porous secondary material and is a mineral gel

[0118] According to one embodiment, the gel consisting of a mineral species is chosen from: -silica gel -activated alumina -titanium oxide -zirconium oxide

[0119] Advantageously, the gel constituting the stationary phase is the porous secondary material and is a mineral gel consisting of silica gel.

[0120] Advantageously, the gel constituting the stationary phase is the porous secondary material and is an organic gel. Consult French application No. 14 59175 by F. Parmentier to find a description of the organic gels that can be used for the present invention.

[0121] An extremely simple method for producing a packing according to the invention consists of starting with a macroscopic capillary tube made of a stretchable material, such as glass, a polymer or a metal. This tube is stretched to the desired diameter, possibly under heat to fluidify the material. Diameters of 0.2 µm can thus be achieved.

[0122] It is internally coated with a film of homogeneous stationary phase by pushing a plug of a liquid precursor along the entire length of the tube. A film is deposited, in which porosity is developed by polymerization with a crosslinking agent in the presence of a solvent and drying, by dissolution, or by drying.

[0123] Tubes from the previous process are cut into sections of the same dimensions and assembled in parallel and possibly glued together in a watertight manner. They can be inserted into a pressure-resistant structure and equipped with fluid inlet and outlet devices such as distributor frits and standard type connections.

[0124] Chromatography is a particular molecular separation process characterized in that it carries out a separation of a mixture of chemical substances under the contradictory action • dynamic entrainment of these species by a current from an eluting phase • retention of these species by a stationary phase.

[0125] Preferably this process is continued until complete elution of the separated species from the stationary phase.

[0126] There are two general categories of chromatographic processes: elution chromatography and affinity chromatography.

[0127] There figure 4 describes an elution chromatography method. According to this method, a continuous flow of mobile phase 28 of composition and temperature possibly varying over time passes through the chromatography column 21 filled with a stationary phase 22. A volume of charge to be separated 23 is injected into the feed flow. Under the antagonistic effect of the reversible retention of the chemical species by the stationary phase and the elution or entrainment by the mobile phase, the species migrate at different speeds along the column 21 and separate into elution bands or peaks 24, 25, 26, etc.

[0128] The separated species are isolated by fractionating the flow exiting the column so as to collect each band as it exits the column into the eluting solvent.

[0129] This fractionation can be temporal in the case of a discontinuous process or angular in the case of a continuous annular device. It can consist of the separation of a head fraction and a tail fraction for a simulated moving bed device.

[0130] The chromatogram represents the concentration peaks of species 24, 25, 26 at the column outlet as a function of time.

[0131] There Figure 5describes an affinity chromatography process for separating molecules, ions or biomolecules. A continuous flow of solvent 30 containing the molecule to be separated 27 feeds the chromatography column 21 filled with a stationary phase 22 having a strong affinity for the molecule to be separated. Under the effect of this strong affinity, the molecule binds to the stationary phase continuously until it is saturated. This binding is almost irreversible under the conditions of this first phase. The progression front 31 of the concentration of 27 is in this case a notch progressing towards the outlet. The column is saturated when the concentration of 27 becomes significant in the solvent at the outlet of the column.

[0132] In a second phase, the properties (pH, ionic strength, etc.) or the nature of the elution solvent 29 are changed so as to reduce or eliminate the affinity of the molecule 27 for the stationary phase 22, and to solubilize the molecule in the solvent 29. The molecule 27 is eluted in the solvent 29 leaving the column 21 until the quantity present in it is exhausted. The column 21 is then regenerated and is ready for a new cycle.

[0133] The chromatograms represent the concentration profiles of species 27 at the column outlet as a function of time, during the fixation and then elution phases.

[0134] There figure 6 represents the Van Deemter curves of a multicapillary packing having variable thicknesses of a porous stationary phase on the internal periphery of its conduits according to the arrangement described figure 3. A Van Deemter curve links the efficiency behavior translated by a theoretical plateau height of the chromatographic packing, to the velocity of the mobile phase for elution chromatography. It can be seen that these Van Deemter curves present a minimum where the efficiency is the best. On the abscissa are the mobile phase velocities in mm / s measured on the section of the conduit including the thickness of porous material. On the ordinate are the theoretical plateau heights in microns. It can be seen that at high speed the Van Deemter curves become all the more parallel to the abscissa as the thickness of stationary phase deposited on the wall is low. This fact constitutes a distinctive feature of the invention, and leads to being able to work at higher flow rates and therefore with greater bed productivities while maintaining higher efficiency than with particulate beds.These curves are given for a diameter of a circular section conduit open to the passage of fluid or a channel of 10 micrometers. The seven curves of the . figure 6 correspond, from top to bottom, to thicknesses of porous material covering the entire wall of the conduit and equal to, from left to right, in micrometers: 10,1 5,6 3,7 2,5 1,7 1,1 0,7 Tablleau 1 Porous material thickness / open duct diameter ratio 1,0057 0,5647 0,3693 0,2529 0,1734 0,1147 0,0691 0,0270 0,0025 0,0003 Fraction of void open to convection 0,8897 0,7795 0,6692 0,5589 0,4487 0,3384 0,2281 0,1000 0,0100 0,0010 Reduced Height 6,6664 3,0252 1,8004 1,2461 0,9617 0,8057 0,7191 0,5632 0,5036 0,4983 Reduced Speed 0,8779 1,7558 2,6337 3,5116 4,3896 5,2675 6,1454 7,1656 7,8822 7,9538 Capillary diameter / Particle diameter 0,2404 0,2290 0,2164 0,2079 0,2042 0,2047 0,2089 0,1997 0,1980 0,1978 Capillary bed length / Particulate bed length 0,6678 0,2887 0,1623 0,1079 0,0818 0,0687 0,0626 0,0469 0,0415 0,0411 Capillary bed / particle bed surface velocity 0,1491 0,6261 1,4911 2,7594 4,3897 6,3045 8,4089 11,9635 14,5964 14,8747 Elution time Capillary bed / particulate bed 4,4781 0,4611 0,1089 0,0391 0,0186 0,0109 0,0074 0,0039 0,0028 0,0028 Capillary bed volume / Particulate bed 0,2233 2,1687 9,1845 25,5650 53,6488 91,7356 134, 3220 255,3355 351,3127 362,1200 Volumetric productivity 0,3311 2,8174 10,2438 23,8154 40,1179 51,7399 51,0740 42,5559 5,8552 0,6035

[0135] There figure 7shows the ratio of the productivities compared per unit of column volume between a multicapillary packing according to the invention and a particulate packing. This comparison is conveniently carried out at the minimum of the Van Deemter curve. The comparison is made for an identical column pressure drop and an identical number of plates between the two packings. It can be seen that this curve has a very pronounced maximum for low thicknesses of stationary phase on the tube wall, between 0.005 and 1.0 times the hydraulic radius of the conduit free to the passage of the fluid. The multicapillary packing is under these conditions up to 50 times more productive than the particulate packing.

[0136] Volumetric productivity is calculated as the flow rate of mobile phase passing through the packing per unit volume reduced to the quantity of porous material present in said volume.

[0137] Table 1 above shows the characteristic quantities leading to the curve of the figure 7 .

[0138] There figure 8 shows the same ratio as the figure 7 in a wider range of operating conditions. The different curves or bands represent for a given dimensionless pressure drop (30 to 2400, optimum of the Van Deemter curve for the value 200), the ratio of the productivities compared per unit of column volume for thicknesses of porous material varying from 10.057 µm to 0.003 µm (diameter of the conduit open to the passage of the fluid or channel equal to 10 µm).

[0139] The following table 2 allows you to find gain factors to apply to the given ratios figure 8 when the reference velocity (or pressure drop) of the particulate bed increases.

[0140] The comparison is all the more favorable to the packing according to the invention as the particulate bed is operated at a high elution speed. Table 2 Pressure drop Postman 200 1 300 1,3691427 600 3,88484339 1200 16,1266904 2400 88,3237398

[0141] Advantageously, the invention uses an elution chromatography method.

[0142] Elution chromatography can be conducted by any known technique, such as discontinuous column chromatography, continuous radial or axial annular chromatography, simulated moving bed.

[0143] Advantageously, the chromatographic process implemented may be an affinity chromatography process.

[0144] Advantageously, the chromatographic process implemented may be an ion exchange process.

[0145] In particular, the porous material can be created using a sol-gel process.

[0146] Without departing from the scope of the invention, this sol-gel process could also be based on an aluminosilicate such as clay, for example.

[0147] Advantageously, the porous material of the fillings according to the invention will consist of silica gel.

[0148] Advantageously, this gel will be deposited on the wall of the conduits by soaking in the form of a liquid precursor.

[0149] By liquid precursor we mean any liquid leading to a silica gel under the conditions of the manufacturing process, such as for example an alkali silicate in aqueous solution, a silica sol, a hydrolyzable alkoxysilane.

[0150] This deposition can be carried out by soaking or wetting the internal wall of the conduits so as to deposit a liquid film of the precursor, evacuation and drainage of the excess liquid, and acidification, hydrolysis, drying or calcination of the deposit.

[0151] It can also be achieved by chemical vapor deposition by, for example, acting with gaseous hydrofluoric acid on a pure silica wall.

[0152] It can be modified by any known surface treatment, such as silanization by octadecyltrialkoxysilane, octyltrialkoxysilane, aminopropyltrialkoxysilane, etc.

[0153] Examples of such treatments applicable to silica gels and organic gels can be found in reference [1]. Example of realization No. 1

[0154] A PEEK capillary tube with an external diameter of 150 µm and an internal diameter of 100 µm is hot drawn to obtain a tube with an internal diameter of 50 µm.

[0155] 100,000 of these fibers are assembled into a 300 mm long bundle and their external surfaces are glued with epoxy resin without sealing their ends. The bundle is inserted and glued into a 300 mm long glass tube with an internal diameter of approximately 30 mm.

[0156] The ducts are coated by dipping with a thin layer of a mixture of styrene (91.6% by weight), 8% by weight of divinylbenzene, and 0.4% by weight of a polymerization activator (azobis isobutyronitrile). The layer is deposited by pushing a liquid plug of this mixture into the bundle under a gentle flow of nitrogen.

[0157] It is placed for 24 hours at 70°C under nitrogen.

[0158] The monolith thus produced is converted into a basic ion exchanger by subjecting it to the action of a stream of a 15% by weight solution of tin tetrachloride in chlorodimethyl ether at 0°C for 6 hours. The packing is then washed with methanol and then with water and quaternized by the action of a stream of a 40% aqueous solution of trimethylamine for a period of ten hours. The packing is then washed to neutrality and the quaternary ammonium is converted into its hydroxylated form. Example of realization No. 2

[0159] A PEEK capillary tube with an external diameter of 150 µm and an internal diameter of 100 µm is hot drawn to obtain a tube with an internal diameter of 50 µm.

[0160] A mixture containing 8 g of hydroxyethyl methacrylate, 32 g of divinylbenzene, 445 mg of azobisisobutyronitrile, 60 g of dodecanol is prepared and degassed under nitrogen for 20 minutes.

[0161] A fraction of this mixture is injected into the previous tube and pushed at constant speed with a slow flow of nitrogen so as to obtain a thickness of 10 µm on the tube wall.

[0162] This tube is heated to 70°C for 24 hours. The mixture polymerizes.

[0163] The polymer thus produced is washed by percolating THF for 30 minutes and dried in an oven at 90°C.

[0164] 100,000 fibers obtained by cutting one or more of the tubes thus produced into equal sections are assembled into a bundle 300 mm long and their external surfaces are glued with epoxy resin without closing their ends. The bundle is inserted and glued into a glass tube 300 mm long and with an internal diameter of approximately 30 mm. Example of realization No. 3

[0165] 200 g of Silica Gel for chromatography with a pore size of 4 nm (SiliCycle ref R10030 A) are ground to an average particle diameter of approximately 3 µm.

[0166] The powder is gradually suspended in 500 ml of a mixture of 200 ml of Grace HS30 silica sol at 30% dry matter and 300 ml of demineralized water.

[0167] A 25 mm diameter glass rod containing 100,000 conduits of 50 µm diameter is produced and processed as follows: A borosilicate glass capillary of 75 µm external diameter and 50 µm internal diameter is produced, cut into 40 cm lengths and 100,000 of these fibers are assembled into a bundle, glued together in the form of a 30 mm diameter rod by an epoxy resin, and inserted into a glass tube.

[0168] The conduits are coated on their internal wall by dipping a thin layer of the previous mixture of silica and silica sol. The layer is deposited by pushing a liquid plug of this mixture into the bundle under a light flow of nitrogen, so as to deposit a thickness of silica of 5 µm on the wall of the bundle.

[0169] The beam is dried in air at atmospheric pressure at 105°C for two hours. Example of implementation No. 4

[0170] The beam obtained in Example No. 3 above is encapsulated in a chromatographic column. With this, a separation test is carried out under the following conditions: Mobile phase: methanol 95 v / v / water 5 v / v. Feed rate 3.3 ml / min. The measured Van Deemter curve shows a minimum at 0.33 ml / min. Test sample: benzyl alcohol 100 ppm by weight in methanol, benzaldehyde 5 ppm by weight in methanol, trimethylamine 5 ppm by weight in methanol. The column has a theoretical plate number of 5200 at the minimum of the Van Deemter curve and 1230 at 3.3 ml / min. Example of implementation No. 5

[0171] The beam obtained in Example No. 3 above is encapsulated in a chromatographic column. With this, a separation test is carried out under the following conditions: Mobile phase: cyclohexane 98 v / v / ethyl acetate 2 v / v. Feed rate 2.4 ml / min. The measured Van Deemter curve shows a minimum at 0.24 ml / min. Test portion: 2-phenyl phenol 50 ppm by weight in cyclohexane, 2-tert-butyl phenol 50 ppm by weight in cyclohexane. The column has a theoretical plate number of 4800 at the minimum of the Van Deemter curve and 1050 at 2.4 ml / min. REFERENCES

[0172] [1] Liquid and supercritical phase chromatography, R. Rosset, M. Caudé, A. Jardy, MASSON 3rd edition, 1991

Claims

1. A method of exchanging material, wherein a gaseous, liquid, or supercritical mobile phase containing species to be separated is circulated through a packing comprising a stationary phase, the packing comprises a plurality of capillary ducts formed in at least one first material, the ducts passing through the packing between an upstream face by which the mobile phase enters the packing and a downstream face by which the mobile phase leaves the packing, each duct comprising, on at least one portion of the inner wall thereof, at least one secondary material which consists of an organic gel or a porous mineral; the thickness of the secondary material defines, inside the duct, at least one empty tubular channel of solid material, the channel being open so as to allow the mobile phase to enter into and be extended continuously between the upstream and downstream faces of the capillary ducts; the cumulative volume of the capillary ducts is more than 15% of the total packing volume; characterised in that the method is carried out on a column, the ducts of which have a thickness of porous secondary material of between 0.01 times and 0.15 times the diameter of the channel, at an elution speed of between 5 times and 25 times the optimum speed of the mobile phase defined by the minimum of the Van Deemter curve of the majority compound being separated under the method conditions.

2. The method according to claim 1, characterised in that the separation of a load is carried out over a plurality of cycles.

3. The method according to one or other of claims 1 and 2, characterised in that the method is carried out with a cycle time of less than 600 seconds, more advantageously less than 180 seconds and even more advantageously less than 30 seconds.

4. The method according to any one of the preceding claims, characterised in that the thickness of the secondary material is borne over a non-porous capillary wall.

5. The method according to any one of the preceding claims, characterised in that the diameter of the channels is less than 150 micrometres, preferably less than 50 micrometres, and better still less than 15 micrometres.

6. The method according to any one of the preceding claims, characterised in that the secondary material is a silica gel.

7. The method according to any one of the preceding claims, characterised in that the secondary material is a polymeric gel.