US 3522172 A
Description (OCR text may contain errors)
July 28, 1970 v, PRETOR|US ETAL 3,522,172
CHROMATOGRAP HIC PROCESSES AND APPARATUS Filed Aug. 10, 1967 2 SheetsSheet l INVENTORS VICTOR PRETORIUS BY HANS HELNUT HAHN ATTO NEY y 8, 1970 VQPRETORIUS A 3,522,172
CHROMATOGRAPHIC PROCESSES AND APPARATUS .3 m 9n n T M w e R Mmm aw w I M A S RL a M 6 OJ R 2 M G F Q r F Filed Aug. 10, 1967 United States Patent 0 3,522,172 CHROMATOGRAPHIC PROCESSES AND APPARATUS Victor Pretorius, Klein Waterkloof, Club Ave., Waterkloof, Pretoria, Transvaal, Republic of South Africa, and Hans Helmut Hahn, 38 Marais St., Baileys Muckleneuk, Pretoria, Transvaal, Republic of South Africa Continuation-impart of application Ser. No. 548,900, May 10, 1966. This application Aug. 10, 1967, Ser. No. 659,632 Claims priority, application Republic of South Africa, Aug. 11, 1966, 66/4,773 Int. Cl. B01d 15/08 US. Cl. 210-31 27 Claims ABSTRACT OF THE DISCLOSURE Chromatographic separations are carried out at flow velocities above an inflection point in the graphical representation of plate height against velocity caused by the onset of convective flow phenomena. Various improved column constructions serve to attain convective flow at lower flow velocities and to achieve a favourable relationship of column capacity and flow velocity. These include baffles in open tube as well as packed columns and an optimalised ratio of particle size to tube diameter.
CROSS-REFERENCES TO RELATED PENDING APPLICATIONS This is a continuation-in-part of Ser. No. 548,900 filed May 10, 1966 and Ser. No. 598,365 filed Dec. 1, 1966, which by reference thereto are to be considered as part of this disclosure.
BACKGROUND OF THE INVENTION The present invention relates to chromatography.
It has been known for some time that for most chromatographic separations there exists a typical relationship between relative speed of movement between the phases on the one hand and that factor of separating efiiciency of the column or equivalent which is usually expressed in terms of theoretical plate height on the other hand. As a general rule it is found that this aspect of efficiency improves with speed initially, reaching an optimum at a comparatively low speed manifested by a minimum of theoretical plate height whence the theoretical plate height increases again.
Hitherto it was believed that any speed increase beyond the aforementioned optimum would invariably be accompanied by a correspondingly increased and rapidly becoming unacceptable plate height, and accordingly it was considered advisable to adjust ones separating conditions as closely as possible to the said optimum, compatible with reasonable speeds of operation.
It is one object of the invention to provide a chromatographic separating process which can be adapted to produce very rapid separations in a given system by comparison with the same system employed under conventional conditions and in some cases permitting the shortening of separating times by one or more orders of magnitude.
Alternatively it is an object of the invention to allow the attainment of improved separations by permitting the use of a larger number of theoretical plates in a given separating time and/or by the beneficial effect of improved radial mixing of the material forwarding phase in a direction transverse to the direction of nett flow.
We have now found surprisingly that, contrary to previous teachings, reduced theoretical plate heights may be experienced once again if the speed is increased be- 3,522,172 Patented July 28, 1970 yond a certain limit, subject to certain conditions which may be realised in many chromatographic systems. Under those conditions it is sometimes possible to attain separating efliciencies of a quite acceptable quality, sometimes of the same order as at the first mentioned optimum but at very considerably higher operating speeds. In gas chromatography separation times may be shortened by a factor of 10; in liquid chromatography the time may be shortened by as much as 10 in spite of longer columns in some cases.
Moreover, we have established that these conditions are capable of practical realisation and have explored the factors necessary for the attainment of practical benefits.
We have even established that advantages are attainable at unusually high flow velocity even if there is no actual or pronounced decrease in plate height but merely an inflection in the curve of plate height against velocity.
SUMMARY OF THE INVENTION Thus, in accordance with the present invention a chromatographic separating process is carried out in a chromatographic system comprising a tubular passage confining a retarding phase and a material forwarding phase, of which at least the latter flows through said tubular passage, and a material to be separated in phase interchange between said phases, individual parts of the retarding phase being restrained throughout said interchange against movement relative to the overall state of movement of the retarding phase in respect of said passage and further comprises:
(a) Adjusting the relative overall flow velocity between the phases to a value in excess of the velocity corresponding to the onset of convective flow phenomena in the forwarding phase, apparent by a downward inflection in the graphical representation of plate height against velocity, and
(b) Carrying out the chromatographic separation at the velocity so adjusted.
The expression restrained against movement does not necessarily entail any special measures except in those cases where the movement of the forwarding phase would otherwise tend to carry along or displace parts of the retarding phase beyond a limit exceeding the order of magnitude of the plate height of the system in the absence of such displacement. An example where special measures are necessary is when operating under fluidised bed conditions.
We employ the term relative flow because the invention is applicable in principle to countercurrent operations, in particular continuous chromatographic separations carried out with both phases moving in opposite directions.
However, the invention is also particularly advantageously and comparatively easily applied to systems in which the retarding phase (e.g. a solid phase or a liquid phase retained by a solid support or a gel) is stationary,
whilst the other, the material forwarding phase (e.g. a
industries. The method is also applicable to various inorganic processes in which the materials being processed are amenable to chromatographic analysis, including the analysis of flue gases in metallurgical processes, e.g. steel refining.
Another aspect of the invention is the vastly increased throughput attainable with a given column or the like, rendering chromatography suitable for separations on a preparative scale where such was previously uneconomical.
In principle the invention is applicable to open tube columns as well as randomly or uniformly packed columns, baffled columns or any other type of column, but it will be understood that the optimum conditions for gaining the maximum benefit of the invention will differ for each type of column.
Whether the convective flow phenomena correspond to true turbulence in the narrowest scientific sense or not, the result in mainly twofold: firstly there is a dramatic reduction in the resistance to mass transfer in the forwarding phase. Secondly as these convective flow phenomena become more noticeable and column wide they flatten the velocity profile to counteract such effects as fingering in packed systems and wall effects.
However, for the convective floW phenomena to the utilisable with advantage it is not essential for their presence to be apparent by a pronounced maximum. Where other contributions to plate height, e.g. that of the retarding phase are high, the maximum may be replaced by a mere inflection, which need not always be very prominent. Even so worthwhile advantages may accrue from exceeding the flow velocity at which the said convective flow phenomena become a dominating factor determining the extent of transport of solutes transverse to the direction of nett flow, since this effect tends to improve the performance also of columns of larger diameter, as the eddy currents become column wide.
Since the performance of chromatographic systems is governed by no less than twenty parameters it is very difiicult to lay down fixed rules valid for all conceivable cases. Broadly speaking there are two main applications: analytical (becoming i.a. increasingly valuable for purposes of process control) and preparative (suitable i.a. for the manufacture of pure chemical substances and their intermediaries).
Where the chromatographic separation is applied to analysis, the analysis time is the primary consideration and preparative efliciency (throughput capacity) is of minor importance, because of the very high sensitivity of modern chromatographic detectors. The analysis time is by approximation linearly proportional to the total plate height divided by the velocity and at high velocities the plate height in turn becomes the product of the velocity and the sum of the resistances to mass transfer in the two phases. Therefore in analysis at least (although such is also possible in some cases in preparative work) and at the expense of some of the analytically unimportant throughput capacity, the contribution to mass transfer in the retarding phase (which in analytical chromatography will invariably be stationary) is limited to depress the graphical representation of plate height against velocity to at least a plateau, the separation being carried out under conditions corresponding to a point on such plateau.
In open tube columns or columns of similar characteristics it is almost invariably feasible, but even in packed columns, particularly in analytical packed columns, it will often be possible and will then be preferred to limit the mass transfer resistance in the retarding phase to a value where the said graphical representation beyond said inflection reaches a maximum and then the separation is carried out under conditions beyond said maximum.
Particularly favourable results for analytical purposes are obtained by packing capillaries of between 1 mm. and 0.2 mm., say 0.5 mm. internal diameter with particles of which all three dimensions are substantially of the same order, in particular spherical beads having a diameter of between /3 and /s the internal capillary diameter, and comprising a stationary phase and carrying out the separation as aforesaid in such system, more particularly by passing therethrough a forwarding phase at said velocity in the region where convective flow phenomena prevail.
Particles other than perfectly spherical beads may be employed, the three dimensions of which are at least approximately equal, through beads are preferred.
Such packed capillaries are considered to fall within the scope of the present invention.
The columns combine some of the most favourable characteristics of open capillary columns with considerably improved capacities and the feature that the favourable convective fiow phenomena occur at considerably lower flow velocities. These columns are also particularly advantageous for use with a liquid stationary phase, pro vided that measures are taken to mitigate a serious cause of resistance to mass transfer in the stationary phase, namely, the tendency of liquids to form wells or puddles in the nips between adjoining particles or between the particles and the tube wall. This may be achieved, for example, if the particles have a porous surface texture, e.g. are graphite coated in a manner known per se, or if the nips between adjoining particles and between the particles and the tube wall are filled by a solid bonding substance, e.g. by sintering of the particles themselves, or with a suitable resin such as epoxy resin or, where the beads are metallic (e.g. copper) by first tinning the beads and then after the column has been packed, heating the column to cause the packing to become soldered together in the said nips.
The optimum film thickness in packed systems is a function of the dimensions of the solid portions of the packing, i.e. the dimensions of the particles in the case of packed particle beds. It is now found that, for example in the case of preparative chromatography, in particular gas chromatography an advantageous relationship of flow velocity to optimum practically obtainable film thickness is attainable at moderate pressure drops through the bed when the packing particles are unusually large, more particularly preferably larger than 3 mm., more particularly larger than 5 mm., preferably between 5 mm. and 5 cm. in diameter, say, substantially in the range of between 7 mm. and 20 mm. in diameter.
Again, particular advantages are attainable if the tube internal diameter is between 1.5 and 5 times the particle diameter, but in excess of 5 mm.
When considering such a system it will be realised that the major contribution to the pressure drop is caused by the obstructions formed by the large particles themselves and that there exists a comparatively unfavourable ratio of the volume of solid packing to the available surface for acting as a support of the retarding phase. With particles of the order of magnitude just referred to it now in accordance with a further aspect of the present invention becomes quite feasible to employ packing bodies having a substantially greater available surface area and/or a smaller impervious cross-section than solid spherical particles of the same average diameter. Thus, it is now proposed to employ, for example, Raschig rings, saddle packings and similar open-structure packing particles in the aforesaid particle range for the packing of chromatographic apparatus in a manner substantially analogous to packed distillative columns and to carry out chromatographic separations on retarding phase supported on such packing.
As a further development of the aforesaid concept applicable to systems where the voids between particles are substantially larger than the maximum film thickness capable of being held stationarily by the surface of the particles, more particularly where the retarding phase is liquid, it now becomes possible to continuously apply to the top of a column or equivalent such liquid retarding phase at a rate designed to maintain a film of retarding phase continuously flowing downwards under gravity over the surface of the bed packing, said film thickness being less than would fill the voids between the packing particles or equivalent. It is now possible to cause the developing phase to flow through the packing in the same direction as the retarding phase but at a higher velocity for batchwise chromatographic development with a retarding film thickness larger than is normally attainable. However, in accordance with the preferred embodiment, chromatographic development takes place in counter current to the direction of flow of the retarding phase and the mixture to be chromatographed is introduced continuously intermediate between the localities of introduction of the retarding phase and the developing phase respectively, thereby to achieve a continuous chromatographic separation.
Referring now once again to chromatography in packed columns in general, it may in some cases not be practical or economical to develop the chromatogram at a flow velocity high enough to achieve the said convective fiow effect, without additional aids. The invention in that case provides for baffles to be included in the packing extending transverse to the direction of flow of the developing phase, each providing a plurality of apertures substantially uniformly distributed over the cross-section, both the apertures and the spacings between adjoining apertures being of a larger order of magnitude than the order of magnitude of the obstructions formed by the packing, e.g. the packing particles.
More particularly, in accordance with the preferred embodiment the apertures in successive baflles are in staggered relationship to one another, i.e. out of axial alignment. The purpose of this arrangement is once again to force the developing phase repeatedly and convectively into a direction of fiow transverse to the nett direction of flow, thereby to flatten the overall streaming profile in the apparatus. In this manner, in particular in the case of large diameter columns, say, columns larger than cm. in diameter, more particularly larger than cm. in diameter, it is possible to achieve more advantageous transverse mixing effects than when using successive baffles designed to produce alternatingly a single axial passage followed by a single peripheral passage and vice versa, Where the packing also is present between all successive bafiles.
Our said main patent application Ser. No. 548,900 deals in some detail with chromatography in open tubes. In addition to that disclosure it has now been established that the optimum ratio of effective film thickness to tube radius is between 0.1 and 0.01 in particular for prepara tive purposes. However, in average cases the maximum attainable stable film thickness is of the order of 10* cm. which means that the maximum tube radius for optimal film thicknesses is between 10- and 10- cm. Thus, a further aspect of the invention deals with various means of overcoming this practical limitation. Thus it is proposed in open tubes to employ tube walls having a whiskered or furred internal surface texture adapted to retain a heavier stable film than would otherwise be possible. A further development of this concept provides for the inclusion inside the tubes of baffie formations specially adapted not only to lower the linear velocity at which the convective flow phenomena become effective but also to hold a greater thickness of retarding phase, more particularly by being wholly or partly in the form of shallow trays, preferably in combination with deflecting means adapted to guide the flow of the developing phase over the layers of retarding phase maintained in said trays. This may, for example, be achieved by arranging successive trays in staggered relationship, e.g, similar in pattern to the baflles described further above for packed columns.
The concept referred to further above in the context of large diameter particle packings of providing thicker than normal films of retarding phase by allowing such films to flow gradually under gravity may also be applied to open tubes or modified open tubes as just described. Where transverse bafiles are provided in such tubes, they may be suitably inclined to induce the gradual flow of a comparatively thick film of retarding phase down the batfles and from one battle to the next down the column.
For the purpose of providing a retarding phase film in movement relative to its support it is not essential to rely wholly or in part on gravity. A similar effect may be attained by centrifugal force, e.g. by employing rapidly spinning discs as baflles.
A particular aspect of the invention deals with carrying out chromatographic separations at relative flow velocities so high that the retarding phase in the form of or supported on solid or solid-like particles is maintained in a condition less dense than its loosest settled condition and with apparatus for that purpose.
Thus one apparatus in accordance with the invention comprises at least one column subdivided by partitions pervious to the forwarding phase and impervious to the retarding phase and transverse to the direction of flow of the forwarding phase into a plurality of column sections, each having a length not exceeding the order of magnitude of the column diameter and comprising column packing material in said sections which in the fully settled condition of the packing material leaves a space devoid of packing material between one section of packing material and the next.
A further apparatus in accordance with the invention comprises a first upright column, adapted to contain a bed of particulate material comprising the retarding phase in a dense phase, expanded, non-turbulent, free-flowing condition, a bed support pervious to the forwarding phase and impervious to the retarding phase at the bottom of said first column and an inlet for forwarding phase below the bed support, an outlet for forwarding phase containing a separated fraction above said bed support, intermediate between the bed support and said outlet for the forwarding phase, an inlet for material to be separated, means for Withdrawing retarding phase from a locality below the inlet for the material to be fractionated, and means adapted to receive the retarding phase thus withdrawn, removing therefrom a further separated fraction and returning the retarding phase to the top of the said first column.
The invention may be applied to the separation or concentration of substantially all substances inherently capable of chromatographic separation or concentration and is adaptable to virtually any known type of chromatography, e.g. liquid-liquid partition chromatography (including reversed phase), liquid-solid chromatography (where the solid phase may be an adsorbent), ion exchange chromatography, gas liquid chromatography or gas solid chromatography.
The process may be applied to the separation, concentration or purification of pharmaceutically active substances, e.g. hormones, vitamines, alkaloids, antibiotics, or essential oils, or of inorganic substances, eg the rare earths, purification of uranium, separation of fission prodducts for the recovery of valuable substances therefrom, chromates, recovering of noble metals, e.g. gold, etc.
Pipelines adapted to function as chromatographic apparatus are considered as falling within the scope of the invention.
Having now defined the invention in general terms, the following description, partly with reference to the drawings and by way of example will serve to explain the invention in greater detail.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 represents diagrammatically the relationship of reduced plate height to flow velocity for liquid and gas chromatography carried out in packed and open tube columns.
FIGS. 2 to 5 represent in vertical longitudinal section various modifications of open tube chromatographic columns designed for the retention of increased thicknesses of retarding phase and to induce convective flow phenomena at reduced flow velocities;
FIGS. 6 to 8 represent views similar to FIGS. 2 to 5 of further developments of the concept for a moving film of retarding phase, e.g. for continuous chromatography; and
FIGS. 9 to 12 represent similar views of improved embodiments in accordance with the invention of packed columns.
FIG. 13 represents diagrammatically the employment of a powder-packed column in accordance with one embodiment of the invention;
FIG. 14 represents diagrammatically an apparatus for continuous chromatography in accordance with the invention;
FIG. 15 represents diagrammatically another apparatus in accordance with the invention for carrying out chromatographic separations under fluidised bed conditions.
DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring to FIG. 1, the ordinate is the reduced plate height h, a convenient dimension-free parameter equal to the true plate height over the particle diameter d in packed columns or the tube radius r in open tubes. The abscissa represents the flow velocity in terms of a type of Reynolds number Re, defined as the product of particle diameter (or tube diameter respectively) and linear velocity divided by the kinematic viscosity.
Curve A represents the typical shape of the curve for liquid or gas chromatography in open tubes whilst curve B illustrates the same for packed columns. No scale has been entered in either the abscissa or the ordinate because the precise positions of the points of the curves will vary widely depending on many parameters requiring no discussion for the present purposes. FIG. 1 merely serves to illustrate certain trends which are in common to a large variety of chromatographic systems but subject to considerable variation in detail. Both curves have a minimum a well down in the typical laminar flow region. The conventional operating range is in the vicinity of that minimum.
Curve A then rises to a pronounced and fairly sudden maximum b. Depending on the precise details of the system there may or may not be a noticeable downward inflection of the curve before point b. Otherwise point b, the maximum, coincides substantially with the inflection point. The operating range in accordance with the invention is on the right hand side of the inflection point, in this case point b, from where the curve first falls rather steeply and then gradually flattens out. In other words, after a certain velocity has been reached no further depression of the plate height due to convective flow phenomena can be achieved, and in fact other contributions to total plate height may result in the curve rising again. As long as the plate height curve does not rise too steeply an increase in velocity will still result in a shortening of the analysis time which is proportional to the plate height and inversely proportional to the velocity. A practical limit is, however, set by the possible expense and technical problems involved in increasing the velocity further. For analytical purposes particularly it is possible to keep the resistance to mass transfer in the retarding phase very low, which means that the curve will follow the general idealised shape fairly closely.
Referring now to curve B this illustrates in a somewhat idealised form the general shape of curve to be expected with liquid or gas chromatography carried out in ordinarily packed columns (the terms packed bed, packed column or packing being employed in this Cir 8 specification in the wider sense to include beds of packed particles as well as integral porous packings, such as packings having a foam structure such as those forming the subject of our application Ser. No. 598,365).
Curve B has an inflection point at c which indicates the onset of convective flow phenomena, as well as the lower limit of the velocity range in which the process in accordance with the invention is carried out. Provided the resistance to mass transfer in the retarding phase is limited sufficiently curve B will flatten out after point c to a plateau, corresponding to the range of conditions at which the process is preferably carried out or as shown in the drawing will even reach a maximum at d, the process then being preferably carried out under conditions corresponding to those on the right hand side of point d.
The resistance to mass transfer in the retarding phase can be limited by favourable textures of the surfaces occupied by the retarding phase, in particular the avoidance of deadend pores and similar surface features tending to trap the substances being separated and by keeping the film thickness of the retarding phase (particularly in the case of liquid or gel-like retarding phases) below predeterminable limits.
The use of the systems which will be described further below with reference to the remaining figures of the drawing, in particular those in accordance with FIGS. 3 to 12 will generally have the effect of moving the inflection point and/or the maximum further to the left of the graph. Certain features to be described with reference to FIGS. 10 and 11 will furthermore have the effect of reducing the resistance to mass transfer in the retarding phase, whilst in addition the remaining features of FIGS. 10 to 12 will tend to produce a curve which in general character is likely to be intermediate between curves A and B.
Referring to FIG. 2, the column walls 1 of an open tube column are internally covered by a layer 2 of a whiskered or furred texture adapted to retain a layer 3 of liquid or gel-like retarding phase to improve the filmholding characteristics of capillaries. Such whiskers may for example be produced in copper tubes or tubes having an internal copper surface by oxidation under strongly alkaline conditions in a manner known per se with an oxidizing agent such as sodium chlorite, preferably in the presence of cyanide ion. The purpose is to increase the capacity of open tube columns without of course exceeding a limit of the film thickness above which the resistance to mass transfer in the retarding phase outweighs the advantages gained by operating at high flow velocities.
Referring to FIG. 3, the column walls 4 circumscribing a column space which, in plan view, is preferably rectangular or square, hold in place transverse baflle formations in the form of horizontal trays 5 arranged in staggered relationship to force the flow of the developing phase along a zig-zag path across the entire surface of the successive trays holding a predetermined thickness of retarding phase layer applied thereon. The flow velocity is adjusted to a value where the convective flow phenomena (eddies) extend across the entire tube crosssection and below a limit at which the calculated resistance to mass transfer in the retarding phase exceeds that in the mobile phase.
In accordance with FIG. 4 the column 6 comprises annular baflles 7 in peripheral contact with the column wall and each comprising a central aperture alternating with tray-shaped baflles dimensioned to leave an annular passage all around the tray. The direction of flow of the developing phase is indicated by an arrow. It is possible for retarding phase to be applied to both types of baffles. However, in accordance with the preferred embodiment the retarding phase application is limited to the top of baffles 8, thereby to gain the advantages in accordance with our application.
In FIG. 5 the column 9 is traversed by closely spaced horizontal transverse baflles 10, each in the form of discs spanning the entire column cross-section, each perforated by a plurality of apertures 11 which, in successive baffles, are relatively staggered as shown. The upper margins of the individual apertures 11 are formed by raised edges 12 to prevent the off-flow of retarding phase covering the upper surface of each baflle. The direction of flow of the developing phase is downwards as indicated by an arrow.
Referring now to FIG. 6, an open tube column 13 is internally provided with spiralled grooves and webs 14 serving as baffle formations. In use liquid retarding phase is applied to the top end of the column and caused to flow down the column gradually whilst essentially following the spiral path prescribed by grooves 14. Thus the flow of the retarding phase is downwards as indicated by arrow 15 whilst in accordance with a preferred manner of using this column, the flow of developing phase is upwards as indicated by arrow 16, thus allowing chromatography to be carried out in counter current and, if desired, continuously in accordance with principles known as such. More particularly the mixture to be separated is introduced continuously, the flow rate of the retarding phase is adjusted to a value intermediate between the rates of advance relative thereto of two fractions to be separated and said fractions are withdrawn continuously at separate localities on opposite sides of the locality of introduction of the mixture in the directions of flow.
According to substantially the same principle the apparatus in accordance with FIG. 3 has been modified in accordance with FIG. 7. The bafiles 17 lack an upturned edge and are slightly downwardly inclined thereby allowing retarding phase to flow downwards along the baffles and from one bafile to the next as indicated by arrows 18. The developing phase is guided in counter current in the general opposite direction (arrow 19).
FIG. 8 represents an apparatus similar to that of FIG. 7 but in addition incorporating some of the concepts of FIG. 5, namely the feature that the flow 20 of the developing phase is essentially upwardly directed through apertures 21 in bafiles 22, said apertures having raised upper edges to prevent the flow 23 of retarding phase through such apertures. The baffles 22 terminate at their downward end close to the column wall 24. Accordingly the dominating flow pattern in accordance with FIG. 8 is counter current with a superimposed cross current on each baffle.
Referring now to FIG. 9, the column 25 is entirely filled with packing 26. The column and packing are traversed at brief intervals by a succession of bafiies 27 providing a staggered arrangement of evenly distributed apertures 28 substantially similar to the pattern in FIG. and substantially larger than the pores in the packing. This serves to lower the overall velocity at which column wide eddies are formed.
As a further development of the concept in accordance with FIG. 8, all baffles 22 may be inclined in the same direction, collecting channels being provided at the bottom end of each baflle for collecting the retarding phase and guiding it to the top of the next lower baffle. In this manner optimum use is made of the concentration gradient achieved along the length of each baffle.
Referring now to FIG. the column wall 29 is tubular and has a diameter d It is packed with particles 30 of substantially uniform size and which are substantially equally large in all three dimensions and in the example shown are substantially spherical and have a diameter d d is between 1.5 and 5 times d For analytical purposes the internal column diameter is between 0.2 mm. and 1 mm, preferably 0.5 mm. For preparative purposes the tube diameter is larger than 5 mm. and the particle diameter is larger than 3 mm., preferably between 5 and 50 mm., more particularly between 7 and mm. The beads may be coated with a solid adsorbent in a manner known per so. They may also be coated with a sol of the stationary phase for increased capacities. They may also ordinarily be coated with a liquid retarding phase. However, in that case steps should be taken to lower the resistance to mass transfer in the retarding phase resulting from the accumulation of retarding phase in the nips between the particles and between particles and column wall. This is achieved if beads 30 are selected having a porous surface texture, eg attained by graphitising the surfaces of glass beads.
Referring now to FIG. 11 the arrangement is substantially the same as in FIG. 10, except that the nips 31 just referred to have been filled up with a solid bonding substance before the application of the retarding phase. The bonding substance may, for example, be a resin applied to the beads, e.g. after packing, in liquid form and which then occupies preferentially the nips (as would otherwise have happened with the liquid retarding phase) and remains there after the resin has set. Substantially the same result may be attained by sintering the particles and column walls together after packing, the bead material itself then providing the bonding substance. According to yet another variation the particles are metal shot par ticles, e.g. of fine copper or brass or bronze shot, which are thoroughly cleaned with acid and then thinly coated with molten tin. The tinned beads are introduced into an internally similarly tinned copper capillary which is then heated above 'the melting point of the tin, preferably in an inert atmosphere and cooled again as a result of which the whole packing structure becomes soldered together.
Refer-ring to FIG. 12 the arrangement is similar as in FIG. 10 except that for preparative chromatography the beads 30 are replaced by Raschig rings 32. Other equivalent open structure particles, i.e. particles providing a higher porosity than solid beads may also be used.
It has been shown further above that the resistance to mass transfer in the retarding phase, whenever possible should be kept as low as feasible. This is achieved by choosing the lowest practical effective film thickness in the retarding phase such that the concentration distribution coefficient in a given system is high, e.g. of the order of of 1000 in the case of gas chromatography and in the case of liquid chromatography.
In typical examples the relative velocity at a, i.e. in the vicinity of the first minimum of the curve is of the order of 5 crn./sec. when using a gas as the forwarding phase, and that is the order of velocity generally employed in gas chromatography. The velocity in regions corresponding to conditions preferably employed in accordance with the invention differs very considerably, depending on the nature of the column employed (and to some extent on the gas). Using an open, smooth walled pipe of 10 mm. diameter, the velocity will be of the order of 2000 cm./sec. Using a 1 mm. capillary, the velocity becomes of the order of 100,000 cm./sec. In both cases the plate height will approach the value of the pipe diameter under thoroughly turbulent conditions provided the resistance to mass transfer in the retarding phase is sufficiently low.
Using liquid forwarding phases, different values for the velocities will apply, depending particularly on the viscosity of the liquid.
Besides by the baffles and like means described further above the velocities required for the desired low plate height can be reduced if desired for any reason by placing judiciously spaced obstructions in the path of the forwarding phase. By judiciously spaced We mean that the spacing does not exceed substantially the distance over which the turbulence inducing effect of the obstruction is effective. For example, struts, e.g. of wire, may be inserted in the tube. The obstructions may also be attached to one or more longitudinal wires, rods or filaments provided inside the pipe, e.g. in the nature of barbed wire strands. The columns may include wire gauze structures of a similar nature as are employed for certain distillation columns.
Grooves or ridges, preferably transverse to the direction of flow may also be provided in the walls to induce turbulence.
All of the above simultaneously help to increase the surface area available to the retarding phase.
Vibrations, in particular ultrasonic vibrations may also be used to induce turbulence at a lower velocity, if for any reason a very high velocity creates problems, e.g. if in a given system the kinetics of exchange constitute a limiting factor, and quite generally to produce advantageous effects.
It is possible to determine the individual contributions to plate height separately. The contribution resulting from the forwarding phase alone (including flow profile effects) may be measured in a known manner when retention is excluded. The total theoretical plate height may also be determined in known manner, and the difference between the two is equivalent to the contribution of the retarding phase.
In order to keep the contribution of the retarding phase as low as possible it is advantageous to employ a retarding phase in which material exchange is confined to the immediate vicinity of the surface. This condition is fulfilled for example by many solid adsorbents (particularly non-porous adsorbents like metals, glass, or porous substances substantially devoid of blind pores, e.g. some types of activated charcoal, alumina, silica gel, molecular sieves and even organic polymers, e.g. cross-linked polymers of styrene, divinyl benzene or their derivatives or inter-polymers); thin liquid films and thin layers of ion exchangers. Such thin films should preferably not exceed cm. and be preferably not in excess of 10- cm. In the case of ion exchangers monomolecular layers of ion exchanger are feasible and preferred. For example, synthetic ion exchanger films on a support may be employed (e.g. produced by polymerisation of divinyl benzene styrene to form a thin film on a support, followed by sulphonation). It is also possible to subject the surface of plastic capillaries or powders, e.g. polyethylene or polyvinyl chloride to sulphonation.
The aforesaid applies equally to open tube and packed columns.
Not only in the case of open tube columns but also in packed columns it is desirable for the eddies of the forwarding phase to extend over the entire column width. This not only serves to assure thorough contact of all parts of the forwarding phase in a minimum of time with the retarding phase but also flattens the flow profile of the forwarding phase due to the advantageous effect of thorough radial mixing. Advantageously complete radial mixing should take place repeatedly and within distances not exceeding the order of magnitude of the column or passage diameter. This can be achieved, for example, solely by means of the effect of thorough turbulence, although it may be aided by vibrations as mentioned further above or various mechanical means, some of which will be referred to below in different contexts.
Because of the high speeds inherent in the process it becomes practical to carry out chromatographic separations in pipelines which, in accordance with the invention are specially adapted as chromatographic separating apparatus, thus combining chromatographic separations, e.g. purifications of materials, with the step of conveying such materials from one locality to another distant locality. It has been observed that when employing the conditions herein specified in an unpacked tube, the walls of which comprise a surface serving as a stationary phase, the theoretical plate height equals by approximation the diameter of the tube. It will thus be readily understood that a pipeline a foot or more in diameter and several miles long corresponds to a considerable number of theoretical plates and allows difficult separations to be achieved on large volumes of material in a reasonable time. Elution development types of separation may, for example, be carried out semicontinuously by introducing 12 the solute material to be separated pulsewise in the form of slugs; in the manner an efficiency corresponding to about of fully continuous operation may be attained in a quite uncomplicated manner.
The comparatively low chromatographic capacities of pipe-lines in which only the pipe wall inner surface is available for material exchange sites of the stationary phase is no great disadvantage in those cases where a valuable substance present in low concentration is to be enriched or isolated or where a minor contaminant is to be removed from a material to be purified. Such separation problems are quite frequent. Pipe walls may, however, be treated or coated in manners known per se to increase the specific surface area.
Enrichment or isolation of a valuable minor com ponent is possible by frontal analysis, a technique which is particularly interesting commercially when applied to pipe-lines in those cases where the medium employed to purge the pipe-line between successive separations is itself also a substance which it is desired to transport from the one end of the pipe-line to the other. These types of separation may be applied to the separation of the components of materials which are traditionally conveyed by pipe-line, including gases, vapours, and liquids, e.g. natural or synthetic petroleum products, organic solvents, coal distillates and pyrollysates, inert gas concentrates, e.g. helium enriched from natural gas, fractions derived from the distillation of air.
The invention may also be applied to the separation of isotopes. Hydrogen gas when conveyed as described through suitably prepared pipe-lines will arrive at the other end wholly or partly separated into isotopes. Similarly heavy water may be produced from steam. Deuterium concentrates may also be obtained by conveying hydrocarbon gases through pipe-lines in the manner described.
When desired or required all the said separations and many others may also be carried out on a large or small scale in apparatus performing no dual function such as conveying the material from one locality to another.
There is no need in the context of the various possible applications referred to above to givea detailed description of each, since the forwarding and retarding phases employed and other conditions may be essentially the same as are employed in convential chromatography for the same separations at slow relative speeds between the phases. The difference resides in the very much higher flow rates employed to attain typical convective flow conditions and the greater than usual care in the selection and/or preparation of the retarding phase to keep the plate height contribution of the latter to a minimum.
The flow velocity required to achieve proper turbulence in the moving phase as a prerequisite for a low theoretical plate height may in some cases be very high in an open tube such as a pipe-line. If operation at lower flow velocity is desirable, e.g. in order to economise on pumping equipment and energy, it is feasible to install judiciously spaced apart or continuous turbulence inducing bodies inside the pipe-line as will be readily understood and which will assist in achieving radial mixing of the forwarding phase. The surface texture of the pipe wall may also be modified to assist in the production of turbulent conditions. Such measures may simultaneously serve to increase the surface area available for active exchange sites.
In some cases the pipe material itself, e.g. metal may be employed as a stationary phase, if necessary after suitable activtion. An aluminium pipe surface may be subjected to oxidation in a manner known per se to produce an active alumina surface. Pipes may also be coated internally by precipitation of a film of colloidal carbon, ion exchange resin, silica gel or other active substance, including a liquid film.
To improve separations and separating capacity whole pipe-lines adapted for the process may also be packed with a stationary phase or a support carrying a stationary phase.
Packed columns, regardless of size, which may be employed in the process, require no special description, since they may be essentially identical with conventional columns, except that the wall strength may have to be dimensioned to withstand higher pressures necessary for the attainment of high flow rates.
In this context it has been found that for the greatest overall benefits to be attainted, the particle size in various forms of packed columns should at least be 0.5 mm. in diameter and preferably at least 1 mm., in fact the particles may be even larger.
FIGS. 13, 14 and 15 illustrate a modification of the process allowing the attainment of high flow rates with considerably less pressure. This is achieved by employing the retarding phase in a column bed of particulate mate rial, maintained by the flow of the turbulent forwarding phase at a bulk volume larger than the bulk volume of the particulate material in its loosest settled condition.
Referring now to FIG. 13 the column 41 comprises a fluid inlet 42 and an outlet 43 separated from the column interior by screens 44 and 45 respectively pervious to the forwarding phase but impervious to the particulate packing 46 in the form of a loose bed. In its loosely settled condition the packing fills the column to level 47. Prior to the actual separation the fluid constituting the forwarding phase is introduced at 42 at a rate controlled by valve 48 sufiiicently high for the particulate material to become fully fluidised without becoming entrained in the forwarding phase. The packing in its fluidised condition (i.e. a condition in which the packing particles are in thoroughly turbulent movement) reaches a level 49. The flow rate of the forwarding phase is now reduced sufficiently for turbulence of the packing particles to cease, which is accompanied by a certain shrinkage of the bed, say to level 50. In this condition the bed has the following important characteristics: It has a lower bulk density and higher porosity than the bed in its loosest condition to which it would settle in the absence of any flow of forwarding phase. Accordingly, for a given pressure drop through the column the flow velocity of the forwarding phase will be higher than the flow velocity resulting from the same pressure drop through the bed prior to the step of full fluidisation. The bed also has free flowing properties almost equal to those of the bed in the fully fluidised condition. How ever, the uncontrolled turbulence of the particles which would result in band widening is absent, whilst conditions are so chosen that the forwarding phase is well inside the turbulent range and capable of flowing freely in all dimensions of the loosened up bed. The material to be separated is introduced at 51a. The fractions are collected one by one from the effluent at 43.
In principle the forwarding phase in this embodiment may be a liquid in which case the retarding phase packing may be solid throughout or particles of a solid support coated with a film of liquid retarding phase or gel or beads of a gelatinous retarding phase, e.g. a resinous or rubbery polymer, say, for example, having ion exchange properties.
In the case of a liquid forwarding phase partition 44 is preferably in the form of a wire screen offering a minimum of flow resistance. A reasonable pressure drop through the bed support 44 is an advantage when employing a gas as the forwarding phase which is preferred with this type of apparatus. For example, a closely woven synthetic fibre filter cloth supported on any rigid perforated or gridlike support will give good results. Porous ceramic plates or sinter glass plates may also be employed. Metal plates with fine perforations may sometimes be employed successfully. Felt is usually less satisfactory. The best sup port for any particular column packing may be determined by simple experiment.
The packing material should preferably be composed of rounded, e.g. approximately spherical, particles, which should preferably be substantially free of random projections or radial structures liable to result in interlocking of the individual particles. A tendency towards lump formation is a disadvantage and should be avoided. Suitable particle sizes will depend, inter alia, on the nature, e.g. shape and specific gravity, of the powder particles, but will usually be in the range -500 mesh, ASTM, the larger sizes applying to powders of low specific gravity. The particles may for example be composed of silica gel, alumina, magnesium silicate, various metals, glass, activated carbon, various organic or inorganic solid adsorbents, natural or synthetic polymers, solid or gelatinous ion exchangers or other substances as will be understood by those skilled in the art.
Data are available allowing calculation or estimation of the most favourable particle size for a given system. Assuming for example that a gas having the density and viscosity of air at normal temperature and pressure is to be employed as the forwarding phase, assuming further that the retarding phase has the density of silica gel or glass beads and is composed of near spherical particles of substantially uniform size, the minimum favourable particle size is in the vicinity of 0.5 mm., since at that particle size a linear gas velocity of the order of 1 m./ sec. may be attained Without fluidising the powder. Such speed is already clearly in the turbulent range. More advantageous will be a powder at least of the order of 1 mm. in diameter.
Under turbulent flow conditions the pressure drop in an expanded non-fluidised bed as described above can be as much as twenty times less for a given flow rate than when the bed is firmly packed.
The condition just described is also characterised by a high degree of free flowing ability which renders the condition particularly suitable for continuously feeding a bed of retarding phase through a tube in countercurrent with the forwarding phase in a continuous chromatographic process.
Referring now to FIG. 14, the bed condition described 'With reference to FIG. 13 is applied to a continuous chromatographic process. The actual separating column is indicated by 51 and contains a packing maintained in the condition just described by a flow of forwarding phase entering through inlet 52 and bed support '53. Material to be separated is introduced continuously at 54. At the bottom end of the column the free flowing packing material 'is continuously withdraw under gravity at a rate adjusted by gate 55 and flows in a condition denser than in column 51 through standpipe 56 into the stripping column having a bottom screen 58 separating the column from space 59 from which a stripping medium is introduced into the column to produce a highly turbulent, preferably fluid entrained condition in column 57. Since the material in column 57 has a much lower bulk density than the material inside column 51, a circulatory flow of packing material results through column 57 towards the broadend top 60 where, due to decreasing flow velocity of stripping medium, settlement of packing material takes place. The material settling out at 60 returns under gravity via standpipe 61 and baffle 62 at the top of column 51. The rate of circulation of the retarding phase is so adjusted in relation to the feed rate of the forwarding phase that one desired fraction of the material leaves column 51 together with the forwarding phase at outlet 63 whilst another fraction leaves column 51 with the retarding phase at 55. This second fraction is stripped off the retarding phase in stripping column 57 and leaves the apparatus with the stripping medium through outlet 64.
Dust separators, e.g. cyclones may be provided if required at outlets 63 and 64. Portion 60 of column 57 may also incorporate the features of a cyclone or equivalent device.
It will be understood that the circulation of re tarding phase may also be assisted, if desired or required, by mechanical means. It is not essential that gravitational effects be relied upon exclusively or at all,
15 although, where practical, such will contribute to the simplicity of the apparatus.
The stripping medium may be the same as the forwarding phase, in which case the spaces underneath bed supports '53 and 58 may be in communication or even integral with one another. In the latter case it is advantageous for the bed support 58 to offer less resistance to How than bed support 53' in order to produce a condition of lower bulk density in column 57 than that prevailing in column 51.
Any other medium suitable for preparing the retarding phase for re-use in column 51 may be employed. For some purposes it is even possible to employ the starting material which is to be separated as a stripping medium and recycling the efiiuent from outlet 64 wholly or partly to inlet '54. This embodiment is particularly useful for purifying a substance in which the contaminant is a minor component. It is furthermore possible to carry out the stripping of retained material off the retarding phase in stages and fractionally by substituting a plurality of columns in series for column 57.
The apparatus is particularly suitable for gas chromatography but may in principle also be designed for use with a liquid forwarding phase.
Referring now to FIG. 15, columns 65 and 66 of which any number may be connected in series as shown by means of connecting pipes 67 which, if desired, may incorporate booster pumps 68. Each column is subdivided into compartments by screens 69 of a type offering little flow resistance to the forwarding phase (introduced at 70) but forming a barrier to the retarding phase. The heights of the individual compartments between successive screens 69 should be of the same order of magnitude and preferably at the most as large as the optimum plate height attainable with the apparatus, i.e. the same order as the column diameter. Each compartment contains particulate retarding phase material, but insuflicient to fill the entire compartment when the material is loosely settled. The apparatus is operated under such conditions of flow velocity of the forwarding phase that the particulate material enclosed in the compartments is maintained in a fully fluidised, i.e. turbulent condition. It is possible in principle to operate this apparatus under dense phase or dilute phase fluidised conditions. Complete radial mixing or only of the forwarding phase but also of the retarding phase is thus assured. Further complete mixing takes place in each booster pump.
The following few examples are picked at random to show but a few of the vast number of potential applications of the invention.
EXAMPLE 1 Separation of palmitic acid and stearic acid The acids are separated by reversed phase partition chromatography. System: medicinal paraffin as retarding phase, 70% aqueous acetone as forwarding phase, temperature 35 C. The alpha value in this example is 1.7.
(a) Conventional packed column, laminar flow Kieselguhr serves as the support. A column height of 85 cm., a diameter of 8 mm. and a pressure head of 50 cm. solvent is employed. Analysis time: appr. 3 hours.
(b) Packed column, convective flow Glass beads, 1 mm. diameter, treated with dichlorodimethyl silane to serve as the support. The support is impregnated with a dilute solution of the medicinal paraffin in ether. After evaporation of the ether the film thickness is appr. 10- cm. The column length is 2.5 m. and pressure drop 5 atm., resulting in a separation time of approximately 50 seconds.
(c) Open tube, laminar flow A very small bore tube, diameter 0.2 mm. is chosen (a larger diameter of say 2 mm. would lengthen the re- 16 quired column length about tenfold and the analysis time a hundredfold). The column length is 100 cm., the pressure head 30 cm. of solvent and the separation time 2 hours.
( 1) Open tube, turbulent flow Here a large, say 2 mm. diameter tube is preferred because, although. a 0.2 mm. capillary would theoretically make separation times of less than 1 sec. possible, the pressure drop necessary therefore would be of the order of 3000 atm. which is too high in practice. The column length is 40 m., the pressure drop 35 atm. and the separation time 4 minutes.
EXAMPLE 2 Separation of transbutene-Z and butene-l by gas/liquid chromatography This example is illustrative of separation problems arising in the field of petrochemistry.
The following system is used: retarding phase: diisodecyl phthalate; forwarding phase: N 50 C. Alpha for this system is approximately 1.3.
(a) Open tube, laminar flow Tube diameter: 0.2 mm. Separation time: appr. 10 sec. Column length: 10 m.
lPressure drop: appr. 10 atm.; or: Tube diameter: 2 mm. Separation time: appr. 4 min. Column length: 50 in.
Pressure head: 30 cm. solvent (b) Open tube, turbulent flow Tube diameter: 0.2 mm. Separation time: less than 1 sec. Column length: 10 In.
Pressure drop: appr. 200 atm.; or: Tube diameter: 2 mm. Separation time: appr. 10 sec. Column length: 200 m.
Pressure drop: appr. atm.
(c) Apparatus in accordance with FIG. 15
Particle size: 0.5 mm.
Total column length: 25 in. Diameter: 10 cm.
250 sieves spaced 10 cm. apart Flow rate: 5 m./sec. Separation time: appr. /2 min.
(d) Apparatus in accordance with FIG. 13
Particle size: 1 mm.
Column length: 10 m. (5 sections of 2 m. in series) Column diameter: 20 cm.
Flow rate: 1 m./sec.
Separation time: appr. 1 min.
Note: In (0) and (d) the exact flow rate is determined empirically for each packing material because of its critical variation with minor differences in particle shape and size.
(e) Apparatus in accordance with FIG. 14
Particle size: 1 mm.
Length of column 51: 10 m.; inlet 54 is halfway up Downwards movement of packing: 20 cm./sec.
Upward flow of gas: 70 cm./ sec. (relative to column walls); column vibrated Flow rate in column 57: appr. 20 m./sec.
Diameter of column 57 is /3 of that of column 51 in this example and blow nozzles may be provided at 58 in the manner known from pneumatic conveying equipment.
EXAMPLE 3 Separation of codeine from heroine This example is typical of alkaloid separations.
The following system is used: retarding phase: silica. gel; forwarding phase: methanol-n-butanol-benzene-water 60:l5:10:15. Alpha for this system is approximately 1.4.
(a) Packed column, laminar flow (Fine particles) Separation time: appr. 25 hrs. Column length: 2 m.
Pressure head: 30 cm. solvent (b) Packed column, convective flow (Packing material 1 mm. particle size) Separation time: 2 /2 min.
Column length: 4 m.
Pressure drop: 15 atm.
(c) Open tube, laminar flow Separation time: 8 hrs. Column length: 4 m.
Pressure head: 40 cm. solvent Column diameter: 0.2 mm.
(d) Open tube, turbulent flow Separation time: 8 min. Column length: 50 m. Pressure drop: 40 atm. Column diameter: 2 mm.
EXAMPLE 4 Separation of atropine from morphine Retarding phase: silica gel; forwarding phase: benzeneacetone-ether-l% aq. ammonia 4:6: 1:03. Alpha for this system is approximately 1.45.
(a) Packed column, laminar flow (Fine packing, conventional) Separation time: appr. 15 hrs. Column length: 1.5 In. Pressure head: 30 cm. solvent (b) Packed column, convective flow (Packing material 1 mm. particle size) Separation time: 2 min.
Column length: 3 m.
Pressure drop: atm.
(c) Open tube, laminar flow Column diameter: 0.2 mm. Column length: 4 m.
Pressure head: 40 cm. solvent Separation time: 9 hrs.
((1) Open tube, turbulent flow Column diameter: 2 mm. Column length: 40 m. Pressure drop: 35 atm. Separation time: appr. 5 min.
(e) Apparatus in accordance with FIG.
The separation requires (for 99% purity) approximately 100 plates. Choosing a column diameter of 10 cm., the column will be 10 m. long, containing 100 sieve plates and silica gel beads to fill each compartment half full. The bead diameter is chosen so that the material is fully fluidised at a flow rate of 2 m./sec.
The separation will be completed in appr. 1 minute.
EXAMPLE 5 Separation of sodium from potassium Retarding phase: ion exchange resin Amberlite I.R. 100; forwarding phase: 0.1 N HCl. Alpha in this system is approximately 2.3.
(a) Packed column, laminar flow Conventional fine column bed 40 cm. long, 1 cm. diameter. Pressure head: 30 cm. of eluant. Separation time: 11 hours.
(b) Packed column, convective flow 1 mm. particlespacked to a height of 1.5 In. Pressure drop: 3 atm. Separation time: appr. 30' secs.
What we claim is: 1. A chromatographic separating process carried out in a chromatographic system comprising a tubular passage confining a retarding phase and a material forwarding phase, at least the latter of said phases flowing through said tubular passage and a material to be separated in phase interchange between said phases, individual parts of the retarding phase being restrained throughout said interchange against movement relative to the overall state of, movement of the retarding phase in respect of said passage and which comprises (a) adjusting the relative overall flow velocity between the phases to a predetermined value in excess of the velocity corresponding to the onset of convective flow phenomena in the forwarding phase, apparent by a downward inflection in the graphical representation of plate height against velocity, and
(b) carrying out the chromatographic separation at the velocity so adjusted.
2. A process as claimed in claim 1 applied to analysis, which comprises limiting the resistance to mass transfer in the retarding phase to a predetermined value at which the graphical representation of plate height against velocity after said inflection is lowered to at least a plateau and carrying out the chromatographic separation under conditions corresponding to a point on such plateau.
3. A process as claimed in claim 2 which comprises limiting the resistance to mass transfer in the stationary phase to a predetermined value for which the said graphical representation beyond said inflection reaches a maximum and carrying out the chromatographic separation under conditions beyond said maximum.
4. A process as claimed in claim 1 which comprises packing capillaries of between 1 mm. and 0.2 mm. internal diameter, with particles of which all three dimensions are substantially equal, being on the average between /a and /s the capillary diameter and comprising a stationary phase and carrying out the separation in such capillary by passing therethrough a forwarding phase at the said velocity.
5. A process as claimed in claim 4 in which the stationary phase is a liquid film on the surface of the particles which have a porous surface texture.
6. A process as claimed in claim 4 in which the stationary phase is a liquid film on the surface of the particles and the nips at the points of contact of the particles with one another and with the capillary are filled with a solid bonding substance.
7. A process as claimed in claim 1 applied to separations in open tubes which comprises lowering the velocity for the onset of convective flow phenomena in the forwarding phase by including in such tubes transverse baflle formations in staggered arrangement, applying to such baffle formations a layer of retarding phase and carrying out the chromatographic separation at a relative flow velocity between the forwarding phase and the retarding phase in the region where said convective phenomena extend across the entire tube cross-section and below the velocity at which the calculated resistance to mass transfer in the retarding phase exceeds that in the mobile phase.
8. A process as claimed in claim 7 in which the retarding phase is a liquid and is applied in a layer thickness of between 0.1 and 0.01 times the tube radius.
9. A process as claimed in claim 7 in which the retarding phase is a liquid and is caused to flow in countercurrent to the forwarding phase, the mixture to be separated is introduced continuously, the flow rate of the retarding phase is adjusted to a value intermediate between the rates of advance relative thereto of two fractions to be 19 separated and said fractions are withdrawn continuously at separate localities on opposite sides of the locality of introduction of the mixture in the directions of flow.
10. A process as claimed in claim 1 applied to preparative chromatography in packed systems which comprises lowering the velocity for the onset of convective flow phenomena in the forwarding phase by including in the packing bafiles in the packing extending transverse to the direction of flow of the forwarding phase, each providing a plurality of apertures substantially uniformly distributed over the cross-section, both the apertures and the spacings between adjoining apertures being of a larger order of magnitude than the order of magnitude of the solid parts of the packing.
11. A process as claimed in claim in which the apertures in successive battles are in staggered relationship to one another.
12. A process as claimed in claim 1 applied to preparative chromatography which comprises packing a tube with particles larger than 3 mm. in diameter and substantially with all three dimensions thereof of the same order of magnitude, the tube diameter being between 1.5 and 5 times the particle diameter and in excess of 5 mm., applying a film of retarding phase to said particles and carrying out the separation by passing through the thus packed tube a forwarding phase at the said velocity.
13. A process as claimed in claim 12 in which the forwarding phase is a gas.
14. An apparatus for carrying out chromatographic separations at a relative flow velocity between the phases at which convective flow phenomena prevail, said apparatus being of the tubular packed column type, the packing being composed of particles the three dimensions of which are at least approximately equally large, the surface of the packing carrying the retarding phase, comprising the additional feature that:
(a) said tube internal diameter is between 1.5 and 5 times the particle diameter;
(b) the tube diameter is in excess of 5 mm., and the particle diameter exceeds 3 mm.
15. An apparatus as claimed in claim 14 wherein the particles are substantially spherical.
16. An apparatus as claimed in claim 15 wherein the particles have a porous surface texture and carry a liquid retarding phase.
17. An apparatus as claimed in claim 15 wherein the particles carry a liquid retarding phase and the nips between adjoining particles and between the particles and the tube wall are filled by a solid bonding substance.
18. An apparatus as claimed in claim 17 in which the nips are filled by sintering of the particles themselves.
19. An apparatus as claimed in claim 14 in which the particle diameter exceeds 3 mm. and said particles having passages formed therethrough.
20. An apparatus for carrying out chromatographic separations at a relative flow velocity between the phases at which convective flow phenomena prevail, said apparatus being of the open-tube column type and comprising the improvement of:
20 bafile formations transverse to the tube axis having surfaces supporting a liquid retarding phase having a film thickness in excess of the stable film thickness maintainable by adhesion of the film to the bafile.
21. An apparatus as claimed in claim 20 in which the bafiie formations take the form of ribs projecting from the tube walls.
22. An apparatus as claimed in claim 20 in which successive baffle formations overlap when viewed in the direction of the tube axis.
23. An apparatus as claimed in claim 20 in which the baffle formations form trays with upturned rims adapted to retain a layer of liquid retarding phase having a film thickness in excess of the stable film thickness maintainable by adhesion of the film to the battle.
24. An apparatus as claimed in claim 20 in which the bafile formations are downwardly inclined, adapted for the retarding phase to flow in countercurrent to an upwardly flowing forwarding phase.
25. An apparatus as claimed in claim 24 in which the bafile formations project from the inner periphery of the column in screw thread fashion.
26. An apparatus as claimed in claim 24 in which the bafile formations project from opposite sides of the column inwardly in staggered arrangement, overlapping one another when viewed in the direction of the column axis.
27. An apparatus for carrying out chromatographic separations at a relative flow velocity between the phases at which convective flow phenomena prevail, said apparatus being of the open-tube column type having column walls surrounding a tubular interior and comprising the improvement of convective flow-inducing formations extending from the walls part of the way into the tubular interior, said formations being traversed by open passages pervious to a mobile phase and having surfaces on which is exposed a chromatographic retarding phase to improve the separating capacity.
References Cited UNITED STATES PATENTS 2,893,955 7/1959 Coggeshall 5567 X 3,005,514 10/1961 Cole et al. 5567 X 3,250,058 5/1966 Baddour 55197 X 3,283,483 11/1966 Halasz et al. 55386 3,298,527 1/ 1967 Wright 55-386 3,374,606 3/1968 Baddour 5567 FOREIGN PATENTS 703,044 2/1965 Canada.
OTHER REFERENCES Keulemans, A. I. M., Gas Chromatography, Reinhold Publishing Co., 1960, QD271K53, pp. -153.
JAMES L. DECESARE, Primary Examiner US. Cl. X.R. 5567; 210-198