US3267646A

US3267646A - Automatic preparative gas chromatograph

Info

Publication number: US3267646A
Application number: US262426A
Authority: US
Inventors: James M Kauss; Urban J Peters; Aaron J Martin
Original assignee: Hewlett Packard Co
Current assignee: HP Inc
Priority date: 1963-03-04
Filing date: 1963-03-04
Publication date: 1966-08-23
Anticipated expiration: 1983-08-23

Description

Aug. 23, 1966 J. M. KAuss ETAL AUTOMATIC PREPARATIVE GAS CHROMATQGRAPH 8 Sheets-Sheet 1 Filed March 4, 1963 INVENTORS JAMES M. KAUSS RBA J. PETERS AARON J-MARTIN 44% 4% 19.5 gag AATT%RNEY5 Aug. 23, 1966 J. M. KAuss ETAL 3,267,646

AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH Filed March 4, 1963 8 Sheets-Sheet 2 nob , 30b 30f 132 A 1&-

0 30C 0 I33 30a F INVENTORS JAMES M- KAUSS URBAN J. PETERS AARON J. MARTIN %M,=7z zw%ffiflfi ATTORNEYS Aug. 23, 1966 J. M. KAUSS ETAL 3,267,646

AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH Filed March 4, 1963 8 Sheets-Sheet :5

INVENTORS u l JAMES M. muss w s2 URBAN J. PETERS Q 2 AARON J. MARTIN ATTORNEYS J. M. KAUSS ET AL AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH Aug. 23, 1966 Pued March 4, 1963 S m n 0 SW N mgmw N K P 6 A J 3W w M U A 7 Aug. 23, 1966 Flled March 4, 1963 J. M. KAuss ETAL 3,267,646

AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH 8 Sheets-Sheet 5 INVENTORS JAMES M- KAUSS URBAN J- PETERS AARON J. MARTIN ATTORNEYS Aug. 23, 1966 J. M. KAUSS ETAL AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH 8 Sheets-Sheet 6 Fll d March 4, 1963 FIG. 9

FIG. 8

INVENTORS JAMES M. KAUSS URBAN J. PETERS AARONJ-MARTIN ATTORNEYi Aug. 23, 1966 J. M. KAUSS ETAL AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH 8 Sheets-Sheet 7 Filed March 4, 1963 *9 0E uuv 0 0m 0Q 0Q ow I 09 ll UQ 01 00 o I om ow o? @901 uuw 0 0m 2 0m ow oo URBAN J. PETERS AARON J.MART|N BY I //Z/z/;, I W/MW ATTORNEYS Aug. 23, 1966 J. M. KAUSS ETAL 3,

AUTOMATIC PREPARATIVE GAS CHROMATOGRAPH Fxled March 4, 1963 8 Sheets-Sheet 8 FIG.H

INVENTORS JAMES M- KAUSS URBAN J. PETERS AARON J- MARTIN ATTORNEY5 nited States The present invention relates to an automtaic preparative gas chromatograph. It pertains particularly to a gas chromatograph which is capable of preparing reagent size quantities of various materials separated by the principle of gas chromatography.

In recent years, preparative scale gas chromatography has developed as a logical outgrowth of analytical chromatography. As the name implies this relatively new technique takes advantage of the high separating efiiciencies of the gas chromatograph to physically separate and collect useful quantities of the components present in a sample material. The components, thus highly purified, are removed from the carrier gas as they are eluted from the column. The materials so prepared may be used for qualitative studies, reaction studies, or they can be marketed as fine chemicals.

Currently, this use of gas chromatography for the separation and isolation of relatively large or macro quantities of material, as compared with analytical or micro-quantity separations, is becoming increasingly important. Although, on a small scale, preparative scale chromatography is often used in conjunction with other techniques as an aid in positive, authoritative identification of components, the use of the principle for direct production or separation of relatively larger and even marketable quantities of material is becoming relatively more important. The combined use of chromatography with other techniques is still of interest but apparently is becoming relatively less important.

The invention has particular applications to such matters as the preparation of spectroscopic solvents or preparation of pure materials for reaction studies, and also for the isolation in marketable quantities of rare or valuable materials such as pharmaceuticals. The preparation of materials for such purposes requires substantially larger sample capacities or throughput than has ordinarily been feasible with gas chromatograph apparatus in the past.

The desired capacities for large scale samples may be obtained, at least in theory, by direct scale-up of conventional chromatographic apparatus. However, the practical increase possible by this means is limited. A simple increase in tube or column capacity by increase of its diameter, or by placing multiple columns in parallel, is of course an easy way to increase throughput. However, there is a rapid decrease in separating efficiency as the column diameter is increased, especially as the increase becomes greater. Large increases in throughput bring problems and complications in control and detection.

According to the present invention, these problems are approached by limiting the scale-up of the apparatus to the point where resolution is not seriously affected and then obtaining higher capacity by automatic and continuously repetitive sampling It has been discovered that considerably larger throughput production can be obtained in this manner than would be expected by routine consideration of scale-up To accomplish substantially greater volume preparation with relatively moderate scale-up is a prime purpose of the present invention.

According to the present invention, then, it has also been found that separating efficiencies reasonably comparable to those of standard small diameter analytical columns in gas chromatographs may be obtained with colatent umns of substantially larger diameter Careful, automatic control of sample introduction tends to improve reliability of separations. For example, analytical columns of a size up to three quarters of an inch, internal diameter, and even up to one inch and possibly larger, may be used without serious loss of separating efiiciency. At the same time, the total volume of sample material separated and of components recovered is increased proportionally more, by automatic, systematic and repetitive injection of identical samples.

Hence, in addition to providing a system wherein the column size may be increased fairly substantially to increase the overall capacity of the apparatus, it is possible to further increase the yields of the apparatus by making it fully automatic. This makes possible a relatively continuous unattended operation of the chromatograph, even over relatively long periods, for example, overnight or over a weekend. It also makes it possible to use the apparatus at or near its very highest efficiency for quantitative separation and collection.

While an apparatus, of the type to which this invention pertains, may be designed for simple isothermal operation, it is also desirable that it be capable of use in or with a variable or programmed temperature operation. This temperature programming, of course, tends to add to the complexity of the system. However, according to the present invention, a relatively simple solution has been worked out. It is found, in fact, that a programmed temperature operation is just as desirable in preparatory scale work as it is in analytical work and in some cases even more desirable. As a result, the equipment or apparatus of this invention can be used through wide ranges of temperature to accomplish the improved separations possible with such programming. A further object of the invention, then, is to take advantage of the newly found possibility of preparatory scale separation combined with programmed temperature operation. An ancillary object, which of course follows directly, is to increase substantially the versatility of the unit.

In order to obtain maximum versatility in the apparatus, the automatic features of the unit, according to the present invention, are placed solely under control of the conditions and operations of the separation being performed. Reliance is not placed merely on a preset timing device. For example, the actual chromatographic peaks, as they appear on the recorder to indicate arrival of a particular component separated from the sample, are used to trigger and control the component collections operations. This requires coordination of a number of major components. For example, it requires the coordinated use of an automatic system for injection and employment of a selective system for collecting the separated discrete components or fractions. In the present case the latter may also be automatic. The eflicient use of recording means is involved and, of course, in the case of programmed temperature operations, the employment of automatic means for controlling or, if necessary, cooling the oven system is also involved.

Accordingly, a primary object of the present invention is to provide a fully integrated and substantially completely automatic apparatus for separating and collecting sizable samples of various components of test or sample materials. At the same time, purity is maintained consistently high with relatively large scale production. All this is accomplished by design of a system requiring almost a minimum of attention on the part of operators.

111 brief summary, the equipment or apparatus of the present invention is an efficient and reliable instrument of Wide versatility capable of sustained and largely automatic operation over substantial periods of time. It is particularly useful for isolating and collecting high purity components from mulit-component or sample materials on either laboratory or a semi-Works scale. Included are such features as a means to adjust the ratio of column pressure to back pressure, means to segregate one, two, or more, up to six (or more if desired) individual components, means to return automatically to a starting position after the desired number of components has been gathered from a particular sample, and many other features which will be set forth in detail hereinafter. The apparatus also comprises a combined but separately operable analytical system of small column type with its own flow indicator-controller as Well as its own column and its separate sample injection facilities.

The invention will be more fully understood by reference to a detailed description which will next be given in connection with the accompanying drawings. In the drawings:

FIGURE 1 is a schematic flow diagram of an instrument made according to the present invention.

FIG. 2 is a partial front elevational view, with certain parts being removed and certain parts being shown only diagrammatically, of an apparatus according to the present invention.

FIGURE 3 is a transverse horizontal sectional view of part of the apparatus of FIGURE 2 taken substantially along the line 3-3 of FIGURE 2.

FIGURE 4 is a vertical sectional view of part of the apparatus comprising the collector manifold and some associated parts, taken substantially along the line 44 of FIGURE 2.

FIGURE 4A is a fragmentary view taken from the right side of FIGURE 4, showing relative arrangement of some of the sample collecting tubes.

FIGURE 5 is a sectional view through a part of the sample collecting apparatus, taken substantially along the line 4- 1 of FIGURE 2.

FIGURE 6 is a transverse sectional view of the apparatus, taken along line 6-6 of FIGURE 5, looking in the direction of the arrows.

FIGURE 7 is a horizontal sectional view of the apparatus shown in FIGURE 4 taken substantially along the line 77 of said FIGURE 4.

FIGURE 8 is a vertical sectional view through the oven, taken substantially along the line 8-8 of FIG- UR-E 2.

FIGURE 9 is a view similar to FIGURE 8, showing certain parts in changed positions.

FIGURES 10A to 10H, inclusive, are chromatogranis taken by the apparatus of the invention, showing the eifect on resolution of various sample sizes.

FIGURE 11 is a diagrammatic front view showing the major operating controls.

Referring first to FIGURE 1, a schematic representation of the preparation scale gas chromatograph is shown, some parts being somewhat out of scale and certain other parts being represented only diagrammatically. This scheme will be described first to outline some of the more important elements and aspects of the invention. Certain of the detailed mechanisms will be described thereafter.

As shown in FIGURE 1, a carrier gas, under appropriate pressure from a supply source, not shown, such as a tank, is supplied through a line 11 controlled by a suittable valve 13. This valve 13 is preferably of the fullyopened, fully-closed type, electromagnetically operated to alternatively cut off flow completely or open to full flow position. From valve 13 the carrier gas, in normal major flow, continues on through line 15 to another solenoid operated valve 17 of generally similar type, but equipped with a connection line ll'g to a pressure gauge G. From here it passes through a line 18 to a control valve 19 and then through line 21 to check valve 23 and on to a preheater 25. Here the temperature of the carrier gas is adjusted to the level desired. The carrier gas then passes on through lines 27 to a preparative scale injection port 29. The samples are supplied to the injector by a i sample dispensing or injector device which is adapted to supply repetitively and automatically samples of predeterminable but identical size or volume over a prolonged period of time. It will be described further, below.

From the sample injection port the carrier gas normally passes into the chromatograph column or columns indicated generally at 39. These columns are substantially larger in diameter than normal analytical columns, being of preparative scale dimensions. These columns may be made or" various lengths and diameters but preferably are not so large in diameter as to cause serious losses in separating efficiency. In a typical preparative scale apparatus they have been made about inch in diameter and 8 feet long, in U-shape, each leg of the U being 4 feet long. However, these sizes can be varied widely and columns of /8 inch, /2 inch and 1 inch diameter have been used successfully. The individual columns are arranged for connecting in series or parallel, or seriesparallel, as may be desirable for the particular operation involved. They may also be used singly if desired.

The metering or measuring of the sample into the carrier gas stream is accomplished preferably by means of a dispenser or injector mentioned above, shown at 28. It comprises a pneumatic-hydraulic cylinder with a reciprocable injector piston. Force to operate the piston is preferably supplied by the carrier gas pressure. Carrier gas is connected to enter the pneumatic side of a diilerential area stepped piston 28' through a line 28 connected to line 21. The pneumatic side of the piston 28' is preferably substantially greater in area than that of the hydraulic liquid sample piston. Hence, when sample injection begins, there is sufficient mechanical advantage in the force of the carrier gas to overcome any back pressure caused when the sample flash vaporizes into the hot injection chamber. The injection port chamber in unit 29 is kept at a suitable high temperature.

The injector, per se, is shown at 28 and sample flow thereto is controlled by a valve 28a, Which connects it selectively to a supply source 2&5 and to a discharge line 2.30. The latter leads to the injection port 29. It is provided also with an electrically operated exhaust valve 28d for the operating gas and a drain valve 282 for removing liquid residue. The dispenser or sample injector preferably is designed to inject any desired quantities from a small fraction of a cubic centimeter to a number of cubic centimeters. In a specific example, it can be adjusted from A to 12 cc. per stroke. In other Words, the ratio of maxnnum to minimum sample size is 50/1 and may be even higher, up to /1. The volume is infinitely variable by a simple screw adjustment which determines precisely the sample volume by limiting the length of the refill stroke of the injector piston. Since the sample itself is stored in reservoir 28!; which is under carrier gas pressure at all times through line 281, connected to line 28" through a check valve 23, the refilling force against the piston insures that the piston will draw a full sample on each stroke. The apparatus is so designed that the largest capacity sample, 12 cc. in the present instance, is completely injected in a very short time, for example, in 5 seconds. The injector 28, per se, is described in greater detail and claimed in a separate application Serial No. 256,337, filed February 5, 1963, by James M. Kauss, now U.S. Patent No. 3,155,289 issued November 3, 196

The injection chamber of port 29 preferably is in the form of a heated cylindrical vessel which has an empty volume of several times the largest sample to be injected. Injection port 29 in a specific example of apparatus which has been built has an empty volume of about 35 cc. It is provided with a heating means and controls therefor, or" conventional type, to bring and maintain its temperature at a selected level, up to 400 C. It is filled with metal shot, preferably of stainless steel, to act as a heat sink. This quickly brings the sample temperature in the chamber to the desired level.

Likewise, the carrier gas preheater is of similar heat capacity to control the temperature of the gas at a desired level. It is similarly equipped or filled with stainless steel shot which acts as a heat sink and serves to bring the carrier gas to the desired operating temperature very quickly. These heat capacities are sufficient to rapidly vaporize more than the maximum sample capacity of material supplied to the injection port by dispenser or injector 28, such as 12 cc. in the example just cited. The dispenser or injector 28 preferably is not heated because it employs liquid sealing elements which perform better at ordinary temperatures.

A manual or syringe injection port, not shown, but of well known type, is also provided for injection of samples by hand, e.g., with a syringe, when this is desired. This may be in the form of a septum in the wall of element 29.

The vaporized sample, whether injected manually or automatically, goes with the carrier gas and passes through the column or columns 30. These columns, indicated individually at 300 to 30f, are incorporated into an oven chamber 31 which can accommodate a variable number of columns. By this means they may be heated, or subjected to variable programmed temperatures, as desired. In this particular installation, as previously noted, the chamber accommodates 6 U-shaped columns. Provisions for heating the oven include the blowers 32, FIGURE 2 and electrical heaters with appropriate controls. The heating means are described more fully below. See also FIGURES 8 and 9.

As the carrier gas and the injected sample material pass through the column, the various component materials in the sample are selectively adsorbed and then desorbed. The carrier gas, with the desorbed components, emerges from the columns and passes out of the oven 31 through a high temperature needle valve 33. This needle valve provides a means for varying and controlling the back pressure on the system. The proper ratio of pressure head to back pressure often is important, particularly in large scale separations. A branch line 34 connects to the pressure gauge G, previously mentioned, which registers both head and back pressure.

The pressure control valve 33 is kept isothermally at or near the temperature of the detector cell through which the sample next passes. This cell is indicated at 35. A thermal conductivity type detector cell is preferred. It is enclosed within a heated chamber which can be controlled in temperature from about 100 to 375 C. The back pressure valve 33 is controlled at the same temperature and may, for convenience, be housed in the same enclosure. The entire flow of carrier gas and separated components passes through the detector.

In an apparatus of the size and type described so far, the volume of carrier gas flow is often more, and may be considerably more, than one liter per minute. Hence the detector unit 35, which otherwise is conventional in type and forms no part of the present invention, must be specially designed, so far as capacity is concerned, to operate at this volume without undue noise, or electrical disturbance.

From the detector unit the carrier gas and the now separated sample components, as the latter come along, pass through a line 37 to a sample collecting trap unit which will be described below.

The detector has a reference side which is supplied by a separate and complete analytical system. This analytical system, which employs a small diameter column, is a complete unit in itself. It has its own flow controller, its own injection port and its own small diameter column. It will now be described.

At the junction indicated at 41, FIGURE 1, a reference flow of carrier gas is taken off through a separate line 43 and passed through a reference flow controller and indicator 45. From there it passes through a line 47 to an analytical injection port 49 which is comparable to the preparatory scale injection port 29 except for its size. From the analytical injection port the analytical sample, in its carrier gas, passes through a line 50 into the analytical column 51 which is also housed within the oven. This analytical column is considerably smaller in diameter than the column 30, being of conventional diameter. It may be packed or coated interiorly (or both) to perform its analytical function in a manner well known in the art. It is indicated diagrammatically in FIGURES 1 and 2.

From the analytical column the analytical stream passes through line 53 and through the reference side of the detector unit 35. The volume of carrier gas and sample material is very small and the efiluent stream is ordinarily exhausted into the atmosphere through outlet line 54.

This arrangement is very useful for column scouting work. Merely by reversing the detector leads to the recorder with a panel mounted switch, mentioned below, the preparative system can provide the reference flow for the small analytical column. The instrument is then useful for more exact analytical work. This eliminates labor which would otherwise be involved in packing and repacking large colunms while determining the best column packing for a given sample. Different prepacked (or interiorly coated) analytical columns may be kept on hand for various analytical or comparative analytical problems. The analytical column also may be used to check the purity of collected sample components. The manner of their collection will be described below.

The preparative scale samples or components separated in the preparative columns pass with the carrier gas through the line 37 to the manifold 61 of the collection system. Manifold 61 is arranged for connection with an indexing valve unit, to be described in detail, so that it can pass the individual separated components each to a separate one of a number of traps. It can also by-pass the carrier gas, with or without any components, through a by-pass cleanup trap 68 by means of a line indicated generally at 65. The indexing fraction collecting valve is indicated generally at 67 and is so arranged that a number of separate components to be trapped or collected, up to six in this specific arrangement, can be separately accumulated. In the example shown, the valve 67 can be indexed successively to 12 consecutive stop positions, including six separate collecting positions and an intermediate by-pass position between each pair of collecting positions. This necessitates a total of seven outlet connections to the manifold 61, in all, since the by-p'ass positions of the valve are all connected to a single outlet.

Before the first fraction is to be collected, all flow normally passes through the by-pa'ss and cleanup trap 63. As component separation begins, the first peak rises to a preselected point on the recorder, indicating arrival of a component to be trapped. A recorder pen activated switch, not shown in FIGURE 1 but described below, causes appropriate movement of the fraction collecting valve. The valve 67 then indexes through 30 igth revolution) to the first collection" position, which is shown in FIGURE 1, position number 1. The mechanism for accomplishing this will be described below.

This operation also closes the normally open by-pass valve 68a as well as opening the exit valve 1. This permits gas which is trapped in the first collector tube or trap A to flow throughout line 69a to the valve 67 and then to the atmosphere through exhaust line 68e. All flow from line 37 and manifold 61 then passes through trap valve unit 1 on the indexing valve 67. The traps A, B, C, etc., are kept at a component condensing temperature and the first component is immediately condensed out of the carrier gas and collected in trap A. The traps are all mounted in a refrigerated compartment so that the heated condensible materials from the manifold are immediately collected. Baffle means inside the traps assist in separating condensed material from the 3,2 7 carrier. The carrier gas from all the traps eventually passes out through exhaust line 63c. Collection in trap A continues until the peak on the recorder drops to the preselected point on its scale.

After the first peak passes the preselected set point on its way down scale, which operation also will be described more fully below, the rotary valve makes another 30 rotation step and the flow is again diverted to the bypass position. This rotation step closes the component trap valve unit it and an operating means described below again causes the by-pass valve 68a to move to its normally open position.

On arrival of a second component at the detector, the valve 67 is again indexed a half-step or 30 to the second collecting position 2. This operation is repeated in similar steps. The by-pass is opened between peaks and closed during the peaks, or during passage of selected parts of peaks to avoid collection or trapping of side band materials. This is repeated until a maximum of six different individual separated components have been collected. The flow thus alternates between by-pass and collection in a trap, the sequence being first a Dy-pass, then collection in the first cold trap A, a by-pass again, then collection in the second cold trap B, a by-pass once more, then a collection in the third trap C, and so on through traps D, E, and F, the indexing valve opening successively at positions 1, 2, 3, 4, and 6 as six separate peaks are reached. The valve can be reset manually in case less than six peaks are employed. Where it is desirable to start the cycle anew without running through all six settings, e.g., where only 1, 2, 3, or up to 5 components are to be collected, the valve will return automatically to its zero point or starting position without stopping idly at positions where there are no peaks.

All valving thus is done on the exit side of each of the traps. The valve 67 is not enclosed either in a heated or in a cooled compartment and thus operates at room temperature. This has the advantage of eliminating problems of high temperature sealing, due to use of plastic glands, etc.; it also eliminates problems of high temperature valve body corrosion. The traps A, B, C, etc., are only open to gas flow while the carrier gas is flowing through them. The trap fractions thus are not exposed to ambient air or moisture at any time because the traps always contain a carrier gas atmosphere. To prevent any diffusion between traps simple gravity ball checks are located in the hot manifold as indicated at 62. These ball checks can Withstand the high temperatures, unlike the seal parts of valve 67. See FIG. 4.

After the last component to be collected from a given sample has been eluted, the collection valve 67 is reset to its zero position which is also the injection position for a new sample. In isothermal operation this resetting operation itself activates the automatic injector or dispenser 28 which then causes another sample to be introduced through the preparative scale injection port 29.

As mentioned above, it is usually desirable that the apparatus also be capable of programmed temperature operation. For such operation the sequence of events is slightly different from that just described for isothermal operation.

Assuming that the last peak is being passed, when it has been passed or has reached the preselected cut-off level, the recorder pen-operated switch causes the rotary component collection or indexing valve 67 to move to the zero or starting position of by-pass between stations 6 and 1. However, this does not automatically activate the automatic injector. Instead, for temperature programming, the temperature programmer to be mentioned further below, continues up scale until the high temperature limit has been reached. This limit can be preset from 50 to 325 C. and is under control of the heating elements 276, 271, etc., FIGURES 8, 9, and their controls. At the highest temperature point on the program, a cooling damper is opened, as will be explained. The tomwas 'a U perature programmer is reversed, and the controller is driven down scale to the starting point for another pro- 7 grammed temperature operation.

The essentials of this apparatus are shown, diagrammatically only, in FIGURE 1. A damper speed control is indicated at 72 in the form of a gas ilow restricting valve. Its control valve '74 is of the electrically operated type but is operated at a controlled rate in closing or opening. A damper opening cylinder 7'6 is provided to control the rate of damper movement and prevent damage to mechanical parts. When this mechanism operates, the blowers 32 will draw air at room temperature into the oven chamber 31 through an inlet for ambient'air. Here the air is circulated over the columns and heaters and passes out through an exhaust duct. Thus the oven temperature is quickly lowered. When a preset starting temperature limit, lower than the first, has been reached the damper 267 closes. The injector 23 then introduces another sample through the injection port 29. The programmer then starts up scale again and the cycle is repeated. The oven damper operation is shown in more detail in FIGURES 8 and 9 and will be referred to again.

Referring now to FIGURES 2 and 3, it will be seen that the several columns Ma, 3911, 3tlc, etc., are connected in series, as herein illustrated, by means of the threaded connectors and the

U tubes

131, 132, 133, etc., at the top. Corresponding connectors, not numbered, are shown at the bottom of FIGURE 2. See also FIGURE 3. Obviously, by interchanging the connections the tubes can be placed in series or in series-parallel as desired.

In normal operation carrier gas from the left, FIGURE- l, picks up the sample supplied by the injector 29 and sweeps it through line 29a into the column assembly 36. After passing through the column the carrier gas and the separated components of the sample pass through the detector and on into the collector. Before being collected they must, of course, be directed to the appropriate collecting vessel and this function is performed by the indexing valve mechanism as just described. The details of this mechanism will now be explained.

Referring to FIGURE 4, the manifold 61 is shown as being connected to a plurality of outlet lines lll, only one of which is shown in this figure. A gravity ball check 62 is provided in the manifold, at each connection to a line 161 to prevent reverse flow. This is to protect collected components in the traps against contamination.

Each. outlet line 161 is connected through a union to a collector tube inlet line 166. One of these lines conmeets to each of the collector tubes or traps, e.g., that indicated at C in FIGURE 4. Similar lines, not shown, connect to each of the other traps A, B, D, E and F.

As previously indicated, carrier gas normally is trapped within each of the tubes A, B, C, etc., and cannot escape as long as the indexing control valve 63 is closed to that tube. Therefore, component material to be collected cannot enter the collecting traps, nor will the carrier gas either, until the proper outlet in the valve 67 is opened. Each collector tube or trap has its own outlet 167 concentric with the inlet tube 166. Through suitable packings 168, 169, the annular gas outlet line 167 from each component trap connects to one of the tubes 69a, or 6%, etc. Through a wall mounting 171 each of these is supported by a suitable collar unit 172. Each line 69a, 6912, etc., is connected through a coupling 173, to a fitting 265a, ZtlSb, 2135c, etc., mounted on a plate 210 which constitutes the non-rotary member of valve 67. Each of these fittings 205a, etc, leads directly to one of the openings 1, 2 or 3, etc., FIGURE 1, controlled by the indexing valve assembly; for example fitting 205a leads to opening 1. However, by-pass line as from tube 68 goes to valve 680.

The manifold 61 is enclosed within insulation shown at 177, 173, FIGURE 4, so that it can be kept hot. An appropriate heating means indicated at H, preferably electrical and controlled by adjustable thermostat controls 304, 304a, FIGURE 11, maintains proper temperature of the manifold. It is usually held at the same temperature as the valve 33 and the detector. To keep the component vaporized, the manifold may be heated to an even higher temperature than the detector if desired. The traps A, B, C, etc., are kept cold.

There are, in the specific instrument shown, six sets of connections 205a, etc. The indexing valve mechanism comprises the two-way valve 68a, controlled by a cam 181 on cam shaft 180, as best seen in the lower part of FIGURE 7. This valve is held open normally, i.e., except when a separated component is being collected in a trap. Cam 181 has a flattened portion 182 which allows valve 68a to close only when fiat 182 is in or near the down position See FIGURE 6. Each time the cam is driven, it rotates a half revolution and stops. These stops occur alternately when the flat portion 182 is down, and indexing shaft 201 is in a trap collecting position, and when the part 182 is up and valve 68a is open to by-pass. Indexing shaft 201, which supports rotary valve 67, likewise comes to periodic halts. By-pass flow is normal and continues until cam shaft 180 is again rotated to the fiatdown position, as it is shown in FIGURE 6.

Gearing is provided as indicated at 183, 184, 185 and 186 so that indexing shaft 201 turns A th turn for each half turn of cam shaft 180, gear ratios being such that the main indexing rotor shaft 201 passes through Ms of a revolution for each full revolution of the cam shaft 180. The latter is driven by a cyclically driven electric motor with an appropriate clutch so that it stops at each half turn until started again by electric control means. This mechanism is indicated generally at 220, 221, FIGURE 4. It is of standard commercial type, so far as clutch, motor and starting controls are concerned, and is not described in detail since it forms no part of the present invention.

During rotation of the cam shaft 180, the peripheral portion of the cam holds the cam follower 192 down until the flat portion 182 is again at the bottom. It then permits the follower to rise under influence of a valve closing spring mechanism, not shown. In its normal stop position for collecting component material in a trap the flat surface 182 is down and the follower 192 rises to its upper position. This movement closes the gas exit for the by-pass trap so that the stream cannot flow to by-pass but this does not occur until one of the lines to a collecting trap A, B, or C, etc., is open.

Assuming that the by-pass valve 68a is being held open by cam 181, when a sample component comes along from the column, which produces a peak on the recorder, the pen which traces the record on a chart closes a switch. By this means the drive motor 220 is tripped to start turning the shaft 180 through a half revolution. The turning movement takes only two or three seconds to bring the flat cam surface 182 to the bottom. This turning movement allows the by-pass outlet valve 68a to close but it also indexes the rotary valve 67 to a numbered position. This opens the collector or trap valve to permit gas flow through one of the collection traps, for example, trap A. In this position, for trap A, assume that the valve is indexed to position 1. Gas will flow through this tr-ap A as long as the cam follower 192 is in its raised, closed position. The details of valve 67 will next be explained.

The indexing valve itself is mounted on the shaft 201 previously mentioned. It bears and is driven by the gear 186 through means of the gear train described above. Through a connection 205, FIGURE 7, U-shaped line 209 connects the valve 68:: with the chamber formed in part by stationary valve plate member 210 mentioned above, as indicated in FIGURES 4 and 7. The stationary valve member 210 forms the left part or member of a valve chamber 212, FIGURE 7. It is mounted concentrically with shaft 201 and bears the connections 205a or 205b, 2050, etc., which couple with

lines

170, 170a, 170b, etc.,

previously mentioned. This plate 210 cooperates with and is spaced slightly from an opposing but rotating plate 211 which is keyed to the drive shaft 200 by means of a pin 213. The latter forms the other half of the valve chamber. Annular sealing rings 214 and 215 are placed between

plates

210 and 211 to provide the sealed chamber between the two plates. For the greater part of its periphery the plate 211 is provided on its left or chamber side with a groove 217 concentric with its axis. This groove, however, is interrupted at one point for a short distance, about 15 to 20 of the circumference. The interrupted or cam surface thus provided serves as an actuator for spring pressed ball valves indicated at 216. A valve 216 is provided in each connector 205a, etc. Each of these valves is adapted to be operated, through an intermediate cam follower ball 218, when pressed to the left, as seen in FIGURE 7. Thus, when the valve plate 211 is indexed to a stop position, the interrupted portion of the groove 217 presses a normally free floating ball 218 to the left. The normally free ball 218 pushes its adjacent spring pressed ball 216 off its seat. That particular ball valve 216 will thus be opened. This opens the flow of gas from the appropriate collector trap, allowing carrier gas to enter the cold collecting chamber where the component is condensed to a liquid and drops to the bottom of the trap tube A, etc.

Since the single revolution electric motor 220 and its control clutch 221 are of conventional type, it is sufficient to say that when a peak is reached by the recorder, due to movement of the recorder pen, the motor is released for an operation cycle. This drives the cam shaft 191 through a half revolution. This causes cam 181 to close the valve 68a by means of its follower 192 and hence the gas must flow through one of the connecting lines 690 or 6%, etc., and one of the valves 216 and out through U-shaped line 209 to discharge line 68c. For each peak that comes along, valve 67 indexes to the next trap collecting position, I, 2, or 3, etc., as the case may be. The revolution is completed to by-pass after the peak is passed and the by-pass valve 68a is again opened when the cam comes to rest with its rounded portion above the cam follower 192.

The parts just described are mounted in a frame consisting of

side plates

240, 241 and

end plates

242 and 243 appropriately fastened together. Plate 241 is a relatively heavy one and constitutes the main support for the indexing valve mechanism. Mounted on

posts

244 and 245, etc., attached to plate 241 is an intermediate plate 246 which supports the shafts and 201 and the

intermediate gearing

183, 184, 185, 186, providing the drive previously described. The

intermediate gears

184, 185 are mounted on a stub shaft 185a supported in journal bearings formed in

plates

241 and 246.

Shafts

180 and 201 are supported in

plates

240 and 241.

The motor 220 and cyclic clutch and control mechanism 221 are mounted in a subframe assembly 250- secured to the plate 241, on the left side thereof as seen in FIGURE 4.

Referring now to FIGURE 8, the oven 31 which contains the columns is shown in vertical cross section. It comprises insulating front and

rear walls

260, 261, with an insulated base 262 and a partly insulated top cover 263. An intermediate partition is provided, as shown at 264, and one or more blowers 265, preferably two, each driven by a motor 266 mounted outside the casing, fits within the bottom part of the oven. Although two blowers are preferably used, a description of the use of one will sufiice. The blower is so arranged that air is circulated from the front part of the oven, at the right "as seen in FIGURE 1, downwardly and up behind the partition 264 in the manner indicated by the arrows. The columns, 30, 30a, etc., are not shown in detail but are located in space 266. A rockable damper 267 hinged on a pivot shaft 268 is mounted for partial rotation to open and close positions so that the blower can be used to draw in ambient air through an opening 269 when the it I damper is turned to the position shown in FIGURE 9. For heating, the blower is closed, as shown in FIGURE 8. Hence the same blower can be used for circulating hot air within the oven or for drawing in cool air and reducing the temperature.

A series of electric heaters 276, 2T1, 272,273 and 274 is provided in the rear compartment. They are controlled by adjustable thermostatic means including a power proportional controller. This device is of known commercial type and need not be described in detail. Obviously, by passing the air over these heaters and recirculating as in FIGURE 8, the temperature of the oven can quickly be brought to the desired level. The combination of adequate heating means and air circulating means, plus the damper mechanism which facilitates circulation of cooling air at appropriate times, effects the quick control over temperature which is highly desirable for the chromatographic separating operation.

The small analytical column may also be mounted in the oven and it is'shown at 51 behind the main columns in FIGURE 2. In the specific example mentioned above, this column is a A inch tube, ordinarily of the conventional packed type, which can be used for comparative analysis alongside of the larger preparatory scale columns.

Typical results obtained by the apparatus are illustrated in the chromatograms of FIGURES 10A to 10H, respectively. They show the effect of sample size on resolution. These runs were made with three 8 foot columns connected in parallel. Samples were injected at a temperature of 120 C. and the oven temperature was programmed up to 190 C. for each sample injected. The volume of samples was varied, as shown in the several figures. Good resolution was obtained for sample volumes up to about 4 cc. of sample. At higher sample volumes the first two components separated were not suificiently resolved for eitective collection although separation of the other two components was adequate up to values as great as 9 cc. sample size. The extraneous small side peaks on the latter components did not represent impurities in the sample but were caused by imperfect matching of the pressure drop across the three parallel columns. By use of a very precise pressure-drop adjuster, which may be incorporated in each of the columns, these peaks can be easily eliminated. This adjuster is described and claimed in a copending application. It involves a screw threaded pressure-drop mechanism, which passes the gas along a slender spiral path provided between matching screw threads. By simple adjustment of one or more of these, the parallel columns can be very closed matched. However, even with appreciably mismatched columns, the collection of the individual components is not substantially impaired.

The function of cutting oil clean components for separation is controlled by the recorder switch 321s. See FIGURE 11 and further explanation below. This switch, operated by the recorder pen 321p, is adjustable and may be set at a point to cut off only the clear upper parts of the peaks. In the case of FIGURES 10A to lQl-l the recorder switch was set at 25 percent of the scale, that is, the peak was intercepted when the lower 25 percent in height of the peak had passed the recorder. Only that portion of a component which was passing through and which was confined between the vertical line intercepts with the peak graph at the selected level (25 percent level in this case) was collected.

In FIGURE 11 the principal controls are shown, some of them only diagrammatically. Electrical connections, in general, are not shown in detail. It is believed that these will be obvious from the following description.

These controls comprise the master power switches 36!, and heater controls 303 and 365 for the injection port and for the back pressure valve 33, respectively. The automatic injector (dispenser 28) is controlled electric-ally by the switch 399 which has three positions. In position 0, the injector is inoperative. In upper posi tion A, the injector works automatically in the manner previously described. By manually turning the switch down to position M the operator can inject a sample (of volume determined by the setting of the micrometer screw of the injector) at any time. This affords a convenient method of injecting reproducible samples during manual operation;

The oven temperature programmer and controller is shown at 31d. It is of commercially known type and is represented only conventionally. The controller is of the proportional type. It controls simultaneously the temperatures of all of the heaters in oven 31. The temperature which the controller will maintain in the oven is determined by the setting of a potentiometer. A temperature sca e is calibrated to guide the operator in setting the potentiometer. It is preferably calibrated in incremerits of 5 C, e.g., from 25 to 325 C.

The temperature is programmed by driving the potentiometer upscale through a set of gears. These gears are not shown but they are so arranged for shifting gear ratios in order that various ratios of temperature change may be obtained. An electric motor of an suitable type drives these gears, under control of a programmer switch.

The programmer switch can be set to any of three positions, viz., automatic program, i othermal, and off. Upper and lower temperature limits for a programmed run are determined by shifting limit switches LS1 and LS2 along the path of the temperature indicator 314E which runs along a predetermined path 3MP.

The switch 313 controls the input leads to the recorder 321. See FIGURE 1. As previously mentioned, these leads may be reversed to assure positive peaks on the recorder during preparative operations (position P) or analytical operations (position A). The third position B by-passes the carrier gas around sample reservoir 28b so that it can be refilled.

Three delay timers are shown at 315, 31% and 317. Timer 3l5 can be used during both isothermal and programrned automatic runs. It allows a delay of up to 15 minutes between the end of one run and the injection of the next sample. This allows sufiicient time for establishment of temperature equilibrium at the lower temperature limit after a programmed run. It also allows time to clear the column of any remaining sample material during isothermal operation.

Timer 316 is provided to delay the temperature programming of the oven for a period of time up to 15 minutes after a new sample is injected. This is useful to permit stripping solvents off the main sample, when such is desirable. This may save operating time by decreasing the total programmed temperature range. Timer 316 is called the post-injection delay timer. It is used only during automatic programmed temperature operatron.

The timer 317 is the upper temperature delay timer. It also is employed only during automatic programmed operation. It allows the column temperature to be held isothermally at the upper temperature limit for a desired period of time, up to 15 minutes, before the column is cooled down (by opening the damper 267, etc.) to start another cycle. This provides another means for making certain that the column is cleared of sample material before the neXt run.

An attenuator 32%) is provided to divide the input signal to the recorder in successive steps. The first step divides by 2, the next by 4, the next by 8, etc., up to the last step which has an infinite divider, i.e., the signal is completely attenuated.

The recorder 321 is of commercial type and represents graphically the separated components by peaks on a chart. These peaks are recorded by a marking pen which is kept in contact continuously with a slowly moving record strip. As previously mentioned, a switch 3215 can be set at various positions on the scale, to be contacted by the recording pen 321? at the desired point on this scale.

aaevgeae 13' The setting of this point represents an indicated percentage of the full scale. As a component passes through the detector the pen starts upscale (across towards the right as seen in FIGURE 11). When it reaches the relay set point it causes switch 3215 to activate the mechanism which indexes valve 67 to its next collection position. The valve stays in this position until the pen passes the switch on its down scale run. The valve 67 is then indexed to the next by-pass position. Only that part of the component represented by the peak area above the set points is collected. The relay switch 3218 can be set at any point but is usually set between the and 95% limits. See shaded area RA, FIGURE A.

Switch 322 controls the oven damper 267 and has three positions. It operates by controlling the gas supplied to cylinder 76, FIGURE 1, which operates the oven damper by a pneumatic piston. One position of the switch opens the damper, another closes it, and the third position places it under control of the temperature programmer mechanism 314, etc., described above.

A switch 323 turns on the power to the oven temperature controller 314, etc. Switch 324 turns on the power to the blowers in the oven. The blowers must be on whenever the oven heaters are on to prevent local overheating.

Valve 67 can be manually controlled by a knob 331 aflixed to cam shaft 180. By this means the valve 67 can be indexed by a 30 step whenever the operator desires. This is accomplished by turning the shaft 180 through 180. A switch 332 also is provided to determine the type of operation for the indexing collection valve 67. It permits manual operation only when in its center position. The upper position is for isothermal operation and the down position'for automatic programmed temperature operation.

Pointer 333 indicates the position of the collection valve 67. It is always in the starting or zero position when injecting a sample for automatic operation. Swtch 334 is a control device for bringing the valve 67 back to starting or zero position after the desired number of components has been collected from a given sample. Elution of the last peak, as seen by the recorder, controls re-injection during automatic operation. Hence it is set for the maximum number of components (not exceeding 6 in this particular apparatus).

To recapitulate the operation briefly, a reference analysis is normally made first by passing a small sample of the material to be separated through the analytical column 51. After the reference has been established at the detector, carrier gas is passed through the larger column or column assembly 30. Samples of predetermined size are dispensed by the injector and forwarded to the injection port 29. Here the sample material joins the carrier gas. Separation of components of the sample occurs in the column 30, being facilitated and controlled by varying the oven temperature, according to a predetermined program.

As long as carrier gas alone is effluent from the column, in normal automatic operation, the stream passes to the bypass line 68a. Cam 181 is stationary and its follower is in the depressed position under the raised cam portion. As soon as a component peak arrives at the detector 35, and the peak rises to the predetermined point on the recorder, where the pen is set, the pen closes control switch 3218 to trip the cyclic motor and clutch mechanism through one cycle. This cycle runs just long enough to rotate cam shaft 180 through 180. As the cycle is completed, cam 181 allows the by-pass valve to open under flat cam portion 182. The valve 67 is indexed from the by-pass position through 30 to the first collection point. This opens the ball valve (by means of cam surface 217) and allows gas to flow out of the collection trap A. The valves remain in this position until the recorder pen again trips switch 3218 on its way down the peak. When this occurs, the cam shaft rotates another half revolution, the indexing valve moves through another 30 and the spring ball valve is closed. Meanwhile, cam 181 has again opened the bypass valve 68a. When the next component peak comes along, the valve 67 is indexed to the next collecting station or position, etc.

It will be obvious that various modifications may be made in the apparatus and in the manner of operating it. It is intended to cover such modifications and changes as would occur to those skilled in the art, as far as the following claims permit and as far as consistent with the state of the prior art.

What is claimed is:

1. In a chromatographic separator of the type which comprises a separating column for separable componentcontaining sample material, and plural collecting means for collecting separated components of said material, the improvement which comprises:

a common manifold means for simultaneously conveying said separated components to all of said collecting means;

a multi-position indexing valve located downstream of said manifold means, having a separate valve inlet from each of said collecting means, by-pass inlet means from said manifold by-passing said valve inlets, and an output means connected for fluid flow from any of said inlets and from said by-pass inlet means;

and means for indexing said valve alternately between a different one of said separate inlets and said bypass inlet means, whereby each of the particular separated components of said material is passed to a different collecting means and contamination of the valve by such components is reduced.

2. The combination set forth in claim 1 which includes a separate collecting means between said by-pass inlet means and said manifold means thereby to further reduce contamination of the valve by the components of said sample material.

3. The combination set forth in claim 1 wherein said manifold means is heated to maintain said sample components vaporized.

4. The combination set forth in claim 1 wherein said collecting means are maintained at a sufiiciently low temperature to condense said sample components.

5. The combination set forth in claim 1 wherein said manifold includes means for preventing fluid circulation between said collecting means.

6. The combination set forth in claim 5 wherein means \for preventing fluid circulation includes a unidirectional flow means with flow path connected between each collecting means and said manifold means.

7. The combination as set forth in claim 1 wherein said indexing valve includes means for continuously maintaining a flow path through one of said inlets, thereby to avert significant flow rate variations in the chromatographic separator.

8. The combination as set forth in claim 7 wherein said indexing valve includes means for establishing a new flow path through one of said inlets before blocking an existing flow path through another of said inlets.

9. The combination as set forth in claim 1 which includes a separate collecting means between said by-pass inlet means and said manifold means thereby to further reduce contamination of the valve by the components of said sample material and wherein said manifold means includes means for preventing fluid circulation between said collecting means.

10. In a chromatographic separator of the type which comprises a separating column for separable componentcontaining sample material, and plural collecting means for collecting separated components of said material, the improvement which comprises:

a common manifold means for simultaneously conveying said separated components to all of said collect ing means;

a rnulti-position indexing valve having a separate valve inlet from each of said collecting means, by-pass inlet means'from said manifold, and an output means connected for fluid flow from any of said inlets;

and means under control of eluent material from said separator for indexing said valve alternately between a different one of said separate inlets and said by-pass inlet means, whereby each of the particular separated components of said material is passed to a dififerent collecting means and contamination of the valve by such components is reduced.

11. In a chromatographic separator of the type which comprises a separating'column for separable componentcontaining sample material, and plural collecting means for collecting separated components of said material, the improvement which comprises:

a multi-position indexing valve having a separate valve inlet from each of said collecting means, by-p-ass inlet means from said manifold, and an output means connected for fluid flow from any of said inlets;

means under control of eluent material from said column for indexing said valve alternately between a difierent one of said separate inlets and said by-pass inlet means, whereby each of the particular separated components of said material is passed to a different collecting means and contamination of the valve by such components is reduced;

and automatic means for injecting new and identical sample quantities over an extended period of time into said column whereby substantial quantities of each of the separated components maybe collected into separate collecting traps under the control of said indexing valve.

12. The combination set forth in claim 11 wherein said valve includes means for establishing a new flow path through one of said inlets before blocking an existing flow path through another of said inlets.

13. A component collection system for a preparative scale gas chromatograph of a type capable of separating multiple components from sample material supplied thereto, said system comprising, in combination:

a chromatograph;

a manifold for receiving efiiuent including the separated components from the chromatograph; exhaust flow means for venting said manifold;

means for maintaining the temperature of said manifold at a level to prevent condensation of any of said components;

first and second individual collecting traps each having inlets and outlets;

means for continuously flow connecting all of said trap inlets downstream of said manifold;

means for maintaining said traps at a temperature to cause condensationof the sample components to be collected;

valve means on each of said outlets for controlling the flow of the etliuent through said traps; additional valve means on said exhaust now means for controlling the flow of the effiuent thcrethrough; and means controlled by the efiluent components for sequentially actuating each of said valve means and said additional valve means to collect a different component in each of said traps and by-pass the remainder of the efiluent away from the traps.

14. A component collection system for a preparative scale gas chromatograph of a type capable of separating multiple components from sample material supplied thereto, said system comprising, in combination:

a chromatograph;

a manifold for receiving effluent including the separated components from the chromatograph;

means for maintaining the temperature of said manifold at a level to prevent condensation of any or" said components;

first and second individual collecting traps each having inlets and outlets;

means for maintaining said traps at a temperature to cause condensation of the sample components to be collected;

valve means on each of said outlets for controlling the flow of the efiiuent through said traps; and

means associated with the inlets of each trap for preventing circulation between individual ones of said traps.

References tilted by the Examiner UNITED STATES PATENTS 2,963,898 12/1960 Reynolds 7323.1 2,981,092 4/1961 Marks 5567 X 3,002,583 10/1961 Findlay 5567 X 3,063,286 11/1962 Nerheim 7223.1

3,124,952 3/1964 Johnson 73'23.1 3,185,211 5/1965 Crawford et al. 5567 X OTHER REFERENCES Atkinson, E. P., and Tuey, G. A. P., An Automatic Preparative Scale Gas Chromatograph Apparatus. in Gas Chromatography, 1958, ed. by D. H. Desty, London, Butterworths Scientific Publications, 1958, pp. 284, 285.

REUBEN FRIEDMAN, Primary Examiner.

'C. N. HART, Examiner.

Claims

1. IN A CHROMATOGRAPHIC SEPARATOR OF THE TYPE WHICH COMPRISES A SEPARATING COLUMN FOR SEPARABLE COMPONENTCONTAINING SAMPLE MATERIAL, AND PLURAL COLLECTING MEANS FOR COLLECTING SEPARATED COMPONENTS OF SAID MATERIAL, THE IMPROVEMENT WHICH COMPRISES: A COMMON MANIFOLD MEANS FOR SIMULTANEOULSY CONVEYING SAID SEPARATED COMPONENTS TO ALL OF SAID COLLECTING MEANS; A MULTI-POSITION INDEXING VALVE LOCATED DOWNSTREAM OF SAID MANIFOLD MEANS, HAVING A SEPARATE VALVE INLET FROM EACH OF SAID COLLECTING MEANS, BY-PASS INLET MEANS FROM SAID MANIFOLD BY-PASSING SAID VALVE INLETS, AND AN OUTPUT MEANS CONNECTED FOR FLUID FLOW FROM ANY OF SAID INLETS AND FROM SAID BY-PASS INLET MEANS: AND MEANS FOR INDEXING SAID VALVE ALTERNATELY BETWEEN A DIFFERENT ONE OF SAID SEPARATE INLETS AND SAID BYPASS INLET MEANS, WHEREBY EACH OF THE PARTICULAR SEPARATED COMPONENTS OF SAID MATERIAL IS PASSED TO A DIFFERENT COLLECTING MEANS AND CONTAMINATION OF THE VALVE BY SUCH COMPONENTS IS REDUCED.