US3587676A

US3587676A - Apparatus for sequential treatment and analysis of samples

Info

Publication number: US3587676A
Application number: US784418A
Authority: US
Inventors: Lars Erik Oehlin; Jan Olof Loefvenmark; Goesta Carlsson
Original assignee: Linson Instrument AB
Current assignee: Linson Instrument AB
Priority date: 1967-12-22
Filing date: 1968-12-17
Publication date: 1971-06-28
Anticipated expiration: 1988-06-28
Also published as: GB1208990A; SE325724B; DE1815642A1; FR1596239A

Abstract

APPARATUS FOR ANALYSIS OR OTHER TERATMENT OF A SERIES OF SAMPLES AND HAVING A CONVEYOR FOR TRANSPORTING THE SAMPLES IN SUCCESSION FROM A FIRST STATION IN WHICH REAGENTS ARE ADDED TO A SECOND STATION IN WHICH THE ANALYSIS RESULTS ARE ADDED TO A SECOND STATION IN WHICH THE ANALYSIS RESULTS ARE DETECTED. THE CONVEYOR INCLUDES A CHAIN OF RELEASABLY INTERCONNECTED LINKS WHICH SERVE TO HOLD ONE SAMPLE CONTAINER EACH. THE CHAIN IS FLEXIBLE AND RUNS BETWEEN THE STATIONS WITHOUT BEING GUIDED LATERALLY SO AS TO FOLLOW A PREDETERMINED PATH, AND THEREFORE THE LENGTH OF THE STRETCH OF THE CHAIN BETWEEN THE STATIONS AND THUS THE TIME FOR TRANSPORTING THE SAMPLES BETWEEN THE STATIONS MAY BE VARIED BY ADDING OR REMOVING LINKS. IDENTIFICATION MARKINGS ARE PORVIDED ON PREDETERMINED LINKS AND AN IDENTIFICATION SYSTEM IS PROVIDED FOR CORRELATING THE ANALYSIS RESULTS WITH THE RESPECTIVE SAMPLES.

Description

United States Patent [72] Inventors Lars Erik Oehlin Stocksund; Jan 0101 Loetvenmark, Huddinge; Goesta Carlsson, Lidingo, Sweden [21] Appl. No. 784,418

[22] Filed Dec. 17, I968 [45] Patented June 28, 1971 [73] Assignee Linson Instrument Aktiebolag Stockholm, Sweden [32] Priority Dec. 22, 1967 [33] Sweden [54] APPARATUS FOR SEQUENTIAL TREATMENT AND ANALYSIS OF SAMPLES 13 Claims, 6 Drawing Figs.

[5 6] References Cited UNITED STATES PATENTS 3,192,968 7/1965 Baruch et a1 Primary Examiner-Manuel A. Antonakas A!t0rney-Hill, Sherman, Meroni, Gross and Simpson ABSTRACT: Apparatus for analysis or other treatment of a series of samples and having a conveyor for transporting the samples in succession from a first station in which reagents are added to a second station in which the analysis results are added to a second station in which the analysis results are detected. The conveyor includes a chain of releasably interconnected links which serve to hold one sample container each. The chain is flexible and runs between the stations without being guided laterally so as to follow a predetermined path, and therefore the length of the stretch of the chain between the stations and thus the time for transporting the samples between the stations may be varied by adding or removing links. Identification markings are provided on predetermined links and an identification system is provided for correlating the analysis results with the respective samples.

, 3.587.676 sum 1 or 3 PATENTEU JUN28 1921 wvsmons LARS ERIK UHLIN JAN OLOF LOFVENMARK GOSTA CARLSSON W q! Arromsvs PATENTEU Juuaamn 3.581676

sum

2 or 3 INVENTORS LARS ERIK OHLI JA N OLOF VE ARK GOSTA CAR ON A TTORNEYS PATENTEUJUNZQBYI I 3587576 SHEET 3 UF 3 IN VE N T ORS LARS ERIK CHLIN JAN OLOF LOFVENMARK GOSTA CARLSSON AT T ORNE Y5 APPARATUS FOR SEQUENTIAL TREATMENT AND ANALYSIS OF SAMPLES The present invention relates to automatic apparatus for sequentially treating a series of samplesin two spaced stations, such as for addition of reagents in one station and subsequent detection of the results of the reactions in the other, and more particularly to apparatus in which the samples to be treated are transported in succession from one station to the other. The invention is particularly, but not exclusively, applicable in automatic analysis of liquid samples and will, therefore, be described below with particular reference to such application.

An object of the invention is to provide an apparatus of the kind mentioned which permits easy changeover for different kinds of samples or types of analyses.

Another object of the invention is to provide an apparatus of the kind mentioned in which the time for transporting the samples between the stations may be varied as desired or required.

Yet another object of the invention is to provide an apparatus of the kind mentioned in which samples may be transferred from a first series of sample containers to a second series of sample containers while maintaining the desired sequential relationship of the samples.

A further object of the invention is to provide an apparatus of the kind mentioned which maintains the samples in the same sequential relationship throughout the entire treating procedure, whereby each sample may be indentified at any time.

A still further object of the invention is to provide in an apparatus of the kind mentioned means for correlating each sample with information about the result of the treatment of the sample.

According to the invention a conveyor device for transporting the samples in succession from one station to the other comprises a flexible chain of releasably interconnected links for holding one sample container each. The chain is adapted to run freely over at least part of the space between the two stations so that the length of the stretch of chain between the stations is variable as desired by adding links thereto or removing links therefrom. Drive means are provided for moving the chain at the same speed through both stations, so that each time they move a link into the space between the stations, they move another link out of it.

Because the chain runs freely, that is without being confined to a predetermined path of movement, between the stations, the number of links of that stretch of the chain which is located between the stations at any instant, and, accordingly, the time for the transport of a given sample from one station to the other, may easily be varied as desired or required. If a long period of time is required between the treatments in the two stations to permit a slow reaction between the samples and a reagent added in the first station to be completed, many links are employed to form the chain stretch between the stations, and if the time between the treatments has to be short, only few links are employed.

In addition to the advantage ofa simple variation of the time for the transport of the samples between the stations, the invention offers other important advantages. Thus, the chain may be composed of sections of, say, ten links, and each such section can then be used as a test tube rack when the samples are collected and while any preliminary treatments of the samples before the actual analysis are carried out. If, for instance, the samples must be centrifuged before they are analyzed, the chain section may be convoluted and placed in a centrifuge. When the analysis is then carried out, the various sections are interconnected to form a continuous chain. The relative order of the sections forming the chain may be discretionary if the apparatus has means for identifying the sections and the corresponding results of the analysis, as will be described hereinafter. Therefore, if a group of newly collected samples should have to be analyzed immediately, the chain already existing may be opened at a point close to the entrance of the first station, so that a chain section holding these samples may be inserted in the chain.

The invention also permits a simple and reliable identification of the samples and the respective results of the analysis, that is correlation of a certain analysis result with the sample from which that analysis result has been obtained. To this end, one or more links of the chain, preferably the first link of each section, in the case the chain is composed of sections, may be treatments as well as for the actual analysis, but if it is desired to use each sample for several different analyses or if, as is often the case, it is necessary to carry out the analysis on a predetermined volume of each sample, the apparatus may be provided with a second sample container chain having the same distance between adjacent sample containers as the chain mentioned previously and running alongside therewith at least through the first station. The first station there has means for transferring a predetermined quantity of the sample in each sample container held by the second chain to an adjacent sample container held by the first chain. Thus, the actual analysis always occurs in the sample containers held by the first chain, which will hereinafter, for simplicity, be referred to as the analysis chain, while the samples are collected and supplied in the sample containers held by the second chain, hereinafter referred to as the sample chain.

If the apparatus has two chains as described above, the identification may be effected in various ways. As, in this case, for obvious reasons, the identification markings are provided on the links of the sample chain, the identification information of each such link must in one way or other be, so to speak, transferred from the sample chain to the corresponding sam ple in the analysis chain. One way is to cause the sensing members to sense the markings of each link when the sample is transferred to the analysis chain and to store the sensed information in a memory from which the information is then read and presented when the reaction result of the sample is detected and presented. The reading of the stored information at the correct instant involves no major difficulties, as the time elapsing between the transfer of a sample and the detection of the corresponding reaction result can easily be ascertained on the basis of the rate of movement of the analysis chain and the length (i.e. the number of links) of the chain stretch between the sample transfer place and the place where the result of the reaction is detected.

Another way is to cause the sample chain to run alongside the analysis chain also at the second station and arrange for both chains to have equal numbers of links in their stretches between the stations. Like the analysis chain, the sample chain may run freely between the stations. Thus, in this case, each sample container held by the sample chain will be transported alongside the corresponding sample container held by the analysis chain in both stations and consequently, as in the case where only one chain is used, the sensing of each identification marking on the sample chain as well as the presentation of the sensed information may take place simultaneously with the detection and presentation of the reaction result of the corresponding sample. Thus, no separate memory is required, as that stretch of the sample chain which is, at any instant, located between the sample transfer place and the sensing place serves as memory.

The foregoing and other objects, features and advantages of the invention will appear more clearly from the following description of exemplary embodiments illustrated in the accompanying drawings.

FIG. 1 is a diagrammatic plan view ofa first embodiment;

FIG. 2 is an elevational view, partly in vertical section, of a four-link section of an embodiment of the chain, one of the links, namely the one to the extreme left, having identification markings;

FIG. 3 shows the chain section in FIG. 2 as seen from above;

FIG. 4 is a cross-sectional view, taken along line IV-IV in FIG. 1, of a bath for heating the samples;

FIGS. 5 and 6 are diagrammatic plan views substantially corresponding to FIG. 1 and showing a second and a third embodiment.

While only certain preferred forms of the invention are shown and described, it should be understood that various changes or modifications may be made within the scope of the appended claims without departing from the underlying idea or principles of the invention.

The apparatus shown in FIG. 1 comprises a first station 1, in which samples are transferred to an endless analysis chain 2 from a sample chain 3 and one or more reagents are added to the transferred samples, a second station 4, in which the results of the reactions of the samples are detected and presented, and a heating bath 5 disposed between the two stations and serving to maintain the samples in the analysis chain at a predetermined temperature for incubation purposes.

An embodiment of the sample chain 3 is shown in FIGS. 2 and 3. The chain is assembled from identical links 6, each consisting of two

tubular parts

7 and 8 which are offset in the longitudinal direction of the chain. The tubular part 7 has an upwardly projecting tubular extension 9 serving as pivot pin for an adjacent link 6 in the assembled chain. The two

parts

7 and 8 are interconnected by a web 10 and provided with vertically extending lateral ribs 11 serving to facilitate the advancement of the chain as described below and to provide identification markings 12 on predetermined links, as likewise described in more detail below. The links are releasably interconnected in that the tubular part 8 of each link is slipped over the extension 9 of the adjacent link. The bore 13 of the tubular part 7 is wide enough to receive a test tube 14 with loose-running fit. If desired, the lower end of the bore may be provided with an inwardly projecting bead or flange (not shown) serving as a stop for the test tube 14 to prevent it from falling through the bore; such a stop facilitates the handling of the chain if the chain sections are used as test tube racks remote from the analysis apparatus, for instance when the samples are collected or subjected to preliminary treatments. The analysis chain 2 as well as the sample chain 3 are supported directly on a platform 15 provided by the top surface of the apparatus, and thus they slide thereon as they are advanced during the course of the analysis. The analysis chain 2 is similar to the sample chain 3. but preferably the bores 12 of the tubular parts 7 of its links have no beads or flanges, so that the test tubes 14 engage the platform 15, as shown for the sample chain 3 in FIG. 2.

At the entrance of the first station 1 the endless analysis chain 2 converges with the sample chain 3 in a passage 16 formed by a guide rail 17 and a sample-transfer and reagentsupply device 18, the links ofone chain being forced to engage between the links of the other. The transfer and supply device 18 has an aspirator 19 by means of which a predetermined quantity of the sample in each test tube 14 held by the sample chain 3 is aspirated and then dispensed to the adjacent test tube held by the analysis chain 2. Further, the device 18 has one or more reagent pipettes 20 by means of which reagents are added to the samples thus transferred to the analysis chain.

At the exit of the station 1 the two

chains

2 and 3 are caused to diverge by a separating member 21. The chain 3 with any remaining portions of the samples is then taken care of in any suitable manner, while the analysis chain 2 with the measured quantities of the samples transferred thereto and the reagents continues to the heating bath 5. Adjacent the exit there is also provided a horizontal drive worm 22 rotated by a motor 23. The helical ridge forming the thread of the drive worm 22 engages the links 6 and ribs 1] of the chain 2 which is therefore pulled through the station I and pushed towards the bath 5 when the drive worm 22 rotates. In the embodiment shown. the drive worm 22 is rotated intermittently such that the chains are moved in steps equal in length to the distance between any two adjacent test tubes, but if the other parts of the apparatus permit, the chain may of course be moved continuously. Because the two

chains

2 and 3 interengage in the aforementioned passage 16, the analysis chain 2 and the sample chain 3 are advanced through the station 1 in unison. Of course, it is also possible to provide for the

chains

2 and 3 to pass one on each side of the drive worm 22. The station 1 also has means, such as switches (not shown), actuated by the ribs 11 of the links of one of the chains to control the motor 23 of the drive worm 22.

In the embodiment shown in FIG. 1, the sample chain 3 is divided into sections of ten links 6, the first link, that is the foremost link as seen in the direction of movement, of each section having the aforementioned identification markings 12, as shown to the left in FIG. 2, and conveniently it has also a color which is contrasting to that of the other links. In FIG. 1 two links having identification markings have been marked in the sample chain 3 by two concentric circles, while the other links have been marked by a single circle. Thus, only the various sections are identified automatically in this embodiment, while the various samples in each section are identified by their positions within the section. Of course, all links of the chain may have identification markings so that each sample is identified independently of the other samples.

As already mentioned, the identification markings preferably are coded according to the binary number system. In FIG. 2 the markings are provided by selectively removed ones of four

segments

12,, 12 12 and 12,, of the ribs 11 of the

tubular parts

7 and 8 of the leftmost link 6. Assuming that the chain section to which that link belongs carries a two-digit decimal identification number, say 38, the marking 12 provided by the removed

segments

12, and 12,, of the rib 11 of the tubular part 8 may represent the tens digit, that is 3 in this case, of the identification number, and the marking 12 provided by the removed

rib segments

12,, 12 and 12, of the tubular part 7 then represents the units digit, that is 8 in this case. In other words, the decimal identification number is here represented in the so-called binary-coded decimal form, which means that each decimal digit is represented by a corresponding binary number.

The identification markings 12 are sensed in the station 1 when the sample in the test tube 14 held by the first link 6 of each chain section of the sample chain 3, that is that link which is provided with the identification markings, is transferred to a test tube 14-held by an adjacent link of the analysis chain 2. The sensing is effected by two

sets

24 and 25 of switches. Each set comprises four switches, one for each

rib segment

12,, 12 12 and 12,, but for convenience only one switch is shown for each set (FIG. 1). The switches are actuated in accordance with the presence or absence of the rib segments, and the sensed identification information is stored in a memory, which is represented by a frame 26 in FIG. 1. When the sample is examined or analyzed in the station 4, the stored information is read from the memory 26 and presented together with the analysis result, as will be explained below.

The memory 26 may be of any suitable conventional from. For instance, it may be a tape punch which is operated by the two

sets

24 and 25 of switches and provided with means for reading the punched identification information and, if necessary or desired, for converting the binary-coded information to decimal form. The length of the stretch or portion of punched tape between the punching members and the reading and converting means is adjusted to correspond to the length of the stretch or portion of chain between the sensing place in the station 1 and the analyzing place in the station 4, so that the read identification information is presented simultaneously with the presentation of the corresponding analysis result.

It will be understood that the identification markings 12 need not necessarily be in the binary-coded form, although this form offers significant advantages over the decimal form. One advantage is that for sensing different markings only eight switches are required if the markings are in the binarycoded decimal form as described, while 20 switches are required if the markings are in noncoded decimal form.

The analysis chain 2 is guided into the heating bath 5 through a passage 27 having an inclined bottom and is guided out of the bath through a similar passage 28. The upper end of the bottoms of the

passages

27 and 28 and the upper edge of the vessel 29 containing the bath liquid are level with the platform so that the links can easily pass between the platform and the passages. In the bath proper, the chain 2 and the test tubes 14 slide on the bottom surface 30 of the vessel 29. Between the two

passages

27 and 28 the chain 2 runs entirely freely, that is without any lateral guidance, andtherefore it may follow an arbitrary or random route, as indicated by a phantom line in FIG. 1. This means, as mentioned above, that the length of the stretch or portion of chain located in the bath and, accordingly, the length of the stretch or portion of chain located between the stations 1 and 4 and thus the time required for transporting the test tubes 14 from the station 1 to the station 4, may be varied as required. If the bath 5 is dispensed with, the chain 2 will of course run freely over the whole space between the stations.

In the station 4, where the analysis results are detected and presented, the analysis chain 2 runs through a passage formed by one side of an analyzing device 3 and a second drive worm 32. The drive worm 32 is constructed and operates in the same way as the drive worm 22 and it is also rotated at the same speed as the latter so that the chain 2 passes through both stationsl and 4 at the same speed. At the exit of the station 4 the platform 15 is provided with an opening 33 through which the test tubes 14 fall into a waste or collecting basket or the like (not shown); this, of course, presupposes that the links 6 of the analysis chain 2 have through bores as indicated above. As, in this case, the analysis chain is endless, the opening 33 may be located anywhere along the return route of the chain from the second station 4 to the first station 1, for instance adjacent a magazine (not shown) which is positioned near the first station 1 and from which fresh test tubes are supplied to the analysis chain. The reaction results may be detected and presented together with the identification information in any suitable way. FIG. 1 shows as an example a photometric system 34 for determining the light absorbency of the samples and a decimal digit printer 34 for presentation of the absorption data and the identification information on a paper tape 36. The photometric system has an aspiration cuvette 37 positioned in the light path between a light source 38 and a phototube 39 and adapted to aspirate a portion of the sample in each test tube 14. The phototube output signal for each sample is caused, after amplification and any other required treatment, to control a printing mechanism of the digit printer 35 which prints out the absorption data for the sample on the tape ,36 as indicated at 40 in FIG. 1. The identification information previously sensed and stored is simultaneously read out from the memory 26 and caused, after conversion into decimal form, if required, to control another printing mechanism for printing out the identification information, such as the number of the sample, by the side of the absorption data on tape 36 as indicated at 41. The arrangement or form of the identification markings, the means for sensing them, the memory and the means for detecting and presenting the reaction results and the identification information may of course be modified and changed from the embodiment described above, which, therefore, is to be taken merely as an example ofthe arrangement and form.

FIGS. 5 and 6 illustrate two modified embodiments of the apparatus shown in FIG. 1 and, for simplicity, only certain parts of the apparatus have been shown, Similar parts of the various embodiments have the same designations throughout.

The embodiment in FIG. 5 differs from that in FIG. 1 in that the sample cliain 3 runs alongside the analysis chain 2 also in the second station 4. The

chains

2 and 3, which both run freely between the two stations, have the same number of links in their stretches between the stations, so that two test tubes 14 positioned side by side in the first station 1 will be positioned side by side also in the second station 4. Therefore, the sensing of the identification information may be effected simultaneously with the detection of the analysis results in the second station. Thus, no separate memory is required in this case; the memory is formed by that stretch of the sample chain 3 which is positioned between the sample transfer place in the first station 1 and the sensing place in the second station 4.

In the embodiment in FIG. 6, only the sample container chain 2A is used, which thus constitutes the sample chain as well as the analysis chain and which may be divided into sections in the same way as the sample chain 3 in FIGS. 1 and 5. As there is no transfer of samples in the first station 1, the sensing of the identification markings is effected simultaneously with the detection of the reaction results in the second station 4, and consequently no separate memory is required in this case either.

The apparatus may be constructed such that it permits changeover between the three embodiments described. For example, the

drive worms

22 and 32 and the guide members 17 and 21 may be adjustable transversely of the direction of movement of the chains, and the

sets

24 and 25 of sensing switches may be doubled and provided in both stations or they may be movable between the stations. It is also possible to employ two or more analysis chains 2 together with one sample chain 3, and provide additional stations similar to the station 4, so that each sample in the sample chain can be subjected to two or more different analyses.

lclaim:

1. An apparatus for sequentially treating a series of samples, comprising:

a. two stations spaced a constant distance apart;

b. a conveyor device interconnecting said stations for transporting the samples in succession from one of said stations to theother of said stations, said conveyor device comprising a first flexible chain of releasably interconnected links each adapted to hold one sample container;

c. means between said stations enabling aportion of said chain to run in a random path over at least part of the space between said two stations, said portion having a length exceeding the effective size of said space, thereby enabling the length of the portion of said chain between said stations to be varied as desired by the addition of links thereto or the removal oflinks therefrom; and

d. drive means connected to said conveyor device at each of said stations for moving said chain at the same speed through both of said stations.

2. An apparatus according to claim 1, including:

a. a second flexible chain of releasably interconnected links each adapted to hold one sample container, said second chain being disposed alongside and comovable with said first chain through said first station; and

b. means provided in said first station for transferring a quantity of the sample in each sample container held by said second chain to an adjacent sample container held by said first chain. An apparatus according to claim 1, including: means by which the samples in each of said sample containers are separately treated therein; b. means forming part of said second station for analyzing the results of such treatment; c. means connected to said analyzing means for indicating the results of such such analyzing; d. identification markings forming a part of certain links of said first chain; and e. means in one of said stations for sensing said link identification markings and connected to said indicating means for indicating the sensed identification with said results of the analyzing of the sample from the corresponding sample container.

4. An apparatus according to claim 2, including:

a. means by which the samples in each of said samplecontainers are separately treated therein;

b. means forming part of said second station for analyzing the results of such treatment;

c. means connected to said analyzing means for indicating the results of the analyzing; 3

d. identification markings forming a part of certain links of for indicating the sensed identification with said results of the analyzing of the sample from the corresponding sample container.

5. An apparatus according to claim 4, in which identification markings are present on less than all of said links of said second chain.

6. An apparatus according to claim 4,

a. said sensing means being arranged to sense said identification markings at said first station;

b. memory means connected to said sensing means for storing the sensed information; and

c. means responsive to said storing means for reading the stored information and transferring it to said indicating means.

7. An apparatus according to claim 4, said second chain being movable through both said first and second stations, the number of links of the portion of chain between said stations being the same for both chains.

8. An apparatus according to claim 7 in which said sensing means are disposed at said second station.

9. An apparatus according to claim 8, said link identification markings being coded according to a binary system.

10. An apparatus according to claim 2, including:

a. a substantially horizontal supporting surface supporting said chains; and g b. each link of said first chain having a vertical through-bore wide enough to enable the sample container to be received therein with freedom of vertical movement, said supporting surface being thereby enabled to directly'support the sample containers. 7

11. An apparatus according to claim 10, said supporting surface having an opening in the path of said first chain beyond said second station for enabling the sample containers to fall therethrough.

12. An apparatus according to claim 1, in which said drive means comprise a pair of worms arranged to be rotated about an axis substantially parallel to the path of movement of an adjacent portion of said first chain and each having its thread engaging the links of said chain, said worms being respectively associated with said spaced stations.

13. An apparatus according to claim 1, each of said links comprising a first tubular portion receptive of one of the sample containers, and a second tubular portion laterally jointed to said first tubular portion and encircling the upper end portion ofa corresponding first tubular portion of an adjacent one of said links.