Automatic chemical analysis apparatus

Hoskins , et al. May 13, 1

Patent Grant 3883305

U.S. patent number 3,883,305 [Application Number 05/341,069] was granted by the patent office on 1975-05-13 for automatic chemical analysis apparatus. This patent grant is currently assigned to Coulter Electronics, Inc.. Invention is credited to Arthur William Dunsmore, Thomas Horne, Douglas Haig Hoskins, Graham Roger Jarman.


United States Patent 3,883,305
Hoskins ,   et al. May 13, 1975

Automatic chemical analysis apparatus

Abstract

An automatic chemical analysis apparatus having separate closed-looped conveyors for sample and reactant containers. At a fixed location, sample portions from a given sample are transferred to a serial sequence of reactant containers. Colourimetric testing is arranged such that all of the reactant products of the given sample are tested simultaneously. Sample and reactant products identification are obtained at the time the reactant containers are at the colourimeter station, at which time the sample container is at a variably positioned identification station, the position being dictated by the number of sample portions being tested for that given sample.


Inventors: Hoskins; Douglas Haig (St. Albans, EN), Horne; Thomas (Woburn Bletchley, EN), Jarman; Graham Roger (Dunstable, EN), Dunsmore; Arthur William (Dunstable, EN)
Assignee: Coulter Electronics, Inc. (Hialeah, FL)
Family ID: 10019398
Appl. No.: 05/341,069
Filed: March 14, 1973

Foreign Application Priority Data

Mar 21, 1972 [GB] 13241/72
Current U.S. Class: 422/65; 422/534; 422/547; 422/67; 422/72; 141/130; 422/69; 422/109
Current CPC Class: G01N 35/021 (20130101); G01N 35/02 (20130101)
Current International Class: G01N 35/02 (20060101); G01n 033/16 (); G01n 001/18 ()
Field of Search: ;23/230,259,253 ;73/425.4P,425.4R ;141/130

References Cited [Referenced By]

U.S. Patent Documents
3193359 July 1965 Baruch et al.
3481709 December 1969 Slone
3607097 September 1971 Auphan et al.
3615239 October 1971 Jones et al.
3687632 August 1972 Natelson
3728079 April 1973 Moran
3753657 August 1973 Downing et al.
Primary Examiner: Serwin; R. E.
Attorney, Agent or Firm: Silverman & Cass, Ltd.

Claims



What is desired to be secured by United States Letters Patent is:

1. An apparatus for automatic chemical analysis comprising: a first sequentially advanceable conveyor for carrying containers holding samples to be tested; a second sequentially advanceable conveyor for carrying reaction tubes in which chemical reactions can be caused to occur; said conveyors defining paths which lie one within the other; first and second transfer stations fixedly positioned along the path of said first and second conveyors, respectively; transfer structure positioned adjacent said first and second stations for sequentially transferring sample portions from each container, when it is at said first station, to a predetermined plurality of the reaction tubes as they are moved past said second station; apparatus capable of adding different reagents to each of said plurality of reaction tubes; a programmed drive arrangement for advancing said first conveyor to present a next sample container to said first station in conjunction with advancing said second conveyor to present a next plurality of reaction tubes sequentially to said second station for sample transferring; and testing equipment for testing the reaction products of each of said plurality of reaction tubes.

2. Apparatus according to claim 1 in which at least one of said conveyors and preferably each said conveyor operates in a horizontally closed loop for carrying its respective containers and tubes in a closed loop.

3. Apparatus according to claim 2 in which said testing equipment includes a testing station which sequentially receives all of said plurality of reaction tubes as a group for substantially simultaneous individual testing of the contents thereof.

4. Apparatus according to claim 1 in which said transfer structure includes a pipette which comprises a pair of electrically conductive members, one of said pair being a tube through which sample can be drawn from said containers, said members being electrically insulated from each other and mechanically linked to one another so as to be moved as a unit relative to the level of the sample within a sample container and be placed in physical and electrical contact with the sample, said tube member having a lower end which extends a determinable distance beyond that of said other member into the sample, and an electrical conductor connected to each said member; whereby, when said pipette is immersed into the sample said determinable distance, a responsive electric signal can be derived from said conductors.

5. Apparatus according to claim 4 which further comprises an identification station for correlation of sample and reaction product identification, such that the test results of each reaction product is identified with respect to its originating sample, said identification station being moveably positionable along the path of and adjacent said first conveyor subsequent to said first transfer station, the position of said identification station being predetermined by the number of reaction tubes in said plurality of reaction tubes for a specific sample, whereby a sample container will have reached said identification station at the same time that all of its associated plurality of reaction tubes will have reached said testing equipment, for simultaneous identification purposes.

6. Apparatus according to claim 1 which further comprises an identification station for correlation of sample and reaction product identification, such that the test results of each reaction product is identified with respect to its originating sample, said identification station being moveably positionable along the path of and adjacent said first conveyor subsequent to said first transfer station, the position of said identification station being predetermined by the number of reaction tubes in said plurality of reaction tubes for a specific sample, whereby a sample container will have reached said identification station at the same time that all of its associated plurality of reaction tubes will have reached said testing equipment, for simultaneous identification purposes.

7. Apparatus according to claim 6 in which said testing equipment is positioned adjacent said second conveyor and is relatively moveable along the path thereof, the positioning of said testing equipment being predetermined and based upon the number of reaction tubes in said plurality of reaction tubes for each specific sample.

8. Apparatus according to claim 1 in which said testing equipment includes a testing station which sequentially receives all of said plurality of reaction tubes as a group for substantially simultaneous individual testing of the contents thereof.

9. Apparatus according to claim 1 which further comprises an identification station for correlation of sample and reaction product identification, such that the test results of each reaction product is identified with respect to its originating sample, said identification station being moveably positionable along the path of and adjacent said first conveyor subsequent to said first transfer station, the position of said identification station being predetermined by the number of reaction tubes in said plurality of reaction tubes for a specific sample, whereby a sample container will have reached said identification station at the same time that all of its associated plurality of reaction tubes will have reached said testing equipment, for simultaneous identification purposes.

10. Apparatus according to claim 1 in which said testing equipment includes colourimetric testing devices arranged parallel said second conveyor for each of said predetermined plurality of reaction tubes.

11. Apparatus according to claim 10 in which said testing equipment includes a light source and structure for directing the illumination energy of said light source toward the reaction products being tested, whilst directing the heat energy from said light source away from said reaction products.

12. Apparatus according to claim 11 in which said energy directing structure comprises a dichroic reflector.

13. Apparatus according to claim 12 in which said dichroic reflector is constructed to transmit energy wavelengths exceeding 1000 nm away from the material to be tested.

14. Apparatus according to claim 1 which further comprises a third sequentially advanceable conveyor for carrying reaction tubes; third and fourth transfer stations fixedly positioned along the path of said first and third conveyors, respectively; a second transfer structure constructed and arranged for transferring at least one sample portion from a container at said third station to at least one reaction tube at said fourth station for subsequent receipt of reagents and testing; and said programmed drive arrangement coordinating the sequential advancing of said third conveyor relative to the advancing of said first conveyor.

15. Apparatus according to claim 14 in which temperature control structure is provided to establish a temperature difference between the contents in the reactant tubes on said second conveyor with respect to the contents in the reactant tubes on said third conveyor.

16. Apparatus according to claim 15 in which at least one of said conveyors and preferably each said conveyor operates in a horizontally closed loop for carrying its respective containers and tubes in a closed loop.

17. Apparatus according to claim 1 in which said transfer structure includes a pipette and translation structure for moving said pipette both horizontally between said fixed transfer stations and vertically with respect to said containers and tubes at said transfer stations.

18. Apparatus according to claim 17 in which said pipette comprises a pair of electrically conductive members, one of said pair being a tube through which sample can be drawn from said containers, said members being electrically insulated from each other and mechanically linked to one another so as to be moved as a unit relative to the level of the sample within a sample container and be placed in physical and electrical contact with the sample, said tube member having a lower end which extends a determinable distance beyond that of said other member into the sample, and an electrical conductor connected to each said member; whereby, when said pipette is immersed into the sample said determinable distance, a responsive electric signal can be derived from said conductors.

19. Apparatus according to claim 18 in which said conductive members are adjustably linked to one another for varying said determinable distance.

20. Apparatus according to claim 18 in which said other member also is a tube and surrounds said sample drawing tube for most of its length, except for said determinable distance.

21. Apparatus according to claim 1 in which said testing equipment includes a testing station which sequentially receives all of said plurality of reaction tubes as a group for substantially simultaneous individual testing of the contents thereof.

22. Apparatus according to claim 21 which further comprises an identification station for correlation of sample and reaction product identification, such that the test results of each reaction product is identified with respect to its originating sample, said identification station being moveably positionable along the path of and adjacent said first conveyor subsequent to said first transfer station, the position of said identification station being predetermined by the number of reaction tubes in said plurality of reaction tubes for a specific sample, whereby a sample container will have reached said identification station at the same time that all of its associated plurality of reaction tubes will have reached said testing equipment, for simultaneous identification purposes.

23. Apparatus according to claim 21 in which said testing equipment includes a plurality of cuvettes in fixed position, equal in number of the maximum number in said predetermined plurality of reaction tubes, and reaction product transfer structure coupled to said cuvettes for effecting transfer to and from said cuvettes of the reaction products of a said plurality of reaction tubes, substantially simultaneously.

24. Apparatus according to claim 23 in which said testing equipment is positioned adjacent said second conveyor and is relatively moveable along the path thereof, the positioning of said testing equipment being predetermined and based upon the number of reaction tubes in said plurality of reaction tubes for each specific sample.

25. For use in an automatic chemical analysis apparatus, a pipette apparatus which comprises a pair of electrically conductive members, one of said pair being a tube through which sample can be drawn from containers, said members being electrically insulated from each other and mechanically linked to one another so as to be moved as a unit relative to the level of the sample within a sample container and be placed in physical and electrical contact with the sample, said tube member having a lower end which extends a determinable distance beyond that of said other member into the sample, and an electrical conductor connected to each said member; whereby, when said pipette is immersed into the sample said determinable distance, a responsive electric signal can be derived from said conductors.

26. Apparatus according to claim 25 in which said conductive members are adjustably linked to one another for varying said determinable distance.

27. Apparatus according to claim 26 in which said other member also is a tube and surrounds said sample drawing tube for most of its length, except for said determinable distance.
Description



The invention relates to apparatus which automatically makes a plurality of chemical tests on a series of individual samples which are fed to the apparatus.

Apparatuses of this type are known particularly in the medical field. For the purposes of lucidity and ease of understanding, the invention will be described in detail as used in the medical field, but it should be understood that the invention is not so limited.

In the medical field, for diagnostic and routine informational purposes, and often for research, certain chemical tests are performed on samples of whole blood or blood serum. Often physical tests are additionally performed on the samples. Classically all such tests were performed manually by trained technicians in laboratories. In a typical chemical test, the patient's blood would be drawn, spun in a centrifuge to separate the serum from the cells, the serum decanted and placed in a container suitably identified with the patient's identification data. The technician would then measure out a small quantity of serum into a reaction tube, mix the serum with a precise proportion of some chemical reagent, mix this thoroughly, place the reaction tube in a water bath maintained at some precise temperature and time its presence, i.e. incubation, in the bath in accordance with the type of test being conducted. This incubation period is sufficient to achieve a certain chemical reaction which will change the color of the diluted specimen. Then the technician would remove the reaction tube from the water bath, pour a quantity into a cuvette, direct a beam of light at some predetermined wave length through the cuvette and measure the absorbance of the light in the solution in the cuvette. This latter operation could be performed in a spectrophotometer or other colorimeter.

Over a period of years, these chemical tests have developed to a relatively high degree of acceptance to ascertain such information as the total protein of the blood; the presence of certain chemicals such as phosphorous, potassium, sodium, and calcium; the amount of creatinine in the blood; the amounts of different enzymes, albumin, etc. Laboratories may perform as little as one or two tests on the available specimen or as many as twenty. The reagent composition, the proportions, the incubation time, the temperature of incubation time and the wave length of the incident light passed through the end solution vary from test to test. Certain problems are inherent in the manual execution of these tests by technicians and the obviation of these problems is the end sought by most automated or semi-automated automatic chemistry apparatus.

Among the problems associated with manual performance of these tests are the likelihood of human errors promoted by the measurements which must be made manually, the need for entering information and data relating to the sample and keeping its identification straight, tediousness and fatigue of the technician, errors in choosing the proper chemicals and the failure to keep the equipment clean of contamination. Other disadvantages in the classical methods are loss of time, expense, waste, etc.

The known automatic chemical analysis apparatuses solve the above problems in varying degree, although not all apparatuses solve all problems. These apparatuses take different forms. Some apparatuses include turntables that rotate samples to a sample withdrawing position. At the sample withdrawing position, the samples are diluted and passed to the processing portion of the apparatus. In one form of apparatus, the diluted samples are passed through conduits one after the other, separated by quantities of diluent and bubbles. In other systems, the diluted samples are carried in reaction tubes on continuous drums or conveyors. In one apparatus a plurality of tubes are mounted on racks, are incubated in a bath and are moved into and out of the bath by chains engaging the racks.

Known automatic chemistry analysis apparatuses have problems, the solutions of which have made such devices complex, expensive, overly large in size and in some instances likely to produce erroneous results. Of importance in the problems are patient indentification and contamination. Some of these apparatuses are continuous and require that all tests be performed on all samples. The apparatus to be described hereinafter provides for selective performance of tests and hence is economical. It also maintains patient identification with relation to tests and test results and provides for efficient cycling of reaction tubes through the apparatus.

Accordingly, the invention provides an apparatus for automatic chemical analysis comprising a first sequentially advanceable conveyor for carrying containers holding samples to be tested, a second sequentially advanceable conveyor carrying reaction tubes in which chemical reactions can be caused to occur, first and second stations fixedly positioned along the path of said first and second conveyors, respectively, transfer structure positioned adjacent said first and second stations for sequentially transferring portions from each container when it is at said first station to a predetermined plurality of the reaction tubes as they are moved past said second station, apparatus capable of adding different reagents to each of said plurality of reaction tubes, a programmed drive arrangement for advancing said first conveyor to present a next sample container to said first station in conjunction with advancing said second conveyor to present a next plurality of reaction tubes sequentially to said second station for sample transferring, and testing equipment for testing the reaction products of each of said plurality of reaction tubes.

Features and advantages of the invention will become apparent from a study of the following description of an embodiment thereof when taken in conjunction with the accompanying drawings in which:

FIG. 1 is a perspective view of an apparatus for automatic chemical analysis;

FIGS. 2a and 2b show a top view of the apparatus shown in FIG. 1;

FIG. 3 shows a piercing device for said apparatus;

FIG. 4a is a section of the sample container used in the apparatus;

FIG. 4b is a perspective view of the said sample container;

FIG. 4c shows the label for said sample container;

FIG. 5 shows the upper portion of a transfer pipette used in the apparatus;

FIG. 5a shows a section along the line X--X of FIG. 5;

FIG. 6 shows the lower portion of a transfer pipette used in the apparatus;

FIG. 6a shows a section along the line X--X in FIG. 6;

FIG. 6b shows a section along the line Y--Y in FIG. 6;

FIG. 7 shows the pipette used in the apparatus;

FIG. 8 shows a valve mechanism and pump;

FIG. 9 shows the operating mechanism for said pump;

FIG. 10 shows the colourimeter head assembly;

FIG. 11 shows another view of the colourimeter head assembly;

FIG. 12 shows the cuvette for use with said colourimeter head assembly;

FIGS. 13a, b, c and d are block diagrams of the electrical system of the apparatus;

FIG. 14 shows waveforms of signals appearing at various points in the system of FIG. 13;

FIG. 15 shows diagrams explanatory of the operation of the sample transfer and wash means;

FIG. 16 is a diagram showing the liquid flow in the apparatus;

FIG. 17 shows the identification device;

FIGS. 18a and b are block diagrams of the electrical system of the colourimeter;

FIG. 19 shows waveforms of signals appearing at various points in the system of FIG. 18;

FIG. 20 is a circuit diagram showing the main timer;

FIG. 21 is a circuit diagram showing the colourimeter timing control;

FIGS. 22a, b and c are circuits explanatory of the operation of the measurement system of the colourimeter; and

FIG. 23 is a graph showing the operation of the system of FIG. 22.

In broad terms, the apparatus to be described hereinafter transfers a portion of the test liquid contained in a sample container to a reaction tube, preferably together with a suitable diluent, adds a reactant appropriate for the constituent of the sample which it is intended to detect, transfers a portion of the resulting liquid to a test cuvette and subjects it to colourimetric analysis. The result of this analysis provides a quantitative determination of the amount of substance, sensitive to the particular reactant, which was present in the sample. The apparatus is suitable, for example, for measurement of various constituents in whole blood, plasma or serum (such as glucose, urea, albumen or total protein content), milk, beer, or sewage. Whilst in the apparatus described herein colourimetric analysis is utilised, it will be evident that the solution after treatment with the reactant may alternatively where appropriate be examined by other means, such as particle analysis, fluorescence analysis, or ion measurement thereby to provide a quantitative determination of the constituents.

The apparatus to be described is capable of carrying out six tests on each of 40 specimens per hour. Alternatively, it may be programmed to carry out five, four, three or two tests on each of the specimens; this will lead to correspondingly higher specimen throughputs. The portion of liquid transferred to the reaction tube is from 25 to 50 microlitres and the amount of diluent is 250 microlitres. The amount of reagent used is 2.5 millilitres. After incubation with the reagent the developed colours are measured using a separate colourimeter for each test, and the results are printed out in concentration terms together with a six digit specimen identification number. For each test, a reagent is chosen which will produce a reaction product which absorbs light.

Referring to FIG. 1, there is shown a perspective view of a complete apparatus in accordance with an embodiment of the invention. It is housed in a cabinet 1 occupying a floor space of approximately 90 cm .times. 70 cm. The samples to be analysed, in containers 21, are carried on a belt 2 which is stretched around motors and idler wheels 12 arranged in a rectangular pattern. The belt 2 is advanced in steps so that each sample container 21 in turn stops at a datum point where a sample of the liquid in it is transferred by a transfer means 33 to a test tube carried by a reaction loop belt 5. At the same time a diluent, for example water, is also added to the test tube. Samples from one tube 21 are added to two, three, four, five or six of the test tubes carried by the belt 5, the number being selected by pressing the appropriate button on the control panel 13. At a selected station, as the reaction loop steps round the closed path, suitable reagents are added to the test tubes and the resultant mixture examined by the colourimetric analyser 41. At a later stage in the path round the loop the tubes are washed by a cleansing apparatus 15 and then returned to the initial point where they can take part in further reactions. The pumps for pumping the reagents, or reactants, into the reaction tubes are contained within the cabinet as shown at 7. The containers for the supplies of reagents are shown at 9, and the containers for the washing water and the waste extracted after washing the tubes are shown at 8. The result of the colourimetric analysis is printed out on to a roll of paper as may be seen at 10. The results from the tests on the two, three, four, five or six specimens from each sample, and relating to different constituents, are printed sequentially and the device 4 contains means for setting identifying letters so that, for example, the measurement of glucose in blood can be prefixed in the print-out by the letters "GLU". The printing mechanism for indentification is set by the operator in accordance with the tests which the machine has been set to perform. Additionally, the result of the analysis together with the identifying letters are available at a terminal for connection to a central processing means.

The horizontal upper surface of the apparatus 1 is shown in greater detail in FIG. 2 in which 20 indicates the upper surface of the cabinet. A plastics belt 2 is carried in a substantially rectangular path around pulleys 12 which are driven by electric motors or idlers. The outside of said belt 2 carries mounts similar to those in a test tube rack whereby sample containers, which will be described in more detail hereafter, can be placed, as for example as shown at 21. When the motor is operated the sample containers advance, carried by the belt 2 in an anticlockwise direction, until a container at a station 32 is opposite the microswitch 22 which operates mechanism to stop the belt. In subsequent operations, after the belt has been re-started, it advances until the container adjacent the container in the belt which was at station 32 occupies station 32, and again the microswitch 22 operates to stop the motors. In this way the belt advances by an amount equal to the distance between sample containers at each step in the operation. It will be appreciated, therefore, that in the operation of the machine the first step is to load the carriers on belt 2 with containers containing the samples to be tested. In the machine described herein there is space for 100 sample containers.

The reaction loop 5 is similar to that associated with belt 2 but is fitted with tubes such as 23 in which reactions can take place. Otherwise it is provided with motors and idlers 24 corresponding to elements 12 and a microswitch 25 corresponding to element 22.

The apparatus is also provided with an inner reaction loop, not visible in FIG. 1, similar to the reaction loop 5 but located still further to the centre of the upper deck. This comprises a belt 26 carrying test tubes such as 27 round two pulley wheels 28. It is surrounded by a wall 29 and is provided with a heater element 30. The purpose of the inner reaction loop is to provide an environment in which reactions which may be required to take place at a different temperature from those in the outer reaction loop 5 may be effected.

Now, considering the operation of the machine, after the outer loop 2 has been loaded with sample containers containing the samples to be tested, a device 31 is provided which as each container comes to rest at its station penetrates the cap of the sample container to cut an X-shaped incision. This is effected so that subsequent operations in the transfer of liquids from the container may be accomplished more readily.

The device 31 is shown in greater detail in FIG. 3. The device comprises a cover 60 mounted on a substantially L-shaped support frame 61. A solenoid 62 is slidably mounted on said frame 61 by means of a screw device 63. This enables adjustment of the height of the solenoid to be effected. The cutting head 64, having an X-shaped cutting means is mounted in said solenoid so that energisation of the solenoid causes the cutting head to be driven downwards. The device 31 is mounted in such a way that the belt 2 carrying the sample containers such as 21 passes through device 31 with the containers passing immediately below the cutting head 64. With a container 21 accurately located under the cutting head 64, the solenoid can be energized so as to drive the cutting head 64 to penetrate the cap of the sample container, cutting an X-shaped incision therein. Alternatively, instead of utilising a solenoid to drive the cutting head 64, it can be driven by an electric motor through a rack and pinion gear.

After the containers have progressed a further two steps around the loop 2, a container with a cap having an X-cut appears at the station 32. Whilst the sample container is stopped at this station a device 33, to be described in more detail hereafter, which comprises a pipette carried on a horizontally swinging arm is positioned over the sample container, lowered into the sample container, extracts 25 to 50 microlitres therefrom, is raised, swung over to the inner reaction track until it is above the reaction tube shown at 34, and transfers the portion of the sample thereto, referred to as an aliquot, adding also a predetermined quantity of diluent such as water. With the outer belt stationary the inner reaction belt 5 moves one step along until another tube occupies the position 34 and the process is repeated so that another portion of the substance in the same sample container is transferred to another reaction tube. According to the setting on the control panel 13 this is repeated until there are two, three, four, five or six tubes on the reaction loop all containing aliquots of the material from the sample container at the station 32. When this has been accomplished the belt 2 moves one step along to present another sample at the station 32 and the process is repeated. If the inner reaction loop is also to be used a similar transfer is made by the device 35, similar to the device 33, which transfers material from a sample container at the station 36 transferring it to a reaction tube on the inner belt 26 at the station 37.

As the tubes on the reaction loop 5 move around the loop one step at a time, they reach a position under a head 38 comprising six discharge nozzles for reactants, and at this point whilst they are stationary the appropriate respective reactants are added to the two, three, four, five or six reaction tubes. These, or additional discharge nozzles, may alternatively be placed at other points in the loop. Subsequently after several further steps the tubes reach a position under a colourimetric head 39 wherein the colourimetric analysis of the reaction products in the respective tubes occurs. As already indicated the result of this measurement is printed out on to the roll of paper at 10 (FIG. 1). At a later stage in the progress round the loop 5 the tubes reach a position under a washing head 40 where the liquid in the reaction tubes is extracted, rinsing water added, the tube emptied, a second rinse added and the tube then emptied. The tubes then as they progress around the loop 5 repeat the cycle with samples extracted from other sample containers in the loop 2.

A similar operation occurs in the inner reaction loop wherein the reaction tube 27 passes under a head 41 where a reactant solution is added. A colourimetric analysis is performed corresponding to that accomplished in connection with the device 38 by means of a colourimetric head 43.

The liquid flow involved in these operations, excluding the colourimetric testing, is shown symbolically in FIG. 16. The sample containers are shown at 900, and a pipette 901 of the device 33 (FIG. 2) extracts a test portion from the sample container by the operation of the syringe 902. This is transferred to one of the reaction tubes at 905 after the pipette 901 has been swung into position thereabove. Diluent contained in the container 903 is also transferred through pipette 901 to said reaction tube, by means of the pump 904, to be described in detail hereinafter. This is repeated as many times as required. The test reagents are contained in the containers 906a, 906b, 906c, only three such systems being shown in the Figure for the sake of clarity. The reagents are transferred through the valves 907a, 907b, 907c by the operation of the pumps 908a, 908b and 908c through valves 909a, 909b, 909c and the discharge nozzles 910a, 910b, 910c into the reaction tubes. After colourimetric analysis the contents of the test tube in the line 905 are removed through a tube 911, a sediment trap 912 and a valve 913 by the operation of pump 914 through valve 915 and an anti-siphon trap 916 to a container 917 for waste. Sediment from the sediment trap 912 falls through a tap 912a into a waste container 917a. A rinsing liquid from a container 918 is then pumped through valve 919 by means of pump 920 through valve 921 and by means of T-junction 922 along tube 923 into the reaction tube. This rinsing liquid is then removed along tube 924 through valve 925 by means of pump 926 through valve 927 to the siphon trap 916 and waste container 917. The rinsing process is then repeated, utilizing again liquid from container 918 which is applied by means of pump 920 along tube 928 into the reaction tube. Finally, the rinsing liquid is removed along pipe 929 through valve 930 by means of pump 931 through valve 932 into the anti-siphon trap 916 and waste container 917.

The sample container for use with the apparatus described above is shown in FIGS. 4a and 4b which respectively show a section a perspective view thereof. The container comprises a portion 101, in the shape of a test tube made of a transparent or translucent material. It is provided with a thickened base portion 103, the outer edge 104 of which is cogged. There is a circular indentation in the bottom 105 of said base 103. An identification label 106 to be described in more detail hereafter is adhered to the outside of the tube. It is preferred that the label does not completely encompass the tube in order that the contents may be visible. A cap 102 of suitable elastomeric plastics material is provided. The belt 2 is provided with rack means 220, 221 (FIG. 5) for supporting the sample container and the depression 105 is adapted to engage with a pin member 222 (FIG. 5) on the rack so that the tube may be rotated by means of a toothed wheel 108 (FIG. 17) which engages with the cogged edge 104. The purpose of this will appear subsequently. It will be obvious to those skilled in the art that other means may be utilized for rotating the tube. The label is shown in FIG. 4c and comprises a matrix of six columns each containing the numbers zero to nine printed on a highly reflective sheet. Along the left-hand edge is a column in which portions corresponding to the lines 0, 2, 4, 6 and 8 are blackened. Along the top there are blackened portions corresponding to each column. When a sample has been put into the container it is identified by a six-figure number and this is indicated by blackening appropriate portions in each column using a suitable dark ink. The squares containing the numbers are separated by portions which tend to inhibit the ink from spreading into an adjacent square. The label shown in FIG. 4c is intended to indicate the identification number 356635.

The mechanism for operating the transfer pipette 901 in FIG. 16 (the device 33 of FIG. 2) is illustrated in FIGS. 5 and 5a. Referring to FIG. 5 which illustrates the portion of the mechanism appearing above the deck 20, the outer band 2 is shown carrying a sample container 200 and the band 5 carrying a reaction tube 201 is shown. The pipette tube 202, which will be decribed in greater detail subsequently, is mounted on an arm 203 carried on a rod member 204 which is capable both of rotary movement and longitudinal up and down movement. Thus it is possible for the member 204 to lower the pipette 202 into the sample container 200, raise and then rotate the pipette into a discharge position over the reaction tube 201. The arm 203 is shown in more detail in the plan view of FIG. 5a from which it will be seen that the arm is capable of adjustment by means of a slot 230 in the end of said arm 203 which is clamped by a bolt 231 to allow the position of the pipette to be adjusted.

Referring now to FIGS. 6, 6a and 6b, which show the side view and sections along lines X-X and Y-Y of FIG. 6 of the part of the mechanism below the deck 20, it will be seen that the member 204 is continued below the deck 20 and is attached by thrust collars 205 to a parallel member 206 provided with a rack engaging with a pinion 207 geared to an electric motor 210. Operation of the motor 210 causes the member 203 to be raised or lowered. Limit switches 208 and 209 are provided in order to allow the extent of the raising to be controlled and to prevent the mechanism lowering the pipette too far in the absence of a sample container 200. Rotation of the member 204 is accomplished by means of the motor 210 which is geared to the member 204. As in the case of the raising and lowering, limit switches 211 and 212 are provided which are adjustable to control the movement of member 204 so that the pipette can be lowered accurately both into the sample container 200 and the test tube 201. The member 204 is provided with a groove 213 which engages with a pin 214 in a tubular member 215 which is coupled to the rotation motor 210. This enables the rotation movement to be transmitted from the drive 210 to the member 204 irrespective of the vertical position thereof.

The pipette is shown in greater detail in FIG. 7 and comprises a gold-plated stainless steel tube 300 of 2 mm outside diameter provided with a bore. The outer diameter tapers to 1 mm within a brass cylindrical member 301 of 5 mm diameter and 5.5 mm length which encompasses said tube 300. Immediately below said member 301 is a black nylon washer 302 of 10 mm diameter and 1 mm thickness in contact with said member 301 and surrounding the tube 300. Below the washer 302 a stainless steel tube 303 of 2.4 mm outside diameter is slipped over tube 300 but is electrically insulated from said tube 300. 5 mm below the washer 302 is a 10 mm diameter brass washer 304 1 mm thick which makes electrical contact with tube 303. The portion of the tube 303 which extends below washer 304 is 66 mm in length and tube 300 projects 2 mm beyond the end of tube 303. Electrical connections 305 and 306 are made to the cylindrical member 301 and the washer 304 respectively. A flexible plastics tube 307 is attached to the top of the pipette whereby vacuum can be applied to the pipette to suck liquids up into it and pressure can be applied to blow them out again. The purpose of the electrical connections 305 and 306 is to provide an indication when the pipette has entererd 2 mm below the surface of the liquid in the sample tube 200 (FIG. 5). The liquid forms an electrical connection between the conductors 305 and 306 and this can be used to operate a relay which prevents further descent of the pipette into the liquid. This is of particular advantage when the sample in the container is a blood sample which has been centrifuged to leave the plasma in the upper portion of the container. By this method samples of the plasma only are extracted for analysis.

It will be appreciated that both the device 33 (FIG. 2) and the device 35 (FIG. 2) utilise the construction illustrated in FIGS. 5, 6 and 7.

The pump for transferring liquids from one container to another is illustrated in FIG. 8. It is constructed principally of glass tubing and referring to FIG. 8 the portion 400 is the barrel of a hypodermic syringe but the piston of said syringe 401 is formed of a Teflon (Registered Trade Mark) member having a shape such as shown in the Figure. The advantage of this shape is that the fit of the piston is less affected by temperature than would otherwise be the case. The drive to the piston is a rod 402 the operating mechanism of which will be described below. A T-junction of glass is sealed to the end of the barrel 400 and to that is sealed a tube 412 which has a narrow bore at each end and opens into a wider portion at the centre. A plug 405 having a conical end as may be seen in the Figure is provided within said tube 412 A constriction 406 is provided in tube 412 to limit the movement of the plug 405. A tube similar to 412 is attached to the remaining outlet of the T-junction 403 and contains a plug 409. A constriction 410 is provided to limit the motion of the plug 409. The end of the last-mentioned tube containing the plug 409, identified as 411 in the Figure, is connected to the source of liquid and the end of tube 412 shown as 407 in the Figure is connected to a pipette. In operation, and starting with the piston 401 at the upper part of its travel, as it is drawn down by motion of the member 402 the plug 405 is forced against the edge 404 sealing the tube 407 and the plug 409 is raised upwards allowing liquid from a first container to be drawn through 411 into the barrel of the syringe. On reversal of the movement of the piston the plug 409 is forced against the edge 408 closing off the path to said source and the plug 405 is raised allowing the liquid to be forced out through the tube 412 to the exit 407 connected to a pipette or discharge nozzle.

The operating mechanism for the piston 401 in FIG. 8 is shown in FIG. 9. It comprises a drive pinion 500 coupled to a rack 503 on the member 402 which connects with the piston 401. The drive pinion 500 is coupled to an electic motor through a friction clutch drive. A staircase shaped member 501 is located in such a position that the end of rod 402 will engage with one of the steps of said staircase when the piston is at its intended lower limit of travel. Movement of the staircase sideways in the Figure is used to control the extent of the descent of the piston 401 to control the quantity of liquid which is drawn into the syringe. A member 502 is attached to rod 402 in such a position that at the intended limit of upward travel of the piston it engages with a stop 504. It has been found that the sudden stopping of the piston produced by the member 502 striking member 504 is effective to prevent drops forming on the end of the pipette.

The colourimeter head assembly is illustrated in FIG. 10. Essentially it is an arrangement whereby light can be directed through the samples of liquid after an appropriate reagent has been added thereto, through an optical filter, to a photocell. The output of the photocell provides a quantitative indication of the amount of a particular constituent in the solution. The assembly shown in FIG. 10 provides means for testing six samples simultaneously which have been subjected to differnt reagents so that each gives an indication of a different constiuent. Light from a light source 602 is directed into six fibre optics paths such as 601 which carry the light to six test points. Samples of the liquid are contained in a cuvette into which the liquid is drawn. One of the six optical filters is shown at 603 and a respective photocell at 604. Thus light passes from the end of the fibre optics tube 601 through the cuvette at 600, through the optical filter 603 to the photocell 604. It will be seen that the six photocells are arranged alternately on each side of the path along which the reaction tubes are travelling. The reason for this is that the dimensions of a photocell are larger than the separation between successive reaction tubes. By arranging them in the staggered manner as shown it is possible to accommodate them in the space available. A similar arrangement but comprising only one test path is provided for the inside reaction loop at 43 (FIG. 2).

Another view of the optical arrangements associated with the colourimetric test portion of the apparatus is shown in FIG. 11. The light source 602 comprises a 6-volt, 10-watt tungsten halogen projector lamp 610, which is supplied from an accurately stabilised regulated power supply 611. The lamp is provided with a surface silvered dichroic semi-ellipsodial reflector 612 constructed to transmit heat energy above 1,000 nm, and to reflect light energy below 1,000 nm. This minimizes heat transfer from the lamp 610 to the colourimetric block 614, even at quite high levels of illumination. The lamp and reflector may be adjusted in relation to each other and the lamp is positioned so that the filament is at one focus of the reflector ellipsoid. An approximately equal amount of light from the lamp is transmitted to each of the six colourimeters along the fibre optic paths 601, one of which is shown in FIG. 11. A black nylon rod 613 is threaded at 615 into the block 614 so that it protrudes into its respective light path between the fibre optics path 601 and the cuvette 600. It is used as a coarse adjustment of the output of the photo cell 604, so as to bring this within the range of the electronic circuitry. The cuvette will be described in more detail below in connection with FIG. 12. After passing through the cuvette 600, the light passes through a filter 603 carried by a filter holder 605. The filter is an interference filter, having a half band width of approximatley 10 nm. It is desirable that for each test a filter is selected such that its pass band coincides with the maximum absorption due to the reaction product.

It will be observed that the colourimetric testing is performed in cuvettes separate from the reaction tubes rather than utilizing the reaction tubes themselves for this purpose. The reason for this is that the reaction vessels are optically inadequate for precise colourimetric analysis. It is economically preferable to provide a small number of optically adequate cuvettes than a much larger number of optically adequate reaction tubes. Furthermore, by utilizing a plurality of cuvettes, each one can be employed exclusively for its own chemical analysis and therefore be adapted to and connected to its own sampling probe.

The cuvette for containing a sample to be tested in the colourimeter is shown in FIG. 12. It comprises a tube 700 of Pyrex (Registered Trade Mark) glass, opaque to light of wavelength shorter than approximately 380 nm, narrowed at one end and sealed to a bored metal tube 701. The other end is also narrowed at 702. A plastics bored plug 704 is forced into the end 703. The tube contains a plug 705 which is provided with a conical portion 706 which engages with a conical portion 707 of the tube. The portions 706 and 707 are ground together during construction.

One end of a length of flexible tube 708 is connected to said tube 701 and a length of stainless steel tube 709 is connected to the other end of said flexible tube 708. In an alternative arrangement the flexible tube 708 is connected directly to the tube 700, the metal tube 701 being omitted. In use the end of tube 709 is lowered into the reaction tube containing the solution to be examined until the end of the tube 709 is below the surface of the liquid in said reaction tube. Vacuum is applied through a pipe to the member 705 and this causes the plug 705 which has been at the bottom of the tube under the influence of gravity to be drawn upwards drawing liquid into the tube. When the plug reaches the top of the tube it closes the vacuum line so as to prevent further liquid being drawn into the apparatus. It remains in this position whilst the tests are being made. After the tests have been made pressure is applied to the member 704 causing the plug 705 to drop forcing liquid out of the tube 709 back into the test tube. When the plug reaches the bottom of the cuvette there is sufficient leakage of air past the sides of the plug 705 to force any remaining liquid out of the tube 709. To ensure said leakage of air past the base of said plug 705, two pips 710 are provided in the base of said tube 700. With the cuvette empty the float 705 rests in the light path reducing the intensity of light reaching the photocell.

At the same time as a test is being made on two, three, four, five or six of the test tubes on the reaction loop 5 and possibly also on the inner reaction loop 26 it is necessary to identify the sample container from which the sample was taken.

To minimize the need for equipment to read, store, transfer, compare, etc. each sample container identification with the identification of the several reaction tubes for each sample container and the associatd colourimetric test results for each respective aliquot, the relative physical positions along the belts 2 and 5 of the sample containers, reaction tubes, and the colourimeter head 39 are flexibly predetermined with respect to the position of a relatively movable sample identification station 42, shown in FIG. 2a adjacent the sample container belt 2. Quite simply, for positive and direct identification of a sample and its aliquot test results, a sample container 21 is to be positioned at the identification station 42 when all of the aliquots from that sample are in the colourimeter station 39. Normally, the colourimeter station 39 will encompass the 43rd to 48th step positions of the reaction tubes on the belt 5 from the transfer point 34 (as shown in FIG. 2b). Since 48 divides evenly into 2, 3, 4 and 6, the first aliquot of a sample will have arrived into the 48th step position in the belt 5 with the arrival of its sample container at the 24th, 16th, 12th or 8th step position along the belt 2 from the transfer point 32, depending upon the number of aliquots per sample, i.e. two, three, four or six, respectively. If there are to be five aliquots per sample, the colourimeter station 39 is moved two steps further, such that its end at the 50th step, and the sample identification station 42 is positioned at the 10th step.

For example, if each of a series of samples are to undergo the same four tests, such tests will be programmed by way of the control panel 13 and the printer control 4. The identification station 42 will be positioned adjacent the 12th step (48 divided by 4) from the transfer point 32 and the colourimeter 39 will encompass positions 43 to 48. When any specific sample container reaches the identification station 42, its four aliquot tubes will be in step positions 49 to 45, such that the corresponding four cuvettes 600 will receive and provide the colourimetric test reactants for data recording. Such data recording will receive the sample container number identification of the sample container then in the indentification station 42.

In FIG. 17 the identification device 42 is shown with a sample container 101. When the sample to be identified reaches the identification station it engages with a pinion 108 which is set in motion to cause the sample container to rotate about its longitudinal axis by engagement with the cogging 104. The depression in the base 105 (FIG. 4a) serves as an axis of rotation. A vertical column of eleven fibre optics bundles is arranged so as to line up accurately with the columns of identification on the label 106 (see also FIG. 4c). A portion of each of the bundles goes to a light source and the remaining portion of each of the bundles goes to separate photosensitive devices so that indications can be provided as to whether the device is "seeing" a blackened portion of the label or a reflective portion of the label. On the rotation of the container the print-out mechanism for printing out the identification ignores all indications until a unique code combination on the photosensitive devices corresponding to the left column of the label is received. This provides the information that the rotation of the container has brought the left-hand side of the label opposite the detection device. Subsequent indications are registered, being gated by pulses obtained from the unnumbered top line of blackening so that the columns are read in succession. These indications are fed to a printer which prints out the number which has been read on the printing mechanism 10 (FIG. 1) followed by the indications from the indicators 4 and the respective outputs of the photocells 604 (FIG. 10).

The electronic and electrical system which controls the operation of the aapparatus is shown in block form in FIG. 13, the waveforms appearing at various points in the system being shown in FIG. 14. Portions FIG. 13a of the diagram shows the circuit which controls the main timer. The reference numerals in FIG. 13 are the same as used in FIG. 20 which shows various parts of the electrical system in greater detail. At rest, before the apparatus is switched on, a line identified as carrying the waveform d (see FIG. 14) applies a potential of 5 volts, the output of a bistable trigger 803, 803a, to a relay 711. The potential is also applied to an oscillator 800 in such a way as to prevent oscillations being generated and to a counter 801 to reset said counter. Oscillator 800 when oscillating, generates oscillations as shown in waveform 14b having a period of 1.5 seconds. The potential applied to relay 711 energises said relay and allows a potential of 24 volts to be applied through a switch 711', which is closed as will appear subsequently when a transfer has been completed from the diluent pump, and a start switch 712 on the front panel of the apparatus to a relay 713. Energisation of relay 713 allows power to be supplied to the motor 24 wich drives the belt 5 (FIG. 2) which carries the reaction tubes. It will be appreciated that the belt 5 starts to move when the start switch 712 has been closed. The motor 24 carries a cam 714 adapted to operate two microswitches 741', and as soon as the motor begins to turn one of said microswitches applies a potential of 24 volts to said relay 713 so as to keep said motor 24 revolving, and thee other microswitch changes the voltage on a line identified as a (waveform 14a) from 5 volts to zero volts. Said a line is connected through an inverter 715 to said bistable trigger 803, 803a and to a bistable trigger 810, 808, to change both their states. Said bistable trigger 810, 808 is utilized to clock a counter included in the test counting system and provides a half cycle command output. The bistable trigger 803, 803a allows the oscillator 800 to commence oscillating and removes the reset from counter 801. When said counter 801 reaches a count of four, the bistable trigger 810, 808 is reset and this removes the half-cycle command output. When said counter 801 arrives at a count of eight, the bistable trigger 803, 803a is reset and this replaces the clamp on oscillator 800 to prevent it oscillating, resets said counter 801, and energizes relay 711. This completes a cycle for the belt 5 of which the duration is approximately 15 seconds. An output from bistable trigger 810, 808 is applied along the line c (waveform 14c) as one input to an AND-gate 808' of which the other input is the waveform a from one of the microswitches 714'. The output of said AND-gate 808' appears at a terminal 809 and is applied to a relay 716 which controls sample transfer and washing, as will be described subsequently.

The test counting system is shown in FIG. 13b. A counter 811 is connected to an output of bistable trigger 810, 808 (FIG. 13a). Said counter 811 has five output terminals and a signal such as f (waveform 14f) appears successively on each of these when 2, 3, 4, 5 and 6 tests have been made on a sample. The respective outputs of counter 811 are applied to the contacts of a switch 812a in the panel 13 of FIG. 1. According to the position in which said switch is set, a signal will appear on the output of the switch when a predetermined number of tests has been accomplished. The output from counter 801 (FIG. 13a) which triggers bistable trigger 810, 808 is also applied to a bistable trigger 815, 816 as a reset.

Said counter 811 also obtains a reset signal through terminal 813 which is the output of an OR-gate 720 which has one input derived from a transport microswitch 721' and the other input derived along a line g (waveform 14g) from a microswitch 722 operated by a cam 722' connected to the drive motor 12 for the sample container belt 2 (FIG. 2). The output of bistable trigger 815, 816 is supplied as one input of an AND-gtae 723 of which the other input is a signal obtained from the microswitch 714' (FIG. 13a) on line a (waveform 14a), through an inverter 724. The output of gate 723, waveform 14h is applied to the colourimetric timing system to start said system as will appear subsequently. The output from switch 812a is applied as one input to an OR-gate 725 of which the other input is a signal derived from microswitch 721' and also along line g from microswitch 722 through an inverter 726. The output of said gate 725 is applied as one input of an AND-gate 727 of which the other input is the output of an OR-gate 728 which has at its inputs a 24 volt signal from switch 721' and a 24 volt signal from a start switch 729. The output of AND-gate 727 is applied to a relay 730 which controls the power to energize the belt drive motor 12 for the sample container belt 2. Another output of the bistable trigger 815, 816 is applied to line e (waveform 14e) as a timing command signal to the reagent sub-system which will be described subsequently. In operation, supposing a "four-test" is selected on switch 812a, at the end of four cycles of the belt 5, relay 730 is energized thus driving the belt 2. As the sample belt moves, the microswitch 722 is released and reactuated. This will stop the main sample drive motor 12, reset counter 811 and set bistable trigger 815, 816. This issues a start command to the colourimetric mechanism timing system. A start command is also taken from the wiper of switch 812a along line 731 to initiate operation of the identification system of FIG. 17.

The sample transfer system is illustrated in FIG. 13c. To the right of the Figure is shown the arm 203 carrying the pipette 202 (see FIG. 5) which transfers portions from the sample container to the reaction tubes 905 (see FIG. 16). The syringes 902 for the aliquot and the diluent pump 904 are also shown. The transfer system is operated in response to signals from relay 716, also shown in FIG. 13a, which is energized by a half cycle command signal as was described in connection with FIG. 13a. During the first half-cycle said relay 716 is energized and passes a 24 volt signal to a relay 740. This relay initiates two functions: first the diluent pump is charged with diluent by operation of a means 741, and second, the probe 202 is rotated by a means 742 until microswitch 212 is released. This energizes a relay 743 which causes the probe to be lowered by a means 744. The lowering continues until either, if the sample tube is empty the probe travels down until microswtich 209 on the member 204 is actuated, stopping the action of the probe-down means 744 or until a liquid surface is sensed which by means of the probe contacts via means for adjusting the sensitivity 745 operates said relay 743 again stopping the downward travel of the probe. Operation of said relay 743 energizes a means 746 causes charging of the aliquot syringe 902 so that the probe picks up a portion of the sample. The system now waits for the half cycle command from the circuit of FIG. 13a to de-energize relay 716. When this happens, a relay 747 is energized, causing operation of a means 748 for raising the probe. The upward motion continues until microswitch 208 on member 204 is operated to release relay 747 and energize a relay 749. Said relay 749 causes operation of a means 750 which rotates the probe back towards the central loop until microswitch 211 is released. This allows energization of a relay 751 which operates a means 752 which causes the aliquot to be discharged until microswtich 755 on said aliquot syringe 902 is actuated. This energizes a relay 753 which operates a means 754 for causing the diluent pump 904 to be discharged. When the diluent is fully discharged microswitch 711' is actuated. Said microswitch is the switch 711' in the circuit of FIG. 13a, and its operation enables the reaction tube belt 5 to be driven on when the main timer circuit is ready.

The successive steps in this operation are illustrated in the diagram of FIG. 15, where (a) shows the half-cycle command signal to the relay 716, (b) shows the relative up and down position of the diluent pump 904, (c) shows the lateral position of the transfer arm 203, (d) shows the relative vertical position of the probe 202, (e) shows the position of the aliquot syringe 902 and (f) shows the half-cycle command to relay 747.

The operation of the washing system for cleansing the reaction tubes after tests have been made is shown in FIG. 13d. This part of the system is also operated from relay 716 (FIG. 13a). During the first half-cycle a relay 760 is energised and during the second half cycle a relay 761 is energized. Relay 760, when energized applies a signal through a microswitch 762a to a means 763 which cause a wash pump to discharge into the test tubes. When the discharge is complete, microswitch 762a actuates and a signal is then applied to a means 764 which causes the waste pumps to empty the contents of the reaction tubes. Furthermore, since relay 761 is de-energized, a signal is applied to a means 765 for lowering the probes into the test tubes. When relay 760 is de-energized during the next half cycle and relay 761 is energized, a signal is applied to a means 766 for lifting the probes and a signal is applied to a means 767 for causing the waste pumps to discharge and to a means 768 for causing the wash psmp to recharge with wash water. The processes involved are shown diagrammatically in FIG. 15 where (g) shows the up-down position of the wash pump, (h) shows the up-down position of the waste pump and (i) shows the up-down position of the wash system probes.

A practical arrangement for timing the operations in the apparatus is shown in more detail in FIG. 20. The timing of operations is effected by a uni-junction oscillator 800. This oscillator generates pulses with a periodicity of 1.5 seconds. The uni-junction device is of the type commercially available under the designation 2N871. The output of the oscillator is connected to a decade counter 801 (commercially available as SN7490). Normally the uni-junction oscillator is prevented from oscillating by the transistor 802 (of the type commercially designated 2N2222A) which is held conducting by means of the flip-flop circuit, or bistable trigger, comprising the two quad 2- input NOR gates 803 and 803a (of the type SN7402) which have as input signals signals obtained from the motors in the apparatus and applied to said bistable trigger through a 2-input NOR gate 804 connected as an inverter. When the motor 24 is in operation, for example having been started by pressure on the start button on control panel 13 (FIG. 1) signals are applied to the terminal 805. The terminal 806 takes the command from the motor which continues to operate by means of the microswitch 714. Through the resistor 807 the counter 801 is held at reset and the transistor 802 is rendered conducting preventing oscillations. When the control is withdrawn the uni-junction is allowed to oscillate and this enables the counter 801. After a count of five, that is after 71/2 seconds, the terminal of counter 801 is connected to a 2- input NOR gate 808 provides a signal which through a terminal 809 initiates a command signal for the reagent pumps, the washing devices, and the sample transfer devices. It will be appreciated that the gate 808 together with the similar gate 810 constitute a bistable trigger. Both 808 and 810, as are all the NOR gates in FIG. 20, are of the type SN7402. Every change of command in the bistable trigger arrangement 808, 810 transfers a signal from 810 to a decade counter 811 (SN 7490). The counter 811 is connected to a binary to decimal decoder 812 (SN 7442) which provides signals in turn on the terminals 812a. The outputs 812a are connected to a selector ssitch to control the relay operating the motor for the outer belt 2. The purpose of this count is to count the number of times the reaction belt 5 has moved and, to allow for the appropriate selection of the number of tests to be effected, to move the outer belt after two, three, four, five or six steps of the reaction belt. A signal is applied to another NOR gate 814 through a terminal 813 from the motor microswitch 722 (FIG. 13b) to indicate that it is turning and this resets the counter 811. Two NOR gates 815 and 816 constituting a bistable trigger device are connected so as to be set by the output from gate 814 and reset by a signal from the lead connecting counter 801 to gate 808. This provides a pulse of 71/2 seconds duration at a terminal 817 of said trigger which is used to control the colourimeter head. The signal at terminal 817 is applied through a transistor 820 (type 2N2222A) and thence to a terminal 819 which supplies signals to control the coloruimeter. A button is provided on the control panel 13 (FIG. 1) which when pressed allows the apparatus to operate without performing any tests, but performing the washing operations. The effect of pressing the button is to apply a signal which inhibits the start output 855 for the colourimeter, whilst the belt 5 continues to move.

The electronic and electrical system which controls the operation of the colourimeter is shown in block form in FIG. 18, the waveforms appearing at various points being shown in FIG. 19. Portion FIG. 18a of the diagram shows the part of the circuit which controls the timer for the mechanism and FIG. 18b shows the part which controls the timing for the colourimeter head. The reference numerals in FIG. 18 are the same as used in FIG. 21 which shows various parts of the electrical system in greater detail. The start command to this portion of the circuit is obtained from the main timer (FIG. 13b) as the output of gate 723 (waveform h in FIG. 14). This is applied through terminal 855 (waveform b, FIG. 19) to a bistable trigger 853,854. The output of bistable trigger 853,854 is applied along a line c (waveform FIG. 19c) through a gate 951, to a relay 952 which controls the motor 953 for raising and lowering the colourimeter probes.

An oscillator 850 is provided which produces oscillations having a period of 1.0 seconds (waveform 19a). The output of bistable trigger 853, 854 also opens a gate 852 to enable oscillations from said oscillator 850 to be applied to a counter 851. Said counter 851 provides outputs at respectively 2, 12, 22 and 26 seconds after commencement of its count. After two seconds, a command is passed along the conductor d (waveform 19d) through an amplifier 954 to energize a vacuum solenoid 955. The energizing circuit has a delay so that the vacuum is applied for approximately nine seconds, the vacuum being used to draw the contents of the reaction tubes into the appropriate cuvettes. During the operation of the vacuum command the sample identification is being read from the marked-up label on the sample container and being fed to the printer to produce identification for the proceeding set of colourimetric results which are relevant to this particular sample container. At the time 12 seconds after start of the count, the colourimeter head timing system is initiated by a signal applied along conductor h (waveform h FIG. 19) to a terminal 862 (FIG. 18b) where said signal is applied to a gate 861 to set a bistable trigger 859, 860. At a time 22 seconds after the start of the count, a signal is applied along a line f (waveform 19f) through an amplifier 956 to a pressure solenoid 957 which is thus energized in the same way as was the vacuum solenoid 955 in order to empty the contents of the cuvettes back into the reaction tubes. At a time 26 seconds after commencement of the count, a signal is applied from counter 851 to reset the bistable trigger 853, 854, thus completing the colourimeter cycle. The lower motion of the motor 953 for the colourimeter probe is obtained in the same way as the raise motion, controlled by a signal from terminal 855 applied through a gate 958 to a relay 959. A move right signal for the colourimeter probes is obtained from the output of relay 730 (FIG. 13b) and applied to the colourimeter probe horizontal motor 960. A move left signal for said motor 960 is obtained from microswitch 714'(FIG. 13a) through relay 961.

Referring to FIG. 18b showing the colourimeter head timing system, there is provided an oscillator 882 generating oscillations having a period of 0.6 seconds (waveform j FIG. 19). The output from bistable trigger 859, 860 is applied to a gate 881 which controls the supply of said oscillations j to a counter 863, 865.

Said counter 863, 865 has six outputs which generate signals respectively after 1,2,3,4,5,6 periods of the oscillations of oscillator 882 on conductors k,l,m,n,o,p (see FIG. 19k,l,m,n,o,p). These signals are applied to the respective six colourimeter heads which enable them so as to perform their read functions sequentially. A seventh output from said counter 863, 865, appearing after seven periods of said oscillations, is applied to bistable trigger 859, 860 to reset it. An output from said bistable trigger 859, 860 is applied along conductor i (waveform i FIG. 19) to enable operation of the printing mechanism for printing out the results of the tests.

The colourimeter timing control shown in greater detail in FIG. 21 includes a uni-junction oscillator 850 supplying pulses at one pulse per second to a decade counter 851 through a 2-input NAND gate 852. This gate, as are all the gates shown in FIG. 21, is of the type designated SN7400. The gate 852 is controlled by a bistable trigger circuit comprising two NAND gates 853 and 854. Normally the pulses from the oscillator 850 are not supplied to the counter 851, but when the terminal 855 is energized from the main timer board, pulses are supplied to the counter. After one second the counter 851 energises the NAND gate 856 to supply an output to the terminal 857 which operates a vacuum pressure switch to apply vacuum to the head and thereby the cuvette probes, which have been lowered by the pulse applied to terminal 855. The tenth pulse from the decade counter 851 is applied to a second decade counter 858. This applies a pulse to the bistable trigger comprising two NAND gates 859 and 880 through a NAND gate 861 so long as a voltage is not applied to gate 861 through terminal 862. Terminal 862 is connected to the wash switch on the control panel 13 (FIG. 1) and operates to prevent the colourimeter acting. The output of the bistable trigger 859, 880 enables a NAND gate 881 to allow pulses from a uni-junction oscillator 882 to reach a decade counter 863 (SN7490) through an inverter 864. This inverter, as are all the inverters shown in FIG. 21, is of the type designated SN7404. The decade counter 863 is connected to a binary to decimal decoder 865. The effect of this is to energise the terminals connected through respective inverters to the output terminals 866 to 871 for two seconds each in sequence. The pulses on these terminals are utilised to control the respective colourimeter heads for the six tests. On the seventh change, the terminal of the decoder 865 connected to conductor 872 resets the bistable trigger 859, 880 and stops the supply of pulses from the uni-junction oscillator 882 to the counter. It also supplies through the bistable trigger a reset pulse to reset the decade counter 863. After 22 seconds a pulse is applied to terminal 873 from counter 851 through NAND gate 874. The pulse on terminal 873 is utilised to apply pressure to discharge fluid from the cuvettes and to lift the probes clear of the reaction tubes. After 26 seconds a pulse is applied through the NAND gate 875 to the bistable trigger 853, 854 to operate gate 852 to remove the supply of pulses to counter 851 from the unijunction oscillator 850.

The signals provided by the photocells in the colourimeter head are dealt with as follows. Beer's Law states that the absorbence A is directly proportional to the concentration C of an absorber, that is

A = KC where K is a constant.

The output current I of the photocell is directly proportional to the quantity of light falling on to it and thus to the transmittance of the sample being tested. By passing this current through a load resistor R, a voltage V is obtained represented by

V = I R = KT where K is a constant.

Since from Beer's Law we have A = -log T, then T = 10.sup..sup.-A. Thus V has an inverse logarithmic relationship to the concentration of reaction product. This is converted to a linear reading of concentrations as follows: Referring to FIG. 22a,V.sub.O is at a maximum when the cuvette is filled with reagent only, for example when distilled water has been substituted for a sample. In this case, the voltage produced by the photocell 1001 across the load resistor 1002 is V.sub.O. By connecting a centre-zero meter 1003 between the output of said photocell 1001 and the wiper of a potentiometer 1004 connected between ground and a stable reference voltage V.sub.R the wiper may be set to provide a voltage V.sub.O. If a capacitor 1005 is now connected to the wiper of the potentiometer 1004 through a switch 1006 (see FIG. 22b) the capacitor 1005 will charge to a potential V.sub.O. If the switch 1006 is now changed over so as to allow the capacitor 1005 to discharge through a resistor 1007 of value R.sub.C, the voltage of said capacitor 1005 will fall in a logarithmic decay curve as shown in FIG. 23. With a sample in the cuvette, the output from the photocell will be V, always less than V.sub.O. If this is compared with the decaying voltage across the capacitor 1005 in a comparison circuit 1008 (FIG. 22c) an output can be obtained from said comparator constituting a pulse P (FIG. 23). The duration of this pulse will be directly proportional to the concentration of reaction product in the cuvette. The pulse duration is measured by a four-decade digital timer 1009 and its output can be displayed and printed.

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