GB1595885A - Automatic chemical analyzer - Google Patents

Description

(54) AUTOMATIC CHEMICAL ANALYZER (71) We, NIHON DENSHI KABUSHIKI KAISHA, a Japanese Company, of 1418 Nakagamicho, Akishimashi, Tokyo, 196, Japan, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to an automatic chemical analyzer.

Apparatus for continuously and automatically analyzing liquid samples such as blood, urine, etc. are presently available and are being used extensively in the clinical and chemical fields. In the larger type of apparatus in which many channels are provided, different analyses of the same sample can be carried out simultaneously. However, in the more compact small-sized apparatus, a lesser number of channels, sometimes only a single channel, are provided.

If, for example, only one channel is provided and it is intended to carry out more than one type of analysis of a given sample, various operations such as selecting the measuring wavelength, washing the flow through system, changing over the reagent, selecting the desired analyzing method, etc.

will be necessary. Of these operations, reagent changeover is the most troublesome.

This is because there is only one pump for a plurality of reagents housed in separate storage tanks, selection of one particular reagent or another being determined by a valve located between these tanks and the pump. In other words, after a given reagent has been force-fed into the reaction chamber through the action of the pump, it is necessary to wash not only the valve and associated feed lines connected to the reaction vessel but the pump too, before the next reagent can be sent to the reaction vessel.

This is very time consuming. Moreover, since the pump is difficult to clean, the chances of traces of the previous reagent remaining are likely so that when the next reagent is passed through, cross-contamination is a possibility. Another drawback with this arrangement is that reagent consumption is uneconomical, since it is necessary to displace reagent in a sufficient amount to reach the pump interior for each analysis.

The present invention seeks to provide an automatic chemical analyzer capable of shortening the washing time when changing over from one type of analysis to another, and which is able to carry out sampling without the adverse effect of cross-contamination.

In accordance with the invention there is provided an automatic chemical analyzer comprising means for extracting a sample to be analysed from a plurality of liquid samples, means for measuring out a fixed dose of said extracted sample, a plurality of reagent storage tanks, each storing a different kind of reagent according to a required analysis, a plurality of pumps each for drawing reagent out of a respective one of said reagent storage tanks, a reaction device comprising a plurality of reaction tubes, each for receiving a mixture comprising a dose of sample and a reagent, reagent selecting means located between said pumps and said reaction device, said reagent selecting means comprising a multiple port selector valve equipped with an outlet connected to said reaction device, a plurality of inlets, and a plurality of directional control valves, each of said plurality of directional control valves being equipped with an inlet and two outlets, each said inlet being connected to a respective one of said reagent storage tanks via a respective one of said pumps, one of said two outlets being connected to one of said inlets of said selector valve, the other of said two outlets being connected to said one of said reagent storage tanks, optical detecting means for detecting the amount of light passing through the mixture in said reaction tubes, and data processing means for processing the output signal from said optical detecting means.

In order that the invention may be better understood, an embodiment thereof will now be described by way of example only and with reference to the accompanying drawings in which: Figure 1 shows one embodiment of an automatic chemical analyzer according to this invention, Figure 2 shows the reagent selector used in the embodiment of Figure 1; Figure 3 shows the rotating block of the flow path changeover valve shown in Figure 2; and Figure 4 is a diagram showing the relation between the multi-flowpath changeover valve and the changeover valves.

Referring to Figure 1, the analyser comprises a reaction device 1 (for details of this type of device, refer to British Patent 1,540,128) comprising a rotating body 2 equipped with holes for supporting a plurality of reaction tubes 3, said rotating body 2 being rotated intermittentlv by a geneva gear or the like. References A, B C, L represent the position of the various reaction tubes. For example, the reaction tube positioned at A is supplied with a metered dose of sample together with a quantity of first reagent, and the reaction tube positioned at F is supplied with a quantity of second reagent.Further, the reaction tube positioned between F and G is supplied with gas so as to agitate and thereby thoroughly mix the sample and reagent, and the reaction tube positioned at J is irradiated with light from a lamp 4, the transmitted light be ing detected by a detector 5 so as to measure the absorbed light intensity. The position between J and K, and the K and L positions are the draining, washing, and washing solution draining positions, respectively.

Samples are dispensed from a sample dispensing device 6 which comprises a turntable 7 driven by a driving means 9, and a plurality of sample tubes 8 arranged around the periphery of the turntable 7. Reference 10 is a sampling head which comprises a suction pipe 11 and a suction pipe shifting device 12. During operation, the shifting device 12 shifts the suction pipe 11 so that the tip of suction pipe 11 enters the sample tube located at the sample sucking position. A quantity of sample is then sucked through the suction pipe. It is also possible to insert the suction pipe 11 into a wash tank 13, as shown by the broken line, so as to wash the tip of the pipe 11.

From the sampling head 10, samples are passed to a sampling valve 14 composed of two fixed members 15 and 16, and a rotating member 17 housed between the two fixed members 15 and 16. The rotating member 17 is equipped with at least two through holes 18a and 18b. The sampling head 10 is connected to the fixed member 15, and the fixed member 16 is connected to a changeover valve 19 which operates so as to connect pump 20 or pump 21 to said fixed member 16. The rotating member 17 rotates to transfer a metered dose of sample across the valve to the right-hand side where it can be flushed through with reagent from a throughpipe 24, as will be explained below.

When pump 20 is connected to the fixed member 16 (as shown in Figure 1), liquid sample contained in that sample tube in which the tip of the suction pipe 11 is inserted, is drawing into through-hole 18a equipped in the rotating member 17. Changeover valve 19 then operates to connect pump 21 to the fixed member 16 and washing solution contained in a wash tank 22 is drawn through so as to flush out the entire sampling system. The fixed member 16 is also connected to the reaction tube positioned at A in the reaction device 1, and the fixed member 15 is also connected to a first reagent selector 25 via the through pipes 26 and 27 also pass through the preheating chamber 23. Of these, through pipe 26 carries the washing solution, sucked up by pump 21, to the reaction tube located at position F.

The first reagent selector 25 comprises a multi-flowpath change-over valve 29 and a plurality of three-way changeover valves 30a, 30b, 30c, 30d, 30e and 30f arranged around the multi-flowpath changeover valve 29. The changeover operation of each of the three-way changeover valves 30a to 30f is interlocked with that of the multi-flowpath changeover 29. One of each of the three through-ways of three-way changeover valves 30a to 30f are connected to a respective first reagent storage tank 32a, 32b, 32c, 32d, 32e and 32f via a respective pump 31a, 31b, 31c, 31d, 31e and 31f. A second of each of said through-ways are connected to the multi-flowpath changeover valve 29, and the remaining third of each of said through-ways are connected to respective return pipes for returning the reagent to a respective reagent storage tanks 32a to 32f.

The reagent flow through system is constructed and operates so that, during analysis, only one three-way valve is connected to the multi-flowpath changeover valve 29 at any one time, while the other three-way valves are connected to the respective reagent return pipes, In Figure 1, valve 30a is connected to valve 29. Accordingly, a quantity of first reagent is drawn out of storage tank 32a and enters one of the reaction tubes 3 via the first reagent selector 25.

The pumps 31a to 31f may each have their own independent driving means, or a single driving means can serve to operate all the pumps. In the former case, although each pump can be operated individually as required, the plurality of driving means increases the cost and size of the analyzer as a whole. On the other hand, in the latter case, although all the pumps are inevitably driven simultaneously, it does have an advantage in terms of cost and size. That is to say, a more compact and economically priced analyzer is feasible.

A second reagent selector 28, identical in construction to the first reagent selector 25, is provided. As in the case of the first re agent selector 25, a plurality of three-way changeover valves 34a to 34f are arranged around a multi-flowpath changeover valve 33, and are connected to respective reagent storage tanks 36a to 36f (designated, in this case, as second reagent storage tanks) via respective pumps 35a to 35f. The second re agent flowpath and its operation are the same as that of the first reagent flowpath.

As shown in Figure 1, reagent from the second reagent storage tank 36a enters the reaction tube, located at the F position in the reaction device 1, via changeover valve 34a. A feed pump 37 is operable to draw up washing solution contained in a tank 38 into the multi-flowpath changeover valves 29 and 33.

Each of the valves 29 and 33 is equipped with twelve equi-distantly spaced inlets and one outlet, every other inlet of said inlets being connected to the washing circuit, the remaining inlets being connected to the three-way changeover valves 30a to 30f and 34a to 34f, respectively for reagent supply purposes. By this arrangement, the flowpath is automatically washed between each reagent changeover. A compressor 39 is operable to supply compressed air via valves 40a and 40b to the reaction tube when posi tioned midway between positions F and G (for stirring purposes), and the reaction tubes positioned midway between positions J and K, and between positions K and L (for draining purposes).

An amplifier 41 is provided to amplify the output signal of the light detector 5. The output of amplifier 41 is passed to an A-D converter 42 which converts the amplified output from the detector 5 into a digital signal. This digital signal is analysed in a computer 43.

Figures 2 to 4 show one embodiment, by way of example only, of the first (second) reagent selector 25 (28). The selector com prises a flanged base plate 45 which supports the changeover valves 30 to 30f at equi distantly spaced positions around the multi flowpath changeover valve 29. Reference 44 is a fixed frame (forming an integral part of the valve 29) which is secured to the base plate 45. Reference 46 is a fixed body formed from an anti-corrosive and anti-erosive material such as Teflon (Registered Trade Mark), the fixed body 46 being held by the fixed frame 44.

The fixed body 46 is equipped with twelve (or more, or less) ducts 47, one opening of each of said ducts being connected to a re spective one of joints 48a to 48f and 49a to 49f built into the fixed frame 44. The other opening of said duets leads out through the base of the fixed body 46, the respective openings describing a circle having a specific radius. Joints 48a to 48f and 49a to 49f are arranged alternately around the fixed frame 44 as shown in Figure 4. -Of these two sets of joints, joints 48a to 48f are connected to joints 50a to 50f, which constitute the reagent outlet flowpaths of respective changeover valves 30a to 30f; whereas joints 49a to 49f are connected to the washing solution feed pump 37 as shown in Figure 1.

Joints 51a to 51f, which constitute the reagent inlet flowpaths of the valves 30a to 30f, are connected to reagent feed pumps 31a to 31f, and joints 52a to 52f are connected to respective return pupes so as to return the reagent to respective reagent storage tanks 32a to 32f.

A hollow shaft 53 is held securely in the frame 44, and a rotating frame 54 rotates around the shaft 53. A block 55, held and supported by the rotating frame 54, rotates en bloc therewith. The block 55 is provided with a single duct 56, the upper opening of which duct is arranged on a circle having the same radius as that on which the ducts 47 are arranged. The opposite opening of said duct 56 is connected to a joint 57. The contact surface pressure of the rotating block 55 and the fixed body 46 is maintained by means of a spring 58, which acts so as to press the rotating block 55 up against the fixed body 46 via the shaft 53 and a bearing.

The rotating frame 54 is rotated by a rotating member 59, said rotating member 59 being, in turn, driven by a driving means 61 via a shaft 62 and a connecting rod 60.

A fixed seal 64 made of Teflon (Registered Trade Mark), for example, and equipped with a duct 63 running length ways through its centre, is arranged in the hollow shaft 53. A joint 65 is provided at the upper end of the fixed seal 64, the joint 65 being connected to the fixed member 15 forming part of the sampling valve 14, in the case of valve 25, and to the reaction tube positioned at F in the reaction device 1 (see Figure 1), in the case of valve 28. At the lower end of the fixed seal 64, a rotating seal 67, having surface contact with said fixed seal 64 and equipped with a duct 66, is provided, said rotating seal being shaped so as to prevent liquid from leaking from the contact surface of the two seals when the rotating seal rotates. The necessary contact surface pressure between the fixed and rotat ing seals is maintained by means of a spring 68.A holding member 69, for hold ing the rotating seal 67, rotates enbloc with the rotating member 59, the holding member 69 being arranged so as to shift said rotat ing seal 67 vertically with respect to the rotating seal 67, and is connected to joint 57 by a pipe 71.

The change over valve 30d comprises a fixed frame 72 secured to the base plate 47 and a shaft 73 held securely and centrally in said fixed frame 72. A fixed block 74, made of Teflon (Registered Trade Mark), is held in said fixed frame, the fixed block 74 being equipped with at least three ducts 75 each of which are connected to joints 50d, 51d, and 52d, respectively. Another block 76 is held by a rotating frame 77, the block 76 being equipped with four equidistantly spaced ducts 78, two of which are connected to each other by a groove 79a, the other two being interconnected by a groove 79b. The necessary surface pressure between the fixed block 74 and the rotating block 76 is provided by means of a spring 80.The rotating frame 77 is secured to a cross-shaped rotating plate 81, said rotating plate 81 being joined to a driving disc 82, which is secured to the rotating member 59, by a pin 83. Another pin, identical to pin 83, is located at an angular distance of, for example, 600 from pin 83 so as to drive two changeover valves simultaneously. By so doing, the leading pin changes over, for example, valve 30d so as to connect joints 50d and 51d, while the lagging pin changes over valve 30c so as to connect joints Sic and 52c. Accordingly, only one changeover valve can be connected to any one flowpath of the multi fiowpath changeover valve at any one time.

In the above described configuration, by driving the driving means 61 in accordance with a preset programme, valve 29 may be rotated so as to link up with a specific pump via any one of the valves 30a to 30f as desired.

Since, in the above described analyzer, each reagent has its own exclusive pump and reagent selection valves are provided between said pumps and a plurality of reaction tubes, it is possible to repeatedly convey reagent to said reaction tubes without having to wash the pumps. Thus, the overall washing time is shortened and the problem of cross-contamination is resolved. Further, when changing over from one type of analysis to another, since it is not necessary to fill the flow system with fresh reagent as in the case of known analyzers, reagent utilization is more economical.

Modifications may be made to the above described analyzer. For example, the reaction device does not necessarily have to be circular and there is no limit on the number of changeover valves and reagents used.

WHAT WE CLAIM IS : - 1. An automatic chemical analyzer comprising means for extracting a sample to be analysed from a plurality of liquid samples, means for measuring out a fixed dose of said extracted sample, a plurality of reagent storage tanks, each storing a different kind of reagent according to a required analysis, a plurality of pumps each for drawing reagent out of a respective one of said reagent storage tanks, a reaction device comprising a plurality of reaction tubes, each for receiving a mixture comprising a dose of sample and a reagent, reagent selecting means located between said pumps and said reaction device, said reagent selecting means comprising a multiple port selector valve equipped with an outlet connected to said reaction device, a plurality of inlets, and a plurality of directional control valves, each of said plurality of directional control valves being equipped with an inlet and two outlets, each said inlet being connected to a respective one of said reagent storage tanks via a respective one of said pumps, one of said two outlets being connected to one of said inlets of said selector valve, the other of said two outlets being connected to said one of said reagent storage tanks, optical detecting means for detecting the amount of light passing through the mixture in said reaction tubes, and data processing means for processing the output signal from said optical detecting means.

2. An automatic chemical analyzer according to claim 1 wherein said multiple port selector valve and said plurality of directional control valves are mounted on a common base plate, said plurality of directional control valves being arranged equidistantly around said multiple port selector valve, with the multiple port selector valve at the centre.

3. An automatic chemical analyzer according to claim 1 in which said multiple port selector valve and said plurality of directional control valves are activated by a single common driving means.

4. An automatic chemical analyzer according to any one of the preceding claims in which said plurality of pumps are driven by one common driving means simultaneously.

5. An automatic chemical analyser substantially as hereinbefore described with reference to the accompanying drawings.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (5)

**WARNING** start of CLMS field may overlap end of DESC **. rotating seal 67, and is connected to joint 57 by a pipe 71. The change over valve 30d comprises a fixed frame 72 secured to the base plate 47 and a shaft 73 held securely and centrally in said fixed frame 72. A fixed block 74, made of Teflon (Registered Trade Mark), is held in said fixed frame, the fixed block 74 being equipped with at least three ducts 75 each of which are connected to joints 50d, 51d, and 52d, respectively. Another block 76 is held by a rotating frame 77, the block 76 being equipped with four equidistantly spaced ducts 78, two of which are connected to each other by a groove 79a, the other two being interconnected by a groove 79b. The necessary surface pressure between the fixed block 74 and the rotating block 76 is provided by means of a spring 80.The rotating frame 77 is secured to a cross-shaped rotating plate 81, said rotating plate 81 being joined to a driving disc 82, which is secured to the rotating member 59, by a pin 83. Another pin, identical to pin 83, is located at an angular distance of, for example, 600 from pin 83 so as to drive two changeover valves simultaneously. By so doing, the leading pin changes over, for example, valve 30d so as to connect joints 50d and 51d, while the lagging pin changes over valve 30c so as to connect joints Sic and 52c. Accordingly, only one changeover valve can be connected to any one flowpath of the multi fiowpath changeover valve at any one time. In the above described configuration, by driving the driving means 61 in accordance with a preset programme, valve 29 may be rotated so as to link up with a specific pump via any one of the valves 30a to 30f as desired. Since, in the above described analyzer, each reagent has its own exclusive pump and reagent selection valves are provided between said pumps and a plurality of reaction tubes, it is possible to repeatedly convey reagent to said reaction tubes without having to wash the pumps. Thus, the overall washing time is shortened and the problem of cross-contamination is resolved. Further, when changing over from one type of analysis to another, since it is not necessary to fill the flow system with fresh reagent as in the case of known analyzers, reagent utilization is more economical. Modifications may be made to the above described analyzer. For example, the reaction device does not necessarily have to be circular and there is no limit on the number of changeover valves and reagents used. WHAT WE CLAIM IS : -

1. An automatic chemical analyzer comprising means for extracting a sample to be analysed from a plurality of liquid samples, means for measuring out a fixed dose of said extracted sample, a plurality of reagent storage tanks, each storing a different kind of reagent according to a required analysis, a plurality of pumps each for drawing reagent out of a respective one of said reagent storage tanks, a reaction device comprising a plurality of reaction tubes, each for receiving a mixture comprising a dose of sample and a reagent, reagent selecting means located between said pumps and said reaction device, said reagent selecting means comprising a multiple port selector valve equipped with an outlet connected to said reaction device, a plurality of inlets, and a plurality of directional control valves, each of said plurality of directional control valves being equipped with an inlet and two outlets, each said inlet being connected to a respective one of said reagent storage tanks via a respective one of said pumps, one of said two outlets being connected to one of said inlets of said selector valve, the other of said two outlets being connected to said one of said reagent storage tanks, optical detecting means for detecting the amount of light passing through the mixture in said reaction tubes, and data processing means for processing the output signal from said optical detecting means.

2. An automatic chemical analyzer according to claim 1 wherein said multiple port selector valve and said plurality of directional control valves are mounted on a common base plate, said plurality of directional control valves being arranged equidistantly around said multiple port selector valve, with the multiple port selector valve at the centre.

3. An automatic chemical analyzer according to claim 1 in which said multiple port selector valve and said plurality of directional control valves are activated by a single common driving means.

4. An automatic chemical analyzer according to any one of the preceding claims in which said plurality of pumps are driven by one common driving means simultaneously.

5. An automatic chemical analyser substantially as hereinbefore described with reference to the accompanying drawings.