JPH0546503B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a multichannel chemical analysis device that can shorten the total sample analysis time. [Prior Art] A biochemical analyzer is usually designed to be able to analyze multiple items for one sample. In such a multi-channel biochemical analyzer for multi-item analysis, collected samples are distributed according to the number of items to be analyzed, and each distributed sample and reagents according to the items to be analyzed are applied to each reaction system. Each reaction system is analyzed for each item. Now, for example, when there are 32 total analysis items and they are to be analyzed, the process is performed as shown in FIG. 6, for example. That is, reaction tubes 50a, 50b, 50c, 50d, 50 containing samples distributed in appropriate amounts
e, 50f, 50g, . . . are set on the rotating body 51, and the rotating body is intermittently rotated in the direction of the arrow.
As shown in the figure, analysis items No. 1 and No. 2. Number 3...
..., a nozzle that supplies reagents compatible with No. 32,
, . . . is moved so that the nozzles in the first row are at the position where the reaction tube passes, and the reagent of the first item is sequentially introduced into the reaction tube 50a from the nozzle. The second item of reagent is supplied from the nozzle to the tube 50b, the third item of reagent is supplied from the nozzle to the reaction tube 50c, the fourth item of reagent is supplied from the nozzle to the reaction tube 50d, and then the second row of nozzles, etc. Move the nozzle body 52 so that it is at the position where the reaction tube passes, and in the same way as above, 5, 6,
7 and 8 reagents are supplied from the nozzle. This process is continued until 32 reagents are supplied. During this time, the concentration of the reaction liquid is measured at, for example, the Z position for the reaction tubes that have been successively moved. [Problems to be Solved by the Invention] However, a sample does not necessarily have to be analyzed for all analysis items, and the items to be analyzed differ depending on the sample. For example, depending on the sample, only the first, second, and 24th items may be analyzed. However, even in such a case, as described above, in a device that moves the nozzle body 52 one row at a time and performs the reagent supply operation four times each time, the reagents of the first and second items are supplied sequentially. Afterwards, I was unable to jump to the reagent supply for the 24th item, and the 3rd item
The operation time of reagent supply (during which no reagent is supplied) of item 23 must pass from item to item 23.
It will be a huge waste of time. As a result,
The total analysis time becomes significantly longer. The present invention is aimed at solving such problems. [Means for solving the problem] In order to achieve this objective, the multi-channel chemical analyzer of the present invention simultaneously executes each analysis cycle performed by mixing a sample and a reagent at the same timing. Multiple channel reaction system 14
b to 14e, and reagent containers u ₁ bb to u ₈ b, u ₁ c to u ₈ c, u ₁ d to u, which are the number of reagent containers corresponding to the total number of analysis items and are grouped by reaction system. _{8d , u1e〜u8e}
and a selection means 13 provided for each reaction system that selects an arbitrary reagent from the reagent containers of each group and sends it to each reaction system at the same timing in each analysis cycle.
b to 13e, means 1, 4, 5, and 6 for sending a sample to each reaction system in each analysis cycle, and generating and supplying a control signal specifying a reagent to be selected in each analysis cycle to each selection means. It is characterized by comprising a control means 8. [Function] In the present invention, for example, a number (for example, 32) of reagent containers corresponding to all analysis items is prepared, and the number (32)
For example, divide it into 8 cycles for each channel number (4), and as shown in Table 1, the 1st to 4th items are the 1st cycle items, the 5th to 8th items are the 2nd cycle items, etc. ..., items 29 to 32 are the 8th cycle items. Also, item 1, item 5
Item,..., item 29 to 1st channel (CH)
items, 2nd, 6th, ..., 30th item as 2nd channel (CH) item, ..., 4th, 8th, ..., 30th item, ..., 4th, 8th, ..., 30th item
32 items are designated as 4th channel (CH) items.

[Table] For example, when analyzing a certain sample for the 1st, 2nd, 19th, and 30th items, first,
The total amount of samples for the 19th and 30th items is aspirated, and the time required for the 1st cycle, 5th cycle, and 8th cycle, in which there is one or more items to be analyzed, is multiplied, but if there is only one item to be analyzed, The time required for unnecessary second, third, fourth, sixth, and seventh cycles is eliminated. However, the 19th item is a 3rd channel item, and since the 3rd channel item is empty up to this 19th item, the 19th item is performed in the 3rd channel of the 1st cycle, and is carried out in the 5th cycle. The required time is also deleted, the 30th item is a second channel item, and since the second channel item is occupied, the 30th item will be performed in the next, ie, eighth cycle. In other words, once the time required for all items in the first cycle has passed, the time required for the second, third, fourth, fifth, sixth, and seventh cycles is cut off, and the time required for all items in the eighth cycle is cut off. It takes a long time. [Example] FIG. 1 is a flow diagram of a multi-channel chemical analyzer for multi-item analysis shown as an example of the present invention. In the figure, 1 is the sample dispensing valve, and stator 2
and a rotor 3. As shown in FIG. 2, on the same radius of the upper surface of the stator 2, there are nine openings a,
b ₁ , b ₂ , c ₁ , c ₂ , d ₁ , d ₂ , e ₁ , e ₂ are opened, and there are 5 openings on the same radius of the surface of stator 2 that is in contact with the rotor. a', b', c', d', and e' are opened, openings a and a' are connected by conduit A, and conduit B ₁ of opening b ₁ and conduit B ₂ of b ₂ are connected by opening b ′, conduit C ₁ of opening c ₁ and conduit C ₂ of c ₂ are opening c′, conduit D _{1 of opening d 1 and} conduit D ₂ of d ₂ are opening d′, conduit E ₁ of opening e _1
The conduits E 2 and e ₂ intersect at the opening e′, respectively. An opening f' is formed on the same radius as the above-mentioned radius on the surface of the rotor 3 in contact with the stator 2, and an opening f is formed on the other surface, and these openings are connected by a conduit F. In opening a, there is a flexible tube T ₁ ,
A pipette 5 is connected via a pipette drive mechanism 4 that moves the pipette vertically and horizontally. Reference numeral 6 denotes a sample container.Although many sample containers are originally arranged, only one is shown for convenience. 7 is a waste liquid tank.
The pipette drive mechanism 4 is operated by a command from a control device 8. A pump 9 is connected to the opening f via a flexible tube _T2 . 10 is
Switch the flow path s so as to connect the opening p connected to the pump and the opening q connected to the cleaning container 11, or
This is a flow path switching device that switches to connect the opening p and the opening r. The pump 9 is operated by a pump control mechanism 12 which is operated by a command from the control device 8. The apertures b ₁ and b ₂ , c ₁ and c ₂ , d ₁ and d ₂ , e ₁ and e ₂ are paired, and the respective apertures b ₁ , c ₁ , d ₁ ,
Reagent feeding mechanisms 13b, 13c, 13d, and 13e for channels 1, 2, 3, and 4 are connected to e ₁ , respectively, and openings b ₂ , c ₂ , d ₂ , and e ₂ are connected to reaction mechanisms for 1 channel, respectively. Mechanism 14b, reaction mechanism 1 for 2 channels
4c, a 3-channel reaction mechanism 14d, and a 4-channel reaction mechanism 14e are connected. Each of the reagent feeding mechanisms is connected to a control device 8, and based on a control signal from the control device 8, each reagent is selected from a plurality of prepared reagents and sent to the reagent feeding channel. It's crowded. Each of the reagent feeding channels of these reagent feeding mechanisms is connected to a flow path switching device 15b, 15c, 15d,
It is connected to openings g ₁ , g ₂ , g ₃ , and g ₄ of 15e. These reagent delivery mechanisms have a configuration as shown in FIG. Although FIG. 3 only shows the reagent liquid feeding mechanism 13b for convenience, other reagent liquid feeding mechanisms have a similar configuration. Incidentally, FIG. 4 shows the reagent delivery mechanism for the first, second, . . . , and fourth channels. In FIG. 3, 21 is a valve consisting of a rotor 22 and a stator 23, and 24 openings h ₁₁ ,
h ₁₂ , h ₁₃ , h ₂₁ , h ₂₂ , h ₂₃ , h ₃₁ , h ₃₂ , h ₃₃ , ...,
h ₇₁ , h ₇₂ , h ₇₃ , h ₈₁ , h ₈₂ , and h ₈₃ are equally spaced. Also, on the side of the stator, there are conduits k ₁₁ ,
k ₁₂ , k ₁₃ , k ₂₁ , k ₂₂ , k ₂₃ , k ₃₁ , k ₃₂ , k ₃₃ , ...,
Through _the openings _{h 11 ,} h _{12 ,} h ₁₃ , h ₂₁ , h ₂₂ , _{h 23} , h ₃₁ , _{h 32 , h 33 ,}
..., openings f _{11 ,} f ₁₂ , f ₁₃ , f _{21 , f 22 ,} f ₂₃ , f ₃₁ , f ₃₂ , f ₃₃ connected to h ₇₁ , h ₇₂ , h 73 , h ₈₁ , h ₈₂ , h ₈₃ ,…
..., f ₇₁ , f ₇₂ , f ₇₃ , f ₈₁ , f ₈₂ , f ₈₃ are opened. Eight V-shaped conduits V ₁ , V ₂ , V ₃ , V ₄ , V ₅ , V ₆ , V ₇ , V ₈ are provided inside the rotor 22, and a Two openings are provided on the same radius and at the same spacing, similar to the openings in the stator. Openings f ₁₁ , f ₂₁ , f ₃₁ , ..., f ₇₁ , made on the side surface of the stator 23
f ₈₁ has the first, second, third, and
..., seventh and eighth reagent containers u ₁ , u ₂ , u ₃ , u ₄ , u ₅ ,
u ₆ , u ₇ , and u ₈ are connected. In addition, as shown in FIG. 4, the reagent feeding mechanism for the first channel includes the first,
The reagent containers u ₁ b, u ₂ b, ..., u ₈ b for the 5th, 9th, 13th, 17th, 21st, 25th, and 29th items are reagent liquid feeding mechanisms for the second channel. 2nd, 6th, 10th,
Reagent containers for items 14, 18, 22, 26, and 30
u ₁ c, u ₂ c, ..., u ₈ c, ..., the reagent feeding mechanism for the fourth channel includes the 4th, 8th, 12th, 16th,
Reagent containers u ₁ e for the 20th, 24th, 28th, and 32nd items,
u ₂ e, ..., u ₈ e are arranged respectively. Aperture f ₁₂ ,
f ₂₂ , f ₃₂ , ..., f ₇₂ , f ₈₂ are respectively connected to the openings p ₁ , p ₂ , p ₃ , p ₄ , p ₅ , and
Connected to p ₆ , p ₇ and p ₈ . The valve is open SH
By switching the channel SR connected to the opening SH, any of these openings is connected to the opening SH. The opening SH
is connected to a reagent feeding pump 25 via a tube. As shown in FIG. 4, the reagent feeding pumps 25b, 25c, 25d, and 25e of each reagent feeding mechanism are connected to the openings g ₁ , g ₂ , and g of the flow path switching devices 15b, 15c, 15d, and 15e. ₃ , connected to _g4 . The openings f ₁₃ , f ₂₃ , f ₃₃ , ..., f ₇₃ , f ₈₃ are connected to the openings p ₁ ', p ₂ ', respectively of the flow path switching valve 24' through tubes
It is connected to p ₃ ′, p ₄ ′, p ₅ ′, p ₆ ′, p ₇ ′, and p ₈ ′.
The valve connects any of these openings to the opening SH' by switching the flow path SR' connected to the opening SH'. In addition, as shown in FIG. 4, each opening SH'b,
SH'c, SH'd, SH'e are connected to the openings b ₁ , c ₁ , d ₁ , e ₁ of the stator 2 of the sample dispensing valve 1 . The flow path switching devices 15b, 15c, 15d, 15
e is _the opening _{g 1 , g 2 ,}
Either switch so as to connect g ₃ , g ₄ and the closed openings r ₁ , r ₂ , r ₃ , r ₄ , or connect the openings g ₁ , g ₂ , g ₃ , g ₄ with the cleaning liquid feeding mechanism 16
Opening h ₁ connected to b, 16c, 16d, 16e,
Either switch to connect h ₂ , h ₃ , h ₄ or connect the openings g ₁ ,
g ₂ , g ₃ , g ₄ and air supply mechanisms 17b, 17c, 1
Either the openings i ₁ , i ₂ , i ₃ , i ₄ connected to 7d and 17e are connected to each other, or the openings j 1 , j ₂ connected to the openings g ₁ , g ₂ , g ₃ , g ₄ and the atmosphere are _connected. , j ₃ and j ₄ are connected. The reagent feeding mechanism, reaction mechanism, flow path switching device, cleaning liquid feeding mechanism, air supply mechanism, etc. described above are all operated by commands from the control device 8. In such an apparatus, a case will be described below in which, for example, a certain sample is analyzed for the first, second, and 24th items. Initially, as shown in FIG. 1, the flow path s of the flow path switching device 10 is switched to connect the opening P and the closed opening r as shown by the solid line, and the sample is measured so that the openings a' and f' overlap. The rotor 3 of the distribution valve 1 is rotated. In this state, the controller 8 sends a command to the pipette drive mechanism 4 to insert the pipette 5 into the sample in the sample container 6. Then, in accordance with the command from the control device, the pump drive mechanism 12 operates to cause the pump 9 to transfer the total sample amount of the 1st item, 2nd item, and 24th item into the conduit F, and to increase the holding capacity of the pipette into the pipette 5, Aspirate so that it is contained within tube T ₁ and conduit A. Next, as shown in FIG. 5a, the rotor 3 is rotated so that the opening f' overlaps the opening b'. Then, by the discharge action of the pump 9, the amount of sample required for the first item is discharged into the conduits _B1 and _B2 . Thereafter, the rotor 3 is similarly rotated so that the opening f' sequentially overlaps the openings c', d', and e' as shown in FIGS. 5b, c, and d. Then, due to the discharge action of the pump 9, the second
Transfer the amount of sample required for the 3rd and 24th items to conduit _C1.
Discharge into C ₂ , D ₁ and D ₂ , and E ₁ and E ₂ . Note that since the third item is not analyzed, a time corresponding to the sample ejection time of the third item passes, but no sample is ejected. Next, as shown in FIG. 1, the rotor 3 is rotated so that the opening f' overlaps a'. At this time, the flow path s of the flow path switching device 10 is switched to connect the openings p and q. Further, the pipette 5 is inserted into a waste liquid tank 6. In this state, by operating the pump 9, the cleaning liquid in the cleaning liquid container 1 is sucked and discharged, and the tube _T2 , the conduits F and A, and the sample line of the tube _T1 are cleaned. During this time, the flow path switching devices 15b, 15c, 15
d, 15e, the respective channels k ₁ , k ₂ ,
k ₃ , k ₄ are open g ₁ , g ₂ , g ₃ , g ₄ and closed r ₁ , r ₂ , r ₃ ,
Switch each flow path so as to connect _r4 . At this time, the fourth
As shown in the figure, in the reagent liquid feeding mechanisms 13b, 13c, 13d, and 13e for channels 1, 2, 3, and 4, flow path switching valves 24b, 24b', 24c,
24c', ..., 24e, 24e' flow path SRb,
SRb′, SRc, SRc′, ..., SRe, SRe′ are the openings SHb and p ₁ b, SHb′ and p ₁ b′, SHc and p ₁ c, SHc′ and
p ₁ c′, ..., switches to connect SHe and p ₁ e, SHe′ and p ₁ e′. Also, the valves 21b, 21c, ..., 2
In 1e, the conduits V ₁ b, V ₂ b, ..., V ₈ b,
V ₁ c, V ₂ c, ..., V ₈ c, ..., V ₁ e, V ₂ e, ...,
As shown by solid lines, V ₆ e, V ₇ e, and V ₈ b are connected to openings of lines that connect the reagent container and the flow path switching devices 24b, c, . . . , e. And each reagent liquid feeding pump 25
b, 25c, and 25e, the amounts of reagents required for the 1st, 2nd, and 24th items are stored in the first reagent container u ₁ b and the second reagent container, respectively.
The reagent containers u ₁ c and 24th reagent container u ₆ e are aspirated into the tube. Next, each of the conduits V ₁ b, V ₂ b,...,
V ₈ b, V ₁ c, V ₂ c, ..., V ₈ c, V ₁ e, V ₂ e, ...,
As shown by the broken lines, V ₆ e, V ₇ e, and V ₈ e are the flow path switching devices 24b, 24c,..., 24e and the flow path switching device 24.
It connects to the opening of the line connected to b', 24c', . . . , 24e'. Then, by the discharge action of each of the pumps, the first reagent, the second reagent, and the 24th reagent are respectively delivered to the conduits B ₁ , B ₂ , C ₁ , C ₂ , D ₁ , D ₂ , E ₁ , 1 channel reaction mechanism 14b, 2 together with the sample in E ₂
It is sent to the channel reaction mechanism 14c and the 4-channel reaction mechanism 14e, and the first, second, and 24th items are analyzed by the respective reaction mechanisms. Then, each container flow path switch 15b, 15c, 15d,
In 15e, each of the channels k ₁ , k ₂ , k ₃ , k ₄ connects the openings g ₁ , g ₂ , g ₃ , g ₄ with the openings h ₁ , h ₂ , h ₃ , h ₄ . Switch the flow path. By this switching, the cleaning liquid flows from the cleaning liquid feeding mechanisms 16b, 16c, 16d, and 16e to the lines from each of the reagent liquid feeding channels to each of the reaction mechanisms, and the lines connecting the reaction mechanisms from each reagent feeding mechanism are cleaned. Ru. Next, in each of the flow path switching devices 15b, 15c, 15d, 15e,
Each channel k ₁ , k ₂ , k ₃ , k ₄ has an opening g ₁ , g ₂ , g ₃ , g ₄
The respective flow paths are switched so as to connect the openings i ₁ , i ₂ , i ₃ , and i ₄ . By this switching, each air supply mechanism 17
Air is sent from b, 17c, 17d, and 17e to the line from each reagent feeding channel to each reaction mechanism, and the cleaning liquid remaining in the line connecting each reagent feeding mechanism to the reaction mechanism is discharged to the outside. blown away. Next, each of the flow path switching devices 15b, 15c, 15
d, 15e, the respective flow paths k ₁ , k ₂ , k ₃ , k ₄ connect the openings g ₁ , g ₂ , g ₃ , g ₄ and the openings j ₁ , j ₂ , j ₃ , j ₄ . Switch the flow path. By this switching, the flow path of each reagent liquid feeding mechanism is opened to the atmosphere, and the line connecting each reagent liquid feeding mechanism to the reaction mechanism is brought into an atmospheric pressure state. Then, in this atmospheric pressure state, the rotor 3 is rotated so that f' overlaps with the opening b' as shown in FIG. The discharge action begins. [Effect of the invention] In the multi-channel chemical analyzer of the present invention,
A multi-channel reaction system in which each analysis cycle is performed by mixing the sample and reagent at the same time, and a number of reagent containers corresponding to the total number of analysis items, which are grouped by reaction system. a selection means for selecting an arbitrary reagent from the reagent containers of each group provided for each reaction system and sending it to each reaction system at the same timing in each analysis cycle; Since it is equipped with a means for sending a sample for each cycle and a control means for generating and supplying a control signal specifying the reagent to be selected for each analysis cycle to each selection means, it is possible to analyze as many items as possible in one analysis cycle. As a result, one sample can be analyzed with a minimum number of analysis cycles.
Therefore, the total analysis time can be significantly shortened,
Particularly, a great effect can be obtained when the number of analysis items for each sample is small.

[Brief explanation of the drawing]

Figure 1 is a first-class family tree of the multi-channel biochemical analyzer used in implementing the device of the present invention, and Figure 2
Figures 3 and 4 are partially detailed views of this device.
5a, b, c, and d are diagrams for supplementary explanation of the operation of the apparatus, and FIG. 6 is an example diagram of a conventional multichannel biochemical analyzer. 1: Sample dispensing valve, 2: Stator,
3: Rotor, a, b ₁ , b ₂ , c ₁ , c ₂ , d ₁ , d ₂ , e ₁ ,
e ₂ , a′, b′, c′, d′, e′, f′, f, p, r: opening,
A, B ₁ , B ₂ , C ₁ , C 2 , D ₁ , D ₂ , E ₁ , E ₂ , F: conduit, T ₁ , T ₂ : tube, ₄ : pipette drive mechanism,
5: Pipette, 6: Sample container, 7: Waste liquid tank, 8:
Control device, 9: Pump, 10: Flow path switch, s:
Channel, 11: Washing container, 12: Pump control mechanism,
13b-13e: Reagent liquid feeding mechanism, 14b-14
e: Reaction mechanism, 15b to 15e: Flow path switch, 1
6b-16e: Cleaning liquid feeding mechanism, 17b-17
e: Air supply mechanism, 21b to 21e: Valve,
V ₁ b, V ₂ b, ..., V ₈ b, V ₁ c, V ₂ c, ..., V ₈ c,
..., V ₁ e, V ₂ e, ..., V ₆ e, V ₇ e, V ₈ e: Conduit,
24b to 24e, 24b' to 24e': flow path switching device,
25b, 25c, 25e: Pumps for reagent delivery.

Claims (1)

[Scope of Claims] 1. A plurality of channel reaction systems 4b to 14e that simultaneously execute each analysis cycle performed by mixing a sample and a reagent at the same timing, and a number of reagents corresponding to the total number of analysis items. Reagent containers that are containers and are grouped by reaction system u ₁ b ~
Select any reagent from the reagent containers of each group provided for each reaction system, such as u ₈ b, u _{1 c} to u ₈ c, u _{1 d} to u 8 d, and u ₁ e to _{u 8} e. Selection means 13b for sending to each reaction system at the same timing every analysis cycle
~13e, means 1, 4, 5, 6 for sending a sample to each reaction system every analysis cycle, and control for generating and supplying a control signal to each selection means specifying a reagent to be selected for each analysis cycle. A multi-channel chemical analysis device characterized by comprising means 8 and.