WO2006132211A1 - Automatic analyzing instrument - Google Patents

Automatic analyzing instrument Download PDF

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Publication number
WO2006132211A1
WO2006132211A1 PCT/JP2006/311278 JP2006311278W WO2006132211A1 WO 2006132211 A1 WO2006132211 A1 WO 2006132211A1 JP 2006311278 W JP2006311278 W JP 2006311278W WO 2006132211 A1 WO2006132211 A1 WO 2006132211A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample
reagent
liquid
transport path
specimen
Prior art date
Application number
PCT/JP2006/311278
Other languages
French (fr)
Japanese (ja)
Inventor
Isao Yamazaki
Kunio Harada
Sakuichiro Adachi
Hideo Enoki
Original Assignee
Hitachi High-Technologies Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hitachi High-Technologies Corporation filed Critical Hitachi High-Technologies Corporation
Publication of WO2006132211A1 publication Critical patent/WO2006132211A1/en

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • B01F33/302Micromixers the materials to be mixed flowing in the form of droplets
    • B01F33/3021Micromixers the materials to be mixed flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • B01F33/3031Micromixers using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0803Disc shape
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867Multiple inlets and one sample wells, e.g. mixing, dilution
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/089Virtual walls for guiding liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427Electrowetting
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1034Transferring microquantities of liquid

Definitions

  • the present invention relates to an automatic analyzer that performs qualitative 'quantitative analysis of biological components such as blood and urine.
  • the present invention relates to an automatic analyzer that is small in size, can be loaded with more reagents, and has a high throughput per hour.
  • Such an automatic analyzer is desired to be compact and capable of performing more types of analysis and to have a high processing speed, and various types of automatic analyzers have been proposed.
  • a plurality of reaction cells are arranged on the circumference, a rotatable reaction disk is used, samples and reagents are dispensed into individual reaction cells with a probe, and the change in absorbance of the mixed solution is measured with a photometer.
  • the reaction cell needs to contain a reaction solution (sample + reagent) larger than the luminous flux diameter of the photometer, and a certain amount or more of the sample Z reagent is required.
  • a reaction solution sample + reagent
  • it is necessary to increase the number of reaction cells.
  • the reaction cell requires a certain volume, which inevitably increases the size of the apparatus.
  • Non-Patent Document 1 applies a technique for manipulating droplets between flat plates on which electrode arrays called electro-watching are arranged to react a specimen with a reagent and use an LED.
  • An example of detecting the absorbance of reaction droplets in an optical system and analyzing the concentration of four types of items was introduced. ing.
  • the droplet transfer technology by electro-etching has advantages such as high reliability because it can handle a small amount of droplets and no mechanical movement mechanism is possible, and there is a possibility of realizing a small and high-throughput analyzer. There is.
  • Patent Document 1 Japanese Patent Laid-Open No. 4 71184
  • Non-Patent Document 1 a specimen container is not used, so that the specimen cannot be put on standby for re-examination.
  • An object of the present invention is to provide an analyzer that is small in size, has a high processing capacity, and requires a very small amount of sample and reagent for analysis, and has a function capable of automatically performing a retest. In particular.
  • Means for solving the problems of the present invention are as follows.
  • a liquid transport mechanism including at least one pair of plate-like members opposed to each other at a predetermined interval and holding a liquid in a gap, wherein the liquid is transported to at least one of the at least one pair of plate-like members.
  • a plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction in which the sample is transported, and at least a sample transport path for transporting a sample liquid and a reagent are supplied to the sample transport path.
  • a measurement mechanism for optically analyzing the reaction between the sample and the reagent sends the sample to the sample transport path from a position where the reagent distribution mechanism supplies the reagent to the sample transport path.
  • Supply position On the side, Automatic analysis including a buffer electrode array that holds a plurality of samples supplied from the sample distribution mechanism and supplies the samples to the sample transport path at a plurality of positions. apparatus.
  • a liquid transport mechanism comprising at least one pair of plate-like members facing each other at a predetermined interval and holding a liquid in the gap, wherein the liquid is carried to at least one of the at least one pair of plate-like members.
  • a liquid transport mechanism comprising: a reagent transport path for supplying a reagent to the plurality of sample transport paths; and a sample flow path that crosses the sample transport path and is capable of transporting a sample between the plurality of sample transport paths;
  • the Automatic analyzer equipped.
  • Conveying means for conveying a plurality of sample containers; an analysis mechanism for measuring optical or electrical properties by reacting droplets separated into predetermined volumes with a reagent; and aspirating a specimen from the sample containers; Dispensing means to be supplied to the analysis mechanism, calculation means for calculating the concentration of the specific component and necessity of re-examination from the measurement result of the analysis mechanism, and droplet holding for storing the sample for re-inspection as a droplet in the analysis mechanism Automatic analyzer with means.
  • a droplet transport device in which a plurality of electrodes are arranged on at least one surface, the two surfaces whose surfaces are covered with a water-repellent film face each other, and the gap is filled with oil.
  • FIG. 1 is a top view showing a schematic configuration of an analyzer according to a first embodiment.
  • FIG. 2 is a cross-sectional view showing a schematic structure of the analysis substrate of the first embodiment.
  • FIG. 3 is a top view showing the main part of the analysis substrate of the second embodiment.
  • FIG. 4 is a perspective view showing a schematic configuration of an analysis flow path according to a third embodiment.
  • FIG. 5 is a top view showing a schematic configuration of an analysis substrate of a third embodiment.
  • FIG. 6 is a top view showing the main part of the analysis flow path of the third embodiment.
  • FIG. 7 is a cross-sectional view showing a main part of a sample port of a third embodiment.
  • Common electrode 62, 66, 68... Water repellent film, 63 ⁇ Second board, 64 ⁇ Control electrode, 65 ⁇ Insulating film, 67 ⁇ 71 ... Oil, 73 ... Waste fluid, 75 ... Sample fluid, 76 ... Diluent, 80 ... Analysis channel, 81 ... Drain channel, 82 ... Second reagent channel, 83 ⁇ 1st reagent flow path, 85 ⁇ reservoir, 88 ⁇ Relay electrode.
  • FIG. 1 is a top view showing the main part of the first embodiment of the present invention
  • FIG. 2 is a cross-sectional view of the main part for explaining the structure of the first embodiment.
  • the analysis substrate 10 is composed of a first substrate 60 and a second substrate 63 as shown in FIG.
  • a common electrode 61 is formed on the lower surface of the first substrate 60 and is further covered with a water repellent film 62.
  • a plurality of control electrodes 64 are arranged on the upper surface of the second substrate 63, and are covered with an insulating film 65 and a water repellent film 66.
  • the common electrode 61 and the control electrode 64 are connected to the control device 12 by wiring, not shown.
  • the first substrate 60, the common electrode 61, the water repellent film 62, the second substrate 63, the control electrode 64, the insulating film 65, and the water repellent film 66 are all made of a material that transmits light.
  • the end surface of the analysis substrate 10 is sealed with a spacer 67, and there is a gap of 0.5 mm between the first substrate 60 and the second substrate 63. Separated. This gap is filled with oil 71 that does not mix with the aqueous solution, and water-soluble droplets 70 are retained.
  • an injection port 16, a drainage port 48, and a photometer 50 are disposed on the first substrate 60, and a light source 52 is disposed below the second substrate 63 so as to face the photometer 50.
  • the injection port 16 represents the sample port 24, the dilution port 25, the first reagent port 31, and the second reagent port 37, which have the same structure.
  • the injection port 16 has a hole which is covered with a water repellent film and penetrates, and the probe 15 is inserted.
  • the probe 15 is connected to a liquid feed pump (not shown), and the tip force discharges a specific amount of liquid.
  • Below the injection port 16 of the second substrate 63 is an electrode that forms a liquid reservoir 85.
  • the liquid port 48 protrudes upward from the analysis substrate 10 and has a hole therethrough. Furthermore, drainage tube 47 penetrates from the side. There is space inside.
  • the analysis substrate 10 is provided with four reaction electrode arrays 56 composed of control electrodes 64 arranged in a line.
  • Each reaction electrode row 56 includes two stirring electrode rows 55, and the separation electrode row 54 is connected to the stirring electrode row 55 from the first reagent port 31 and the second reagent port 37.
  • photometers 50 are arranged at two locations.
  • One end of the reaction electrode array 56 is connected to the drain port 48 through the electrode array.
  • the other end is connected to the transport electrode array 57, and the transport electrode array 57 is connected to the sample port 24, dilution port 25, drainage port 48, and buffer electrode array 58 through the electrode array.
  • a dilution electrode row 59 is arranged between the sample port 24 and the dilution port 25.
  • the periphery of the analysis substrate 10 is sealed with a spacer 67.
  • the transport electrode row 57 is composed of two electrode rows, and is branched in the middle and connected to the reaction electrode row 56.
  • the buffer electrode array 58 includes three electrode arrays, and the terminal ends are connected to the transport electrode array 57 and the drain port 48. In addition, there is a branch on the way, and it is connected to the transfer electrode array 57 from there.
  • the control device 12 is electrically connected to each electrode of the analysis substrate 10 and further connected to each mechanism of the entire device and the display device 13.
  • the analyte to be analyzed is injected by the probe 15 from the sample port 24.
  • the voltage is applied between the common electrode 61 and the control electrode 64, it spreads over the control electrode 64 due to the electroetching force. Power works.
  • a voltage is applied to the electrode of the liquid reservoir 85, and the discharged specimen liquid is filled with oil sandwiched between the water-repellent films 62 and 66 on the liquid reservoir 85 as a droplet. Get into the area.
  • the probe 15 that has ejected the specimen is pulled out from the sample port 24 and washed, and another specimen is dispensed.
  • the droplet is stretched by applying a voltage to the two electrodes connected from the liquid reservoir 85, and then removing the voltage applied to the electrode between them. It is divided into small droplets. The divided droplets are transported by moving the electrodes to which the voltage is applied one by one. The droplets separated from the specimen are conveyed to the dilution electrode array 59. The liquid droplet remaining in the liquid reservoir 85 is conveyed to the drainage port 48.
  • the dilution liquid is inserted from the dilution port 25, and is also divided into a predetermined amount of droplets by the sorting electrode array 54 and conveyed to the dilution electrode array 59.
  • the specimen droplet and the diluent are mixed and rotated on the annular electrode array to be stirred to form uniform diluted specimen droplets.
  • two stages of mixing and stirring can be performed to prepare diluted specimens with different concentrations.
  • the diluted analyte droplets are divided into smaller droplets.
  • the divided droplets of the diluted specimen are transported to the selected reaction electrode array 56 via the transport electrode array 57 by the number of items required for the sample, and at the same time, a predetermined number of droplet forces S It is conveyed to the buffer electrode array 58.
  • a reagent corresponding to the item to be analyzed is injected from the first reagent port 31 and the second reagent port 37.
  • the reagent droplets injected from the first reagent port 31 are stored in the liquid reservoir 85 and then divided into a predetermined amount of droplets in the sorting electrode array 54.
  • the divided reagent droplets are mixed with the diluted specimen droplets transported from the transport electrode array 57 and rotated on the electrodes of the stirring electrode array 55 to be stirred.
  • the stirred liquid mixture moves on the reaction electrode array 56 by one electrode at regular intervals.
  • the photometer 50 detects the amount of light irradiated from the light source 52 that has passed through the droplet, and transmits the result to the controller 12.
  • the reagent droplets injected from the second reagent port 37 are also divided into a certain amount of droplets by the sorting electrode array 54, and then the liquid droplets of the mixed liquid conveyed on the reaction electrode array 56 Coupled to the stirring electrode array Stir at 55.
  • the mixed droplet mixed with the second reagent is also moved one by one on the reaction electrode array 56 and optical detection is performed when the position reaches the position of the photometer 50, and the result is sent to the control device 12.
  • the mixed droplet is conveyed to the drainage port 48.
  • the liquid droplets that have reached the drainage port 48 float due to the difference in specific gravity with the oil 71 and are sucked into the drainage tube 47 as a waste liquid 73 and discharged.
  • the diluted specimen droplets conveyed to the buffer electrode array 58 are moved one electrode at a time interval.
  • the next droplet is transported with an interval of two electrodes.
  • the control device 12 receives the signal from the photometer 50, calculates the concentration of the specific component and transmits it to the display device 13, and at the same time determines from the calculation result whether reexamination is necessary. Retesting is necessary, for example, when the concentration obtained exceeds the range where a suitable analysis can be performed. In such a case, retesting with a high sample dilution rate is required.
  • the diluted specimen liquid droplet transported through the buffer electrode array 58 is transported to the reaction electrode array 56 via the transport electrode array 57, and the analysis is performed again.
  • Diluted droplets of the sample that are determined to need re-examination pass through the buffer electrode array 58 and are then transported to the drain port 48 and discharged.
  • the specimen that may be retested does not react! Because it forms a droplet wrapped in oil and waits, the waiting specimen is isolated from the ambient air. Therefore, it is possible to carry out high-accuracy re-examination that is not affected by reaction with oxygen or carbon dioxide in the air or alteration due to evaporation.
  • the present embodiment since a plurality of the row of nother electrodes 58 are arranged, a large number of liquid droplets can be made to stand by in a narrow space, and the small size of the apparatus can be reduced. Is possible.
  • an electrode array for taking out droplets is also provided in the middle of the nother electrode array 58, so that the specimen for which reexamination is required is behind the other standby droplets. Even in this case, the re-inspection can be performed first, and an analyzer that can output the results quickly can be realized.
  • a diluted sample having a different concentration can be prepared. Therefore, a diluted sample having a concentration different from that of the initial analysis can be kept waiting for retesting, and a diluted sample having a suitable concentration can be prepared. Since the specimen can be re-examined, high-precision analysis is possible.
  • concentration analysis of a plurality of items can be performed for each sample, but the number of standby droplets for reexamination can be made smaller than the number of analysis items.
  • the required capacity of the buffer electrode array 58 can be reduced, and a small device can be provided.
  • FIG. 3 is a top view showing a portion of the buffer electrode array of the second embodiment of the present invention.
  • the main difference from the first embodiment is that the liquid reservoir 85 is installed at a location different from the sample port 24, and the liquid reservoir 85 'is also included in the kaffa electrode array.
  • the specimen droplet injected from the sample port 24 is transported to both the liquid reservoir 85 connected to the transport electrode array 57 and the selected liquid reservoir 85 in the buffer electrode array 58.
  • the liquid reservoir 85 connected to the transport electrode array 57 droplets are divided by a certain amount and transported to the transport electrode array 57 for analysis.
  • the sample transported to the liquid reservoir 85 in the buffer electrode array 58 waits until the necessity of retesting of the sample is confirmed. If retesting is necessary, the droplet is divided and transported to the transport electrode array 57. And re-inspect. The remaining specimen droplet is transported to the drain port 48 and discharged.
  • a plurality of waiting areas are prepared in the buffer electrode array 58, so that a plurality of samples can be kept waiting.
  • FIG. 4 to 7 are explanatory views of a third embodiment of the present invention.
  • 4 is a perspective view showing the outline of the whole
  • FIG. 5 is a top view showing a schematic configuration of the analysis substrate
  • FIG. 6 is a top view showing the main part of the analysis flow path
  • FIG. 7 is a cross-sectional view showing the main part of the sample port. It is.
  • a reagent disc 41, a first reagent probe 30, a second reagent probe 35, a sample disc 20, a sample probe 22, a control device 12, and a display device 13 are arranged around the ring-shaped analysis substrate 10.
  • a photometer 50 supported by a moving mechanism 51 is disposed inside the analysis substrate 10.
  • a plurality of reagent containers 40 are mounted on the reagent disk 41.
  • a plurality of sample containers 21 are mounted on the sample disk 20.
  • the first reagent probe 30, the second reagent probe 35, and the sample probe 22 can independently move up and down and rotate. Each probe is connected to a syringe pump (not shown).
  • the first reagent port 31, the second reagent port 37, the sample port 24, and the washing port 26 are arranged on the probe path.
  • Dilution port 25 is installed adjacent to sample port 24.
  • the analysis substrate 10 is provided with four drainage ports 48 to which a drainage tube 47 is connected.
  • the photometer 50 includes a light source that emits light in a wide wavelength range, a diffraction grating, and a detector that detects light of a plurality of wavelengths.
  • a plurality of analysis flow paths 80 extending in the radial direction are arranged in a circle.
  • a drainage flow path 81, a second reagent flow path 82, a sample flow path 83, and a first reagent flow path 84 are arranged in the circumferential direction so as to intersect the analysis flow path 80.
  • a sample port 24, a dilution port 25, a first reagent port 31, a second reagent port 37, and a plurality of drainage ports 48 are arranged outside the first reagent channel 84.
  • each solid square frame represents a control electrode 64.
  • the analysis channel 80 is composed of 23 electrodes arranged in a radial direction from al to al23.
  • each electrode is a square having a side of about 2.8 mm.
  • Electrodes al, a3, a5, and al 2 have a relay electrode 88 disposed between the adjacent analysis flow paths, and the first reagent flow path 84, sample flow path 83, and second reagent that are transport flow paths in the circumferential direction.
  • a flow path 82 and a drainage flow path 81 are formed.
  • the electrodes al8, al9, and a20 are photometric areas.
  • the structure of the dilution port will be described with reference to FIG.
  • the dilution port 25 installed in the vicinity of the sample port 24 protrudes upward from the analysis substrate 10 like the sample port 24, and the diluent probe 23 is inserted.
  • the diluent probe 23 is connected to a diluent pump (not shown), and the amount can be controlled to discharge the diluent.
  • reagent disk 41 On the reagent disk 41, two types of reagents, a first reagent and a second reagent, are placed in the reagent container 40 and mounted corresponding to each analysis item.
  • the dispensing of the reagent of a certain item to the analysis substrate 10 is performed as follows. Rotate 41 so that the reagent container 40 containing the first reagent of the item is at the suction position of the first reagent probe 30, and aspirate 80 ⁇ l of the first reagent with the first reagent probe 30.
  • the first reagent probe 30 is raised and rotated and inserted into the first reagent port 31. After insertion, the reagent is dispensed in 8 microliter portions in 10 doses.
  • a voltage is sequentially applied to the control electrode 64 in conjunction with the reagent discharge, and the discharged reagent is transported to the first reagent channel 84 as a droplet and circulates on the first reagent channel 84.
  • the same operation as in the case of the first reagent is performed, and 40 microliters of the second reagent is aspirated from the reagent container 40 by the second reagent probe 35 and 4 microliters from the second reagent port 37.
  • Each torr is discharged in 10 times, moves as a droplet to the second reagent channel 82, and circulates on the second reagent channel 82.
  • the first reagent probe 30 and the second reagent probe 35 move to the cleaning port 26, and the inner surface and outer surface of the probe are cleaned with cleaning water.
  • Dispensing is continued for the first reagent and second reagent of the item to be analyzed, and each reagent circulates on the first reagent channel 84 and the second reagent channel 82 as droplets.
  • sample disk 20 On the sample disk 20, a sample of known concentration for calibration and accuracy control and a sample to be analyzed are placed in a sample container 21 and mounted.
  • the sample is dispensed onto the analysis substrate 10 as follows.
  • the sample disk 20 rotates so that the sample container 21 containing the target specimen is positioned at the suction position of the sample probe 22, and the sample probe 22 sucks the specimen from the sample container 21.
  • the amount of aspiration is greater than that required for testing and retesting all items analyzed on the specimen.
  • Sample probe 2 2 rises, rotates and is inserted into the sample port 24. After insertion, the aspirated specimen is discharged. At this time, the diluted solution is discharged from the dilution port 25, and the sample solution 75 is rubbed so as to be discharged into the diluted solution 76.
  • the amount of diluted solution and sample solution to be discharged is adjusted according to the type of analysis to be performed.
  • the sample probe 22 moves to the cleaning port 26 after dispensing, and the inner surface and outer surface of the probe are cleaned with cleaning water.
  • the control device 12 selects an analysis flow path 80 for performing analysis of a certain item of a certain sample.
  • the diluted specimen and reagent droplets circulating around the selected analysis channel 80 move. First, the diluted specimen droplets are held in alO, and the first reagent droplets are held in a7 and a8. Next, the specimen droplet is transported to a20 by sequentially moving the applied electrode from alO. Subsequently, the first reagent droplet is transported to al8 and al9 by sequentially moving the application electrodes a7 and a8. Here, the droplet of the specimen and the first reagent are combined to form the first reaction solution, which is held on the three electrodes al8, al9, and a20.
  • the droplet reciprocates, and the specimen and the first reagent in the first reaction liquid droplet are agitated and evenly mixed. Become.
  • the applied electrode is then fixed to al8, al9, a20, and the droplet is held for 5 minutes during the first reaction time.
  • the photometer 50 is rotated by the moving mechanism 51 at a speed of one rotation in 30 seconds.
  • light is applied to the droplets on al8, al9, and a20, and the amount of transmitted light of the selected wavelength is measured and transmitted to the controller 12.
  • the controller 12 calculates the absorbance. Periodic measurements are taken during the first reaction time.
  • a second reagent is prepared during the first reaction time. Reagent droplet force circulating around the second reagent channel 82 is transported to the electrode al4 of the selected analysis channel 80.
  • the second reagent droplet is transferred to al8 by sequentially moving the applied electrode from al4.
  • the second reagent is combined with the first reaction solution to form the second reaction solution.
  • the droplet reciprocates, and the second reaction liquid is stirred and becomes uniform.
  • the applied electrode is then fixed to al8, al9, a20, a21, and the droplet is held for 5 minutes during the second reaction time.
  • the photometer Periodic measurements are made.
  • the droplets of the second reaction liquid pass through the drainage flow path 81 and are conveyed to the drainage port 48.
  • the droplet 70 of the second reaction liquid enters the drainage port 48 due to the surface force with the water repellent films 62 and 69 and rises due to the difference in specific gravity with the oil 71.
  • the floated waste liquid 73 is sucked into the drainage tube 47 and discharged.
  • the analysis proceeds in parallel in a plurality of analysis flow paths 80. Also, during the second reaction time, the specimen and the first reagent droplet for the next analysis wait on the electrodes alO, a7, and a8, and immediately after the analysis is completed and the second reaction solution is discharged. The next analysis begins.
  • the control device 12 derives the relationship between the change in absorbance and the concentration obtained in the analysis of the sample for calibration for each analysis item, and stores the relationship as calibration data.
  • the sample is analyzed, and if the result does not fall within the predetermined range, an abnormal alarm is transmitted to the display device 13.
  • the concentration of the analysis item is calculated using the calibration data and transmitted to the display device 13 for display.
  • re-examination is executed. Re-examination is performed with the droplet of the diluted specimen circulating around the sample channel 83. Diluted specimens to be retested may be selected at different dilutions than in the initial analysis.
  • the specimen droplet transport channel also serves as a specimen droplet standby area, it is possible to achieve a reduction in the size of the apparatus without the need to provide a special standby area.

Abstract

A small analyzing instrument exhibiting high processing capacity, requiring extremely small quantities of sample and reagent, and having a function capable of performing reexamination automatically. The automatic analyzing instrument comprises a liquid transport mechanism having a plurality of liquid transport passages provided with a plurality of electrodes arranged at a predetermined intervals along the direction in which the liquid is transported and composed of a sample transport passage (83) for transporting a sample liquid and passages (82, 84) for supplying a reagent to the sample transport passage (83), a specimen distribution mechanism for supplying a specimen to the sample transport passage, a reagent distributing mechanism for supplying a reagent to the reagent transport passages, and a measurement mechanism for analyzing the reaction of the specimen and the reagent optically in the liquid transport passage. At a position far from the position where the reagent distribution mechanism supplies the reagent and near to the position where the specimen distribution mechanism supplies the specimen to the sample transport passage, a buffer electrode array (58) holding a plurality of specimens and having a transport passage for supplying the held specimens to the sample transport passage at a plurality of positions is provided.

Description

明 細 書  Specification
自動分析装置  Automatic analyzer
技術分野  Technical field
[0001] 本発明は血液、尿等の生体成分の定性'定量分析を実行する自動分析装置に係り The present invention relates to an automatic analyzer that performs qualitative 'quantitative analysis of biological components such as blood and urine.
、特に小型で、より多くの試薬を搭載でき、かつ時間あたりの処理能力の高い自動分 析装置に関する。 In particular, the present invention relates to an automatic analyzer that is small in size, can be loaded with more reagents, and has a high throughput per hour.
背景技術  Background art
[0002] 血液等の生体試料を自動的に分析し、結果を出力する自動分析装置は、患者数 の多い大病院、中小病院、医院力 検査を請け負い検査を行う検査センターなどに ぉ 、て効率良く分析を行うのになくてはならな 、装置になって 、る。  [0002] Automatic analyzers that automatically analyze biological samples such as blood and output the results are highly efficient for large hospitals, small and medium hospitals with a large number of patients, and inspection centers that undertake clinic power tests. It is necessary to perform analysis well, and it becomes a device.
[0003] そのような自動分析装置は、コンパクトでより多種類の分析ができ、かつ処理速度 の高いものが望まれており、従来種々のものが提案されている。例えば特許文献 1に は複数の反応セルを円周上に配置し、回転可能な反応ディスクを用い、個々の反応 セルに検体、試薬をプローブで分注し、混合液の吸光度の変化を光度計で検出して 検体の特定成分の濃度を分析する装置が開示されている。  [0003] Such an automatic analyzer is desired to be compact and capable of performing more types of analysis and to have a high processing speed, and various types of automatic analyzers have been proposed. For example, in Patent Document 1, a plurality of reaction cells are arranged on the circumference, a rotatable reaction disk is used, samples and reagents are dispensed into individual reaction cells with a probe, and the change in absorbance of the mixed solution is measured with a photometer. Discloses an apparatus for detecting the concentration of a specific component of a specimen.
[0004] この方法では、全ての反応セルが反応ディスクの回転により光度計を通過して測光 されるので、必要な光度計は 1つのみであり、全てのセルに対して同一の条件でばら つきの小さい分析が可能である。また、検体、試薬の分注はどの反応セルに対しても 可能なので、必要な分析が自由な順番で実施することができ、処理能力の高い分析 が可能である。  [0004] In this method, all the reaction cells are measured by passing through the photometer by the rotation of the reaction disk. Therefore, only one photometer is required, and all the cells vary under the same conditions. A small analysis is possible. In addition, specimens and reagents can be dispensed into any reaction cell, so the necessary analyzes can be performed in any order and analysis with high throughput is possible.
[0005] しかし、この方法では、反応セルに光度計の光束径以上の反応液 (検体 +試薬)が 入っている必要があり、一定量以上の検体 Z試薬が必要である。また、処理速度を 大きくするためには反応セルの数を多くする必要がある力 一方で反応セルには一 定容積が必要であり、必然的に装置が大型化してしまうという問題があった。  However, in this method, the reaction cell needs to contain a reaction solution (sample + reagent) larger than the luminous flux diameter of the photometer, and a certain amount or more of the sample Z reagent is required. In addition, in order to increase the processing speed, it is necessary to increase the number of reaction cells. On the other hand, there is a problem in that the reaction cell requires a certain volume, which inevitably increases the size of the apparatus.
[0006] これに対して非特許文献 1には、エレクトロウヱツチングと称する電極列の配置され た平板間に液滴を操作する技術を応用して、検体と試薬を反応させ LEDを用いた光 学系で反応液滴の吸光度を検出して 4種類の項目の濃度を分析した例が紹介され ている。エレクトロウエッチングによる液滴搬送技術は、小さな量の液滴を扱える、機 械的に動く機構が不要なので信頼性が高いなどの利点があり、小型で高処理能力の 分析装置を実現できる可能性がある。 [0006] On the other hand, Non-Patent Document 1 applies a technique for manipulating droplets between flat plates on which electrode arrays called electro-watching are arranged to react a specimen with a reagent and use an LED. An example of detecting the absorbance of reaction droplets in an optical system and analyzing the concentration of four types of items was introduced. ing. The droplet transfer technology by electro-etching has advantages such as high reliability because it can handle a small amount of droplets and no mechanical movement mechanism is possible, and there is a possibility of realizing a small and high-throughput analyzer. There is.
[0007] 特許文献 1 :特開平 4 71184号公報  [0007] Patent Document 1: Japanese Patent Laid-Open No. 4 71184
特干文献 1: Clinical diagnostics on human whole blooa、 plasma、 serum、 urine ^ sail va、 sweat、 and tears on a digital microfluidic platform μ TAS2003  Special Reference 1: Clinical diagnostics on human whole blooa, plasma, serum, urine ^ sail va, sweat, and tears on a digital microfluidic platform μ TAS2003
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0008] 臨床検査のための自動分析装置では、サンプルの濃度が適切でな力つた等の原 因で、 1回の検査で分析結果が得られな力つた場合、同じサンプルを再度分析する 必要がある。自動分析装置にはこのような再検査が必要な検体が入った検体容器を 自動的に分析装置に戻し、同じ検査項目を実行できるものが知られて ヽる。  [0008] In an automated analyzer for clinical tests, if the analysis results are not obtained in a single test due to the appropriate concentration of the sample, it is necessary to analyze the same sample again There is. It is known that automatic analyzers can automatically return specimen containers containing such specimens that need to be retested to the analyzer and perform the same test items.
[0009] しかし、非特許文献 1に記載の方法では、検体容器を用いな 、ため、再検のため検 体を待機させることができな 、。  However, in the method described in Non-Patent Document 1, a specimen container is not used, so that the specimen cannot be put on standby for re-examination.
[0010] 本発明の目的は、小型、高処理能力でかつ分析に要する試料、試薬が微量です む分析装置であって、再検査が自動で実施可能な機能を備えた分析装置を提供す ることにめる。  [0010] An object of the present invention is to provide an analyzer that is small in size, has a high processing capacity, and requires a very small amount of sample and reagent for analysis, and has a function capable of automatically performing a retest. In particular.
課題を解決するための手段  Means for solving the problem
[0011] 本発明の課題解決手段は次の通りである。  [0011] Means for solving the problems of the present invention are as follows.
[0012] 所定間隔で対向させ、間隙に液体を保持する少なくとも 1対の板状部材を備えた液 体搬送機構であって、前記少なくとも 1対の板状部材の少なくとも一方に、液体を搬 送する方向に沿って複数の電極を所定間隔で配置した液体搬送路を複数備え、か っ該液体搬送路には、少なくともサンプル液体を搬送するサンプル搬送路と、該サン プル搬送路に試薬を供給する試薬搬送路と、を備えた液体搬送機構と、前記サンプ ル搬送路に検体を供給する検体分配機構と、前記試薬搬送路に試薬を供給する試 薬分配機構と、前記液体搬送路中での検体と試薬の反応を光学的に分析する測定 機構と、を備え、更に、前記試薬分配機構が前記サンプル搬送路に試薬を供給する 位置より、前記検体分配機構が前記サンプル搬送路に検体を供給する位置の側に、 前記検体分配機構から供給された複数の検体を保持し、かつ保持して!/、る検体を前 記サンプル搬送路に複数の位置で供給する搬送路を備えたバッファ電極列を備え た自動分析装置。 [0012] A liquid transport mechanism including at least one pair of plate-like members opposed to each other at a predetermined interval and holding a liquid in a gap, wherein the liquid is transported to at least one of the at least one pair of plate-like members. A plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction in which the sample is transported, and at least a sample transport path for transporting a sample liquid and a reagent are supplied to the sample transport path. A reagent transport path, a sample distribution mechanism that supplies a sample to the sample transport path, a reagent distribution mechanism that supplies a reagent to the reagent transport path, and a liquid transport mechanism in the liquid transport path. A measurement mechanism for optically analyzing the reaction between the sample and the reagent, and further, the sample distribution mechanism sends the sample to the sample transport path from a position where the reagent distribution mechanism supplies the reagent to the sample transport path. Supply position On the side, Automatic analysis including a buffer electrode array that holds a plurality of samples supplied from the sample distribution mechanism and supplies the samples to the sample transport path at a plurality of positions. apparatus.
[0013] また、以下のような構成であっても良い。  [0013] The following configuration may also be used.
[0014] 所定間隔で対向させ、間隙に液体を保持する少なくとも 1対の板状部材を備えた液 体搬送機構であって、前記少なくとも 1対の板状部材の少なくとも一方に、液体を搬 送する方向に沿って複数の電極を所定間隔で配置した液体搬送路を複数備え、か っ該液体搬送路には、少なくとも放射状にサンプル液体を搬送するサンプル搬送路 と、該サンプル搬送路を横断し、複数の前記サンプル搬送路に試薬を供給する試薬 搬送路と、該サンプル搬送路を横断し、複数の前記サンプル搬送路間にサンプルを 搬送可能なサンプル流路と、を備えた液体搬送機構と、前記サンプル搬送路に検体 を供給する検体分配機構と、前記試薬搬送路に試薬を供給する試薬分配機構と、 前記液体搬送路中での検体と試薬の反応を光学的に分析する測定機構と、を備え た自動分析装置。  [0014] A liquid transport mechanism comprising at least one pair of plate-like members facing each other at a predetermined interval and holding a liquid in the gap, wherein the liquid is carried to at least one of the at least one pair of plate-like members. A plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction in which the sample transport path is provided, and the liquid transport path includes at least a sample transport path for transporting the sample liquid in a radial manner and a crossing the sample transport path. A liquid transport mechanism comprising: a reagent transport path for supplying a reagent to the plurality of sample transport paths; and a sample flow path that crosses the sample transport path and is capable of transporting a sample between the plurality of sample transport paths; A sample distribution mechanism for supplying a sample to the sample conveyance path, a reagent distribution mechanism for supplying a reagent to the reagent conveyance path, and a measurement mechanism for optically analyzing the reaction between the sample and the reagent in the liquid conveyance path; The Automatic analyzer equipped.
[0015] 上記構成を機能的な面力も表現すると以下のようになる。  [0015] The above configuration can also be expressed in terms of functional surface power as follows.
[0016] 複数のサンプル容器を搬送する搬送手段と、所定の体積に分離された液滴を試薬 と反応させて光学的あるいは電気的性質を測定する分析機構と、サンプル容器から 検体を吸引し、分析機構に供給する分注手段と、分析機構の測定結果より特定成分 の濃度および再検査の要否を演算する演算手段と、分析機構内に液滴として再検 查用の検体を蓄える液滴保留手段を備えた自動分析装置。  [0016] Conveying means for conveying a plurality of sample containers; an analysis mechanism for measuring optical or electrical properties by reacting droplets separated into predetermined volumes with a reagent; and aspirating a specimen from the sample containers; Dispensing means to be supplied to the analysis mechanism, calculation means for calculating the concentration of the specific component and necessity of re-examination from the measurement result of the analysis mechanism, and droplet holding for storing the sample for re-inspection as a droplet in the analysis mechanism Automatic analyzer with means.
[0017] サンプル搬送路の構成の詳細は以下の通りである。少なくとも一方の面に複数の 電極が配置され、表面が撥水性の膜で覆われた 2つの面を対向させ、隙間をオイル で満たされた液滴搬送デバイス。  The details of the configuration of the sample transport path are as follows. A droplet transport device in which a plurality of electrodes are arranged on at least one surface, the two surfaces whose surfaces are covered with a water-repellent film face each other, and the gap is filled with oil.
発明の効果  The invention's effect
[0018] 以上に示したように、本発明においては、検体の液滴を反応しないオイルに包まれ た液滴を形成して待機させるので、再検査を待つ間に検体が変質することがなぐ精 度の高 、分析が可能な自動分析装置を提供することが可能である。  [0018] As described above, according to the present invention, since the droplet of the specimen is formed and waited for the liquid that is not reacted, the specimen is not deteriorated while waiting for the retest. It is possible to provide an automatic analyzer capable of analyzing with high accuracy.
図面の簡単な説明 [0019] [図 1]第 1実施例の分析装置の概略の構成を示す上面図。 Brief Description of Drawings FIG. 1 is a top view showing a schematic configuration of an analyzer according to a first embodiment.
[図 2]第 1実施例の分析基板の概略構造を示す断面図。  FIG. 2 is a cross-sectional view showing a schematic structure of the analysis substrate of the first embodiment.
[図 3]第 2実施例の分析基板の要部を示す上面図。  FIG. 3 is a top view showing the main part of the analysis substrate of the second embodiment.
[図 4]第 3実施例の分析流路の概略の構成を示す斜視図。  FIG. 4 is a perspective view showing a schematic configuration of an analysis flow path according to a third embodiment.
[図 5]第 3実施例の分析基板の概略構成を示す上面図。  FIG. 5 is a top view showing a schematic configuration of an analysis substrate of a third embodiment.
[図 6]第 3実施例の分析流路の要部を示す上面図。  FIG. 6 is a top view showing the main part of the analysis flow path of the third embodiment.
[図 7]第 3実施例のサンプルポートの要部を示す断面図。  FIG. 7 is a cross-sectional view showing a main part of a sample port of a third embodiment.
符号の説明  Explanation of symbols
[0020] 10···分析基板、 12···制御装置、 13···表示装置、 15···プローブ、 16···注入ポート 、 24···サンプルポート、 25…希釈ポート、 31···第 1試薬ポート、 37···第 2試薬ポート 、 47···排液チューブ、 48···排液ポート、 50· "光度計、 52···光源、 54···分取電極列 、 55···攪拌電極列、 56···反応電極列、 57···搬送電極列、 58···バッファ電極列、 59 …希釈電極列、 60…第 1基板、 61…共通電極、 62、 66、 68…撥水膜、 63···第 2基 板、 64···制御電極、 65···絶縁膜、 67···スぺーサ、 70···液滴、 71…オイル、 73···廃 液、 75…検体液、 76…希釈液、 80···分析流路、 81···排液流路、 82···第 2試薬流 路、 83···サンプル流路、 84···第 1試薬流路、 85···液溜め、 88···中継電極。  [0020] 10 ... Analytical substrate, 12 ... Control device, 13 ... Display device, 15 ... Probe, 16 ... Injection port, 24 ... Sample port, 25 ... Dilution port, 31 ··· 1st reagent port, 37 ··· 2nd reagent port, 47 · · · drain tube, 48 · · · drain port, 50 · "photometer, 52 · · · light source, 54 · · · min Picking electrode row, 55 ··· Stirring electrode row, 56 ··· Reaction electrode row, 57 ··· Transport electrode row, 58 ··· Buffer electrode row, 59 ... Dilution electrode row, 60 ... First substrate, 61 ... Common electrode, 62, 66, 68… Water repellent film, 63 ··· Second board, 64 ··· Control electrode, 65 ··· Insulating film, 67 ················ 71 ... Oil, 73 ... Waste fluid, 75 ... Sample fluid, 76 ... Diluent, 80 ... Analysis channel, 81 ... Drain channel, 82 ... Second reagent channel, 83 ··································································· 1st reagent flow path, 85 ··· reservoir, 88 ··· Relay electrode.
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0021] 以下、図面を用いて本発明の実施の形態を説明する。  Hereinafter, embodiments of the present invention will be described with reference to the drawings.
[0022] (実施例 1)  [0022] (Example 1)
図 1は本発明の第 1実施例の主要部分を示す上面図であり、図 2は第 1実施例の構 造を説明するための主要部分の断面図である。  FIG. 1 is a top view showing the main part of the first embodiment of the present invention, and FIG. 2 is a cross-sectional view of the main part for explaining the structure of the first embodiment.
[0023] 分析基板 10は図 2に示すように第 1基板 60、第 2基板 63で構成されている。第 1基 板 60の下面には、共通電極 61が構成され、さらに撥水膜 62で覆われている。第 2基 板 63の上面には複数の制御電極 64が配置され、その上を絶縁膜 65、撥水膜 66で 覆われて 、る。共通電極 61および制御電極 64は図示しな 、配線で制御装置 12に 接続している。第 1基板 60、共通電極 61、撥水膜 62、第 2基板 63、制御電極 64、絶 縁膜 65、撥水膜 66は全て光を透過する材料でできている。分析基板 10の端面はス ぺーサ 67で封止されており、第 1基板 60と第 2基板 63の間は 0.5mmの隙間をもつ て隔てられている。この隙間には、水溶液と混じり合わないオイル 71が満たされ、水 溶性の液滴 70が保持される。 The analysis substrate 10 is composed of a first substrate 60 and a second substrate 63 as shown in FIG. A common electrode 61 is formed on the lower surface of the first substrate 60 and is further covered with a water repellent film 62. A plurality of control electrodes 64 are arranged on the upper surface of the second substrate 63, and are covered with an insulating film 65 and a water repellent film 66. The common electrode 61 and the control electrode 64 are connected to the control device 12 by wiring, not shown. The first substrate 60, the common electrode 61, the water repellent film 62, the second substrate 63, the control electrode 64, the insulating film 65, and the water repellent film 66 are all made of a material that transmits light. The end surface of the analysis substrate 10 is sealed with a spacer 67, and there is a gap of 0.5 mm between the first substrate 60 and the second substrate 63. Separated. This gap is filled with oil 71 that does not mix with the aqueous solution, and water-soluble droplets 70 are retained.
[0024] また、第 1基板 60には注入ポート 16、排液ポート 48、光度計 50が配置され、第 2基 板 63の下には光度計 50に対向して光源 52が配置されている。  In addition, an injection port 16, a drainage port 48, and a photometer 50 are disposed on the first substrate 60, and a light source 52 is disposed below the second substrate 63 so as to face the photometer 50. .
[0025] 注入ポート 16はサンプルポート 24、希釈ポート 25、第 1試薬ポート 31、第 2試薬ポ ート 37を代表するものであり、それらは同様の構造をしている。注入ポート 16には内 面が撥水膜で覆われて貫通した穴があり、プローブ 15が挿入される。プローブ 15は 図示しない送液ポンプに接続し、先端力も特定量の液を吐出する。第 2基板 63の注 入ポート 16の下の部分には液溜め 85を形成する電極がある。  [0025] The injection port 16 represents the sample port 24, the dilution port 25, the first reagent port 31, and the second reagent port 37, which have the same structure. The injection port 16 has a hole which is covered with a water repellent film and penetrates, and the probe 15 is inserted. The probe 15 is connected to a liquid feed pump (not shown), and the tip force discharges a specific amount of liquid. Below the injection port 16 of the second substrate 63 is an electrode that forms a liquid reservoir 85.
[0026] 液ポート 48は分析基板 10から上に突き出て、穴が貫通している。更に側面から 排液チューブ 47が貫入している。内部には空間がある。  [0026] The liquid port 48 protrudes upward from the analysis substrate 10 and has a hole therethrough. Furthermore, drainage tube 47 penetrates from the side. There is space inside.
[0027] 図 1に示すように分析基板 10には、 1列に並んだ制御電極 64で構成される反応電 極列 56が 4本配置されて ヽる。それぞれの反応電極列 56には 2箇所の攪拌電極列 55が含まれ、攪拌電極列 55には第 1試薬ポート 31および第 2試薬ポート 37から分 取電極列 54が接続している。また、 2箇所に光度計 50が配置されている。反応電極 列 56の一方の端は排液ポート 48まで電極列で接続されて 、る。他方の端は搬送電 極列 57に接続され、搬送電極列 57にはサンプルポート 24、希釈ポート 25、排液ポ ート 48、バッファ電極列 58と電極列で接続している。サンプルポート 24と希釈ポート 25の間には希釈電極列 59が配置されている。分析基板 10の周囲はスぺーサ 67で 封止されている。  As shown in FIG. 1, the analysis substrate 10 is provided with four reaction electrode arrays 56 composed of control electrodes 64 arranged in a line. Each reaction electrode row 56 includes two stirring electrode rows 55, and the separation electrode row 54 is connected to the stirring electrode row 55 from the first reagent port 31 and the second reagent port 37. In addition, photometers 50 are arranged at two locations. One end of the reaction electrode array 56 is connected to the drain port 48 through the electrode array. The other end is connected to the transport electrode array 57, and the transport electrode array 57 is connected to the sample port 24, dilution port 25, drainage port 48, and buffer electrode array 58 through the electrode array. A dilution electrode row 59 is arranged between the sample port 24 and the dilution port 25. The periphery of the analysis substrate 10 is sealed with a spacer 67.
[0028] 搬送電極列 57は 2本の電極列で構成され、途中で分岐して反応電極列 56に接続 している。バッファ電極列 58は 3本の電極列で構成され、終端が搬送電極列 57およ び排液ポート 48に接続している。また途中に分岐があり、そこからも搬送電極列 57に 接続している。  The transport electrode row 57 is composed of two electrode rows, and is branched in the middle and connected to the reaction electrode row 56. The buffer electrode array 58 includes three electrode arrays, and the terminal ends are connected to the transport electrode array 57 and the drain port 48. In addition, there is a branch on the way, and it is connected to the transfer electrode array 57 from there.
[0029] 制御装置 12は電気的に分析基板 10の各電極と接続し、更に装置全体の各機構 および表示装置 13に接続して 、る。  The control device 12 is electrically connected to each electrode of the analysis substrate 10 and further connected to each mechanism of the entire device and the display device 13.
[0030] 次に、第 1実施例の動作を説明する。 [0030] Next, the operation of the first embodiment will be described.
[0031] 分析される検体は、サンプルポート 24からプローブ 15によって注入される。液滴に は、撥水膜 62、 66およびオイルにより排斥される力が働くが、共通電極 61と制御電 極 64の間に電圧が印加されているときはエレクトロウエッチング力により制御電極 64 の上に広がる力が働く。液滴注入時は液溜め 85の電極に電圧が印加されており、吐 出された検体液は液滴として液溜め 85の上の撥水膜 62、 66に挟まれたオイルの満 たされた領域に入り込む。検体を吐出したプローブ 15は、サンプルポート 24から引き 抜かれて洗浄され、別の検体の分注を行う。 The analyte to be analyzed is injected by the probe 15 from the sample port 24. Into droplets However, when the voltage is applied between the common electrode 61 and the control electrode 64, it spreads over the control electrode 64 due to the electroetching force. Power works. When the droplet is injected, a voltage is applied to the electrode of the liquid reservoir 85, and the discharged specimen liquid is filled with oil sandwiched between the water-repellent films 62 and 66 on the liquid reservoir 85 as a droplet. Get into the area. The probe 15 that has ejected the specimen is pulled out from the sample port 24 and washed, and another specimen is dispensed.
[0032] 液滴は、液溜め 85から連なる 2つの電極に電圧を印加して引き伸ばしてから、間の 電極の電圧印加を削除することによって、電極 1つのサイズで決定される一定量の小 さな液滴に分割される。分割された液滴は、電圧を印加する電極を 1つずつ移動す ることにより、搬送される。検体から分割された液滴は希釈電極列 59に搬送される。 液溜め 85に残った液滴は、排液ポート 48に搬送される。  [0032] The droplet is stretched by applying a voltage to the two electrodes connected from the liquid reservoir 85, and then removing the voltage applied to the electrode between them. It is divided into small droplets. The divided droplets are transported by moving the electrodes to which the voltage is applied one by one. The droplets separated from the specimen are conveyed to the dilution electrode array 59. The liquid droplet remaining in the liquid reservoir 85 is conveyed to the drainage port 48.
[0033] 希釈液は希釈ポート 25から挿入され、これも分取電極列 54により一定量の液滴に 分割されて希釈電極列 59に搬送される。  The dilution liquid is inserted from the dilution port 25, and is also divided into a predetermined amount of droplets by the sorting electrode array 54 and conveyed to the dilution electrode array 59.
[0034] 希釈電極列 59では検体液滴と希釈液を混合し、環状の電極列上で回転させること で攪拌して均一な希釈検体の液滴を形成する。図 1の場合は混合攪拌を 2段階実施 し、異なる濃度を希釈検体を作製できる。希釈検体の液滴は更に小さな液滴に分割 される。希釈検体の分割された液滴は、その検体で必要な項目数だけ、搬送電極列 57を経由して選ばれた反応電極列 56に搬送されると同時に、定められた数の液滴 力 Sバッファ電極列 58に搬送される。  In the diluted electrode array 59, the specimen droplet and the diluent are mixed and rotated on the annular electrode array to be stirred to form uniform diluted specimen droplets. In the case of Fig. 1, two stages of mixing and stirring can be performed to prepare diluted specimens with different concentrations. The diluted analyte droplets are divided into smaller droplets. The divided droplets of the diluted specimen are transported to the selected reaction electrode array 56 via the transport electrode array 57 by the number of items required for the sample, and at the same time, a predetermined number of droplet forces S It is conveyed to the buffer electrode array 58.
[0035] 分析する項目に対応する試薬が、第 1試薬ポート 31および第 2試薬ポート 37から 注入される。第 1試薬ポート 31から注入された試薬液滴は、液溜め 85で蓄えられた あと、分取電極列 54で一定量の液滴に分割される。分割された試薬液滴は、搬送電 極列 57から搬送されてきた希釈検体の液滴と混合し、攪拌電極列 55の電極上で回 転して攪拌される。攪拌された混合液は、一定時間ごとに 1電極ずつ反応電極列 56 上を移動する。光度計 50の位置に達したとき、光源 52から照射された光が液滴を透 過した量を光度計 50で検出し、結果を制御装置 12に送信する。  A reagent corresponding to the item to be analyzed is injected from the first reagent port 31 and the second reagent port 37. The reagent droplets injected from the first reagent port 31 are stored in the liquid reservoir 85 and then divided into a predetermined amount of droplets in the sorting electrode array 54. The divided reagent droplets are mixed with the diluted specimen droplets transported from the transport electrode array 57 and rotated on the electrodes of the stirring electrode array 55 to be stirred. The stirred liquid mixture moves on the reaction electrode array 56 by one electrode at regular intervals. When the position of the photometer 50 is reached, the photometer 50 detects the amount of light irradiated from the light source 52 that has passed through the droplet, and transmits the result to the controller 12.
[0036] 第 2試薬ポート 37から注入された試薬液滴も、分取電極列 54で一定量の液滴に分 割された後、反応電極列 56上を搬送されてくる混合液の液滴に結合し、攪拌電極列 55で攪拌される。第 2試薬と混合した混合液滴も、反応電極列 56上を 1電極ずつ移 動し、光度計 50の位置に達したときに光学的検出を行い、結果は制御装置 12に送 られる。混合液滴は、排液ポート 48に搬送される。 [0036] The reagent droplets injected from the second reagent port 37 are also divided into a certain amount of droplets by the sorting electrode array 54, and then the liquid droplets of the mixed liquid conveyed on the reaction electrode array 56 Coupled to the stirring electrode array Stir at 55. The mixed droplet mixed with the second reagent is also moved one by one on the reaction electrode array 56 and optical detection is performed when the position reaches the position of the photometer 50, and the result is sent to the control device 12. The mixed droplet is conveyed to the drainage port 48.
[0037] 排液ポート 48に到達した液滴は、オイル 71との比重の違いにより浮き上がり、廃液 73として排液チューブ 47に吸引されて排出される。  The liquid droplets that have reached the drainage port 48 float due to the difference in specific gravity with the oil 71 and are sucked into the drainage tube 47 as a waste liquid 73 and discharged.
[0038] バッファ電極列 58に搬送された希釈検体の液滴は、一定時間間隔ごとに 1電極分 ずつ移動させられる。 2電極分の間隔を空けて、次の液滴が搬送される。  [0038] The diluted specimen droplets conveyed to the buffer electrode array 58 are moved one electrode at a time interval. The next droplet is transported with an interval of two electrodes.
[0039] 制御装置 12は光度計 50からの信号を受け取り、特定成分の濃度を演算して表示 装置 13に送信すると同時に、演算結果から再検査が必要かどうかを判定する。再検 查が必要なのは、例えば得られた濃度が好適な分析が可能な範囲を超えた場合な どで、その場合は検体の希釈率を高くしての再検査が必要である。  The control device 12 receives the signal from the photometer 50, calculates the concentration of the specific component and transmits it to the display device 13, and at the same time determines from the calculation result whether reexamination is necessary. Retesting is necessary, for example, when the concentration obtained exceeds the range where a suitable analysis can be performed. In such a case, retesting with a high sample dilution rate is required.
[0040] 再検査が必要と判断された場合、バッファ電極列 58を搬送されている希釈検体液 滴が、搬送電極列 57を経由して反応電極列 56に搬送され、再度分析が実施される  [0040] When it is determined that retesting is necessary, the diluted specimen liquid droplet transported through the buffer electrode array 58 is transported to the reaction electrode array 56 via the transport electrode array 57, and the analysis is performed again.
[0041] 再検査が必要な 、と判断された検体の希釈液滴はバッファ電極列 58を通過後排 液ポート 48に搬送されて排出される。 [0041] Diluted droplets of the sample that are determined to need re-examination pass through the buffer electrode array 58 and are then transported to the drain port 48 and discharged.
[0042] 本実施例の場合は、再検査の可能性のある検体を、反応しな!、オイルに包まれた 液滴を形成して待機させるので、待機中の検体は周囲空気から隔離されており、空 気中の酸素、二酸化炭素などとの反応や蒸発による変質を受けることがなぐ精度の 高 ヽ再検査を実施することが可能である。 [0042] In the case of the present embodiment, the specimen that may be retested does not react! Because it forms a droplet wrapped in oil and waits, the waiting specimen is isolated from the ambient air. Therefore, it is possible to carry out high-accuracy re-examination that is not affected by reaction with oxygen or carbon dioxide in the air or alteration due to evaporation.
[0043] また、本実施例の場合は、分析基板内に再検査用の検体を待機させる領域を持つ ため、分析基板に分注した後の検体を待機し、再検査時に帰還させる機構が不要で あり、装置の小形化と低コストィ匕が実現可能である。 [0043] In addition, in the case of the present embodiment, since there is an area for waiting for a sample for retesting in the analysis substrate, a mechanism for waiting for the sample after dispensing to the analysis substrate and returning it at the time of retesting is unnecessary. Therefore, downsizing of the device and low cost can be realized.
[0044] また、本実施例の場合は、検体を希釈した液滴を再検用に待機させるため、再検 で必要とする検体の量が少なくてすみ、検体必要量の小さい分析装置が実現可能 である。 [0044] Further, in the case of the present embodiment, since the specimen-diluted liquid droplet is put on standby for re-examination, the amount of specimen required for re-examination can be reduced, and an analyzer with a small specimen requirement can be realized. is there.
[0045] また、本実施例の場合は、ノ ッファ電極列 58が複数列並んで 、るため、狭 、スぺ ースで多くの液滴を待機させることができ、装置の小形ィ匕が可能である。 [0046] また、本実施例の場合は、ノ ッファ電極列 58の途中にも液滴を取り出す電極列が 設けてあるので、再検査の必要が確定した検体が他の待機液滴よりも後ろにある場 合でも、先に再検査を実施することができ、結果を早く出力できる分析装置を実現で きる。 In the case of the present embodiment, since a plurality of the row of nother electrodes 58 are arranged, a large number of liquid droplets can be made to stand by in a narrow space, and the small size of the apparatus can be reduced. Is possible. In the case of the present embodiment, an electrode array for taking out droplets is also provided in the middle of the nother electrode array 58, so that the specimen for which reexamination is required is behind the other standby droplets. Even in this case, the re-inspection can be performed first, and an analyzer that can output the results quickly can be realized.
[0047] また、本実施例の場合、濃度の異なる希釈検体を作製できるので、最初の分析と濃 度の異なる希釈検体を再検査用に待機させておくことが可能で、好適な濃度の希釈 検体で再検査ができるので、高 、精度の分析が可能である。  [0047] In addition, in the case of the present embodiment, a diluted sample having a different concentration can be prepared. Therefore, a diluted sample having a concentration different from that of the initial analysis can be kept waiting for retesting, and a diluted sample having a suitable concentration can be prepared. Since the specimen can be re-examined, high-precision analysis is possible.
[0048] また、本実施例の場合、それぞれの検体に対して複数の項目の濃度分析が可能で あるが、再検査用の待機液滴の数は分析項目数より少なくすることが可能であり、バ ッファ電極列 58の必要容量を少なくして小型の装置を提供することができる。  [0048] Further, in the present embodiment, concentration analysis of a plurality of items can be performed for each sample, but the number of standby droplets for reexamination can be made smaller than the number of analysis items. Thus, the required capacity of the buffer electrode array 58 can be reduced, and a small device can be provided.
[0049] (実施例 2)  [0049] (Example 2)
図 3は本発明の第 2実施例のバッファ電極列の部分を示す上面図である。第 1実施 例との主な違いは、液溜め 85がサンプルポート 24とは別の場所に設置されており、 ノッファ電極列の中にも液溜め 85' が含まれる点である。  FIG. 3 is a top view showing a portion of the buffer electrode array of the second embodiment of the present invention. The main difference from the first embodiment is that the liquid reservoir 85 is installed at a location different from the sample port 24, and the liquid reservoir 85 'is also included in the kaffa electrode array.
[0050] この場合は、サンプルポート 24から注入された検体液滴は搬送電極列 57に接続 する液溜め 85と、バッファ電極列 58内の選ばれた液溜め 85の両方に搬送される。 搬送電極列 57に接続する液溜め 85からは一定量ずつ液滴が分割されて搬送電極 列 57に搬送され、分析が行われる。バッファ電極列 58内の液溜め 85に搬送された 検体は、その検体の再検査の要否が確定するまで待機し、再検査が必要な場合は 液滴を分割して搬送電極列 57に搬送して再検査を実施する。残された検体液滴は 排液ポート 48に搬送されて排出される。  In this case, the specimen droplet injected from the sample port 24 is transported to both the liquid reservoir 85 connected to the transport electrode array 57 and the selected liquid reservoir 85 in the buffer electrode array 58. From the liquid reservoir 85 connected to the transport electrode array 57, droplets are divided by a certain amount and transported to the transport electrode array 57 for analysis. The sample transported to the liquid reservoir 85 in the buffer electrode array 58 waits until the necessity of retesting of the sample is confirmed. If retesting is necessary, the droplet is divided and transported to the transport electrode array 57. And re-inspect. The remaining specimen droplet is transported to the drain port 48 and discharged.
[0051] 本実施例の場合は、バッファ電極列 58の中に複数分の待機領域が用意されてい るので、複数の検体を待機させておくことができる。  [0051] In the case of the present embodiment, a plurality of waiting areas are prepared in the buffer electrode array 58, so that a plurality of samples can be kept waiting.
[0052] また、本実施例の場合は、待機中は液溜め 85に留めておくので、継続的に移動す る必要がなぐ単純な制御で行え、信頼性が高い。  [0052] In the case of the present embodiment, since it is kept in the liquid reservoir 85 during standby, it can be performed with simple control that does not require continuous movement, and has high reliability.
[0053] また、本実施例の場合は、検体を分析基板 10に注入したときに再検査用の液滴ま で分割することがないので、液滴の分割に要する時間を短縮することができ、高い処 理能力の分析装置が実現できる。 [0054] (実施例 3) [0053] Further, in the case of this embodiment, when the specimen is injected into the analysis substrate 10, it is not divided into droplets for re-examination, so that the time required for dividing the droplets can be shortened. Therefore, it is possible to realize an analyzer with high processing capacity. [Example 3]
図 4から図 7は本発明の第 3実施例の説明図である。図 4は全体の概略を示す斜視 図、図 5は分析基板の概略構成を示す上面図、図 6は分析流路の要部を示す上面 図、図 7はサンプルポートの要部を示す断面図である。  4 to 7 are explanatory views of a third embodiment of the present invention. 4 is a perspective view showing the outline of the whole, FIG. 5 is a top view showing a schematic configuration of the analysis substrate, FIG. 6 is a top view showing the main part of the analysis flow path, and FIG. 7 is a cross-sectional view showing the main part of the sample port. It is.
[0055] リング状の分析基板 10の周囲に試薬ディスク 41、第 1試薬プローブ 30、第 2試薬 プローブ 35、サンプルディスク 20、サンプルプローブ 22、制御装置 12、表示装置 13 が配置されている。分析基板 10の内側には移動機構 51に支持された光度計 50が 配置されている。試薬ディスク 41には複数の試薬容器 40が搭載されている。サンプ ルディスク 20には複数のサンプル容器 21が搭載されている。第 1試薬プローブ 30、 第 2試薬プローブ 35、サンプルプローブ 22はそれぞれ独立して上下動、回転が可 能である。それぞれのプローブは図示しないシリンジポンプに接続されている。プロ ーブの移動経路に第 1試薬ポート 31、第 2試薬ポート 37、サンプルポート 24、および 洗浄ポート 26が配置されている。サンプルポート 24に近接して希釈ポート 25が設置 されている。また、分析基板 10には 4つの排液ポート 48が設けられ、それらには排液 チューブ 47が接続されて 、る。  A reagent disc 41, a first reagent probe 30, a second reagent probe 35, a sample disc 20, a sample probe 22, a control device 12, and a display device 13 are arranged around the ring-shaped analysis substrate 10. A photometer 50 supported by a moving mechanism 51 is disposed inside the analysis substrate 10. A plurality of reagent containers 40 are mounted on the reagent disk 41. A plurality of sample containers 21 are mounted on the sample disk 20. The first reagent probe 30, the second reagent probe 35, and the sample probe 22 can independently move up and down and rotate. Each probe is connected to a syringe pump (not shown). The first reagent port 31, the second reagent port 37, the sample port 24, and the washing port 26 are arranged on the probe path. Dilution port 25 is installed adjacent to sample port 24. The analysis substrate 10 is provided with four drainage ports 48 to which a drainage tube 47 is connected.
[0056] 光度計 50は、広 、波長範囲の光を放射する光源と、回折格子と、複数の波長の光 を検出する検出器が内蔵されている。  The photometer 50 includes a light source that emits light in a wide wavelength range, a diffraction grating, and a detector that detects light of a plurality of wavelengths.
[0057] 分析基板 10の構造を図 5で説明する。半径方向にのびた複数の分析流路 80が円 周状に多数並んでいる。分析流路 80に交差して、周方向に排液流路 81、第 2試薬 流路 82、サンプル流路 83、第 1試薬流路 84が並んでいる。第 1試薬流路 84の外側 には、サンプルポート 24、希釈ポート 25、第 1試薬ポート 31、第 2試薬ポート 37、複 数の排液ポート 48が配置されて 、る。  [0057] The structure of the analysis substrate 10 will be described with reference to FIG. A plurality of analysis flow paths 80 extending in the radial direction are arranged in a circle. A drainage flow path 81, a second reagent flow path 82, a sample flow path 83, and a first reagent flow path 84 are arranged in the circumferential direction so as to intersect the analysis flow path 80. A sample port 24, a dilution port 25, a first reagent port 31, a second reagent port 37, and a plurality of drainage ports 48 are arranged outside the first reagent channel 84.
[0058] 図 6により、分析基板 10の電極配置を説明する。図で、実線の四角い枠は、それぞ れ制御電極 64を示す。分析流路 80は半径方向に並んだ alカゝら a23まで 23個の電 極で構成されている。本実施例の場合、個々の電極は一辺が約 2.8mmの正方形で ある。電極 al、 a3、 a5、 al 2は、隣の分析流路との間に中継電極 88が配置され、周 方向に搬送流路である第 1試薬流路 84、サンプル流路 83、第 2試薬流路 82、排液 流路 81を形成している。また電極 al8、 al9、 a20の部分は測光領域である。 [0059] 図 7により、希釈ポートの構造を説明する。サンプルポート 24に近接して設置されて いる希釈ポート 25は、サンプルポート 24と同様に分析基板 10から上に突き出ており 、希釈液プローブ 23が挿入される。希釈液プローブ 23は図示しない希釈液ポンプに 接続されており、量を制御して希釈液を吐出することができる。 The electrode arrangement of the analysis substrate 10 will be described with reference to FIG. In the figure, each solid square frame represents a control electrode 64. The analysis channel 80 is composed of 23 electrodes arranged in a radial direction from al to al23. In this embodiment, each electrode is a square having a side of about 2.8 mm. Electrodes al, a3, a5, and al 2 have a relay electrode 88 disposed between the adjacent analysis flow paths, and the first reagent flow path 84, sample flow path 83, and second reagent that are transport flow paths in the circumferential direction. A flow path 82 and a drainage flow path 81 are formed. The electrodes al8, al9, and a20 are photometric areas. [0059] The structure of the dilution port will be described with reference to FIG. The dilution port 25 installed in the vicinity of the sample port 24 protrudes upward from the analysis substrate 10 like the sample port 24, and the diluent probe 23 is inserted. The diluent probe 23 is connected to a diluent pump (not shown), and the amount can be controlled to discharge the diluent.
[0060] つぎに本実施例の動作を説明する。  Next, the operation of the present embodiment will be described.
[0061] 試薬ディスク 41には、個々の分析項目に対応して第 1試薬と第 2試薬の 2種類の試 薬が試薬容器 40に入れられて搭載される。  [0061] On the reagent disk 41, two types of reagents, a first reagent and a second reagent, are placed in the reagent container 40 and mounted corresponding to each analysis item.
[0062] ある項目の試薬の分析基板 10への分注は次のように行われる。その項目の第 1試 薬が入った試薬容器 40が第 1試薬プローブ 30の吸引位置に来るように 41を回転し 、第 1試薬プローブ 30で第 1試薬を 80マイクロリットル吸引する。第 1試薬プローブ 3 0は上昇、回転して、第 1試薬ポート 31に挿入される。挿入後、試薬を 8マイクロリット ルずつ 10回に分けて吐出する。試薬吐出と連動して制御電極 64に順次電圧が印 加され、吐出された試薬は液滴となって第 1試薬流路 84まで搬送され、第 1試薬流 路 84上を周回する。  [0062] The dispensing of the reagent of a certain item to the analysis substrate 10 is performed as follows. Rotate 41 so that the reagent container 40 containing the first reagent of the item is at the suction position of the first reagent probe 30, and aspirate 80 μl of the first reagent with the first reagent probe 30. The first reagent probe 30 is raised and rotated and inserted into the first reagent port 31. After insertion, the reagent is dispensed in 8 microliter portions in 10 doses. A voltage is sequentially applied to the control electrode 64 in conjunction with the reagent discharge, and the discharged reagent is transported to the first reagent channel 84 as a droplet and circulates on the first reagent channel 84.
[0063] 第 2試薬に対しても第 1試薬の場合と同様の動作で、第 2試薬プローブ 35で試薬 容器 40から第 2試薬を 40マイクロリットル吸引し、第 2試薬ポート 37から 4マイクロリツ トルずつ 10回に分けて吐出し、液滴として第 2試薬流路 82に移動し、第 2試薬流路 8 2上を周回する。  [0063] For the second reagent, the same operation as in the case of the first reagent is performed, and 40 microliters of the second reagent is aspirated from the reagent container 40 by the second reagent probe 35 and 4 microliters from the second reagent port 37. Each torr is discharged in 10 times, moves as a droplet to the second reagent channel 82, and circulates on the second reagent channel 82.
[0064] 第 1試薬プローブ 30および第 2試薬プローブ 35はそれぞれ試薬吐出後、洗浄ポー ト 26に移動し、洗浄水でプローブ内面、外面を洗浄される。  [0064] After the reagent is discharged, the first reagent probe 30 and the second reagent probe 35 move to the cleaning port 26, and the inner surface and outer surface of the probe are cleaned with cleaning water.
[0065] 分析する予定の項目の第 1試薬および第 2試薬について引き続き分注が行われ、 それぞれの試薬が液滴として第 1試薬流路 84および第 2試薬流路 82上を周回する。  [0065] Dispensing is continued for the first reagent and second reagent of the item to be analyzed, and each reagent circulates on the first reagent channel 84 and the second reagent channel 82 as droplets.
[0066] サンプルディスク 20にはキャリブレーションおよび精度管理用の濃度既知の検体、 被分析検体がサンプル容器 21に入れられて搭載される。  [0066] On the sample disk 20, a sample of known concentration for calibration and accuracy control and a sample to be analyzed are placed in a sample container 21 and mounted.
[0067] 検体の分析基板 10への分注は次のように行われる。目的の検体が入ったサンプル 容器 21がサンプルプローブ 22の吸引位置に来るようにサンプルディスク 20が回転し 、サンプルプローブ 22がサンプル容器 21から検体を吸引する。吸引量はその検体 で分析する全項目のテストおよび再検査に必要な量以上である。サンプルプローブ 2 2は上昇、回転し、サンプルポート 24に挿入される。挿入後、吸引した検体を吐出す る。このとき希釈ポート 25から希釈液を吐出し、検体液 75は希釈液 76の中に吐出さ れるよう〖こする。吐出する希釈液と検体液の量は、行われる分析の種類によって調整 される。吐出は、その検体で分析が行われる回数と、再検査用の分が行われ、希釈 液と検体液が混合した液滴は、第 2試薬流路 82に搬送され、第 2試薬流路 82上を周 回する。サンプルプローブ 22は、分注後洗浄ポート 26に移動し、洗浄水でプローブ 内面、外面を洗浄される。 [0067] The sample is dispensed onto the analysis substrate 10 as follows. The sample disk 20 rotates so that the sample container 21 containing the target specimen is positioned at the suction position of the sample probe 22, and the sample probe 22 sucks the specimen from the sample container 21. The amount of aspiration is greater than that required for testing and retesting all items analyzed on the specimen. Sample probe 2 2 rises, rotates and is inserted into the sample port 24. After insertion, the aspirated specimen is discharged. At this time, the diluted solution is discharged from the dilution port 25, and the sample solution 75 is rubbed so as to be discharged into the diluted solution 76. The amount of diluted solution and sample solution to be discharged is adjusted according to the type of analysis to be performed. The number of times the sample is analyzed and the amount for retesting are discharged, and the liquid droplet in which the diluent and the sample liquid are mixed is transported to the second reagent channel 82 and the second reagent channel 82 Go around the top. The sample probe 22 moves to the cleaning port 26 after dispensing, and the inner surface and outer surface of the probe are cleaned with cleaning water.
[0068] ある検体のある項目の分析は次のように行われる。 [0068] An analysis of a certain item of a certain sample is performed as follows.
[0069] 制御装置 12により、ある検体のある項目の分析を実施する分析流路 80が選ばれる 。選ばれた分析流路 80に周回している希釈検体、試薬の液滴が移動し、まず希釈 検体液滴は alOに、第 1試薬液滴は a7、 a8に保持される。次に alOから印加電極を 順次移動することで検体液滴を a20まで搬送する。続いて、 a7、 a8の印加電極を順 次移動することで第 1試薬液滴を al8、 al9まで搬送する。ここで、検体と第 1試薬の 液滴は合体し、第 1反応液となって 3つの電極 al8、 al9、 a20上に保持される。次に al6から a23の間で電圧を印加している位置を往復移動することで、液滴は往復運 動し、第 1反応液の液滴中の検体と第 1試薬は攪拌されて均一になる。その後印加 電極は al8、 al9、 a20に固定されて、第 1反応時間の 5分間液滴は保持される。  [0069] The control device 12 selects an analysis flow path 80 for performing analysis of a certain item of a certain sample. The diluted specimen and reagent droplets circulating around the selected analysis channel 80 move. First, the diluted specimen droplets are held in alO, and the first reagent droplets are held in a7 and a8. Next, the specimen droplet is transported to a20 by sequentially moving the applied electrode from alO. Subsequently, the first reagent droplet is transported to al8 and al9 by sequentially moving the application electrodes a7 and a8. Here, the droplet of the specimen and the first reagent are combined to form the first reaction solution, which is held on the three electrodes al8, al9, and a20. Next, by reciprocating the position where voltage is applied between al6 and a23, the droplet reciprocates, and the specimen and the first reagent in the first reaction liquid droplet are agitated and evenly mixed. Become. The applied electrode is then fixed to al8, al9, a20, and the droplet is held for 5 minutes during the first reaction time.
[0070] 光度計 50は移動機構 51により 30秒で 1回転の速度で旋回する。分析流路 80上を 通過するとき、 al8、 al9、 a20上の液滴に光を照射し、選ばれた波長の透過光量を 測定し、制御装置 12に送信する。制御装置 12では吸光度を演算する。第 1反応時 間間、周期的に測定が行われる。  [0070] The photometer 50 is rotated by the moving mechanism 51 at a speed of one rotation in 30 seconds. When passing through the analysis flow path 80, light is applied to the droplets on al8, al9, and a20, and the amount of transmitted light of the selected wavelength is measured and transmitted to the controller 12. The controller 12 calculates the absorbance. Periodic measurements are taken during the first reaction time.
[0071] 第 1反応時間の間に、第 2試薬が準備される。第 2試薬流路 82上を周回している試 薬液滴力 選ばれた分析流路 80の電極 al4まで搬送される。  [0071] A second reagent is prepared during the first reaction time. Reagent droplet force circulating around the second reagent channel 82 is transported to the electrode al4 of the selected analysis channel 80.
[0072] 第 1反応時間経過後、第 2試薬の液滴は、印加電極を al4から順次移動して al8に 搬送される。ここで第 2試薬は第 1反応液と合体し、第 2反応液となる。次に al6から a 23の間で電圧を印加している位置を往復移動することで、液滴は往復運動し、第 2 反応液は攪拌されて均一になる。その後印加電極は al8、 al9、 a20、 a21に固定さ れて、第 2反応時間の 5分間液滴は保持される。第 2反応時間の間も光度計による周 期的な測定が行われる。 [0072] After the first reaction time has elapsed, the second reagent droplet is transferred to al8 by sequentially moving the applied electrode from al4. Here, the second reagent is combined with the first reaction solution to form the second reaction solution. Next, by reciprocating the position where voltage is applied between al6 and a23, the droplet reciprocates, and the second reaction liquid is stirred and becomes uniform. The applied electrode is then fixed to al8, al9, a20, a21, and the droplet is held for 5 minutes during the second reaction time. During the second reaction time, the photometer Periodic measurements are made.
[0073] 第 2反応時間の後、第 2反応液の液滴は排液流路 81を通る経路を通り、排液ポー ト 48まで搬送される。第 2反応液の液滴 70は撥水膜 62、 69との表面力により、排液 ポート 48の内部に入り込み、オイル 71との比重の違いで浮き上がる。浮き上がった 廃液 73は排液チューブ 47に吸引されて排出される。  [0073] After the second reaction time, the droplets of the second reaction liquid pass through the drainage flow path 81 and are conveyed to the drainage port 48. The droplet 70 of the second reaction liquid enters the drainage port 48 due to the surface force with the water repellent films 62 and 69 and rises due to the difference in specific gravity with the oil 71. The floated waste liquid 73 is sucked into the drainage tube 47 and discharged.
[0074] 分析は、複数の分析流路 80で並列して進められる。また、第 2反応時間の間に、次 の分析のための検体と第 1試薬の液滴が電極 alOおよび a7、 a8に待機し、分析が終 了して第 2反応液を排出した後すぐに次の分析が開始する。  [0074] The analysis proceeds in parallel in a plurality of analysis flow paths 80. Also, during the second reaction time, the specimen and the first reagent droplet for the next analysis wait on the electrodes alO, a7, and a8, and immediately after the analysis is completed and the second reaction solution is discharged. The next analysis begins.
[0075] 制御装置 12では、分析項目毎にキャリブレーション用の検体の分析で得られた吸 光度の変化と濃度との関係を導出し、キャリブレーションデータとして格納するまた、 定期的に精度管理用の検体の分析を実施し、その結果が所定の範囲に入らない場 合は異常のアラームを表示装置 13に送信する。被分析検体に対しては、キヤリブレ ーシヨンデータを用いて分析項目の濃度を演算し、表示装置 13に送信して表示する 。濃度の演算結果が所定の範囲カゝら外れている場合は、再検査が実行される。再検 查は、サンプル流路 83を周回している希釈検体の液滴で実行される。再検査が行わ れる希釈検体は、最初の分析の場合と異なった希釈率のものが選ばれることもある。  [0075] The control device 12 derives the relationship between the change in absorbance and the concentration obtained in the analysis of the sample for calibration for each analysis item, and stores the relationship as calibration data. The sample is analyzed, and if the result does not fall within the predetermined range, an abnormal alarm is transmitted to the display device 13. For the analyte, the concentration of the analysis item is calculated using the calibration data and transmitted to the display device 13 for display. When the density calculation result is out of the predetermined range, re-examination is executed. Re-examination is performed with the droplet of the diluted specimen circulating around the sample channel 83. Diluted specimens to be retested may be selected at different dilutions than in the initial analysis.
[0076] サンプル流路 83を周回している希釈検体液滴で、その検体の再検査の必要がな いと確定したものは、排液ポート 48に搬送されて、排出される。  [0076] Diluted specimen droplets circulating around the sample flow path 83, which are determined not to require re-examination of the specimen, are transported to the drain port 48 and discharged.
[0077] 本実施例の場合も、再検査の可能性のある検体を、反応しな!、オイルに包まれた 液滴を形成して待機させるので、待機中の検体は周囲空気から隔離されており、空 気中の酸素、二酸化炭素などとの反応や蒸発による変質を受けることがなぐ精度の 高 ヽ再検査を実施することが可能である。  [0077] In the case of the present embodiment as well, a specimen that may be retested does not react! It forms a droplet wrapped in oil and waits, so that the waiting specimen is isolated from the ambient air. Therefore, it is possible to carry out high-accuracy re-examination that is not affected by reaction with oxygen or carbon dioxide in the air or alteration due to evaporation.
[0078] また、本実施例の場合は、検体液滴の搬送流路が検体液滴の待機領域を兼ねて いるので、待機領域を特別に設ける必要がなぐ装置の小形化が実現できる。  Further, in the case of the present embodiment, since the specimen droplet transport channel also serves as a specimen droplet standby area, it is possible to achieve a reduction in the size of the apparatus without the need to provide a special standby area.
[0079] また、本実施例の場合、待機液滴が円周上のサンプル流路 83を周回しているので 、再検査が必要と確定したとき、近くの空いている分析流路 80ですぐに分析を開始 することができ、分析の結果を早く出力することができる。  [0079] Further, in the case of the present embodiment, since the standby droplet circulates around the circumferential sample flow path 83, when it is determined that re-examination is necessary, immediately in the nearby empty analysis flow path 80 Analysis can be started immediately, and analysis results can be output quickly.

Claims

請求の範囲 The scope of the claims
[1] 所定間隔で対向させ、間隙に液体を保持する少なくとも 1対の板状部材 (60、 63) を備えた液体搬送機構であって、  [1] A liquid transport mechanism comprising at least one pair of plate-like members (60, 63) facing each other at a predetermined interval and holding liquid in the gap,
前記少なくとも 1対の板状部材の少なくとも一方に、液体を搬送する方向に沿って 複数の電極 (61, 64)を所定間隔で配置した液体搬送路を複数備え、  At least one of the at least one pair of plate-like members includes a plurality of liquid transport paths in which a plurality of electrodes (61, 64) are arranged at predetermined intervals along the direction of transporting the liquid,
かつ該液体搬送路には、少なくともサンプル液体を搬送するサンプル搬送路(83) と、該サンプル搬送路に試薬を供給する試薬搬送路 (82、 84)と、を備えた液体搬送 機構と、  The liquid transport path includes at least a sample transport path (83) for transporting a sample liquid, and a reagent transport path (82, 84) for supplying a reagent to the sample transport path,
前記サンプル搬送路に検体を供給する検体分配機構と、  A sample distribution mechanism for supplying a sample to the sample transport path;
前記試薬搬送路に試薬を供給する試薬分配機構と、  A reagent distribution mechanism for supplying a reagent to the reagent transport path;
前記液体搬送路中での検体と試薬の反応を光学的に分析する測定機構と、 を備え、  A measurement mechanism for optically analyzing the reaction between the specimen and the reagent in the liquid conveyance path, and
更に、前記試薬分配機構が前記サンプル搬送路に試薬を供給する位置より、前記 検体分配機構が前記サンプル搬送路に検体を供給する位置の側に、前記検体分配 機構から供給された複数の検体を保持し、かつ保持して!/、る検体を前記サンプル搬 送路に複数の位置で供給する搬送路を備えたバッファ電極列(58)を備えたことを特 徴とする自動分析装置。  Further, a plurality of samples supplied from the sample distribution mechanism are placed closer to a position where the sample distribution mechanism supplies a sample to the sample conveyance path than a position where the reagent distribution mechanism supplies a reagent to the sample conveyance path. An automatic analyzer characterized by comprising a buffer electrode array (58) provided with a transport path for holding and holding the sample to be held and supplied to the sample transport path at a plurality of positions.
[2] 請求項 1記載の自動分析装置において、 [2] The automatic analyzer according to claim 1,
前記サンプル搬送路は異なる検体を並行して搬送できるよう複数設けられ、前記バ ッファ電極列は、複数の該サンプル搬送路間で連結されていることを特徴とする自動 分析装置。  2. The automatic analyzer according to claim 1, wherein a plurality of the sample transport paths are provided so that different specimens can be transported in parallel, and the buffer electrode array is connected between the plurality of sample transport paths.
[3] 請求項 2記載の自動分析装置において、  [3] The automatic analyzer according to claim 2,
前記バッファ電極列は並行して複数設けられ、更に複数のノッファ電極列を接続 する少なくとも 1列の電極列を備えたことを特徴とする自動分析装置。  An automatic analyzer comprising a plurality of the buffer electrode rows provided in parallel, and further comprising at least one electrode row for connecting a plurality of nother electrode rows.
[4] 請求項 2または 3記載の自動分析装置にお!、て、 [4] In the automatic analyzer according to claim 2 or 3,!
前記バッファ電極列には複数回分の分析が実行可能な検体を蓄えることが可能な サンプル溜めが接続されて ヽることを特徴とする自動分析装置。  An automatic analyzer characterized in that a sample reservoir capable of storing a sample that can be analyzed a plurality of times is connected to the buffer electrode array.
[5] 所定間隔で対向させ、間隙に液体を保持する少なくとも 1対の板状部材を備えた液 体搬送機構であって、 [5] A liquid provided with at least one pair of plate-like members facing each other at a predetermined interval and holding the liquid in the gap A body transport mechanism,
前記少なくとも 1対の板状部材の少なくとも一方に、液体を搬送する方向に沿って 複数の電極を所定間隔で配置した液体搬送路を複数備え、  At least one of the at least one pair of plate-like members includes a plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction of transporting the liquid,
かつ該液体搬送路には、少なくとも放射状にサンプル液体を搬送するサンプル搬 送路と、該サンプル搬送路を横断し、複数の前記サンプル搬送路に試薬を供給する 試薬搬送路と、該サンプル搬送路を横断し、複数の前記サンプル搬送路間にサンプ ルを搬送可能なサンプル流路と、を備えた液体搬送機構と、  The liquid transport path includes at least a sample transport path for transporting a sample liquid radially, a reagent transport path that crosses the sample transport path and supplies a reagent to the plurality of sample transport paths, and the sample transport path A liquid flow mechanism that includes a sample flow path that crosses the plurality of sample transfer paths and that can transfer samples between the plurality of sample transfer paths,
前記サンプル搬送路に検体を供給する検体分配機構と、  A sample distribution mechanism for supplying a sample to the sample transport path;
前記試薬搬送路に試薬を供給する試薬分配機構と、  A reagent distribution mechanism for supplying a reagent to the reagent transport path;
前記液体搬送路中での検体と試薬の反応を光学的に分析する測定機構と、 を備えたことを特徴とする自動分析装置。  An automatic analyzer comprising: a measurement mechanism for optically analyzing a reaction between a specimen and a reagent in the liquid conveyance path.
[6] 請求項 1〜5のいずれかに記載の自動分析装置において、  [6] In the automatic analyzer according to any one of claims 1 to 5,
前記測定機構での分析結果に基づき、再検査の要否を判断する判断手段と、 該判断手段が特定検体の特定分析項目での再検査が必要と判断した場合は、前 記バッファ電極列に保持された前記特定検体と同一の検体が前記サンプル搬送路 に搬送されるようにバッファ電極列を制御する制御手段とを備えたことを特徴とする自 動分析装置。  Based on the analysis result of the measurement mechanism, a determination means for determining whether or not reexamination is necessary, and if the determination means determines that reexamination for a specific analysis item of a specific sample is necessary, the buffer electrode array An automatic analyzer comprising: control means for controlling a buffer electrode array so that the same specimen as the held specific specimen is transported to the sample transport path.
[7] 請求項 6に記載の自動分析装置において、  [7] In the automatic analyzer according to claim 6,
前記検体分配機構の近傍に検体の希釈液を供給する希釈液供給機構を備え、 該検体分配機構がサンプル搬送路に検体を供給する際に、該希釈液供給機構が 該サンプル搬送路に希釈液を供給することにより、希釈した検体をサンプル搬送路 内で生成し、希釈された検体を前記バッファ電極列に保持するよう制御する制御手 段を備えたことを特徴とする自動分析装置。  A diluent supply mechanism for supplying a sample diluent in the vicinity of the sample distribution mechanism is provided, and when the sample distribution mechanism supplies a sample to the sample transport path, the diluent supply mechanism is supplied to the sample transport path. An automatic analyzer comprising a control means for controlling to generate a diluted specimen in the sample transport path by supplying and to hold the diluted specimen in the buffer electrode array.
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US10379112B2 (en) 2007-02-09 2019-08-13 Advanced Liquid Logic, Inc. Droplet actuator devices and methods employing magnetic beads
US9574220B2 (en) 2007-03-22 2017-02-21 Advanced Liquid Logic, Inc. Enzyme assays on a droplet actuator
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US9861986B2 (en) 2008-05-03 2018-01-09 Advanced Liquid Logic, Inc. Droplet actuator and method
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US9545640B2 (en) 2009-08-14 2017-01-17 Advanced Liquid Logic, Inc. Droplet actuator devices comprising removable cartridges and methods
US9707579B2 (en) 2009-08-14 2017-07-18 Advanced Liquid Logic, Inc. Droplet actuator devices comprising removable cartridges and methods
JP2011058943A (en) * 2009-09-09 2011-03-24 Univ Of Tsukuba Liquid feeding device
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US9492822B2 (en) 2011-05-09 2016-11-15 Advanced Liquid Logic, Inc. Microfluidic feedback using impedance detection
US9513253B2 (en) 2011-07-11 2016-12-06 Advanced Liquid Logic, Inc. Droplet actuators and techniques for droplet-based enzymatic assays
US10731199B2 (en) 2011-11-21 2020-08-04 Advanced Liquid Logic, Inc. Glucose-6-phosphate dehydrogenase assays
US9238222B2 (en) 2012-06-27 2016-01-19 Advanced Liquid Logic, Inc. Techniques and droplet actuator designs for reducing bubble formation
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