JP4969061B2 - Automatic analyzer - Google Patents

Description

  The present invention relates to an automatic analyzer that performs qualitative / quantitative analysis of biological components such as blood and urine, and more particularly to an automatic analyzer that is small in size, can be loaded with more reagents, and has a high throughput per hour.

  Automatic analyzers that automatically analyze biological samples such as blood and output the results can be used for efficient analysis at large hospitals, small and medium hospitals, and clinics with large numbers of patients. It is an indispensable device.

  Such an automatic analyzer is desired to be compact and capable of 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, a sample and a reagent are dispensed to each reaction cell with a probe, and a change in absorbance of the mixed solution is measured with a photometer. Discloses an apparatus for analyzing the concentration of a specific component of a specimen.

  In this method, all the reaction cells are measured by passing through the photometer by the rotation of the reaction disk, so only one photometer is required, and all cells are analyzed under the same conditions and with little variation. Is possible. In addition, since sample and reagent can be dispensed to any reaction cell, necessary analysis can be performed in any order, and analysis with high throughput is possible.

  However, in this method, the reaction cell needs to contain a reaction solution (specimen + reagent) that is larger than the luminous flux diameter of the photometer, and a certain amount of specimen / reagent is required. Further, 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 that the reaction cell needs a certain volume, and the apparatus is inevitably enlarged.

  On the other hand, Non-Patent Document 1 applies a technique for manipulating droplets between flat plates on which electrode rows called electrowetting are arranged to react a specimen and a reagent and react with an optical system using an LED. An example of detecting the absorbance of a droplet and analyzing the concentration of four types of items is introduced. Electrowetting droplet transport technology has advantages such as high reliability because it can handle a small amount of droplets and no mechanical movement mechanism is required, and there is a possibility of realizing a small and high-throughput analyzer. is there.

Japanese Patent Laid-Open No. 4-71184

Clinical diagnostics on human whole blood, plasma, serum, urine, saliva, sweat, and tears on a digital microfluidic platform ”μTAS2003

  With the technique described in Non-Patent Document 1, it is possible to analyze specific items, but it is not possible to automatically select and analyze necessary items from multiple types of items for a plurality of samples.

  An object of the present invention is to provide a high-speed and highly flexible automatic analyzer that can reduce the number of mechanical dispensing of samples and reagents and automatically select and analyze necessary items for a plurality of samples. is there.

  The problem solving means of the present invention is as follows.

  A droplet transfer device formed by opposing two surfaces having a plurality of electrodes arranged on at least one surface, and a plurality of sample droplets and reagent droplets mixed, reacted, and optically measured in the droplet transfer device Analysis path, sample distribution mechanism that can distribute sample droplets to multiple analysis paths, reagent distribution mechanism that can distribute reagent droplets to multiple analysis paths, and combination of sample and reagent Each control mechanism is controlled so as to lead to the above, and a control device for calculating the concentration of the component contained in the specimen from the result of the optical measurement is provided.

  More preferably, the configuration is 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 along a direction of transporting the liquid. A plurality of liquid transport paths in which a plurality of electrodes are arranged at a predetermined interval are provided, and the liquid transport path includes at least a sample transport path for transporting a sample liquid radially, and a plurality of the sample transports crossing the sample transport path. A liquid transport mechanism that supplies a reagent to the 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 the liquid transport An automatic analyzer equipped with a measurement mechanism for optically analyzing the reaction between a sample and a reagent in the road.

  The automatic analyzer may have a photometer for measuring the optical properties of the droplet and a moving mechanism for moving the photometer so that the photometer can optically measure through a plurality of analysis paths.

  In addition, the reagent store is a reagent disk that can be rotated by mounting a plurality of reagent containers on the circumference, and the reagent dispensing mechanism sucks the reagent from the reagent container at a specific position on the reagent disk and supplies a droplet. The reagent probe may be discharged to a specific position.

  In addition, the reagent probe may suck the amount of reagent required for a plurality of analyzes at a time and discharge it to the droplet transport device.

  Further, a reagent reservoir may be provided in the droplet transport device, and the reagent droplet may be transported to the analysis path after being held in the reagent reservoir.

  In addition, the reagent reservoir holds the amount of droplets required for multiple analyzes as a single unit, and is divided into the amount of droplets required for one analysis in the fractionation path connected to the reagent reservoir and then into the analysis path. It may be conveyed.

  In addition, the reagent reservoir may be configured to hold a plurality of droplets and to be transported to the analysis path by changing the order.

  Further, a plurality of reagent reservoirs are provided, and the reagents held in each reagent reservoir may be the same type of reagent.

  In addition, the types of reagents held in the individual reagent reservoirs are not fixed, and different types of reagents may be held in a common reagent reservoir.

  The sample dispensing mechanism is a sample probe that sucks the sample from the sample container and discharges the sample to a specific position of the droplet transport device, and the sample probe may aspirate a sample of an amount necessary for a plurality of analyzes at a time. .

  Further, there is a specimen reservoir in the droplet transport device, and the specimen droplet may be transported to the analysis path after being held in the specimen reservoir.

  In addition, the sample reservoir holds the amount of droplets required for multiple analyzes as a single unit, and is divided into the amount of droplets required for one analysis in the sorting path connected to the sample reservoir, and then into the analysis path. It may be conveyed.

  The sample reservoir may be configured to hold a plurality of droplets and exchange them in the order so as to be transported to the analysis path.

  Moreover, it may have a dilution mechanism for diluting the specimen at different dilution rates, and the diluted specimen may be supplied to the droplet transport device.

  The sample dispensing mechanism may be a sample probe that sucks the sample from the sample container, and the sample may be diluted at the sample discharge position of the droplet transport device.

  The analysis path, the sample distribution mechanism, and the reagent distribution mechanism are each composed of a plurality of electrode arrays, and the electrode array that forms the analysis path intersects with the electrode arrays that form the sample distribution mechanism and the reagent distribution mechanism. Thus, the droplet may move between the respective electrode arrays.

  Alternatively, a single droplet may be held by applying a voltage to a plurality of continuous electrodes, and droplets having different volumes may be conveyed on a common electrode array.

  In addition, the droplet transport device may be circular, the electrode rows forming a plurality of analysis paths may be aligned in the radial direction, and the electrode rows forming the sample distribution mechanism and the reagent distribution mechanism may be aligned in the circumferential direction.

  In addition, a plurality of analysis paths may be arranged on the circumference, and the photometer may rotate to perform optical measurement.

  Further, either or both of a transport path for distributing the specimen droplets to the analysis path and a transport path for distributing the reagent droplets to the analysis path may be selectable from a plurality of paths.

  It is possible to provide an automatic analyzer with a high speed and a high degree of freedom, in which the number of mechanical dispensing of samples and reagents is small and necessary items can be selected and analyzed for a plurality of samples.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a perspective view of a first embodiment of the present invention. A reagent disk 41, a first reagent probe 30, and a second reagent probe 35 are arranged in the ring-shaped analysis substrate 10. A sample disk 20, a sample probe 22, a photometer 50 supported by a moving mechanism 51, a control device 12, and a display device 13 are arranged outside 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 be moved up and down and rotated independently. Each probe is connected to a syringe pump (not shown). A first reagent port 31, a second reagent port 37, a sample port 24, and a washing port 26 are arranged on the probe movement path. 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.

  FIG. 2 is a schematic diagram showing a cross section of the analysis substrate 10 of the first embodiment. The analysis substrate 10 includes a first substrate 60 and a second substrate 63. 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 disposed 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 the first substrate 60 and the second substrate 63 are separated by a gap of 0.5 mm. This gap is filled with oil 71 that does not mix with the aqueous solution, and water-soluble droplets 70 are retained.

  FIG. 3 is a top view of the analysis substrate 10 of the first embodiment. A large number of analysis flow paths 80 extending in the radial direction are arranged in a circle. The drainage flow path 81, the second reagent flow path 82, the sample flow path 83, and the first reagent flow path 84 are arranged in the circumferential direction so as to intersect the analysis flow path 80. 84, a sample port 24, a plurality of sample reservoirs 86, a first reagent port 31, a second reagent port 37, a plurality of reagent reservoirs 85, and a plurality of drainage ports 48 are arranged. A supply flow path 87 is disposed above. Although omitted in the figure, about 100 reagent reservoirs 85 are arranged on the entire circumference.

FIG. 4 is a top view showing a part of electrode arrangement of the analysis substrate 10 of the first embodiment. In the figure, each solid square frame represents a control electrode 64. The analysis channel 80 is composed of 23 electrodes a1 to a23 arranged in the radial direction. In this embodiment, each electrode has a side of about 2.8.
mm square. The electrodes a1, a3, a5, and a12 have a relay electrode 88 disposed between adjacent electrodes, and the first reagent channel 84, the sample channel 83, and the second reagent flow, which are transport channels in the circumferential direction. A channel 82 and a drainage channel 81 are formed. The width of the relay electrode 88 is smaller than the width of the electrode forming the analysis channel 80. The portions of the electrodes a18, a19, a20 are photometric areas.

FIG. 5 is a top view showing another partial electrode arrangement of the analysis substrate 10 of the first embodiment. Similar to the first reagent channel 84, the supply channel 87 is constituted by an electrode array arranged in the circumferential direction. The first reagent port 31 is disposed between the first reagent channel 84 and the supply channel 87, and electrodes are connected from the first reagent port 31 to the supply channel 87. A reagent reservoir 85 of an electrode larger than the other electrodes is arranged in the middle of the electrode row that continues from the supply channel 87 to the first reagent channel 84. In the case of this embodiment, this electrode is circular with a diameter of 14 mm.

  FIG. 6 is a cross-sectional view showing the structure of the first reagent port 31 of the first embodiment. The first reagent port 31 protrudes upward from the analysis substrate 10 and has a hole therethrough. A water repellent film 68 is formed on the inner surface. A structure in which the first reagent probe 30 is inserted into the first reagent port 31 and the droplet 70 is discharged inside the analysis substrate 10 is formed.

  The second reagent port 37 and the sample port 24 have the same structure as the first reagent port 31. The sample reservoir 86 has the same shape as the reagent reservoir 85.

  FIG. 7 is a cross-sectional view showing the structure of the drainage port 48 of the first embodiment. The drainage port 48 protrudes upward from the analysis substrate 10 and has a hole therethrough. Further, a drainage tube 47 penetrates from the side. There is space inside.

  Next, the operation of the first embodiment will be described.

  Two types of reagents, a first reagent and a second reagent, are placed in the reagent container 40 and mounted on the reagent disk 41 corresponding to each analysis item.

  Dispensing a certain item of reagent to the analysis substrate 10 is performed as follows. 41 is rotated so that the reagent container 40 containing the first reagent of the item comes to the suction position of the first reagent probe 30, and 80 microliters of the first reagent is sucked by the first reagent probe 30. The first reagent probe 30 is raised and rotated and inserted into the first reagent port 31. After insertion, 80 microliters of reagent are discharged. A voltage is sequentially applied to the control electrode 64 along the path 90 connecting from the first reagent port 31 to the reagent reservoir 85 selected for the reagent in conjunction with the reagent discharge. The discharged reagent enters the region sandwiched between the water-repellent films 62 and 66 as a droplet 70, but a suction force due to electrowetting is generated on the control electrode 64 to which a voltage is applied. And is guided to the reagent reservoir 85. When the discharge from the first reagent probe 30 is finished, the voltage application to the control electrode 64 on the path 90 is sequentially cut off, and only the reagent reservoir 85 is left and the reagent is held on the reagent reservoir 85.

  The second reagent is aspirated by 40 microliters of the second reagent from the reagent container 40 with the second reagent probe 35 and discharged from the second reagent port 37 in the same manner as in the case of the first reagent. It is transported and held to a reagent reservoir 85 selected separately from the reagent.

  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.

  The first reagent and the second reagent of all items to be analyzed are dispensed and held on different 85s.

  The dispensing of the reagent to the analysis substrate 10 is performed when the operation starts and when the amount of the reagent held in each reagent reservoir 85 falls below a predetermined amount.

  A sample disk 20 is loaded with a sample having a known concentration for calibration and accuracy management and a sample to be analyzed in a sample container 21.

  The dispensing of the sample to the analysis substrate 10 is performed as follows. The sample disk 20 rotates so that the sample container 21 containing the target specimen comes to 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 all items analyzed with the sample. The sample probe 22 is raised and rotated and inserted into the sample port 24. After insertion, the aspirated specimen is discharged. A voltage is sequentially applied to the control electrode 64 in conjunction with the discharge of the sample along a path connecting from the sample probe 22 to the sample reservoir 86 selected corresponding to the sample. The discharged specimen enters the portion sandwiched between the water-repellent films 62 and 66 as a droplet 70, but a suction force is generated by electrowetting on the control electrode 64 to which a voltage is applied. It is led to the sample reservoir 86 through. When the discharge from the sample probe 22 is completed, the voltage application to the control electrode 64 on the path is sequentially cut off, and only the sample reservoir 86 is left and the specimen is held on the sample reservoir 86. The sample probe 22 moves to the cleaning port 26 after dispensing, and the inner and outer surfaces of the probe are cleaned with cleaning water.

  An analysis of an item of a sample is performed as follows.

  The control device 12 selects one of the reagent reservoir 85 that holds the first reagent used for the analysis, the reagent reservoir 85 that holds the second reagent, and one analysis channel 80 that is empty.

A voltage higher than that applied to the reagent reservoir 85 is applied to the four electrodes continuous from the reagent reservoir 85 holding the first reagent to the outer peripheral side. By cutting off the application of the second electrode among the four electrodes after a certain period of time, approximately 8 microliters of a first reagent droplet is formed on the third and fourth electrodes. By sequentially moving the electrodes to which the voltage is applied from the reagent reservoir 85 along the path 91 passing through the first reagent channel 84, the droplets of the first reagent are conveyed to the selected analysis channel 80. .

  The specimen applies a voltage higher than that applied to the sample reservoir 86 to the three electrodes continuous from the sample reservoir 86 to the outer peripheral side, and cuts off the application of the second electrode among the three electrodes after a certain period of time. As a result, a specimen droplet of about 4 microliters is formed on the third electrode. The specimen droplet is conveyed to the selected analysis channel 80 by sequentially moving the electrode to which the voltage is applied along the path in the sample channel 83. After the necessary amount of sample is collected, the sample remaining in the sample reservoir 86 is transported to the drain port 48 and discarded.

  In the analysis flow path 80, the specimen droplet is first held in a10, and the first reagent droplet is held in a7 and a8. Next, the specimen droplet is transported to a20 by sequentially moving the application electrode from a10. Subsequently, the first reagent droplets are conveyed to a18 and a19 by sequentially moving the application electrodes a7 and a8. Here, the specimen and the first reagent droplet are combined to form a first reaction liquid, which is held on the three electrodes a18, a19, and a20. Next, by reciprocating the position where the voltage is applied between a16 and a23, the droplet reciprocates, and the specimen and the first reagent in the droplet of the first reaction liquid are stirred and become uniform. . Thereafter, the application electrode is fixed to a18, a19, and a20, and the droplet is held for 5 minutes during the first reaction time.

  The photometer 50 is turned at a speed of one rotation in 30 seconds by the moving mechanism 51. When passing through the analysis flow path 80, the droplets on the a 18, a 19, a 20 are irradiated with light, the transmitted light amount of the selected wavelength is measured, and transmitted to the control device 12. The controller 12 calculates the absorbance. Measurements are taken periodically during the first reaction time.

  A second reagent is prepared during the first reaction time. A voltage higher than that applied to the reagent reservoir 85 is applied to the three electrodes continuous from the reagent reservoir 85 holding the second reagent to the outer peripheral side, and the second electrode of the three electrodes is applied after a certain period of time. To form a second reagent droplet of about 4 microliters on the third electrode. The second reagent droplet is transported to the electrode a14 of the selected analysis channel 80 by sequentially moving the electrodes to which the voltage is applied along the path passing through the second reagent channel 82.

  After the first reaction time has elapsed, the droplets of the second reagent are transported to a18 by sequentially moving the application electrode from a14. Here, the second reagent is combined with the first reaction solution to become the second reaction solution. Next, by reciprocating the position where a voltage is applied between a16 and a23, the droplet reciprocates, and the second reaction liquid is stirred and becomes uniform. Thereafter, the application electrode is fixed to a18, a19, a20, a21, and the droplet is held for 5 minutes in the second reaction time. Periodic measurement with a photometer is also performed during the second reaction time.

After the second reaction time, the droplet of the second reaction liquid passes through the path through the drainage flow path 81 and is 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 raised waste liquid 73 is sucked into the drainage tube 47 and discharged.

  During the second reaction time, the specimen for the next analysis and the droplet of the first reagent wait on the electrodes a10, a7, and a8, and immediately after the analysis is finished and the second reaction liquid is discharged, Analysis begins.

  While analysis of an item of a sample is performed in one analysis channel 80, analysis of another sample or another item is advanced in parallel in another analysis channel 80.

  The control device 12 derives the relationship between the change in absorbance and the concentration obtained by analyzing the sample for calibration for each analysis item, and stores it as calibration data. For the sample to be analyzed, the concentration of the analysis item is calculated using the calibration data, and transmitted to the display device 13 for display. In addition, a sample for quality control is periodically analyzed, and if the result does not fall within a predetermined range, an abnormal alarm is transmitted to the display device 13.

  The control device monitors the state of the entire device. A voltage is applied to each control electrode 64 at the time of maintenance, and when the capacitance and current between the common electrode 61 are detected and abnormal, the electrode is stored, and an analysis flow path 80 including the electrode is stored. Control not to use for analysis.

  In the case of the present embodiment, a function of supplying specimen droplets and reagent droplets to each of the plurality of analysis channels 80, a function of mixing droplets, a function of transporting specimens, reagents and mixtures thereof, and reacting the mixture Since a region having a function to be incorporated is incorporated and can be performed in parallel without being synchronized with other analysis channels, a plurality of analyzes can be freely started, progressed, and terminated in a free analysis channel 80. The analysis flow path 80 can be used with less free time, and an analyzer with high processing capacity per unit time can be realized.

  In the case of this embodiment, since the analysis substrate is fixed and the photometer is configured to rotate, droplet movement, mixing, agitation, etc., even during photometry of any analysis flow path Therefore, it is possible to realize an analyzer having a high processing capability.

  In addition, operations such as droplet movement, mixing, and stirring can be performed in parallel in multiple analysis channels, so it is possible to increase the time required for each operation, and heat is generated by operating at an unreasonable speed. Adverse effects such as turbulence and flow turbulence can be avoided, and stable and highly accurate analysis is possible.

  In addition, since droplet conveyance, mixing, and stirring are performed only by controlling the voltage application to the electrodes, even if these functions are incorporated in each of the many analysis channels, the mechanism is not complicated, and the structure is small with a simple configuration. A highly reliable analyzer can be realized.

  In the case of this embodiment, specimens and reagents can be transported to all the analysis channels 80, and any item can be analyzed in any analysis channel, so that analysis with high efficiency and high throughput is possible. Is possible.

  In the case of the present embodiment, each of the plurality of analysis channels 80 has a built-in region having a function of temporarily storing a sample, a reagent, and a mixture thereof. There is no need to match the timing of supplying the sample droplets and reagent droplets to the flow channel 80 with the progress of analysis, and the sample and reagent can be efficiently supplied to a plurality of analysis flow channels, and the analysis has a high processing capacity. Is possible.

  In the case of the present embodiment, the specimen and the reagent are encased in oil that does not react with the aqueous solution in the analysis board, and no alteration occurs due to evaporation or the like. There is no need to match.

  Further, in this embodiment, analysis of all items can be performed in any analysis flow path, and analysis can be started and advanced at any timing in any analysis flow path. Therefore, it is possible to perform analysis with high processing capacity by efficiently using the analysis flow path.

  In addition, since the analysis flow path can be freely selected by the control device, it is possible to shorten the transport time by selecting the analysis flow that requires quick processing to be performed in the analysis flow path close to the sample reservoir. Can be output.

  In this embodiment, since the same photometer is used for all the analysis channels 80, the same characteristics can be analyzed in any channel, and highly accurate analysis with little variation is possible. is there.

  In the case of the present embodiment, since the photometer is scanned and used, only one photometer and a detection electric system are required, and a low-cost analyzer can be realized.

  In the case of this embodiment, since the same photometer is used for all the analysis channels, the calibration does not need to be performed for all the analysis channels, and the sample and time required for calibration are saved. Cost can be reduced.

  In the case of this embodiment, the reaction droplets are stationary during the reaction time, and periodic measurement is performed at the same place. Therefore, the droplets are subject to changes in the shape of the droplets and conditions such as bubbles. Difficult and accurate analysis is possible.

  In the case of this embodiment, since the sample, reagent droplet transport, mixing, and stirring are performed only by controlling the voltage application to the electrodes, the analysis substrate 10 has no mechanical operation, and the photometer 50 Since it rotates without stopping and photometry can be performed, the integration time of each photometry can be extended, and high-precision analysis with little noise is possible.

  In the case of the present embodiment, the photometer can take a long photometric time, so that it is possible to analyze the absorbance even when the optical path length of the reaction solution is short, and an analyzer with a small amount of sample and reagent and a low running cost. realizable.

  In the case of this embodiment, the inner surfaces of the analysis substrate, sample port, and reagent port are all covered with a water-repellent film, and the inside is filled with an oil that does not dissolve in an aqueous solution. Since the droplet does not come into direct contact with the wall surface, the wall surface is not contaminated with the specimen or reagent, and high-precision analysis without carryover is possible.

  In the case of the present embodiment, since the dispensing with the reagent probe from the reagent container 40 to the analysis substrate 10 is performed in an amount required for 10 analyzes at a time, the number of operations of the reagent disk and the reagent probe is analyzed. Less than the number of times, an analyzer with high processing capability can be realized even with a low-speed dispensing mechanism.

  In the case of this embodiment, a reagent disk and a reagent probe are used, and the reagent probe is washed at the washing port. Therefore, different reagents can be supplied by a common dispensing mechanism, and there is no difference between the dispensing mechanisms. Accurate analysis is possible. In addition, the number of dispensing mechanisms is small, and a low-cost and space-saving analyzer can be realized.

  In the case of the present embodiment, since the reagent container is mounted on the reagent disk, it is not necessary to connect the reagent container and the analysis substrate with a pipe, and the reagent can be replaced easily.

  Further, in the case of the present embodiment, the dispensing of the sample probe 22 from the specimen container 21 to the analysis substrate 10 is performed in a single operation for the amount of a plurality of analyzes, so the number of operations of the sample probe 22 is the number of analyzes. Therefore, it is possible to realize an analyzer having a high throughput even with a low-speed dispensing mechanism.

  In the case of the present embodiment, since the reagent and the specimen are held in the reagent reservoir 85 and the sample reservoir 86, respectively, a predetermined amount is collected and transported to the analysis channel. In addition, it is possible to perform the analysis by reacting the sample and the reagent in any combination, and it is possible to realize an analyzer with high analysis efficiency and high processing capacity.

  In the case of the present embodiment, the size of each control electrode in the analysis channel is a size that holds a droplet of 4 microliters. Since the sample, the first reagent, the second reagent, the first reaction liquid, and the second reaction liquid have droplets of 4, 8, 4, 12, and 16 microliters, respectively, they are one, two, and one. Held by one, three, and four electrodes. Since it is configured to handle a plurality of droplets that are an integral multiple of the amount held by one control electrode and hold the droplets to a plurality of electrodes in this way, different sizes and types in a common path Droplets can be transported. As a result, it is possible to freely set the arrangement of the path of the specimen, reagent, drainage, etc., and the apparatus can be downsized. In particular, in the present embodiment, the flow path for supplying the sample and the reagent and the flow path for the drainage liquid are arranged so as to intersect with the analysis flow path, and the liquid droplets can freely move back and forth between them. This analysis can be performed in any analysis flow path, and the analysis is highly flexible and efficient.

  In the case of the present embodiment, the path for transporting droplets to the selected analysis channel from the sample port and the reagent port and the route for transporting droplets from the analysis channel to the drainage port are the other analysis channels. Pass through, but where to go can be selected from multiple routes. As a result, a route that does not interfere with other analysis can be selected, and an analyzer with high processing capability can be realized.

  Furthermore, in the case of this embodiment, analysis of each item can be performed in any analysis flow path, and since the transfer route can be selected from a plurality of, it is possible to avoid analysis even if there is a defective electrode. It is. Therefore, even if a defect occurs in a part of the analysis board, analysis cannot be performed, and it is possible to improve the reliability of the apparatus, reduce the frequency of replacement of the board, and reduce the running cost.

  In the case of the present embodiment, there are separate specimen and reagent droplet standby areas on the analysis flow path 80 and reaction areas, and the reaction area droplets can be discharged without passing through the standby area. Therefore, the next analysis can be executed immediately after the end of one analysis, and an analysis with high efficiency and high processing capability is possible.

  In the case of the present embodiment, since the analysis substrate 10 is circular, the photometer 50 can perform photometry of all the analysis flow paths 80 by a rotational movement, and there is no need to stop or change the direction, thereby wasting time. And a highly reliable analyzer can be realized.

  In this embodiment, the analysis substrate 10 is circular, and the first reagent channel 84, the sample channel 83, and the second reagent channel 82 are formed in a circumferential shape. It can be efficiently conveyed to all the analysis channels 80.

  In the case of the present embodiment, the width of the relay electrode 88 is narrower than the width of the electrode forming the analysis flow path 80. Therefore, the size of the analysis substrate 10 can be reduced, and a space-saving analyzer can be obtained. It is feasible.

  In the present embodiment, the photometer 50 measures absorbance, but it may measure scattered light or fluorescence. Further, a combination thereof may be used, and in that case, the types of items that can be analyzed are increased, and there is an advantage that immunoassay and the like can be realized with the same apparatus.

  In the present embodiment, one photometer is scanned, but two or more sets of photometers may be scanned. In that case, there is an advantage that the change in absorbance can be measured at short intervals.

  In this embodiment, the analysis substrate is a disc-shaped integrated structure, but can be divided into a plurality of fan-shaped substrates. In that case, it is possible to configure so that the droplets can move to another substrate, but it is also possible to configure so that oil and droplets do not move independently for each substrate. At that time, each divided substrate has a sample port, a reagent port, and a drainage port. In this case, since each substrate can be small, the equipment for manufacturing the substrate can be small, and can be manufactured at low cost. In addition, there is an advantage that substrate exchange and oil exchange can be easily performed.

  In this embodiment, the four transport channels in the circumferential direction are specialized for the same purpose of droplet transport as the sample, the first reagent, the second reagent, and the drain, respectively. It can also be used to select any flow path. Further, it is possible to control to select a flow path that can reach the target transport position quickly by fixing the transport direction for each flow path, providing a clockwise flow path and a counterclockwise flow path. In this case, an analysis apparatus with higher efficiency and high processing capability can be realized.

  In FIG. 1, the liquid transport mechanism is in a disk shape, but a sample supply path and reagent supply path are provided across each sample transport path, and a loop is formed in which the sample supply path and reagent supply path are closed. It should be. That is, if the sample transport path is radial, the same effect can be obtained even in a rectangular shape.

  Further, the measurement mechanism does not need to be a rotating photometer, and an LED as described in Non-Patent Document 1 may be provided in each sample transport path.

Next, a second embodiment of the present invention will be described. 8 is a perspective view of a second embodiment of the present invention, FIG. 9 is a top view of the analysis substrate 10, and FIG. 10 is a cross-sectional view showing a portion of the sample port 24. The main difference from the first embodiment is that the moving mechanism 51 and the photometer 50 are arranged inside the analysis substrate 10, and that the reagent disk 41, the first reagent probe 30, and the second reagent probe 35 are the analysis substrate 10. The dilution port 25 is installed in the vicinity of the sample port 24, the opening / closing mechanism 42 is installed in the proximity of the reagent disk 41, the reagent reservoir 85 and the sample reservoir 86. There is no. The arrangement of the analysis flow path 80 is the same as that in FIG. 4 except that the electrode a1 is on the outer peripheral side and the electrode a23 is on the inner peripheral side, unlike the case of the first embodiment.

  The dilution port 25 installed in the vicinity of the sample port 24 protrudes upward from the analysis substrate 10 similarly to the sample port 24, and the diluent probe 23 is inserted therein. The diluent probe 23 is connected to a diluent pump (not shown), and can discharge the diluent by controlling the amount.

  A snap cap 43 is provided at the opening of the reagent container 40 and can be opened and closed by an opening / closing mechanism 42.

In the second embodiment, the reagent is supplied to the analysis substrate 10 as follows. First, the snap cap 43 is opened by the opening / closing mechanism 42. Next, the reagent disk 41 is rotated to move the reagent container 40 to the suction position. In the case of the first reagent, 80 microliters is sucked by the first reagent probe 30 and discharged to the first reagent port 31. At that time, 8 microliters are divided into 10 times and discharged intermittently, and conveyed to the first reagent channel 84 as small droplets. The droplets orbit around the first reagent channel 84 until needed for analysis. In the case of the second reagent, 40 microliters are sucked by the second reagent probe 35 and discharged to the second reagent port 37. At that time, 4 microliters are intermittently ejected 10 times and are transported to the second reagent channel 82 as small droplets. The droplet circulates in the second reagent channel 82 until it is required for analysis. After the suction, the reagent container 40 is closed with the snap cap 43 by the opening / closing mechanism 42.

  The specimen is supplied to the analysis substrate 10 as follows. The sample disk 20 rotates and the sample is sucked from the sample container 21 by the sample probe 22. The sample probe 22 is moved and inserted into the sample port 24. The ejection is performed a number of times obtained by adding a preliminary number for retesting to the number of analyzes performed on the sample. Prior to the discharge of the specimen from the sample probe 22, the diluent is discharged from the diluent probe 23. The discharge amount of the diluent and the sample is controlled by the control device 12 so as to be an amount determined according to the analysis item. The sample liquid 75 discharged from the sample probe 22 is conveyed to the selected analysis flow path 80 via the sample flow path 83 while being mixed with the dilution liquid 76 discharged from the dilution liquid probe 23. Preliminary droplets for reexamination do not enter the analysis flow path 80 and go around the sample flow path 83.

  The analysis procedure in the analysis flow path 80 is the same as in the first embodiment. When the second reaction time is over and the analysis is finished, the control device 12 calculates the concentration of the analysis item, and if the result is out of the predetermined range, the retest is performed using a preliminary drop for retesting. To do. When retesting is not necessary, preliminary droplets for retesting are discharged from the drainage port 48.

  In the case of the present embodiment, the specimens and reagents for a plurality of analyzes are separated into droplets of a size required for individual analysis when injected into the analysis substrate 10 and provided to the transport channel, so that a large-capacity liquid reservoir is not necessary. A compact analyzer can be realized.

  In the case of the present embodiment, since the sample and the reagent are dispensed from the probe in a single amount and separated into droplets, the volume of the droplets can be controlled with high accuracy and high accuracy. Analysis is possible.

  In the case of this embodiment, since the reagent is not stored in a large-capacity liquid reservoir, it is possible to realize an analyzer with little reagent waste and low running cost.

  In the case of the present embodiment, the specimen is discharged into the diluent and separated into droplets. Therefore, even in specimens with different characteristics such as viscosity, the difference in characteristics is alleviated by the diluent, and high-precision dispensing is possible. It is possible and a highly accurate analysis is possible.

  Furthermore, since the amount of the diluted solution and the amount of the specimen can be changed for each droplet, an optimal dilution rate can be set for the analysis item, and high-precision analysis is possible.

  In the case of the present embodiment, the specimen for reexamination is made to circulate on the sample flow path 83 as a droplet, and the analysis is performed when the reexamination is necessary. Since it is not necessary to leave the sample container 21 for reinspection and the required number of sample disks 20 is small, a space-saving analyzer can be realized.

  In the case of this embodiment, since the reagent for a plurality of times is sucked from the reagent container at one time, the snap cap 43 can be closed by the opening / closing mechanism 42 after the reagent is sucked from the reagent container 40, Alteration can be prevented, and running costs can be reduced and analysis accuracy can be improved.

  In the case of the present embodiment, since the photometer 50 and the moving mechanism 51 are inside the analysis substrate 10, the rotation radius of the moving mechanism 51 is small, and a small and highly reliable analyzer can be realized.

In the case of the present embodiment, the sample disk 20 and the reagent disk 41 are outside the analysis substrate 10, so that the specimen and reagent can be easily replaced and replenished even during operation.

The perspective view which shows the structure of the outline of the analyzer of 1st Example. Sectional drawing which shows the principal part of the analysis board | substrate of 1st Example. The top view which shows schematic structure of the analysis board | substrate of 1st Example. The top view which shows the principal part of the analysis flow path of 1st Example. The top view which shows the reagent port and reagent reservoir principal part of 1st Example. Sectional drawing which shows the principal part of the reagent port of 1st Example. Sectional drawing which shows the principal part of the drainage port of 1st Example. The perspective view which shows the structure of the outline of the analyzer of 2nd Example. The top view which shows schematic structure of the analysis board | substrate of 2nd Example. Sectional drawing which shows the principal part of the sample port of 1st Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Analysis board | substrate, 12 ... Control apparatus, 13 ... Display apparatus, 20 ... Sample disk, 21 ... Sample container, 22 ... Sample probe, 23 ... Diluent probe, 24 ... Sample port, 25 ... Dilution port, 26 ... Washing port , 30 ... 1st reagent probe, 31 ... 1st reagent port, 35 ... 2nd reagent probe, 37 ... 2nd reagent port, 40 ... Reagent container, 41 ... Reagent disc, 42 ... Opening / closing mechanism, 43 ... Snap cap, 47 ... drainage tube, 48 ... drainage port, 50 ... photometer, 51 ... moving mechanism, 60 ... first substrate, 61 ... common electrode, 62, 66,
68 ... Water repellent film, 63 ... Second substrate, 64 ... Control electrode, 65 ... Insulating film, 67 ... Spacer, 70 ... Droplet, 71 ... Oil, 73 ... Waste liquid, 75 ... Sample liquid, 76 ... Diluent liquid, 80 ... analysis channel,
81 ... Drainage channel, 82 ... Second reagent channel, 83 ... Sample channel, 84 ... First reagent channel, 85 ... Reagent reservoir, 86 ... Sample reservoir, 87 ... Supply channel, 88 ... Relay electrode, 90, 91 ... route.

Claims (11)

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 a gap,
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,
The liquid transport path includes at least a sample transport path for transporting the sample liquid radially, and a reagent transport path that crosses the sample transport path and supplies reagents to the plurality of sample transport paths. Mechanism,
A sample distribution mechanism for supplying a sample to the sample transport path;
A reagent distribution mechanism for supplying a reagent to the reagent transport path;
A measurement mechanism for optically analyzing the reaction between the specimen and the reagent in the liquid conveyance path;
An automatic analyzer characterized by comprising: The automatic analyzer according to claim 1, wherein
The automatic analyzer further includes a sample flow path that crosses the sample transfer path and supplies a sample to the plurality of sample transfer paths in the liquid transfer path. The automatic analyzer according to claim 2,
An automatic analyzer comprising: a plurality of sample supply mechanisms for supplying different samples to the sample flow paths; and a plurality of reagent supply mechanisms for supplying different reagents to the reagent transport paths. The automatic analyzer according to claim 3,
An automatic analyzer, wherein the sample supply mechanism and the reagent supply mechanism are each provided with a sample reservoir or a reagent reservoir for temporarily storing a specimen or a reagent that can be analyzed a plurality of times. In the automatic analyzer in any one of Claims 1-4,
An automatic analyzer comprising a waste liquid flow path that discharges a reaction liquid that has been analyzed from a plurality of the sample transport paths across the sample transport path. The automatic analyzer according to claim 5, wherein
An automatic analyzer comprising: a waste liquid port for taking out the waste liquid from the waste liquid channel to the outside of the liquid transport mechanism; and a waste liquid suction mechanism that is inserted into the waste liquid port and sucks the waste liquid. In the automatic analyzer in any one of Claims 1-6,
The measurement mechanism is a photometer including a light source and a light receiver that receives light emitted from the light source and transmitted through the reaction solution, and changes a relative positional relationship between the photometer and the plurality of sample transport paths. An automatic analyzer comprising a positional relationship changing mechanism. The automatic analyzer according to claim 7,
2. The automatic analyzer according to claim 1, wherein the relative positional relationship changing mechanism is a moving mechanism of the photometer, and rotates around the outer periphery or inner periphery of the sample transport path. The automatic analyzer according to claim 4,
The reagent reservoir is provided with a droplet dividing mechanism for dividing the reagent reservoir into a quantity of droplets required for one analysis in a reagent transport path connected to the reagent reservoir and transporting it to the sample transport path apparatus. The automatic analyzer according to claim 3,
2. The automatic analyzer according to claim 1, wherein the sample supply mechanism includes a sample probe for sucking a sample from a sample container, a sample probe moving mechanism for moving the sample probe, and a sample port for inserting the sample probe. In the automatic analyzer according to any one of claims 1 to 10,
An automatic analyzer comprising a diluent supply port for supplying a diluent for diluting a specimen in the vicinity of the sample port.

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