JP2007183140A - Chemical analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a chemical analyzer capable of enhancing reliability of an analytical process itself concerned in a flow of a sample or a reagent. <P>SOLUTION: This chemical analyzer has a holding disk 12 supported rotatably by a motor 11, and a plurality of inspection modules 2 filled with the liquid sample or the reagent and mounted on the holding disk, and is constituted to operate the holding disk according to protocols of a rotational speed, a rotation time and a stop time required for the analytical process, and to analyze the liquid sample or the reagent while fluidized. In the chemical analyzer, an imbalance amount accompanied to the rotation of the holding disk and a generation angle from a reference point therein are found to determine a trouble as to the flow of the liquid sample or the reagent, in relation to at least either of the imbalance amount or the generation angle. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a chemical analyzer that extracts and analyzes a specific chemical substance in a liquid sample, and is particularly suitable for a device that extracts, amplifies, and detects viral nucleic acid using whole blood as a sample.

Conventionally, as a chemical analysis device that extracts and analyzes a specific chemical substance such as nucleic acid from a sample containing a plurality of chemical substances, the sample is quantified using the centripetal force of the rotating disk, and the rotation speed and rotation time are sequentially changed, A nucleic acid PCR (Polymerase Chain Reaction) gene amplification apparatus that extracts a nucleic acid by flowing a specific reagent is known, and is described in Patent Document 1, for example.

  It is also known to provide a resistive sensor in the flow path inside the cartridge containing the fluid sample and the lysis reagent, and detect the electrical output to detect the movement of the fluid sample and the lysis reagent. It is described in Document 2.

  Further, in a centrifuge, it is known to irradiate a germicidal lamp in order to detect an imbalance in a rotor chamber serving as a rotating body on which a sample is mounted and to sterilize the rotor chamber. Yes.

Special table 2003-502656 gazette JP-T-2001-527220 (paragraph 0046, FIG. 2) Japanese Patent No. 3641987

  In the above-described one disclosed in Patent Document 1, attention has not been paid to the flow quality of the sample and the reagent, and there is a possibility that the reliability of the analyzer may be impaired.

  In addition, in the case where the resistive sensor is provided in the flow path described in Patent Document 2, it is difficult to take out the output, and in particular, it is difficult to ensure reliability in order to detach the cartridge and make the cartridge disposable. It was also disadvantageous for lower prices.

  Furthermore, in the thing of patent document 3, only imbalance is detected and safety | security and reliability are improved, and the reliability of analysis itself does not improve, but was inadequate.

  The object of the present invention is to solve the above-mentioned problems of the prior art and improve the reliability of the analysis process itself related to the flow of samples and reagents. In particular, abnormalities in the extraction, amplification and detection processes of viral nucleic acids using whole blood as a sample The purpose of this is to improve the reliability by quickly identifying and quickly analyzing.

  In order to achieve the above object, the present invention includes a holding disk rotatably supported by a motor, and a plurality of test modules that are loaded with the liquid sample or reagent and are mounted on the holding disk. In a chemical analyzer for analyzing a liquid sample or reagent by operating the disk according to the rotation speed, rotation time, and stop time protocol required for the analysis process, the imbalance amount accompanying the rotation of the holding disk; A generation angle from a reference point is obtained, and a problem relating to the flow of the liquid sample or reagent is determined in relation to at least either the imbalance amount or the generation angle.

  According to the present invention, the imbalance amount associated with the rotation of the holding disk and the generation angle from the reference point are obtained, and defects related to the flow of the liquid sample or reagent inside the cartridge are determined. The flow quality of the sample or reagent can be easily determined. Therefore, even if the cartridge can be attached and detached, or the cartridge is made disposable, there is no fear of impairing the reliability of the analyzer.

  Hereinafter, an embodiment will be described in detail with reference to the drawings.

  FIG. 1 is an overall configuration diagram of a genetic test apparatus according to the present invention. A genetic analysis apparatus 1 includes a holding disk 12 rotatably supported by a motor 11 and a plurality of test modules 2 arranged on the holding disk 12. A punching machine 13 used for controlling the flow of the liquid, a heating device 14 and a detection device 15 are provided.

  The operator prepares the test module 2 for each test item, attaches it to the holding disk 12, and activates the genetic test apparatus 1. FIG. 2 is a configuration diagram of the inspection module 2. The inspection module 2 is configured by mounting the reagent cartridge 20 on the inspection cartridge 30, and the reagent cartridge 20 has a transparent reagent cartridge cover 22 bonded to the reagent cartridge main body 21, The inspection cartridge 30 has a transparent inspection cartridge cover 32 joined to an inspection cartridge main body 31.

  Each reagent is dispensed by a predetermined amount in each reagent container 220, 230, 240, 250, 260, 270, 280, 290 in advance. The reagent cartridge 20 (FIG. 3) is provided with reagent outlets 221, 231, 241, 251, 261, 271, 281, and 291 communicating with each reagent container, and the reagent cartridge 20 is attached to the test cartridge 30. Thus, the reagent cartridges 321, 331, 341, 361, 381, and 391 of the test cartridge 30 shown in FIG. When the reagent cartridge 20 is attached to the test cartridge 30, the reagent containers communicate with each other in the test cartridge through the reagent outlets and the corresponding reagent inlets.

  5 shows main portions of the longitudinal sectional view of the reagent cartridge 20 and the test cartridge 30 in the AA section shown in FIG. 2, and FIG. 6 shows the above-mentioned A- with the reagent cartridge 20 attached to the test cartridge 30. The longitudinal cross-sectional view corresponding to A part is shown.

  A reagent cartridge protective sheet 23 is adhered to the connection protrusion surface of the reagent cartridge 20 in order to prevent leakage and evaporation of the reagent stored in advance in the reagent cartridge 20. In order to prevent contamination inside 30, an inspection cartridge protection sheet 33 is adhered.

  The operator peels off the reagent cartridge protection sheet 23 and the inspection cartridge protection sheet 33 and attaches the reagent cartridge 20 to the inspection cartridge 30. The protrusions (for example, 299 in FIG. 5) serving as the reagent outlets are fitted with the reagent inlets, thereby positioning the cartridges and preventing the reagent from leaking out of the test cartridge. Further, by attaching an adhesive to the inspection cartridge cover 32 to which the inspection cartridge protective sheet is adhered, it is possible to adhere the joint surface of the reagent cartridge and prevent the reagent from leaking. Note that the protrusions provided on the reagent cartridge (for example, 299 in FIG. 5) are the same even if provided on the inspection cartridge side.

  Hereinafter, the extraction and analysis of viral nucleic acid when whole blood is used as a sample will be described.

  The operator injects whole blood collected by a vacuum blood collection tube or the like into the sample container 310 from the sample injection port 301 of the test cartridge 30 in FIG. 4, and the reagent cartridge protection sheet 23 and the test cartridge protection sheet 33 shown in FIG. After peeling off, the reagent cartridge 20 is mounted on the inspection cartridge 30 (FIG. 6).

  A necessary number of the assembled test modules 2 are mounted on the holding disk 12 of FIG. 1, the gene test apparatus 1 is operated, a virus gene is extracted from the whole blood, and finally the gene is amplified and detected. FIG. 7 shows the entire process chart of this inspection.

  The test is divided into a nucleic acid extraction step and an amplification step from whole blood. In the nucleic acid extraction step in the figure, the holding disk has a predetermined rotation speed and rotation time required for centrifugation and flow, and a stop time and the like. Operating according to the protocol, nucleic acids are extracted into a given port. In the amplification process, in the case of RNA testing for infectious diseases by the NASBA method, the reaction mixture in which the sample and nucleic acid extracted from the port are mixed is held at 65 ° C. for about 5 minutes, and then the enzyme is optimized. The temperature is lowered to 41 ° C. and the enzyme is added, and then kept at 41 ° C. for about 90 minutes. By measuring the fluorescence emission amount at this time in real time, the gene amount of the virus can be evaluated.

  Next, the flow state of the liquid in each operation within the genetic test apparatus 1 will be described with reference to FIG.

After injecting whole blood into the whole blood port 301, the holding disk 12 is rotated by the motor 11. The whole blood injected into the sample container 310 flows to the outer peripheral side by the action of the centrifugal force generated by the rotation of the holding disk 12, fills the blood cell storage container 311 and the serum quantitative container 312, and excess whole blood flows into the overflow tubule flow. It flows from the path 313 to the whole blood disposal container 315 through the overflow thick pipe channel 314. Since the connecting portion from the overflow narrow tube flow path 313 to the overflow large tube flow path 314 is abruptly expanded and is located on the innermost peripheral side (radius position 601) of the overflow thin tube flow path 313, the whole blood flows into the overflow narrow tube flow path. In a state where 313 is satisfied, the connection portion is cut. Accordingly, since there is no liquid on the inner peripheral side from the radial position 601, the liquid level of the serum quantitative container 312 is also in the radial position 601. The whole blood also flows into the serum capillary 316 branched from the serum quantification container 312, and the innermost peripheral portion of the whole blood is at the radial position 601 here.

  If the rotation continues further, the whole blood is separated into blood cells and serum or plasma (hereinafter referred to as serum) (centrifugation), the blood cells move to the blood cell storage container 311 on the outer peripheral side, and the serum quantitative container 312 contains only serum. .

  During the above series of serum separation operations, the vent holes (for example, 222 part of the reagent container 220) of each reagent container in the reagent cartridge 20 are covered with the reagent cartridge cover 22 (FIG. 5) so that air does not enter. It has become. Each reagent flows out from the outer peripheral side of the reagent container due to the centrifugal force. However, since air does not enter the container, the pressure in the reagent container decreases, and the reagent cannot flow out in balance with the centrifugal force. However, when the rotational speed increases and the centrifugal force increases, the pressure in the reagent container gradually decreases, and bubbles are generated when the pressure is lower than the saturated vapor pressure of the reagent. Therefore, as shown in FIG. 8, by setting a flow path (for example, the return flow path 223 of the reagent container 220) that returns the reagent flowing out from the outer peripheral side of each reagent container to the inner peripheral side, Suppresses pressure drop and prevents bubbles. Therefore, during the serum separation operation, each reagent does not flow while being held in the reagent container.

  When the serum separation operation is completed after rotating for a predetermined time, the test module 2 is stopped, and a part of the serum in the serum quantitative container 312 flows into the capillary capillary 316 by surface tension due to surface tension, and is connected to the serum capillary 316. To the mixing unit 410, which fills the serum capillary 316.

  Next, one hole is made in the vent hole upstream of each reagent container by the punching machine 13, and the motor 11 is further rotated to cause each reagent to flow by centrifugal force.

  Next, the operation after completion of serum separation will be described.

  The lysing solution container 220 is dispensed with a lysing solution for dissolving the viral membrane protein in the serum. When the motor 11 is rotated after the perforator 13 has made a hole in the solution vent hole 222, the solution flows from the solution container 220 through the solution return channel 223 into the mixing unit 410 due to the action of centrifugal force. .

Further, since the innermost peripheral side of serum in the serum quantitative container 312 (radial position 601 at the end of serum separation) is located on the inner peripheral side from the mixing unit 410 (radial position 602), the serum quantitative container 312 is caused by a head difference due to centrifugal force. The serum in the serum capillary 316 flows into the mixing unit 410. The mixing unit 410 is composed of a member that mixes serum and lysate, and is composed of a porous filter or fiber such as resin, glass, or paper, or a protrusion such as silicon or metal manufactured by etching or machining. .

Serum and lysate are mixed in the mixing unit 410 and flow into the reaction vessel 420. Since the branching portion 317 (radius position 603) from the serum quantitative container 312 to the serum capillary 316 is located on the inner peripheral side from the mixing portion 410 (radius position 602), all the serum in the serum capillary 316 is transferred to the mixing portion 410 due to the siphon effect. Flows out. On the other hand, since the serum in the serum quantitative container 312 flows into the serum capillary 316 by centrifugal force, the serum flows out to the mixing part 410 until the liquid level of the serum in the serum quantitative container 312 reaches the branching portion 317 (radius position 603). Then, when the serum level reaches the branching portion 317, air enters the serum capillary 316 and becomes empty, and the flow ends. That is, the serum in the serum quantitative container 312, the overflow capillary channel 313 and the serum capillary channel 316 from the radial position 601 to the radial position 603 at the end of serum separation flows out into the mixing unit 410 and is mixed with the lysate.

  If the serum quantification container 312, the overflow capillary channel 313 and the serum capillary channel 316 from the radial position 601 to the radial position 603 are designed to have a predetermined volume (required serum amount), the ratio of serum to whole blood is whole blood. Even if it differs from sample to sample, the serum used for the analysis can be quantified. For example, when the blood cell storage container has a volume of 250 microliters and the required serum volume is designed to be 200 microliters, if 500 microliters of whole blood is dispensed, 50 microliters of whole blood overflows into the whole blood disposal container 315. The remaining 450 microliters is separated into serum and blood cells, and 200 microliters of the separated serum flows out to the mixing unit 410. With this device, it is possible to analyze a whole blood sample having a serum amount of 200 microliters or more with respect to 450 microliters of whole blood. For whole blood with a low serum ratio, the volume of the blood cell storage container may be increased to increase the number of whole blood samples.

  In the reaction container 420, the mixed serum and the lysate react. Since the liquid level in the reaction vessel 420 after the mixed solution of serum and lysate flows into the reaction vessel 420 is on the outer peripheral side of the innermost peripheral portion (radius position 604) of the reaction solution flow path 421, the reaction solution The innermost peripheral portion of the flow path 421 cannot be exceeded, and the mixed liquid is held in the reaction vessel 420 during rotation.

  The lysing solution functions to dissolve the membrane from viruses, bacteria, and the like in the serum to elute the nucleic acid, and further promotes adsorption of the nucleic acid to the nucleic acid binding member 301. As such a reagent, guanidine hydrochloride may be used for elution and adsorption of DNA, guanidine thiocyanate may be used for RNA, and a porous material such as quartz or glass or a fiber filter may be used as the nucleic acid binding member.

  After the serum and the lysate are held in the reaction container 420, the motor 11 is stopped, the additional liquid vent hole 232 for supplying air to the additional liquid container 230 is made by the punching machine 13, and the motor 11 is rotated again. Then, the additional liquid flows from the additional liquid container 230 through the additional liquid return channel 233 into the reaction container 420 by the action of the centrifugal force, and moves the liquid level of the mixed liquid in the reaction container to the inner peripheral side. When the liquid level reaches the innermost peripheral part (radius position 604) of the reaction liquid flow path 421, the mixed liquid flows out beyond the innermost peripheral part of the reaction liquid flow path, and passes through the converging flow path 701 to the nucleic acid binding member 301. Flows in. As the additional liquid, for example, the above-described dissolving liquid may be used. Note that, depending on the sample, the wettability of the mixed liquid to the wall surface is good, and in the stopped state, the mixed liquid may flow in the reaction liquid channel 421 by capillary action, and in this case, no additional liquid is required.

  When the mixed solution of the lysate and serum passes through the nucleic acid binding member, the target nucleic acid in the serum and the nucleic acid as an internal control are adsorbed on the nucleic acid binding member 301, and the liquid flows into the eluent recovery container 390.

The waste liquid after passing through the nucleic acid binding member 301 is once held in the eluent recovery container 390 for the waste liquid return flow path 393 as in the case of the mixing container 420. Since the volume is sufficiently small, the waste liquid passes the innermost peripheral side of the waste liquid return flow path 393 and flows out to the waste liquid storage container 402 through the waste liquid outflow path 399.

Next, when the motor 11 is stopped and the perforator 13 opens a hole in the first cleaning liquid vent 242 for supplying air to the first cleaning liquid container 240, and then the motor 11 is rotated again, the centrifugal force acts. The first cleaning liquid flows from the first cleaning liquid container 240 into the nucleic acid binding member 301 via the first cleaning liquid return flow path 243 and the merge flow path 701 to wash unnecessary components such as proteins adhering to the nucleic acid binding member 301. As the first cleaning liquid, for example, the above-described dissolution liquid or a liquid with a reduced salt concentration may be used. The waste liquid after washing flows out to the waste liquid storage container 402 through the eluent recovery container 390, like the above-described mixed liquid.

  The same cleaning operation is repeated several times. Following the first cleaning liquid, with the motor stopped, the perforator 13 opens a hole in the second cleaning liquid vent hole 252 for supplying air to the second cleaning liquid container 250, rotates the motor 11 again, and causes the nucleic acid binding member 301 to rotate. Wash away unnecessary components such as attached salt. As the second cleaning liquid, for example, ethanol or an aqueous ethanol solution may be used.

  Similarly, a hole is made in the lid of the third cleaning liquid vent hole 262 for supplying air to the third cleaning liquid container 260. The third cleaning liquid flows directly into the eluent recovery container 390 and cleans components such as salt attached to the eluent recovery container 390. As the third cleaning liquid, for example, sterilized water or an aqueous solution whose pH is adjusted to 7 to 9 may be used.

  Next, after the nucleic acid binding member 301 and the eluent recovery container 390 are washed, the process proceeds to a nucleic acid elution step.

  With the motor stopped, a hole is made in the lid of the eluent vent hole 272 for supplying air to the eluent container 270 by the perforator 13 and the motor 11 is rotated again to flow the eluent through the nucleic acid binding member 301. The eluent is a liquid that elutes nucleic acid from the nucleic acid binding member 301, and water or an aqueous solution adjusted to pH 7 to 9 may be used. In particular, it is desirable to heat to 40 degrees or more in order to facilitate elution. The heating device 14 shown in FIG. 1 is used for heating. After the elution, the sample flows into a cuvette 390 that becomes a cuvette for a detection process.

  Next, the first reagent solution in the first reagent solution container 280 is caused to flow by perforation. The test cartridge 30 flows into the test container 390 while dissolving the first reagent obtained by drying the internal control or the amplification reagent containing the fluorescent dye as the first reagent. After maintaining at the first reaction temperature, for example, 65 ° C. for 5 minutes, and reaching the second reaction temperature, for example, 41 ° C., the second reagent solution 290 container is punctured to flow the second reagent solution. The inspection cartridge 30 at the end of the flow path reaches the inspection container 390 while dissolving the freeze-dried enzyme serving as the second reagent.

  Next, gene amplification is performed by holding at a second reaction temperature of 41 ° C. for 90 minutes. By rotating the holding disk 2 during this time, the detection device 15 is moved under the eluent recovery container 390 serving as a test container, and the fluorescence emission amounts of the target nucleic acid and the internal control nucleic acid are detected.

  Internal controls are pre-quantified nucleic acids or synthetic products containing nucleic acids, and are extracted, amplified, and detected using exactly the same reagents, cartridges, and testing equipment as the extraction, amplification, and detection of target nucleic acids in serum. Therefore, if the extraction / amplification / detection steps are functioning normally, a signal such as predetermined fluorescence or absorbance can be detected from the internal control. On the other hand, if the signal intensity is low and not detected at all, it can be seen that there is an abnormality in any of the extraction, amplification, and detection processes due to a defect in the reagent, cartridge, inspection device, or the like. Further, the target nucleic acid concentration can be quantitatively evaluated by comparing the detection signal of the target nucleic acid with the detection signal of the internal control that has been quantified in advance.

  Next, details of the genetic testing device are shown in a block diagram. This will be described with reference to FIG.

  A plurality of inspection modules 2 are mounted on the holding disk 12, and a vibration meter 801 is attached to the surface of the motor 11 at two upper and lower bearing outer peripheral portions. An optical tachometer 802 is attached to the rotation shaft 807, and the rotation angle of the shaft 807 is detected, and the rotation speed is obtained from the rotation angle for a fixed time. Signals from the vibrometer 801 and the tachometer 802 are guided to an imbalance detection device 803, and the rotation speed, rotation time, and rest time of the motor 11 are controlled by the protocol control device 804. Further, the signal of the imbalance detection device 803 and the signal of the protocol control device 804 are led to the failure location determination device 805, and the signals of the protocol control device 804 and the failure location determination device finally reach the display device 806.

The imbalance caused by the flow failure of the sample and reagent of the cartridge is detected by the vibrometer 801, and the imbalance detection device 803 detects the imbalance from the absolute value of the imbalance and the reference point based on the output of the vibrometer and the signal of the tachometer 802. The generation angle is calculated.

  The generated angle from the imbalance reference point is obtained by measuring the largest angle of the amplitude signal of the vibrometer 801 with the tachometer 802. As the tachometer, a high-resolution rotary encoder is suitable.

  The absolute amount of imbalance is the same as that for a general rotating body imbalance correction device. The correlation between the amount and the amplitude obtained by the vibrometer 801 is obtained in advance, and the absolute amount of imbalance is calculated from the amplitude obtained by the vibrometer 801 when the actual rotation speed is a predetermined number of revolutions and the previous correlation.

  During operation, the defect location determination device 805 always receives signals from the imbalance detection device 803 and the protocol control device 804, while the protocol control device 804 monitors which reagent is flowing. Therefore, it is possible to determine which reagent flows when an imbalance has occurred, based on a signal from the imbalance detection device 803. It is also possible to determine which inspection cartridge has been generated by verifying with the previous imbalance generation angle. Further, the result of the defect is displayed on the display device 806 as a defective cartridge and a defective reagent.

  As described above, the flow defect can be detected and determined. However, a flow defect in which the imbalance of a plurality of inspection cartridges on the disk is offset, for example, a flow defect in which all the inspection cartridges on the disk are generated simultaneously cannot be detected. However, when a flow failure occurs in several test cartridges, the imbalance amount obtained by vector synthesis of each and the angle from the reference point are detected, so that the imbalance occurrence angle is not on the test cartridge. Thus, it can be seen that this occurred in a plurality of cartridges.

  With reference to FIG. 10 and subsequent figures, a case where an imbalance due to a flow failure occurs will be described.

  FIG. 10 shows a state in which six inspection modules 2 are mounted on the holding disk 12, and two inspection cartridges 201 are arranged in pairs, each at an equal angle of 60 degrees, with the rotation shaft 807 as the center. . The hatched portion of each container shows the specimen and reagent, and shows the state after the test cartridge is rotated for whole blood centrifugation.

  In this example, the air holes are insufficiently pierced in one cartridge, the flow defect occurs, and the whole blood does not flow. That is, in the five cartridges including 204, the whole blood flows to the blood cell storage container 311 up to a position having the rotation radius circle 605 as the inner periphery, but in the test cartridge 201, the whole blood flows from the whole blood container 310. Absent. Such a case is one of the flow failure phenomena, and the test cannot be performed normally because the sample does not flow. Therefore, in the worst case as it is, there is a possibility that a negative test result is obtained even in a positive sample, and a flow defect is determined together with the internal control.

  FIG. 11 shows another example of the failure phenomenon, in which the third cleaning liquid 260 flows about halfway forward in only one cartridge of the inspection cartridge 201, and the gas-liquid interface having the radial position circle 606 as the inner periphery in the container. Is done. Also in this case, the reaction port 390 is not sufficiently cleaned, and there is a concern about abnormal inspection. Even when washing of the inhibitor of nucleic acid amplification is insufficient, gene amplification is inhibited, resulting in an erroneous test result.

  FIG. 12 schematically shows the force imbalance (imbalance) in FIG. 11, and the six test cartridges on the holding disk 12 are indicated by broken lines. The third cleaning liquid of the cartridge 204 that opposes the cartridge 201 from which the third cleaning liquid 260 has flowed out first is full. Therefore, this corresponds to the occurrence of an unbalanced weight m for the reagent that pre-flowed from the reference position of 201 to the position of angle θ from the reference position of 201 at the position of radius r from the center of rotation in the third cleaning liquid portion of test cartridge 201. When rotating at high speed in this state, vibration due to unbalance increases. Therefore, the imbalance weight and position are detected by the imbalance detection device, and the position is analyzed by the failure location determination device, thereby specifying the failure cartridge and the type of reagent. In addition, the operator can confirm from the display that a problem of the flow failure of the third cleaning liquid has occurred in the inspection cartridge 201 during the inspection. Furthermore, at the initial stage of the inspection, the operator can add the third cleaning liquid and restart the inspection again.

  FIG. 13 is a diagram for explaining the above procedure. The horizontal axis indicates the progress of the protocol required for the analysis step, and the vertical axis indicates the detected imbalance amount. In FIG. 13A, a broken line indicates a normal inspection, and the inspection ends with a predetermined small imbalance amount. On the other hand, the solid line indicates the case where the reagent leaks to the outside due to some factor in the protocol of reagent 1 starting from the flow of the whole blood of the specimen. From the figure, it can be seen that a small imbalance amount immediately after the start of the protocol is instantly changed to a large imbalance amount simultaneously with the occurrence of a liquid leak. Further, in the subsequent protocol, the liquids of the other cartridges also move sequentially toward the outer peripheral side, so that the difference in the imbalance amount tends to become smaller as the protocol progresses.

  The dotted line in FIG. 13 (b) shows an example in which the flow of the reagent is delayed, and when the flow of the reagent 1 is delayed for some reason, the imbalance amount increases from the moment of delay as shown in the figure. . In this case, the maximum imbalance amount is smaller than that in FIG. 13A, and the imbalance amount becomes a normal value if it returns to normal. However, when it does not flow even at the final time point, it tends to be larger than the value indicated by normal flow as shown in FIG.

  The imbalance amount is deliberately preliminarily leaked, leading flow, etc., and a simulation test is performed to find and record the absolute value and change pattern of the imbalance amount, and compare it with the actual case. By doing so, it is determined what kind of event has occurred.

  In addition, as a method of acquiring an imbalance pattern assumed on a desk, an unbalance amount and an angle are obtained by assuming a flow defect for each of a plurality of reagents in one test cartridge. (This can be easily done by using a three-dimensional CAD in which the shape of the test cartridge, the amount of reagent encapsulated, and the specific gravity are input.) And, the problem with one cartridge is actually compared with this data. Is possible.

  In addition, if it is assumed that a flow failure occurs in multiple cartridges, vector synthesis is performed for the unbalanced amount of multiple cartridges and the angle from the reference point, and multiple possible patterns are acquired in advance. Therefore, the pattern closest to the imbalance change of the actual flow failure may be set as the flow failure pattern. In the imbalance pattern comparison, the relationship between the protocol and the imbalance amount is compared with an assumed pattern by using a personal computer.

  FIG. 14 shows a case where the liquids of the five inspection cartridges represented by the other 203 flow into the waste liquid storage container 402 without the liquid of the inspection cartridge 201 flowing at all. Even in this case, a large imbalance causes a problem that the apparatus vibrates greatly.

  FIG. 15 shows the movement of the center of gravity of the cartridge accompanying the actual movement of the liquid. The horizontal axis of the figure shows the length of the cartridge from the center of the shaft and the position in the centrifugal direction, and the vertical axis shows the direction perpendicular to it. Indicates the position. FIG. 15A corresponds to the situation of FIG. 12, and shows a change when one sample of the cartridge moves. Since the liquid weight is constant at 0.5 gram, the unbalanced amount of movement of the center of gravity is detected as the imbalance amount.

  FIG. 15B corresponds to a situation where the entire liquid of one cartridge in FIG. 14 has moved to the waste liquid storage container. In this case as well, the liquid weight of 3 grams is constant, and the movement of the center of gravity of the cartridge in which all the liquid has moved to the outer peripheral side from the initial liquid position changes the imbalance amount.

The perspective view which shows the genetic test | inspection apparatus by one Embodiment in this invention. The perspective view which shows the test | inspection module by one Embodiment. The perspective view which shows a reagent cartridge among the test | inspection modules in FIG. The perspective view which shows a test | inspection cartridge among the test | inspection modules in FIG. FIG. 5 is a partial sectional view showing the reagent and the test cartridge in FIGS. 3 and 4 when they are not connected. The fragmentary sectional view which shows the time of the connection of the reagent and test | inspection cartridge in FIG. 3, FIG. The flowchart showing the flow of the inspection process by one embodiment. The front view which shows the flow path and liquid flow of the test | inspection module by one Embodiment. The block diagram of the analyzer by one embodiment. The front view which shows an example of the flow defect in one embodiment. The front view which shows the other example of the flow defect in one Embodiment. FIG. 12 is a schematic diagram for explaining the relationship between a flow failure and imbalance in FIG. 11. The graph which shows the relationship between the flow defect in the analysis protocol in one Embodiment, and an imbalance. The front view which shows the further another example of the flow defect in one Embodiment. The graph which shows the relationship between the flow defect and imbalance in one embodiment.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Gene test | inspection apparatus (chemical analyzer), 2 ... Test module, 11 ... Motor, 12 ... Holding disk, 801 ... Vibrometer, 802 ... Tachometer, 803 ... Imbalance detection apparatus, 804 ... Protocol control apparatus, 805 ... Defective point determination device, 806... Display device, 807.

Claims (8)

A holding disk that is rotatably supported by a motor, and a plurality of test modules in which a liquid sample or a reagent is placed and attached to the holding disk, and the rotation speed required for the analysis step of the holding disk; In a chemical analyzer that operates according to the protocol of rotation time and stop time and analyzes the liquid sample or reagent by flowing,
Obtaining an imbalance amount accompanying the rotation of the holding disk and a generation angle from a reference point, and determining a problem relating to the flow of the liquid sample or reagent in relation to at least either the imbalance amount or the generation angle. Characteristic chemical analyzer.   The apparatus according to claim 1, comprising: a vibrometer that detects vibration associated with rotation of the holding disk; and a tachometer that detects a rotation angle of the holding disk, and the output of the vibrometer and the tachometer A chemical analyzer for calculating an imbalance amount and a generation angle from a reference point.   The chemical analysis apparatus according to claim 1, wherein the inspection module in which a defect has occurred related to the generation angle is specified.   The chemical analyzer according to claim 1, wherein the imbalance amount is calculated with the progress of the analysis step, and liquid leakage or flow delay of the liquid sample or reagent is determined.   The liquid sample or reagent is specified and displayed together with the inspection module determined to be defective in the analysis step in relation to the imbalance amount and the generation angle. Chemical analysis equipment.   2. The apparatus according to claim 1, wherein when the value detected by the vibrometer is detected to be larger than a predetermined value, the liquid sample or reagent flowed in the analysis step is displayed as a defect. Chemical analyzer.   2. The liquid according to claim 1, wherein a state in which the flow of the liquid sample or reagent is abnormal is determined in advance, the imbalance amount at that time is recorded, and the liquid generated in the analysis step based on the recorded value A chemical analysis device characterized by identifying a defect related to a flow of a sample or a reagent. 2. The liquid sample or the liquid sample according to claim 1, wherein the imbalance amount is calculated as the analysis step proceeds, and the liquid sample or the inspection module determined to be defective based on the imbalance amount and the generation angle. A chemical analyzer characterized by identifying and displaying reagent leakage.

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