JP5837449B2 - Nucleic acid testing apparatus, method for determining allocation of reaction waiting container, and program - Google Patents

Description

  The present invention relates to a nucleic acid test apparatus for a specimen derived from a living body, an allocation determination method and a program for a waiting reaction container.

  Nucleic acid amplification techniques are used for testing nucleic acids contained in biological samples. Examples of the nucleic acid amplification technique include a polymerase chain reaction (hereinafter referred to as “PCR”) method. In the PCR method, the temperature of a reaction solution in which a sample and a reagent are mixed is controlled according to predetermined conditions, and a target base sequence is specifically amplified to detect a very small amount of nucleic acid with high sensitivity. In the nucleic acid amplification method, various conditions (protocols) such as a reagent to be used, a set temperature, and an inspection time are different depending on a measurement item (a base sequence to be amplified).

  Patent Document 1 describes an analyzer that uses a plurality of blocks with temperature adjustment functions (hereinafter referred to as “temperature control blocks”) and can analyze different analysis items in parallel. The plurality of temperature control blocks are arranged along the outer periphery of a holder base formed in a disc shape, and each temperature control block holds a reaction vessel containing a reaction liquid. Each temperature control block is provided with a temperature adjusting device capable of individually controlling the temperature. Through the control of the temperature adjusting device, the analyzer described in Patent Document 1 individually adjusts the reaction temperature of each reaction solution corresponding to each block. That is, the analyzer of Patent Document 1 can control the temperature of each temperature control block and the timing of temperature change independently of other temperature control blocks. With this mechanism, the analyzer of Patent Document 1 can process a plurality of types of samples having different measurement items in parallel, and can also start processing another sample during the processing of one sample. it can. Note that the temperature adjustment device is configured by, for example, a Peltier element.

Japanese Unexamined Patent Publication No. 2011-234639

  In nucleic acid amplification, when multiple types of specimens with different measurement items are processed in parallel, the protocol for each measurement item, that is, the temperature specified in the temperature control procedure such as the set temperature and the holding time of the temperature, and the control time are set. It is necessary to set for each measurement item.

  However, when the temperature of the reaction solution is individually adjusted using a plurality of temperature adjusting devices, there are individual differences in the “temperature control ability such as time required for temperature change” of each temperature adjusting device. In addition, the temperature control capability of each temperature adjusting device varies depending on the individual deterioration state. As described above, the actual time required for the inspection depends on the temperature control capability of the temperature control block to be used. For example, when a temperature control block having a high temperature control capability is used, the inspection time is shorter than the theoretical inspection time.

  Therefore, the present invention presupposes the use of a plurality of temperature control devices having different temperature control capabilities, and a nucleic acid test device capable of realizing an efficient nucleic acid test according to the test purpose, and determination of the allocation of test waiting reaction containers therefor Provide a method.

  The present invention provides a nucleic acid test apparatus for amplifying and testing a nucleic acid contained in a reaction solution, a plurality of temperature control blocks each holding at least one reaction container containing the reaction solution, and each of the plurality of temperature control blocks A temperature adjusting device that adjusts the temperature of the reaction solution, an arm that delivers a reaction vessel between the temperature control block, the arm, and the temperature control capability and inspection of each temperature adjusting device Based on the contents, a control unit that determines the allocation relationship between the reaction waiting container and the temperature control block is provided.

  According to the present invention, inspection efficiency can be improved by efficiently using a plurality of temperature control blocks having different temperature control capabilities. Problems, configurations, and effects other than those described above will become apparent from the following description of embodiments.

The figure which shows roughly the whole structure of a nucleic acid test | inspection apparatus. The top view which shows schematic structure of a nucleic acid amplifier. The figure explaining the progress procedure of analysis processing, and exchange of data. The figure which illustrates an example of a temperature control protocol notionally. The figure explaining the difference in the inspection time by the difference in the temperature control capability of a temperature control block. The figure which shows an example of the relationship between the evaluation point which gives the temperature control capability of a temperature control block, and a priority. The flowchart which shows the process sequence performed when evaluating temperature control capability. The figure which shows an example of the conversion table used when converting each evaluation item into an evaluation score. The flowchart explaining the operation mode which gives priority to the output of the test result of a standard sample. The figure explaining the difference in the inspection time when not assigning when the reaction container containing a standard sample is assigned to the temperature control block with high temperature control capability. The flowchart explaining the operation mode which gives priority to all inspection time length. The figure explaining the difference in inspection time when not assigning when the reaction container with long inspection time is assigned to the temperature control block with high temperature control capability. The flowchart explaining the operation mode which gives priority to the number of processed samples. The figure explaining the difference in inspection time when not assigning when the reaction container with short inspection time is assigned to the temperature control block with high temperature control capability. The figure explaining the operation mode which allocates the reaction container after waiting for the temperature control block with high temperature control capability to be vacant. The figure explaining the difference between the inspection time when starting an analysis immediately using an unused temperature control block and the inspection time when starting an analysis after waiting for a temperature control block with high temperature control capability to be available. The figure explaining the operation mode which changes the allocation of the reaction container under test | inspection when the temperature control block with high temperature control capability is vacated after the start of a test | inspection. The figure explaining the difference in test | inspection time when not changing the case where the reaction container under test | inspection is changed to the temperature block with high temperature control capability.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. The embodiment of the present invention is not limited to the embodiments described later, and various modifications can be made within the scope of the technical idea.

[Overall configuration of nucleic acid testing device]
In FIG. 1, the schematic structure of the whole structure of the nucleic acid test | inspection apparatus 100 which concerns on this embodiment is shown. A nucleic acid test apparatus 100 shown in FIG. 1 includes a plurality of sample containers 101 containing specimens containing nucleic acids to be amplified, a sample container rack 102 containing a plurality of sample containers 101, and a sample container rack A plurality of reagent containers 103 containing various reagents, a reagent container rack 104 containing a plurality of reagent containers 103, a reaction container 105 for mixing a sample and a reagent, and an unused reaction container 105. A plurality of reaction container racks 106 and unused reaction containers 105 are placed, and a reaction liquid adjustment position 107 for dispensing a sample and a reagent from each of the sample container 101 and the reagent container 103 to the reaction container 105, and a sample A capping unit 108 that seals the reaction vessel 105 containing a reaction solution, which is a mixed solution of a reagent and a reagent, with a lid member (not shown); And stirring unit 109 for stirring the contained reaction solution in the reaction vessel 105 is provided.

  Further, the nucleic acid test apparatus 100 has a robot arm X-axis 110 provided so as to extend in the X-axis direction (left-right direction in FIG. 1) and a Y-axis direction (vertical direction in FIG. 1). A robot arm device 112 having a robot arm Y-axis 111 movably arranged in the X-axis direction on the robot arm X-axis 110 and a robot arm Y-axis 111 movably provided in the Y-axis direction, A gripper unit 113 that holds the reaction container 105 and conveys it to each part of the nucleic acid test apparatus 100 and a robot arm Y-axis 111 are provided so as to be movable in the Y-axis direction, and aspirate the sample in the sample container 101 and the reagent in the reagent container 103. Then, the dispensing unit 114 that discharges (dispenses) into the reaction container 105 placed at the reaction liquid adjustment position 107, and the sample or reagent of the dispensing unit 114 is contacted. A nozzle chip 115 to be mounted at a site, a nozzle chip rack 116 in which a plurality of unused nozzle chips 115 are accommodated, and a nucleic acid amplifying apparatus for subjecting the reaction liquid accommodated in the reaction vessel 105 to nucleic acid amplification processing, fluorescence detection, etc. 1, a disposal box 117 for discarding a used nozzle chip 115 and a used (tested) reaction container 105, an input device 118 such as a keyboard and a mouse, and a display device 119 such as a liquid crystal monitor, and a nucleic acid amplification device 1 and a control device 120 that controls the overall operation of the nucleic acid amplification device 100 including 1.

  Each sample container 101 is managed by identification information such as a barcode for each contained specimen, and is managed by position information such as coordinates assigned to each position of the sample container rack 102. Similarly, each reagent container 103 is managed by identification information such as a barcode for each stored reagent, and managed by position information such as coordinates assigned to each position of the reagent container rack 104. These identification information and position information are registered and managed in advance in the control device 120. Further, each reaction vessel 105 is similarly managed by identification information and position information.

  In FIG. 2, the structure which looked at the nucleic acid amplifier 1 from the upper direction is shown. The nucleic acid amplification device 1 is provided with a holder 3. The holder 3 includes a disk-shaped holder base 4 and a plurality of temperature control blocks 10 (16 pieces in the case of FIG. 2) arranged along the outer periphery of the holder base 4. The temperature control block 10 is provided with at least one installation position 12 (one in the case of FIG. 1) capable of holding the reaction vessel 105. The holder base 4 is attached to the holder 3 so as to be rotatable in the circumferential direction around its rotation axis. The holder base 4 is rotationally driven by a stepping motor (not shown) disposed between the holder 3 and the holder 3. The holder base 4 and the temperature control block 10 are formed of a heat conductor such as aluminum, copper, or various alloys. The temperature control block 10 is formed integrally with the holder base 4. The plurality of temperature control blocks 10 arranged along the outer periphery of the holder base 4 are separated from each other by a notch portion 16 extending in the center direction from the outer periphery of the holder base 4. Thus, a space is provided between adjacent temperature control blocks 10. This space realizes a high heat insulation capacity between the temperature control blocks. A temperature sensor 15 that detects the temperature of the reaction liquid in the reaction vessel 105 by detecting the temperature in the vicinity of the installation position 12 and the Peltier element 17 as a temperature adjusting device is provided for each temperature control block 10. Yes. The Peltier element 17 is attached such that one of the two surfaces on which heat exchange is performed is in close contact with the temperature control block 10 and the other surface is in close contact with the holder base 4.

  At the center of the holder base 4 is a Peltier element 18 as a temperature adjusting device, a temperature sensor 15a for detecting the temperature in the vicinity thereof, a radiating fin (not shown) connected to the Peltier element 18, and a fan for blowing air to the radiating fin. 40 is provided. The temperature of the holder base 4 can be kept constant (for example, 40 ° C.) by the Peltier element 18. For this reason, the efficiency of heat dissipation and heat absorption of the Peltier element 17 of the temperature control block 10 can be improved. In the PCR method, which is one of nucleic acid amplification techniques, a temperature cycle defined by the temperature rise and fall in the temperature control block 10 is repeatedly added to the reaction vessel 105. At this time, by setting the holder base 4 to an appropriate temperature, the temperature change rate can be improved and the balance between the ascending speed and the descending speed can be controlled.

  Furthermore, at least one (four in the case of FIG. 2) fluorescence detectors 6 that detect fluorescence of the reaction solution contained in the reaction vessel 105, and a cover 7 (see FIG. 1) that covers the entire nucleic acid amplifier 1 are provided. I have. The cover 7 covers the temperature control block 10 and the fluorescence detector 6 together with the holder 3 so as to prevent light from entering the fluorescence detection unit 6 of the nucleic acid amplification device 1 or the inside of the nucleic acid amplification device 1. It is used for heat insulation that maintains the temperature of (inside the cover 7). The cover 7 is provided with at least one openable / closable gate 7a (one in the case of FIG. 1). The reaction vessel 105 is exchanged between the inside and outside of the cover 7 (that is, inside and outside of the nucleic acid amplification device 1) via the gate 7a.

  The fluorescence detector 6 detects an excitation light source (not shown) for irradiating the lower part (exposed part) of the reaction vessel 105 held at the installation position 12 of the temperature control block 10 and fluorescence from the reaction solution. And a detection element (not shown). The fluorescence detectors 6 are arranged side by side along the outer circumference of the flow line of the temperature control block 10 that moves on the same circumference by the rotational drive of the holder base 4. By rotating the holder base 4, the reaction vessel 105 held by the temperature control block 10 passes through the detection position. Thereby, the fluorescence detection of the reaction container 105 held by the temperature control block 10 is performed. In the reaction solution stored in the reaction vessel 105, the base sequence to be amplified is fluorescently labeled with a reagent. For this reason, fluorescence detection is performed by passing excitation light through the detection position of the reaction vessel 105. In the reaction liquid stored in the reaction vessel 105, the base sequence to be amplified is fluorescently labeled with a reagent. Accordingly, when the reaction vessel 105 is irradiated with excitation light from the excitation light source and the fluorescence from the reaction solution generated at that time is detected by the fluorescence detector 6, the base sequence to be amplified contained in the reaction solution is quantified over time. be able to. The plurality of fluorescence detectors 6 detect or measure the reaction liquid in the reaction vessel 105 independently of each other. The detection result is transmitted to the control device 120. For example, a light emitting diode (LED), a gas laser, a semiconductor laser, a xenon lamp, or a halogen lamp is used as the excitation light source. As the detection element, a photodiode, a photomultiplier, a CCD, or the like is used.

  The control device 120 controls the overall operation of the nucleic acid test device 100. The basic configuration of the control device 120 is a computer. Therefore, the control device 120 has a configuration such as a CPU, a ROM, a RAM, and an external storage device (not shown). Based on the protocol of the measurement item set by the input device 118, the control device 120 executes various software stored in advance in a storage unit (not shown) to perform nucleic acid amplification processing and fluorescence detection, and the fluorescence detection result The analysis results such as the above and the operating status of the nucleic acid testing device 100 are stored in the storage unit or displayed on the display device 119.

  In the nucleic acid amplification processing executed in the nucleic acid amplification device 1 constituting the nucleic acid testing device 100, the sample (reaction solution contained in the reaction vessel 105) prepared according to the protocol determined by the measurement item is prepared. Applying the temperature control specified in the protocol, the target base sequence is selectively amplified.

  In the present embodiment, the configuration in which the excitation light is irradiated from below the reaction container 105 held at the installation position 12 of the temperature control block 10 and fluorescence is detected is adopted. Excitation light irradiation and fluorescence detection may be performed from the side or from above, and excitation light is irradiated from below, above or from the side of the reaction vessel 105, which is different from the excitation light irradiation direction. A method of detecting fluorescence in the direction may be adopted.

  Moreover, the number of the fluorescence detector 6, the temperature control block 10, and the gate 7a is not limited to the number demonstrated by this embodiment, You may adjust a number as needed.

  The reaction container 105 is erected by gripping the reaction container 105 on the stirring unit 109 by the gripper unit 113 provided in the robot arm device 112, passing through the gate 7a, and controlling the temperature control of the nucleic acid amplification device 1. 10 is carried out by erection at the erection position 12 on the upper side. Further, after the reaction vessel 105 is installed on the temperature control block 10, temperature control for the amplification reaction is performed by the Peltier element 17. However, even before installation, the temperature control block 10 is subjected to temperature control (preheating) by the Peltier element 17 before the amplification reaction. The construction process and temperature control of the reaction vessel 105 shown thereafter are performed in the same manner.

[Functional structure of nucleic acid testing device]
Next, the functional configuration of the nucleic acid test apparatus 100 will be described. The nucleic acid test apparatus 100 is functionally equipped with a preprocessing unit for preprocessing a sample, a temperature adjustment unit for amplifying nucleic acid, a detection unit for detecting nucleic acid amplification in real time, and a sample from the pretreatment unit to the temperature control unit Or it has a conveyance mechanism which carries out the sample which completed measurement from a temperature control part to a pre-processing part, a control part which controls these, and an analysis part which analyzes detection data.

  In the following description, “specimen” means “standard sample” and “test sample”. The standard sample is a sample for guaranteeing the inspection quality, and includes, for example, a positive standard sample, a negative standard sample, and a quantitative standard sample.

  The “pretreatment unit” may include all the steps performed as a pre-process of nucleic acid amplification and real-time detection, or may include only a process immediately before the amplification / detection process. For example, in the case of a nucleic acid test for real-time PCR, it may include a pre-dispensing step of a blood sample, a nucleic acid extraction step, an amplification reaction solution preparation step, or only an amplification reaction solution preparation step.

  The “temperature adjusting unit” according to the present embodiment refers to a configuration that can freely change the temperature between 40 ° C. and 100 ° C. As long as a standard PCR reaction can be performed, the temperature control unit may use any temperature control mechanism.

  FIG. 3 shows the flow of nucleic acid analysis processing by the nucleic acid test apparatus 100 and the exchange of data. The registration of the test item for the sample is performed through the input / output device 201 and stored as analysis request data 205 in a storage area (not shown). Here, the input / output device 201 corresponds to the input device 118 and the display device 119 of FIG.

  The analysis planning unit 202 determines whether the analysis can be executed based on the analysis request data 205 and the analysis status 206 of the apparatus, and calculates an analysis plan 207. The analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs the analysis of the sample. The analysis plan unit 202 calculates the analysis plan 207 by calculating the time required for the test of each sample based on the test contents of each sample given by the analysis request data 205 and the temperature control block 10 used for the analysis. In addition, when calculating the theoretical value of test | inspection time, it assumes that the temperature control block 10 of standard temperature control capability is used. The analysis plan unit 202 has several priority modes, and calculates the analysis plan 207 according to each priority mode.

  The analysis execution unit 203 controls the movement of the reaction vessel 105 and the dispensing operation according to the analysis plan 207. The data processing unit 204 reads the detection data of each specimen and stores it as analysis result data 208 in a storage area (not shown). The input / output device 201 displays the analysis status 206 and the analysis result 208 on the work screen.

  Each process of the analysis planning unit 202, the analysis execution unit 203, and the data processing unit 204 is realized through a program executed on a computer constituting the control device 120. The selection of the priority mode used by the analysis planning unit 202 is also realized through a program executed on the computer.

[Temperature control protocol]
FIG. 4 shows an example of a temperature control protocol used when nucleic acid amplification of the reaction solution in the reaction vessel 105 is performed. Note that the temperature adjustment of the reaction liquid in the reaction vessel 105 is realized through the temperature control of the Peltier element 17 as a temperature adjusting device disposed in the temperature control block 10 as described above.
The temperature of the reaction solution is changed (temperature rise) from the temperature T12 to the temperature T11, and the temperature of the reaction solution is maintained at the temperature T11 for a time t11. As shown in FIG. 4, the time t11 includes a transition time from the immediately preceding temperature T12 to the temperature T11.
-Change the temperature of the reaction solution from temperature T11 to temperature T12 (decrease temperature), and maintain the temperature of the reaction solution at temperature T12 for time t12. As shown in FIG. 4, the time t12 includes the transition time from the immediately preceding temperature T11 to the temperature T12.
-The above combination is defined as one cycle, and the number of cycles (N1) specified in the temperature control protocol is repeated. Of course, if the temperature control protocol has a specified cycle other than the above-described temperature cycle, the temperature and time are set following the above cycle.

[Time required for amplification detection]
The time required for testing using the PCR temperature cycle is affected by the following factors.
(A) Temperature designated value / holding time In the case of FIG. 4, the temperature designated values are two temperatures T11 and T12. A temperature change is performed between the two different temperatures. The holding time at each temperature specified value is time t11, t12.

(B) Number of detection cycles This is the number of repetitions of one cycle given by the temperature specified value and the holding time. In the case of FIG. 4, one cycle is repeated N1 times.

(C) Temperature control ability The ability to control the temperature of the reaction solution by the temperature control block 10 is given. As the evaluation item, for example, the following (c-1), (c-2), and (c-3) can be considered.
(C-1) Change (up / down) speed: Δ ° C / Sec
The faster the change speed value, the higher the ability to change the temperature. This is the most basic evaluation item. The simplest evaluation of temperature control capability is performed only by the rate of change.
(C-2) Stability: Sec
Represents the speed of convergence to the target temperature. The shorter the time until the temperature is maintained at the target temperature, the higher the temperature control capability.
(C-3) Control amount:%
The percentage of the maximum capacity of the temperature control block 10 indicates that the predetermined temperature control can be realized. The smaller this value, the higher the temperature control capability.
Of the above-described factors, items (a) and (b) are specified by the temperature control protocol. The item (c) is different for each temperature control block 10.

[Temperature control capability for each temperature control block]
As described above, the temperature control capability of the temperature control block 10 varies. Factors that cause variation include individual differences and deterioration, for example.

  FIG. 5 shows how the difference in temperature control capability of the temperature control block 10 affects the inspection time even when the same temperature control protocol is executed. Graph A shown in the upper part of the figure is the temperature change of the reaction liquid when using the temperature control block 10 having a high temperature control capability. On the other hand, a graph B shown in the lower part of the figure shows a change in the temperature of the reaction solution when the temperature control block 10 having a low temperature control capability is used. As shown in FIG. 5, even when the same temperature control protocol is executed, a difference appears in the time required for executing one temperature cycle due to a difference in temperature control capability. As shown in FIG. 5, the cycle 501 when using the temperature control block 10 with high temperature control capability is shorter than the cycle 502 when using the temperature control block 10 with low temperature control capability. That is, a time difference 503 is generated. The time difference 503 multiplied by the number of temperature cycles is the time difference required for inspection.

[Evaluation of temperature control capability]
The temperature control capability is evaluated according to the following timing and procedure.
(A) During maintenance This is performed during maintenance when the nucleic acid test apparatus 100 is not used for analysis processing. The execution of the evaluation is instructed by a user or a service person. A measurement result necessary for evaluation of the temperature control capability is acquired by applying a temperature control protocol defined in advance to the corresponding temperature control block 10 and performing temperature control. FIG. 6 shows a correspondence relationship between the values of the evaluation items individually measured for the temperature control block 10, the evaluation points, and the priorities. As will be described later, this correspondence is stored in a storage area (not shown). FIG. 7 exemplifies a temperature control capability evaluation operation procedure.

  First, one temperature control block 10 selected as an evaluation target is controlled according to a predetermined temperature control protocol, and the temperature change of the reaction liquid in the reaction vessel 105 at that time is measured by the temperature sensor 15. Thereby, the information of the temperature control result is acquired (step 701). For example, the temperature control block No. In the case of 3, the change rate Δ ° C./second is 3.2, the stability is 10 seconds, and the controlled variable is 25%.

  In step 702, a value obtained by quantifying the temperature control capability is calculated based on the acquisition result (step 702). In this calculation, an evaluation point conversion table stored in a storage area (not shown) is used. FIG. 8 shows an example of the conversion table. (A) is a conversion table of change speed and evaluation points. (B) is a conversion table of stability and evaluation points. The conversion from the controlled variable to the evaluation score is performed by a predetermined conversion formula. In the present embodiment, a value obtained by multiplying the control amount by the coefficient 0.4 is used as the evaluation score.

  For example, the temperature control block No. In the case of 3, the evaluation score corresponding to 3.2 of the change speed is 50 points, the evaluation score corresponding to 10 seconds of the stability is 20 points, and the evaluation score corresponding to 25% of the control amount is 10 points. . Therefore, the temperature control block No. The evaluation score of 3 is given as 80 points (= 50 + 20 + 10) which is the sum of the evaluation points of these individual evaluation items.

  The calculation result of the evaluation point giving the temperature control capability of each temperature control block 10 is stored in a storage area (not shown) in the table format shown in FIG. 6 (step 703). The measurement, calculation, and storage processes described above are sequentially executed for all the temperature control blocks 10 constituting the nucleic acid test apparatus 100. In the case where it is not necessary to consider the influence of the mutual temperature change, the measurement, calculation and storage processes are performed simultaneously for all or a plurality of temperature control blocks 10.

  When the calculation of the evaluation points for all the temperature control blocks 10 is completed, step 704 is executed. In step 704, priority is given to the temperature control block 10 in the order of the evaluation score. When the priority order is determined for all the temperature control blocks 10, the determined order is stored in a storage area (not shown), and the table shown in FIG. 6 is completed (step 705). By referring to the priority order, the relationship of the relative temperature control capability of the temperature control block 10 can be understood. In the present embodiment, this priority relationship is referred to when determining the assignment of the temperature control block 10 used for the specimen examination.

  The table shown in FIG. 6 is stored every time maintenance is performed. Therefore, if the previously stored priority order is compared with the currently stored priority order, it is possible to confirm a change in the relative order of the temperature control capability between the temperature control blocks due to variations in the progress of deterioration. If the table shown in FIG. 6 is displayed on the work screen of the display device 119, the user or service person can visually confirm the temperature control capability of the temperature control block 10.

(B) During analysis The temperature control capability can be evaluated not only during maintenance but also during analysis processing. That is, it is possible to measure the change speed, temperature change, and control amount based on the temperature control protocol used for the analysis, calculate the evaluation point of the temperature control capability from those values, and give priority.

[Analysis plan according to priority mode]
Here, a specific example of the analysis plan 207 provided by the analysis plan unit 202 (FIG. 3) will be described. In the nucleic acid test apparatus 100 according to this embodiment, a plurality of priority modes are prepared. Below, the difference in the allocation method of the reaction container 105 and the temperature control block 10 according to priority mode is demonstrated in detail. The priority mode used for creating the analysis plan 207 is selected by the user before the analysis is started, for example.

[In case of standard inspection priority mode]
In the field of nucleic acid analysis, there is a demand for obtaining an analysis result of a standard sample faster than a test sample. This is because the analysis result of the standard sample is used to determine the quality of the analysis result of the inspection sample. FIG. 9 shows a flowchart executed in the operation mode in which priority is given to the output of the inspection result of the standard sample. The designation of the operation mode is given to the control device 120 through the input device 118. The same applies to the other operation modes. However, a preset mode may be applied as the operation mode.

  First, the analysis planning unit 202 identifies a reaction container 105 that is waiting for an inspection and that contains a standard sample (step 901). Note that the reaction container 105 that stores the standard sample may be input from the user through the input device 118.

  The analysis planning unit 202 determines whether or not the reaction container 105 waiting for inspection contains a standard sample (step 902). If a negative result is obtained, there is no reaction vessel 105 that should be prioritized for inspection, and thus this mode is terminated. In this case, the assignment destination of the reaction vessel 105 is selected from the unused temperature control blocks 10 according to another operation mode.

  If an affirmative result is obtained in step 902, the analysis planning unit 202 acquires the priority of the temperature control capability for each temperature control block 10 (step 903). The priority order should just be acquired about the unused temperature control block 10 at least.

  The analysis planning unit 202 assigns the reaction containers 105 containing the standard samples in order from the highest priority among the unused temperature control blocks 10 (step 904). In addition, about the reaction container 105 which accommodates a test sample, the temperature control block 10 is allocated by a general method. For example, the assignment is simply determined in order. Thereafter, the analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs execution of the analysis.

  The analysis execution unit 203 drives and controls the robot arm X-axis 110 and the robot arm Y-axis 111 according to the analysis plan 207, and transfers the reaction container containing the standard sample and the inspection sample to the specific temperature control block 10 to which the analysis is performed. Place. The analysis is started in order from the temperature control block 10 in which the placement is completed (step 905).

  FIG. 10 shows the difference in inspection time between when the mode is executed and when the mode is not executed. The twelve bar graphs (A) shown in the upper part of the figure represent the theoretical values of the inspection time corresponding to the inspection (analysis) items set for the reaction liquid in each reaction vessel 105. Since it is a theoretical value, the temperature control capability of the temperature control block 10 is calculated as a standard value. The length in the horizontal axis direction of each bar graph corresponds to the inspection time length. In the case of FIG. 10, there are three inspection items, A group, B group, and C group. The theoretical value of the inspection time is the longest in group C, the second longest in group A, and the third longest in group B. In any of the inspection items, two standard samples and two inspection samples are inspection targets. As shown in the upper part of FIG. 10, the inspection is started in the order of the inspection items A group, B group, and C group.

  The twelve bar graphs (B) shown in the lower part of FIG. 10 represent the inspection time when the inspection priority mode of the standard sample is applied. Note that the inspection is started in the order of the inspection items A group, B group, and C group, as in the upper case. As can be seen by comparing the upper and lower stages, in the inspection priority mode of the standard sample, the inspection time is shorter than the theoretical value for any inspection item. Of course, this is because the temperature control capability of the temperature control block 10 assigned to each inspection item is higher than the temperature control capability assumed by the theoretical value.

  In FIG. 10, a state in which the inspection end time of the standard sample is finished earlier than the theoretical value in the case where the inspection priority mode of the standard sample is applied to the inspection item C having a relatively long inspection time is indicated by a broken line. In FIG. 10, the inspection time of the reaction container 105 that stores the inspection sample is shown not only longer than the inspection time of the standard sample but also longer than the theoretical value. However, in this mode, the assignment for the test sample is arbitrary. Therefore, the inspection time of the reaction container 105 that contains the inspection sample is not always longer than the theoretical value.

  On the other hand, since the temperature control capability of the temperature control block 10 to which the reaction vessel 105 containing the standard sample is allocated is guaranteed to be higher than the temperature control capability of the temperature control block 10 to which the reaction vessel 105 storing the test sample is allocated, If the inspection contents are at least the same, the inspection of the standard sample is completed earlier than the inspection sample.

[All inspection time length priority mode]
In general, the inspection time for inspection items with a large number of temperature cycles is longer than the inspection time for inspection items with a small number of temperature cycles. Therefore, when the reaction vessel 105 containing the reaction liquid in which the inspection item having a large number of temperature cycles is designated is assigned to the temperature control block 10 having a low temperature control capability, the inspection time becomes larger than the theoretical value, and the inspection end time is reached. Becomes slower.

  However, in the analysis site, there are cases where it is desired to end all tests that start tests at the same time as soon as possible. In such a case, the all inspection time length priority mode is selected.

  FIG. 11 shows a flowchart executed in this operation mode. First, the analysis planning unit 202 acquires the theoretical value of the inspection time for the reaction container 105 waiting for inspection (step 1101). The theoretical value of the test time may be calculated by a control unit (not shown) of the nucleic acid test device 100, or may be calculated by the control device 120.

  Next, the analysis planning unit 202 acquires the priority order of the temperature control capability for the unassigned temperature control block 10 (step 1102).

  Subsequently, the analysis planning unit 202 assigns the temperature control blocks 10 having the highest priority of the temperature control capability in order from the reaction container 105 having the long inspection time (step 1103). Thereafter, the analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs execution of the analysis.

  The analysis execution unit 203 drives and controls the robot arm X-axis 110 and the robot arm Y-axis 111 according to the analysis plan 207, and places each reaction vessel 105 on the specific temperature control block 10 that is the allocation destination. The analysis is started in order from the temperature control block 10 in which the placement is completed (step 1104).

  FIG. 12 shows the difference in inspection time between when the mode is executed and when the mode is not executed. The twelve bar graphs (A) shown at the top of the figure represent the theoretical values of the inspection time corresponding to the inspection (analysis) items set for the reaction liquid in each reaction vessel 105. Since it is a theoretical value, the temperature control capability of the temperature control block 10 is calculated as a standard value. The length in the horizontal axis direction of each bar graph corresponds to the inspection time length. Also in the case of FIG. 12, there are three inspection items, A group, B group, and C group. The theoretical value of the inspection time is the longest in group C, the second longest in group A, and the third longest in group B. In addition, an inspection shall be started in order of inspection item A group, B group, and C group.

  The twelve bar graphs (B) shown in the middle part of FIG. 12 show an example in which the reaction vessel 105 is appropriately assigned to the temperature control block 10. In this case, the inspection time of each reaction vessel 105 depends on the temperature control capability of the assigned temperature control block 10. Therefore, the end time of all inspections is not always shorter than the theoretical end time. In FIG. 12, although the final inspection end time coincides with the theoretical value, there is generally no guarantee.

  The twelve bar graphs (C) shown in the lower part of FIG. 12 represent a case where the reaction container 105 of the inspection item having a long inspection time is preferentially applied to the temperature control block 10 having a high priority of the temperature control capability. Note that the inspection is started in the order of the inspection items A group, B group, and C group, as in the upper case.

  In this case, the inspection time of the inspection item C having a long inspection time is surely shortened. As a result, as shown in the bar graph (C), the inspection time corresponding to the reaction container 105 corresponding to the inspection item C is all shortened. As a result, the inspection end time of the inspection item C, which is theoretically late in the inspection end time, ends earlier than the theoretical value.

  In FIG. 12, although the inspection time of the second shortest inspection item A and the shortest inspection item B is the same as the theoretical value, the theoretical value of the inspection time is the same as that of the temperature control block 10 used. This is because the temperature control capability matches the theoretical value. In general, since the temperature control block 10 having a relatively lower priority of temperature control capability is assigned, the possibility that the inspection time becomes longer than the theoretical value increases. However, since the inspection time is relatively short in the first place, even if the inspection time increases, in general, the theoretical value of the inspection time does not exceed the inspection end time of the inspection item C having the longest time.

  As described above, when this operation mode is employed, the time length of the entire inspection to be performed simultaneously can be shortened from the theoretical value.

[When processing sample priority mode]
At the analysis site, when there is a sample group in which an analysis request is registered and waiting for preprocessing, it is necessary to secure the temperature control block 10 necessary for analyzing the sample at an early stage. . In this operation mode, in order to ensure the required number of temperature control blocks 10 at an early stage, a temperature control block having a high temperature control capability is preferentially assigned from the reaction container 105 of the test item having a short test time. . In this case, since there is a high possibility that an examination with a short examination time will be completed early, it is possible to start preprocessing for a waiting sample group at an early stage.

  FIG. 13 shows a flowchart executed in this operation mode. First, the analysis planning unit 202 acquires the theoretical value of the inspection time for the reaction vessel 105 waiting for inspection (step 1301). The theoretical value of the test time may be calculated by a control unit (not shown) of the nucleic acid test device 100, or may be calculated by the control device 120.

  Next, the analysis plan part 202 acquires the priority of a temperature control capability about the unallocated temperature control block 10 (step 1302).

  Subsequently, the analysis planning unit 202 assigns the temperature control blocks 10 having a higher priority of the temperature control capability in order from the reaction container 105 having a shorter inspection time (step 1303). Thereafter, the analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs execution of the analysis.

  The analysis execution unit 203 drives and controls the robot arm X-axis 110 and the robot arm Y-axis 111 according to the analysis plan 207, and places each reaction vessel 105 on the specific temperature control block 10 that is the allocation destination. The analysis is sequentially started from the temperature control block 10 in which the placement is completed (step 1304).

  FIG. 14 shows the difference in inspection time between when the mode is executed and when the mode is not executed. The twelve bar graphs (A) shown at the top of the figure represent the theoretical values of the inspection time corresponding to the inspection (analysis) items set for the reaction liquid in each reaction vessel 105. Since it is a theoretical value, the temperature control capability of the temperature control block 10 is calculated as a standard value. The length in the horizontal axis direction of each bar graph corresponds to the inspection time length. Also in the case of FIG. 14, there are three inspection items, group A, group B, and group C. The theoretical value of the inspection time is the longest in group C, the second longest in group A, and the third longest in group B. In addition, an inspection shall be started in order of inspection item A group, B group, and C group.

  The twelve bar graphs (B) shown in the middle part of FIG. 14 show an example in which the reaction vessel 105 is appropriately assigned to the temperature control block 10. In this case, the inspection time of each reaction vessel 105 depends on the temperature control capability of the assigned temperature control block 10. Therefore, the end time of all inspections is not always shorter than the theoretical end time. The bar graph (B) represents a state in which the six reaction containers 105 reserved for execution of the inspection item D are on standby. In the case of the bar graph (B), the six temperature control blocks 10 are free at the timing indicated by the dotted line. Therefore, in the nucleic acid test apparatus 100 to which this operation mode is not applied, the test of the test item D is started from the timing indicated by the dotted line.

  The twelve bar graphs (C) shown in the lower part of FIG. 14 represent a case where the reaction container 105 of the inspection item having a short inspection time is preferentially applied to the temperature control block 10 having a high priority of temperature control capability. Note that the inspection is started in the order of the inspection items A group, B group, and C group, as in the upper case.

  As shown in the bar graph (C), the inspection times of inspection items B and A having a short inspection time are surely shortened. In FIG. 14, the inspection time is shortened only for a part of the inspection item A having the second longest inspection time. In this case, among the 12 usable temperature control blocks 10, the timing at which the sixth temperature control block 10 becomes empty is indicated by a dotted line. As can be seen by comparing the bar graphs (B) and (C), the timing at which the next six samples can be loaded is advanced.

  As a result, the inspection results of the six reaction vessels 105 corresponding to the inspection item D can be obtained earlier than in the case of the bar graph (B). In the case of this operation mode, the temperature control block 10 having a low priority is assigned to the inspection item C having the longest inspection time. For this reason, there is a possibility that the inspection time for the inspection item C may be longer. However, if the time when all 18 inspections are completed is compared, the operation mode can end the inspection earlier.

[In end time priority mode]
In the above-described operation mode, basically, the assignment of the reaction vessel 105 to the temperature control block 10 that is not assigned (that is, not used for the inspection) is determined at the time when the inspection reservation is made. Here, the temperature control block currently in use is also included in the allocation candidates, and priority is given to the allocation with the earlier examination end time.

  FIG. 15 shows a flowchart executed in this operation mode. First, the analysis plan part 202 acquires the priority of the temperature control capability of the unused temperature control block 10 (step 1501).

  Subsequently, the analysis planning unit 202 calculates a scheduled test end time 1 when the temperature control block 10 having the highest priority order among the unused temperature control blocks 10 is assigned to the reaction vessel 105 waiting for the test (step 1502). ). At this time, the analysis planning unit 202 acquires information on the inspection items registered for the reaction vessel 105 and information on the temperature control capability of the temperature control block 10 to be used, and ends the inspection that started the inspection based on these information. The scheduled time 1 is calculated. For example, the analysis planning unit 202 corrects the inspection time based on the relative ratio between the standard value (evaluation point) of the temperature control capability and the evaluation point of the temperature control block 10 used for the inspection, and calculates the scheduled inspection end time 1. .

  Next, the analysis planning unit 202 assigns the reaction container 105 waiting for the inspection to the temperature control block 10 in use, and calculates the scheduled end time 2 for inspection when the next inspection is started after the end of the current inspection. (Step 1503). Also in this case, the inspection end scheduled time 2 is calculated by the same method as in step 1502.

  Next, the analysis planning unit 202 compares the scheduled examination end times 1 and 2 and selects an assignment that ends earlier (step 1504). After that, the analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs execution of the analysis.

  The analysis execution unit 203 drives and controls the robot arm X-axis 110 and the robot arm Y-axis 111 according to the analysis plan 207, and places each reaction vessel 105 on the specific temperature control block 10 that is the allocation destination. The analysis is sequentially started from the temperature control block 10 in which the placement is completed (step 1505).

  FIG. 16 shows a difference in inspection time between when the mode is executed and when the mode is not executed. The eight bar graphs (A) shown at the top in the figure automatically assign reaction vessels 105 waiting for inspection to four of the temperature control blocks 10 that are not currently in use, which have a higher priority for temperature control capability. Represents the inspection time when the inspection is executed. On the other hand, the eight bar graphs (B) shown in the lower part of FIG. 16 wait for the temperature control block 10 having a high temperature control capability, which was in use, to become empty when the four reaction vessels 105 waiting for inspection are received. In this example, assignment is determined so that the inspection can be started.

  In this operation mode, as the determination process of step 1504 is provided, it is not always the case that the inspection end time is earlier when the inspection is started after the temperature control block 10 being used is empty. However, by preparing this operation mode, the temperature control block 10 having a high temperature control capability can be effectively used, and the inspection end time can be advanced.

[In case of changing mode]
In any of the aforementioned operation modes, after the assignment was determined, the inspection was started according to the determined assignment, and all of the inspections were performed. However, when the temperature control capability of the temperature control block 10 that has started the inspection is low, when the temperature control block 10 having a relatively high temperature control capability can be used, the temperature control block 10 used for the inspection is changed. There is a possibility that the inspection will be completed earlier if it is replaced. In this operation mode, such a case is assumed.

  FIG. 17 shows a flowchart executed in this operation mode. First, the analysis planning unit 202 calculates the scheduled test end time 1 when the temperature control block 10 having the highest priority order among the unused temperature control blocks 10 is assigned to the reaction vessel 105 waiting for the test (step 1701). . At this time, the analysis planning unit 202 acquires information on the inspection items registered for the reaction vessel 105 and information on the temperature control capability of the temperature control block 10 to be used, and ends the inspection that started the inspection based on these information. The scheduled time 1 is calculated. For example, the analysis planning unit 202 corrects the inspection time based on the relative ratio between the standard value (evaluation point) of the temperature control capability and the evaluation point of the temperature control block 10 used for the inspection, and calculates the scheduled inspection end time 1. .

  Next, the analysis planning unit 202 assigns the reaction container 105 waiting for the inspection to the temperature control block 10 in use, and calculates the scheduled end time 2 for inspection when the next inspection is started after the end of the current inspection. (Step 1702). Also in this case, the inspection end scheduled time 2 is calculated by the same method as in step 1701.

  Next, the analysis planning unit 202 compares the scheduled test end times 1 and 2 and selects an assignment that ends earlier (step 1703). After that, the analysis planning unit 202 gives the calculated analysis plan 207 to the analysis execution unit 203 and instructs execution of the analysis.

  The analysis execution unit 203 drives and controls the robot arm X-axis 110 and the robot arm Y-axis 111 according to the analysis plan 207, and places each reaction vessel 105 on the specific temperature control block 10 that is the allocation destination. The analysis is sequentially started from the temperature control block 10 in which the placement is completed (step 1704).

  Note that even if the temperature control block 10 is in use at the time of determination, the temperature control block 10 may be in an empty state earlier than planned, so it is desirable that the flowchart shown in FIG. 17 is repeatedly executed at regular intervals. Alternatively, when the temperature control block 10 that has been inspected earlier than the scheduled end time appears, the flowchart shown in FIG. 17 may be automatically executed.

  FIG. 18 shows the difference in inspection time between when the mode is executed and when the mode is not executed. In the eight bar graphs (A) shown at the top of the figure, four temperature control blocks 10 are used for the inspection of the inspection item A group, and the temperature control capability of these four temperature control blocks 10 is not used. It is assumed that the temperature control block 10 is higher. The bar graph (A) represents a case where the inspection is started using four of the eight temperature control blocks 10 that are not used for the inspection item B group having a short inspection time, and which has a high temperature control capability.

  The eight bar graphs (B) shown in the middle part of FIG. 18 represent a case where the inspection of the inspection item A group is completed earlier than scheduled. For example, depending on the inspection contents, there is a case where the necessity of further inspection is eliminated only by the initial inspection result. In such a case, as shown in the bar graph (B), the four temperature control blocks 10 having a high temperature control capability may be vacant.

  The eight bar graphs (C) shown in the lower part of FIG. 18 are cases where this operation mode is applied. It is confirmed that the inspection of the inspection item B group can be completed quickly by replacing the other four reaction containers 105 that have been inspected with the four temperature control blocks 10 used for the inspection of the inspection item A group. Therefore, it shows a state where the repositioning has been performed.

[Other examples]
The present invention is not limited to the above-described embodiments, and includes various modifications. The above-described embodiments have been described in detail for easy understanding of the present invention, and it is not always necessary to have all the configurations described. Moreover, it is possible to replace a part of a certain form example with the structure of another form example, and it is also possible to add the structure of another form example to the structure of a certain form example. Moreover, it is also possible to add, delete, or replace another structure with respect to a part of structure of each form example.

  In addition, each of the above-described configurations, functions, processing units, processing means, and the like can be realized in part or in whole as, for example, an integrated circuit or other hardware. Further, each configuration, function, and the like described above may be realized as a program executed by a processor. Information such as programs, tables, and files for realizing each function can be stored in a memory, a hard disk, a storage device such as an SSD (Solid State Drive), or a storage medium such as an IC card, an SD card, or a DVD.

  Control lines and information lines indicate what is considered necessary for the description, and do not represent all control lines and information lines necessary for the product. In practice, it can be considered that almost all components are connected to each other.

  DESCRIPTION OF SYMBOLS 1 ... Nucleic acid amplification device, 3 ... Holder, 4 ... Holder base, 6 ... Fluorescence detector, 7 ... Cover, 7a ... Gate, 10 ... Temperature control block, 12 ... Installation position, 15, 15a ... Temperature sensor, 16 DESCRIPTION OF SYMBOLS ... Notch part 17, 18 ... Peltier element, 40 ... Fan, 100 ... Nucleic acid test | inspection apparatus, 101 ... Sample container, 102 ... Sample container rack, 103 ... Reagent container, 104 ... Reagent container rack, 105 ... Reaction container, 106 ... reaction container rack, 107 ... reaction liquid adjustment position, 108 ... capping unit, 109 ... stirring unit, 110 ... robot arm X axis, 111 ... robot arm Y axis, 112 ... robot arm device, 113 ... gripper unit, 114 ... minutes Injection unit, 115 ... nozzle tip, 116 ... nozzle tip rack, 117 ... disposal box, 118 ... input device 119 ... Display device, 120 ... Control device, 201 ... Input / output device, 202 ... Analysis planning unit, 203 ... Analysis execution unit, 204 ... Data processing unit, 205 ... Analysis request data, 206 ... Analysis status, 207 ... Analysis plan, 208 ... analysis result

Claims (10)

In a nucleic acid test apparatus for amplifying and testing a nucleic acid contained in a reaction solution,
A plurality of temperature control blocks each holding at least one reaction vessel containing the reaction solution;
A temperature adjusting device that is provided in each of the plurality of temperature control blocks and adjusts the temperature of the reaction solution;
An arm for transferring the reaction vessel to the temperature control block,
Get the examination content registered for the reaction vessel, the controls the arm, a control unit can determine the allocation of preferentially the reaction vessel temperature adjusting block having a higher temperature adjusting device having temperature control capability and,
A nucleic acid test apparatus having The nucleic acid test apparatus according to claim 1,
The controller is
A nucleic acid test device characterized in that a temperature control block having a temperature control device having a high temperature control capability is preferentially assigned to a reaction vessel waiting for a test containing a standard sample. The nucleic acid test apparatus according to claim 1,
The controller is
For reaction vessels awaiting inspection, calculate the theoretical value of the inspection time according to the content of the inspection, and in order from the longest calculated inspection time, give priority to the temperature control block with a temperature control device with high temperature control capability A nucleic acid test apparatus characterized by being assigned to The nucleic acid test apparatus according to claim 1,
The controller is
For reaction vessels waiting for inspection, calculate the theoretical value of the inspection time according to the contents of the inspection, and in order from the shorter inspection time, give priority to the temperature control block with the temperature control device with high temperature control capability A nucleic acid test apparatus characterized by being assigned to The nucleic acid test apparatus according to claim 1,
The controller is
A process of calculating a first scheduled test end time when a reaction vessel waiting for inspection is assigned in order from a temperature control block having a temperature control device with high temperature control capability among unused temperature control blocks;
A process of assigning a reaction container waiting for inspection to a temperature control block currently in use, calculating a second scheduled end time of inspection when waiting for the end of the current inspection and starting inspection of the reaction container waiting for inspection; ,
And a process of selecting an assignment that ends earlier among the first and second scheduled test end times. The nucleic acid test apparatus according to claim 1,
The controller is
A process of calculating a first scheduled test end time when a reaction vessel waiting for inspection is assigned in order from a temperature control block having a temperature control device with high temperature control capability among unused temperature control blocks;
A process of calculating the second scheduled end time of the test when the reaction container waiting for the inspection is replaced with the temperature control block that is in use at the time of the allocation but is subsequently unused, and the inspection is continued,
And a process of selecting an assignment that ends earlier among the first and second scheduled test end times. The nucleic acid test apparatus according to claim 1,
The controller is
A nucleic acid test apparatus characterized by receiving selection of an operation mode used for determining an allocation relationship between a reaction vessel and a temperature control block through an operation input. The nucleic acid test apparatus according to claim 1,
The controller is
A nucleic acid test apparatus characterized by calculating an evaluation point of the temperature control capability of each temperature control block, determining a priority relationship, storing it in a storage unit, and / or displaying it. A plurality of temperature control blocks for holding at least one reaction vessel containing a reaction solution, respectively, provided in each of said plurality of temperature control blocks, and a temperature adjustment device for adjusting the temperature of the reaction solution, the temperature control block In the method for determining a temperature control block to which the nucleic acid test apparatus assigns a test waiting reaction container, in the nucleic acid test apparatus having an arm for delivering the reaction container to and a control unit for controlling the arm,
Processing for obtaining the temperature control capability of each temperature control device;
Processing to obtain the inspection contents of the reaction vessel awaiting inspection;
And a process for determining the allocation of reaction vessels to the temperature control block having a high temperature control capability of each temperature adjusting device. A plurality of temperature control blocks for holding at least one reaction vessel containing a reaction solution, respectively, provided in each of said plurality of temperature control blocks, and a temperature adjustment device for adjusting the temperature of the reaction solution, the temperature control block a computer for determining an arm for transferring the reaction vessel, the assignment to the inspection awaiting reaction vessel of the temperature control block in the nucleic acid test apparatus and a control section for controlling the arm,
Processing to acquire the temperature control capability of each temperature control device;
Processing to acquire the inspection contents of the reaction container waiting for inspection;
A program for executing a process of determining allocation of reaction vessels to a temperature control block having a high temperature control capability of each temperature control device.

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