Genetic testing device

Abstract

Provided is a genetic testing device that can execute nucleic acid amplification processes with different temperature control profiles in parallel and has a reduced device size. In each temperature control block 303 of a plurality of temperature control units 106, one end of each fiber of a fiber pair 201 including a first fiber and a second fiber is disposed so as to be mutually facing, and the other end of each fiber of the fiber pair is connected to a fluorescence detector 107. The fluorescence detector is configured to emit excitation light toward the first fiber at the same constant cycle for each of the connected fiber pairs and detect the fluorescence transmitted via the second fiber. A control device 30 sets a different temperature control profile for each of the temperature control units, and each temperature control unit controls the temperature according to the temperature control profile that has been set.

Description

Genetic testing equipment

[0001] The present invention relates to a genetic testing device.

[0002] When testing for nucleic acids contained in a biological sample, a nucleic acid amplification method is used to amplify and detect the amount of nucleic acid to a detectable level. Examples of such nucleic acid amplification techniques include PCR (Polymerase Chain Reaction). PCR allows for selective amplification of a desired base sequence by periodically controlling the temperature of a reaction solution containing a mixture of a sample and a reagent according to predetermined conditions. Other examples include TMA (Transcription Mediated Amplification) and NASBA (Nucleic Acid Sequence Based Amplification). The TMA and NASBA methods are classified as constant temperature amplification methods, and allow for amplification of a base sequence by controlling the temperature of a reaction solution containing a mixture of a sample and a reagent at a predetermined constant temperature.

[0003] These nucleic acid amplification techniques analyze changes in the intensity of fluorescence emitted from fluorescent dyes labeled with nucleic acids over time. Nucleic acid analyzers have been developed that perform this analysis by controlling the temperature of a reaction solution containing a mixture of a sample and a reagent used for nucleic acid amplification, and measuring changes in fluorescence intensity. Nucleic acid analyzers are also actively used in clinical testing, for example, for diagnosing viral infections, and there is a demand for automation to improve testing efficiency, labor savings, and accuracy. Furthermore, in clinical testing, there is a demand for simultaneous processing of multiple tests.

[0004] Patent Document 1 describes a nucleic acid testing device capable of individually and in parallel controlling the temperature of each temperature control block. This device is configured so that multiple temperature control blocks are installed along the outer edge of a circular carousel that can rotate around a rotation axis, and Peltier elements serving as temperature control devices are placed between the carousel and the temperature control blocks for each temperature control block. The reaction vessels held in the temperature control blocks are independently and in parallel temperature-controlled at temperatures and times according to the protocols for the amplification targets, enabling individual nucleic acid analyses of multiple types of samples to be performed simultaneously in accordance with multiple protocols.

[0005] JP 2012-75413 A

[0006] Genetic testing devices extract target nucleic acids from specimens, such as blood or urine, and amplify the extracted nucleic acids using PCR for testing. Users load specimens into the device and register a test request, including test items for the specimen, to perform genetic testing on the device. Genetic testing requires different extraction conditions depending on the target nucleic acid in the nucleic acid extraction process, and different test protocols (test conditions) depending on the test items in the nucleic acid analysis process. Therefore, for genetic testing devices to efficiently perform tests, it is important for the device hardware to have a multiplexed processing mechanism so that the necessary processes can be performed simultaneously and in parallel, and for the software to schedule the processing of as many specimens as possible simultaneously and in parallel to increase testing throughput.

[0007] However, since multiplexing the processing mechanism leads to an increase in the scale of the device, it is desirable to use the smallest possible configuration that can be expected to be efficient through scheduling and software. The following points should be considered in this case:

[0008] (1) Number of extraction units in the nucleic acid extraction unit and number of temperature control units in the nucleic acid analysis unit The nucleic acid extraction unit performs a process to extract target nucleic acids from samples, and the nucleic acid analysis unit amplifies and analyzes the nucleic acids extracted by the nucleic acid extraction unit. Naturally, nucleic acid analysis cannot be performed until the nucleic acid extraction process is completed. Generally, the time required for nucleic acid extraction (approximately 20 minutes) is approximately double that time (40 to 50 hours) for diffusion analysis. In addition, multiple types of analysis may be performed on the extracted nucleic acids.

[0009] (2) Analysis Contents of Real-Time PCR (Intercalator Method) Depending on the test item, real-time PCR may only acquire the Ct value (Threshold Cycle), or may require acquisition of the Tm value following acquisition of the Ct value. The Ct value represents the cycle number at which the PCR amplification product (amplified DNA) reaches a certain threshold and is used to quantify the amount of target gene contained in the sample. The Tm value (Melting Temperature) refers to the temperature at which half of double-stranded DNA denatures and becomes single-stranded DNA, and is used to confirm whether the target gene has been amplified. The Tm value is acquired after acquisition of the Ct value, and the temperature control operations and fluorescence detection operations of the two methods are completely different.

[0010] In Patent Document 1, measurements are performed using multiple fluorescence detectors installed along the outer edge of each temperature control block. Installing multiple fluorescence detectors corresponding to the temperature control blocks leads to an increase in the size of the device. Furthermore, Patent Document 1 does not describe how to perform measurements using a temperature control profile that is completely different from PCR cycle temperature control, such as Tm value measurement performed in real-time PCR.

[0011] A genetic testing device according to one embodiment of the present invention includes a plurality of temperature control units on which a well plate is placed, the temperature control units controlling the temperature of a plurality of temperature control blocks provided corresponding to each of a plurality of wells of the well plate, a fluorescence detector, and a control device, wherein each of the temperature control blocks of the temperature control units has one end of a fiber pair including a first fiber and a second fiber arranged so as to face each other, and the other end of the fiber pair is connected to the fluorescence detector, the first fiber of the fiber pair transmitting excitation light from the fluorescence detector, and the second fiber of the fiber pair transmitting fluorescence generated by irradiation of the excitation light onto the reaction solution in the well to the fluorescence detector, the fluorescence detector emitting excitation light toward the first fiber at the same constant period for each of the connected fiber pairs and detecting the fluorescence transmitted via the second fiber, and the control device setting a different temperature control profile for each of the temperature control units, and the temperature control units controlling the temperature according to the set temperature control profile.

[0012] The present invention provides a genetic testing device that can perform nucleic acid amplification processes with different temperature control profiles in parallel and has a reduced size. Other objects and novel features will become apparent from the description of this specification and the accompanying drawings.

[0013] 1 is a diagram illustrating the overall configuration of a genetic testing device. FIG. 2 is an example of the hardware configuration of a control device. FIG. 3 is an example of a program stored in a storage device. FIG. 4 is an example of a detection mechanism including a temperature control unit and a fluorescence detection unit. FIG. 5 is a schematic top view of a temperature control unit. FIG. 6 is a schematic cross-sectional view of a well temperature control unit. FIG. 7 is a schematic configuration diagram of a fluorescence detection unit. FIG. 8 is an example of PCR cycle temperature control performed for Ct value measurement. FIG. 9 is an example of a temperature control profile (step temperature control) performed for Tm value measurement. FIG. 10 is an example of a temperature control profile conventionally performed for Tm value measurement. FIG. 11 is a process flow for extracting target nucleic acid from a specimen. FIG. 12 is a process flow for amplifying nucleic acid. FIG. 13 is a time chart for cases where the multiplexing numbers of extraction units and temperature control units provided in a genetic testing device are different.

[0014] Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that the specific embodiments shown below are for the purpose of understanding the present invention and are not to be construed as limiting the present invention.

[0015] 1 is a diagram showing the overall configuration of a genetic testing apparatus. The genetic testing apparatus 1 includes a nucleic acid extraction unit 10 that extracts target nucleic acids from a sample, a nucleic acid analysis unit 20 that amplifies and analyzes the nucleic acids extracted by the nucleic acid extraction unit 10, and a control device 30 that controls the overall operation of the genetic testing apparatus 1. By including the nucleic acid extraction unit 10 and the nucleic acid analysis unit 20, it is possible to perform genetic testing from a sample using a single apparatus.

[0016] The nucleic acid extraction unit 10 primarily comprises a specimen input unit 101, a first consumables supply unit 102, an extraction unit 103, and a first transport mechanism 108. A specimen contained in a specimen container is input into the device through the specimen input unit 101, and the specimen container from which the amount required for analysis has been removed is discharged from the specimen input unit 101. The specimen is a biological sample such as blood or urine. The first consumables supply unit 102 stores consumables used in the nucleic acid extraction unit 10. The consumables stored in the first consumables supply unit 102 include, for example, a reagent used to extract nucleic acids from a specimen, a first well plate for dispensing and mixing the specimen and reagent, a nozzle tip attached to a dispensing nozzle each time a specimen is dispensed to prevent contamination between specimens, and a second well plate for containing a nucleic acid extract extracted by the extraction unit 103 (described below). A well plate is a plate with numerous depressions called wells. Each well can contain a different specimen or a liquid derived from a different specimen. The genetic testing device 1 processes multiple samples simultaneously in parallel. Therefore, by using well plates, multiple samples can be transported at once, improving the efficiency of the nucleic acid extraction process. Because these consumables are discarded after use, the first consumable supply unit 102 is equipped with a trash can for disposing of used consumables. The extraction unit 103 is a mechanism for extracting target nucleic acids from samples. The nucleic acid extraction method is not particularly limited. The extraction unit 103 can simultaneously extract nucleic acids from multiple samples (e.g., eight samples) in parallel, provided that the nucleic acid extraction conditions are identical. This example includes two extraction units 103. When multiple extraction units need to be distinguished, an identifying letter is added to the end of the reference numeral (103). The first transport mechanism 108 is shown schematically here and includes, for example, a working head and guide rails for moving the working head in the X and Y directions within the nucleic acid extraction unit 10. The working head includes, for example, a barcode reader, a gripper unit, and a dispensing nozzle. The barcode reader is used to link (trace) the consumables used in nucleic acid extraction with the measurement data. The gripper unit grips the consumables for transport.The dispensing nozzle aspirates liquid from a specimen container or a reagent container, and dispenses the aspirated liquid into a well plate.

[0017] The nucleic acid analysis unit 20 primarily comprises a reagent input unit 104, a second consumables supply unit 105, a temperature control unit 106, a fluorescence detection unit 107, and a second transport mechanism 109. Here, the nucleic acid analysis unit 20 performs nucleic acid amplification using real-time PCR (intercalator method). Reagents used for nucleic acid amplification are input into the device from the reagent input unit 104 and stored therein. The second consumables supply unit 105 stores consumables used in the nucleic acid analysis unit 20. Examples of consumables stored in the second consumables supply unit 105 include a third well plate for dispensing and mixing the nucleic acid extract and reagent used for nucleic acid amplification, and a nozzle tip attached to the dispensing nozzle each time a sample is dispensed to prevent contamination between samples. Because these consumables are discarded after use, the second consumables supply unit 105 also includes a trash can for discarding used consumables.

[0018] In real-time PCR (intercalator method), a specific fluorescent substance is added to a nucleic acid extract solution, and nucleic acid amplification is performed while applying a specific temperature change. When the fluorescent substance binds to double-stranded DNA synthesized by PCR, it emits fluorescence when irradiated with excitation light. The intercalator method utilizes this property to quantitatively monitor the amount of PCR amplified product produced by measuring the fluorescence intensity upon irradiation with excitation light. To this end, the nucleic acid analysis unit 20 includes a temperature control unit 106 that controls the temperature of the reaction solution containing the nucleic acid extract solution and reagents, and a fluorescence detection unit 107 that irradiates the reaction solution, whose temperature is controlled by the temperature control unit 106, with excitation light and detects fluorescence. This example includes three temperature control units 106. Multiple temperature control units are identified by adding a distinguishing alphabet to the end of the reference numeral (106). The second transport mechanism 109 has a configuration similar to the first transport mechanism 108 and transports consumables and dispenses liquids.

[0019] As shown in FIG. 2A , the control device 30 primarily comprises a processor (Central Processing Unit: CPU) 401, memory 402, storage device 403, input interface (I / F) 404, output I / F 405, communication I / F 406, and bus 407. The processor 401 functions as a functional unit that provides a predetermined function by executing processing according to a program loaded in the memory 402. The storage device 403 stores data and programs used by the functional unit. The input I / F 404 is connected to input devices such as a keyboard, pointing device, and operation panel, and the output I / F 405 is connected to a display device. The communication device I / F 406 enables communication with other computers via a network. These components are connected to each other via the bus 407 so that they can communicate with each other.

[0020] In the following description, when describing processing by a program, the program or functional units may be described as the main components, but the main hardware component of these components is a processor or a computer system including the processor. The computer system executes processing according to a program loaded into memory using resources such as memory and a communication interface as appropriate. While FIG. 2A shows an example of a CPU as the processor, a GPU (Graphical Processing Unit) or the like may also be used. Furthermore, processing to realize a function is not limited to software program processing, and can also be implemented using a dedicated circuit. Examples of the dedicated circuit include a field programmable gate array (FPGA) and an application specific integrated circuit (ASIC).

[0021] 2B shows examples of programs stored in the storage device 403. The operation interface program 411 displays information using a GUI (Graphical User Interface) on a display device connected to the output I / F 405, and causes the control device 30 to execute an interface function that allows the user to input information required for the genetic testing device 1 and instruct operations. The analysis program 412 causes the control device 30 to execute an analysis function that records and analyzes measurement data acquired by the nucleic acid analysis unit 20 for test items requested by the user. The scheduling program 413 causes the control device 30 to execute a scheduling function for efficiently performing genetic testing on a large number of samples input into the genetic testing device 1.

[0022] 3 shows a detection mechanism including a temperature control unit 106 and a fluorescence detection unit 107. The detection mechanism of this embodiment is characterized in that the fluorescence detection unit 107 is provided in common for a plurality of temperature control units 106. This makes it possible to configure the detection mechanism more compactly than in a configuration in which a temperature control unit 106 and a fluorescence detection unit 107 are provided in a one-to-one correspondence.

[0023] 4A is a top view (schematic diagram) of the temperature adjustment unit 106. The temperature adjustment unit 106 has a third well plate placed thereon and is equipped with a temperature adjustment mechanism 202 that controls the reaction solution dispensed into each well at a predetermined temperature. The temperature adjustment mechanism 202 is equipped with well temperature adjustment parts 301 corresponding to the arrangement of the wells in the third well plate. In this example, one temperature adjustment mechanism 202 is equipped with eight well temperature adjustment parts 301.

[0024] FIG. 4B is a cross-sectional view (schematic diagram) of one well temperature adjustment unit 301 with a third well plate 310 mounted on the temperature adjustment mechanism 202. The well temperature adjustment unit 301 includes a temperature measuring device 302 capable of measuring temperature, such as a thermistor or resistance thermometer, a temperature adjustment block 303 to be temperature-controlled, a Peltier element 304 for heating or cooling the temperature adjustment block 303, and a heat sink 305 for dissipating heat from the Peltier element. The temperature measuring device 302 measures the temperature of the reaction solution in the wells. The temperature adjustment block 303 has a recess, and the third well plate 310 is placed on the temperature adjustment mechanism 202 so that the wells 311 of the third well plate 310 are inserted into the recess of the temperature adjustment block 303. The well temperature adjustment unit 301 shown in FIG. 4B includes individual Peltier elements 304 and temperature measuring devices 302, enabling different temperature control for each well. This allows simultaneous measurement in the same temperature control unit 106 even if the temperature and cycle of temperature control are different, thereby reducing scheduling constraints. Of course, the temperature control mechanism 202 may be provided with a common Peltier element and temperature measuring device for multiple wells. In this case, the same temperature control is applied to multiple wells, simplifying the temperature control of the temperature control mechanism 202, but the degree of freedom in scheduling is reduced because the same temperature control is applied to these multiple wells.

[0025] The third well plate 310 is provided with a transparent lid 312 to prevent the reaction solution from evaporating due to heating by the well temperature adjustment unit 301. Excitation light is irradiated onto the reaction solution in the wells 311 via the lid 312 from the fluorescence detection unit 107 through a fiber, and the resulting fluorescence is detected by the fluorescence detection unit 107 through the fiber.

[0026] FIG. 5 shows a schematic configuration of the fluorescence detection unit 107. The fluorescence detection unit 107 primarily comprises a base 320 and a slider 330 that is driven in the longitudinal direction (X1 direction) of the base 320 by a drive mechanism (not shown). An excitation light source 321 that emits excitation light and a photodetector 322 that detects fluorescence are arranged on the base 320 in the transverse direction (Y1 direction) of the base 320, and pairs of excitation light source 321 and photodetector 322 are arranged in the longitudinal direction (X1 direction) of the base 320. Each of the multiple excitation light sources 321 emits excitation light of a different wavelength. This allows multiple different fluorescent dyes to be measured simultaneously. While this example shows an example in which six excitation light sources 321 are arranged, the number and wavelength of the excitation light sources are determined depending on the test protocol that can be performed by the nucleic acid analysis unit 20.

[0027] The slider 330 is provided with connectors 331 and 332 for fixing the fiber pair 201. For convenience of illustration, in Fig. 3, the fiber pair 201 arranged between one well temperature adjustment unit 301 and the fluorescence detection unit 107 is shown by a single solid line, but the fiber pair 201 shown as a single solid line in Fig. 3 is a set of a first fiber for transmitting excitation light and a second fiber for transmitting fluorescence. The first fiber and the second fiber constituting the fiber pair are connected to connectors 331 and 332, respectively, which are aligned in the Y1 direction.

[0028] The drive mechanism is configured using, for example, a stepping motor, and moves the slider 330 intermittently at a constant cycle. The slider 330 is controlled to, for example, move intermittently from the left end (home position) of the base 320 to the right, return to the home position when it reaches the right end, and then move intermittently again to the right. This configuration makes it possible to irradiate all well temperature control sections 301 of the multiple temperature control units 106 with excitation light at the same cycle and detect fluorescence. Note that this configuration is merely an example; for example, connectors 331 and 332 may be disposed on the base 320, and an excitation light source 321 and a light receiver 322 may be disposed on the slider 330. In this example, by moving the base 320 and the slider 330 relative to each other at a constant cycle, each reaction solution can be measured at the same constant cycle. The relative movement is not limited to linear movement and may be circumferential movement. Furthermore, regardless of relative movement, an excitation light source and a light receiver may be provided for each fiber pair 201.

[0029] The control device 30 controls the operation of the nucleic acid analysis unit 20 by executing the analysis program 412, and links the fluorescence measurement data detected at regular intervals for each reaction solution by the fluorescence detection unit 107 with the temperature measurement data measured by the temperature measuring device 302 during the temperature control period, and stores the linked data in the storage device 403.

[0030] The Ct value measurement and Tm value measurement performed by the detection mechanism described above will now be described. Normally, these measurements are performed at different timings for fluorescence measurement.

[0031] FIG. 6 shows an example of PCR cycle temperature control, which is a temperature control profile set for Ct value measurement, and shows a PCR temperature control cycle 501 and fluorescence measurement timing 502. The horizontal axis represents time, and the vertical axis represents the temperature (control target value) of the temperature control block 303. In Ct value measurement, fluorescence measurement is performed at a fixed cycle, and the fluorescence measurement and the temperature control cycle are asynchronous. In general, in nucleic acid amplification using the PCR method, fluorescence measurement is performed at a fixed cycle of fluorescence measurement timing 502 during a period in which the reaction solution is subjected to temperature control using a PCR temperature control cycle 501, which repeats two or three temperature stages a specified number of times. The fixed cycle of fluorescence measurement timing 502 can be achieved by intermittently moving the slider 330 in one direction on the base 320 at a fixed cycle in the fluorescence detection unit 107.

[0032] On the other hand, FIG. 7B shows an example of a step temperature control profile conventionally used for Tm value measurement, showing a temperature control profile 511 and fluorescence measurement timing 513. The horizontal axis represents time, and the vertical axis represents the temperature (control target value) of the temperature control block 303. The temperature control profile set for Tm value measurement is a step temperature control that increases the temperature in steps, and fluorescence measurement is performed in synchronization with the temperature profile. The temperature control profile 511 indicates a control target value, and it takes time for the reaction solution to actually reach that control target value. When the temperature is determined to be stable by monitoring temperature changes, a fluorescence measurement trigger is issued, and the control target value is updated after the fluorescence measurement. Therefore, the detection mechanism configuration of this embodiment does not allow such Tm value measurement and Ct value measurement to be performed simultaneously.

[0033] FIG. 7A shows an example of step temperature control, a temperature control profile used for Tm value measurement in this embodiment, showing a temperature control profile 511 and a fluorescence measurement timing 512. The horizontal axis represents time, and the vertical axis represents the temperature (target control value) of the temperature control block 303. Compared to FIG. 7B, the temperature control profile 511 is the same, whereas the fluorescence measurement timing 512 is asynchronous with the temperature control profile 511 and is performed at a fixed interval. Specifically, it is the same as the fluorescence measurement timing 502 (see FIG. 6) for Ct value measurement. By executing the analysis program 412, the control device 30 thins out the fluorescence measurement data acquired at the fluorescence measurement timing 512 so that one fluorescence measurement data is obtained for each temperature step. In FIG. 7A, the fluorescence measurement timing 512b corresponding to the remaining fluorescence measurement data after thinning is indicated by a bold line. The control device 30 calculates the Tm value using the fluorescence measurement data and temperature measurement data measured at the fluorescence measurement timing 512b. This makes it possible to measure the Tm value and the Ct value simultaneously in parallel.

[0034] In this way, in the detection mechanism of this embodiment, both the Ct value measurement and the Tm value measurement are performed at a fixed cycle that is asynchronous with the temperature control, so that one fluorescence detection section 107 is used for multiple temperature control units 106, and temperature control can be performed independently for each temperature control unit 106 or smaller, thereby allowing for a high degree of flexibility in the measurement schedule while keeping the detection mechanism compact.

[0035] Next, a description will be given of the operational workflow of the genetic testing device 1. The operational workflow is executed by the control device 30 executing the scheduling program 413.

[0036] FIG. 8 shows a flow chart of the process of extracting target nucleic acids from a sample by the nucleic acid extraction unit 10. When a user starts the device, the nucleic acid extraction unit 10 enters a sample waiting state (S01). When a user inputs a sample into the sample input unit 101 (S02), the sample is identified, and then samples undergoing the same extraction process are grouped, i.e., grouped by test item, based on the test request details registered for that sample (S03). Each extraction unit 103 in this embodiment can simultaneously extract eight samples. Therefore, the number of grouped samples is counted (S04), and if eight samples have been grouped, a nucleic acid extraction instruction is issued for this group of eight samples (S05). For samples in a group in which eight samples for simultaneous extraction are not completed, the nucleic acid extraction instruction is held in abeyance, and the system returns to the sample waiting state (S01).

[0037] When a nucleic acid extraction instruction is issued, the control device 30 checks the operating status of the extraction units 103 (S06). If all extraction units 103 are operating, the control device 30 transitions to an extraction instruction waiting state and waits until one of the ongoing nucleic acid extraction processes is completed. If there is an extraction unit 103 that is not operating, the stop times of the extraction units 103 are compared (S07). At this time, the stop time of the operating extraction unit 103 is set to 0. If the stop time of unit 1 is equal to or longer than the stop time of unit 2, nucleic acid extraction processing is performed in unit 1 (S08). If the stop time of unit 1 is less than the stop time of unit 2, nucleic acid extraction processing is performed in unit 2 (S09).

[0038] This flow is merely an example, and various variations are possible. For example, even if a group does not contain eight samples, a nucleic acid extraction instruction (S05) may be issued if certain conditions are met, such as a certain amount of time having passed since the samples were input. It is also possible to select an extraction unit 103 based on conditions other than the downtime. It is sufficient if the extraction unit 103 to be operated can be uniquely determined based on some condition.

[0039] In nucleic acid extraction processing, the first transport mechanism 108 grasps the consumables installed in the first consumable supply unit 102 and transports them to the extraction unit 103 to be used. Thereafter, the specimen is aspirated from the specimen container placed in the specimen input unit 101 by a dispensing nozzle provided on the working head of the first transport mechanism 108, and is discharged into the extraction unit 103. After the specimen is discharged, the extraction unit 103 performs nucleic acid extraction processing from the specimen.

[0040] FIG. 9 shows the flow of the nucleic acid analysis unit 20 amplifying nucleic acids extracted by the nucleic acid extraction unit 10. When the user starts the device, the nucleic acid analysis unit 20 enters an extraction waiting state (S11). After the extraction process is completed by the extraction unit 103 (S12), the extract (sample) is grouped by test item (S13). The temperature control unit 106 of this embodiment can simultaneously control the temperature of eight samples, as shown in FIG. 4A. Therefore, the number of grouped samples is counted (S14), and when eight samples have been grouped, a PCR command (temperature control command) is issued for this group of eight samples (S15). For samples in a group in which eight samples to be simultaneously extracted are not complete, the PCR command is held in reserve, and the system returns to the extraction waiting state (S11).

[0041] When a PCR command is issued, the control device 30 checks the operating status of the temperature adjustment units 106 (S16). If all temperature adjustment units 106 are operating, the control device 30 transitions to a PCR command waiting state and waits until one of the ongoing nucleic acid amplification processes is completed. If there is an inactive temperature adjustment unit 106, the downtime of the temperature adjustment units 106 is compared (S17). At this time, the downtime of the operating temperature adjustment unit 106 is set to 0. If there is a difference in the downtime of the temperature adjustment units 106, the PCR amplification process is performed by the temperature adjustment unit with the longest downtime (S18), and the nucleic acid amplification process is performed by the temperature adjustment unit with the smallest unit number (S19).

[0042] This flow is also one example, and various variations are possible. For example, even for a group that does not have all eight samples, a PCR command (S15) may be issued if certain conditions are met, such as a certain amount of time having passed since the completion of nucleic acid extraction. It is also possible to select a temperature adjustment unit 106 based on conditions other than the downtime. It is sufficient if the temperature adjustment unit 106 to be operated can be uniquely determined based on some condition.

[0043] In the nucleic acid amplification process, the second transport mechanism 109 grasps the consumables installed in the second consumable supply unit 105 and transports them to the temperature adjustment unit 106 to be used. After the consumables have been transported, the reagent installed in the reagent input unit 104 is aspirated by a dispensing nozzle provided on the working head of the second transport mechanism 109 and dispensed into the consumables (third well plate) installed in the temperature adjustment unit 106. Similarly, the extract extracted by the extraction unit 103 is also aspirated by the dispensing nozzle of the second transport mechanism 109 and dispensed into the consumables (third well plate) installed in the temperature adjustment unit 106. Then, the nucleic acid amplification process is performed in the temperature adjustment unit 106.

[0044] 3 and 5, even if a temperature control unit 106 is not in operation, fluorescence measurement data is output when at least one temperature control unit 106 provided in the nucleic acid analysis section 20 is in operation. The control device 30 processes such data as, for example, invalid data.

[0045] In this way, the extraction unit 103 and the temperature control unit 106 can each process multiple samples simultaneously in parallel, which allows for efficient testing, but because nucleic acid amplification is performed after nucleic acid extraction is complete, there is a limit to the efficient use of the device if each unit can only process multiple samples. This will be explained using the time chart in Figure 10.

[0046] Time chart 600 is a time chart for a genetic testing device (Comparative Example 1) equipped with one extraction unit 103 and one temperature control unit 106. A single nucleic acid extraction process performed by the extraction unit 103 includes pre-processing 701, nucleic acid extraction 702, and post-processing 703. Pre-processing 701 includes removing consumables and dispensing samples, while post-processing 703 includes disposing of used consumables. Similarly, a single nucleic acid amplification process performed by the temperature control unit 106 includes pre-processing 711, nucleic acid amplification 712, and post-processing 713. Pre-processing 711 includes removing consumables and dispensing extraction solution and reagents, while post-processing 713 includes disposing of used consumables. Here, it is assumed that an average processing time for a single nucleic acid amplification process is more than twice that of a single nucleic acid extraction process. The same applies to time charts 610 and 620, which will be described later.

[0047] As shown by the time chart 600, in Comparative Example 1, the nucleic acid extraction process and the nucleic acid amplification process are performed sequentially, resulting in long non-operating times Tnw1 and Tnw2 in the extraction unit 1 and the temperature adjustment unit 2, respectively.

[0048] Time chart 610 is a time chart for a genetic testing device (Comparative Example 2) equipped with one extraction unit 103 and two temperature adjustment units 106. In Comparative Example 2, nucleic acid extraction processing is performed during the period that was the non-operating time Tnw1 in Comparative Example 1, and by operating the temperature adjustment units 106 in parallel during the processing time, it is possible to suppress the occurrence of long non-operating times in the extraction unit 1. However, on the other hand, each of the duplicated temperature adjustment units still experiences a long non-operating time Tnw2'.

[0049] Time chart 620 is a time chart for a genetic testing device (embodiment) in which both the extraction units 103 and the temperature control units 106 are multiplexed, with the number of multiplexed temperature control units 106, which have longer processing times, being greater than the number of multiplexed extraction units 103. This time chart shows a genetic testing device with two extraction units 103 and three temperature control units 106, which is the minimum configuration that satisfies the above multiplexing conditions. In this embodiment, by operating the extraction units 103 and the temperature control units 106 in parallel, it is possible to reduce the occurrence of significant downtime for both the extraction units 103 and the temperature control units 106. In practice, multiple types of tests may be performed on nucleic acids extracted by nucleic acid extraction processing, or Tm value measurement may be performed following Ct value measurement. In a genetic testing device with such a configuration, the number of extraction units 103 and temperature control units 106 allows for a processing schedule with minimal downtime, even in such cases. Therefore, by implementing the scheduling shown in Figures 8 and 9, it is possible to efficiently perform genetic testing of samples.

[0050] The above embodiments and modifications have been described in detail to make the present invention easier to understand, and are not necessarily limited to those including all of the described configurations. Furthermore, it is possible to replace part of the configuration of one embodiment or modification with the configuration of another embodiment or modification, and it is also possible to add the configuration of another embodiment or modification to the configuration of one embodiment or modification. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment or modification with other configurations.

[0051] 1: Genetic testing device, 10: Nucleic acid extraction unit, 20: Nucleic acid analysis unit, 30: Control device, 101: Sample input unit, 102: First consumable supply unit, 103: Extraction unit, 104: Reagent input unit, 105: Second consumable supply unit, 106: Temperature control unit, 107: Fluorescence detection unit, 108: First transport mechanism, 109: Second transport mechanism, 201: Fiber pair, 202: Temperature control mechanism, 301: Well temperature control unit, 302: Temperature measuring device, 303: Temperature control block, 304: Peltier element, 305: Heat sink, 310: Third well plate, 311: Well, 312: Lid, 320: Base, 321: Excitation light source, 322: Photodetector , 330: slider, 331, 332: connector, 401: processor (CPU), 402: memory, 403: storage device, 404: input interface, 405: output interface, 406: communication interface, 407: bus, 411: operation interface program, 412: analysis program, 413: scheduling program, 501: PCR temperature control cycle, 502, 512, 513: fluorescence measurement timing, 511: temperature control profile, 600, 610, 620: time chart, 701, 711: pre-processing, 702: nucleic acid extraction, 703, 713: post-processing, 712: nucleic acid amplification.

Claims

1. A genetic testing device comprising: a plurality of temperature control units on which a well plate is placed and which control the temperature of a plurality of temperature control blocks provided corresponding to each of a plurality of wells of the well plate; a fluorescence detector; and a control device, wherein each of the temperature control blocks of the temperature control units has one end of a fiber pair including a first fiber and a second fiber arranged so as to face each other; the other end of the fiber pair is connected to the fluorescence detector, the first fiber of the fiber pair transmits excitation light from the fluorescence detector, and the second fiber of the fiber pair transmits fluorescence generated by irradiation of the excitation light on the reaction solution in the well to the fluorescence detector, the fluorescence detector is configured to emit excitation light toward the first fiber at the same constant period for each of the connected fiber pairs and measure the fluorescence transmitted via the second fiber; the control device sets a different temperature control profile for each of the temperature control units, and the temperature control units control the temperature according to the set temperature control profile.

2. A genetic testing device according to claim 1, wherein the temperature control unit is provided with a well temperature control section that controls the temperature for each of the temperature control blocks, and the control device sets a different temperature control profile for each of the well temperature control sections, and the well temperature control sections control the temperature in accordance with the set temperature control profile.

3. A genetic testing device according to claim 2, wherein the well temperature control unit comprises a temperature measuring device for measuring the temperature of the reaction solution in the well, a Peltier element for heating or cooling the temperature control block, and a heat sink for dissipating heat from the Peltier element.

4. A genetic testing device as claimed in claim 1, wherein the control device sets PCR cycle temperature control as the temperature control profile for one of the temperature control units, and the control device calculates the Ct value of the target nucleic acid based on the temperature measurement data of the reaction solution in the well and the fluorescence measurement data measured at the regular intervals by the fluorescence detector during the period in which the temperature control unit performs temperature control in accordance with the PCR cycle temperature control.

5. A genetic testing device according to claim 1, wherein the control device sets step temperature control for one of the temperature control units, which increases the temperature in steps as the temperature control profile, and the control device calculates the Tm value of the target nucleic acid based on temperature measurement data of the reaction solution in the well and fluorescence measurement data measured at the regular intervals by the fluorescence detector during a period in which the temperature control unit performs temperature control in accordance with the step temperature control, and the control device calculates the Tm value by thinning out the fluorescence measurement data so that there is one fluorescence measurement data for one temperature step in the step temperature control.

6. A genetic testing device as claimed in claim 2, wherein the control device sets PCR cycle temperature control as the temperature control profile for one of the well temperature control units, and the control device calculates the Ct value of the target nucleic acid based on temperature measurement data of the reaction solution in the well and fluorescence measurement data measured at the regular intervals by the fluorescence detector during the period when the well temperature control unit performed temperature control in accordance with the PCR cycle temperature control.

7. A genetic testing device according to claim 2, wherein the control device sets step temperature control for one of the well temperature control units, which increases the temperature in steps as the temperature control profile, and the control device calculates the Tm value of the target nucleic acid based on temperature measurement data of the reaction solution in the well and fluorescence measurement data measured at the regular intervals by the fluorescence detector during a period in which the well temperature control unit performs temperature control in accordance with the step temperature control, and the control device calculates the Tm value by thinning out the fluorescence measurement data so that there is one fluorescence measurement data for one temperature step in the step temperature control.

8. The genetic testing device according to claim 1, wherein the well plate is provided with a lid, and the well plate is placed on the temperature control unit with the lid on.

9. A genetic testing device according to claim 1, wherein the fluorescence detector is provided with a plurality of excitation light sources that emit excitation light of different wavelengths.

10. A genetic testing device having a nucleic acid extraction section that extracts nucleic acid from a sample and a nucleic acid analysis section that amplifies the nucleic acid extracted by the nucleic acid extraction section, wherein the nucleic acid extraction section has a plurality of extraction units that each extract nucleic acid, and the nucleic acid analysis section has a plurality of temperature control units that each amplify nucleic acid, and the number of temperature control units provided in the nucleic acid analysis section is greater than the number of extraction units provided in the nucleic acid extraction section.

11. A genetic testing device according to claim 10, wherein the extraction unit and the temperature control unit are each capable of processing a plurality of specimens simultaneously in parallel.

12. A genetic testing device according to claim 10, comprising a control device for scheduling input samples.

13. A genetic testing device according to claim 12, wherein the control device operates the plurality of extraction units and the plurality of temperature control units in parallel.

14. A genetic testing device according to claim 10, comprising two of the extraction units and three of the temperature control units.

15. A genetic testing device according to claim 10, wherein the average processing time for the temperature control unit to perform nucleic acid amplification processing is at least twice the average processing time for the extraction unit to perform nucleic acid extraction processing.

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