JP6660910B2 - Automatic sample processing device - Google Patents

Description

  The present invention relates to an automatic sample processing apparatus.

  In recent years, the ratio of drug-resistant bacteria has increased due to abuse of antibacterial agents in patients with bacterial infections, and the number of hospital-acquired infections has been increasing accordingly. However, the development of new antimicrobial agents is on a downward trend. Therefore, based on the results of bacterial tests, prescribing a narrow-spectrum antibacterial agent suitable for the infectious disease-causing bacteria will not suppress the emergence of drug-resistant bacteria, without abusing broad-spectrum antibacterial agents that are effective against a wide variety of bacterial species. It is important for preventing the spread of nosocomial infections, reducing mortality, and improving the prognosis of patients.

  Among bacterial infections, sepsis has a high mortality rate (in-hospital mortality rate of 30 to 60%) and requires an early treatment of an effective antibacterial agent against the causative bacteria. Usually, when sepsis is suspected, blood is collected from a patient, and a bacterial identification test (ID: Bacterial identification test) and a drug susceptibility test (AST: Antimicrobial susceptibility test) of the causative bacterium are performed. In the conventional method, a sample collected from a patient is first subjected to blood culture. When bacteria are present in the blood, the blood culture is determined to be positive, and usually takes about 1-2 days. Next, the infection-causing bacterium is identified from the positive blood culture bottle, and the isolation culture is performed for 24 hours to obtain a single colony. After the isolation and culturing, a bacterial solution having a certain concentration is prepared by using the bacterium that has formed a single colony, dispensed into a container in which a drug / antibiotic is placed, and identification culture and drug-sensitive culture are carried out all day and night. After the cultivation, the degree of proliferation of the bacterium is determined by turbidity, and the ID of the bacterium causing the infection and the result of AST are obtained. Patients with suspected sepsis are given antimicrobial agents that show a broad antimicrobial spectrum without waiting for ID / AST results (empirical treatment) and are needed after ID / AST results are obtained Change to an appropriate antibacterial agent according to Therefore, after a sample is collected from a patient, appropriate medication is performed at the earliest on or after the fourth day. Depending on the bacterial species, the growth rate is slow and a long period of cultivation may be required, so that appropriate dosing requires additional days. Therefore, in recent years, a method that can quickly obtain drug susceptibility results from the viewpoint of reducing the mortality of patients due to early optimization of antimicrobial agents, shortening the hospital stay by improving the prognosis, reducing medical costs, and suppressing the emergence of drug-resistant bacteria. It has been demanded.

  As a method for rapidly detecting the growth of bacteria without using culture, Patent Document 1 discloses a method using ATP (adenosine triphosphate) possessed by bacteria. The firefly-derived enzyme luciferase oxidizes ATP present as an energy source in the bacteria and luciferin as a substrate to emit light. Since the amount of luminescence is proportional to the amount of ATP, the growth of bacteria can be quickly evaluated from the change in the amount of luminescence.

  To speed up the AST test, it is necessary to examine the sensitivity of the drug without performing blood culture or separation culture. However, in a sample represented by blood, since human-derived cells such as blood cells contain a large amount of ATP, it is difficult to detect only bacterial-derived ATP and test the sensitivity. Therefore, Patent Document 2 discloses a specimen processing method for removing only human-derived cells without killing bacteria.

WO2016 / 103433 A1 JP 2014-235076 A

  When realizing a device that automatically performs sample processing including centrifugation, supernatant removal, and reagent dispensing, it is necessary to transport the sample container many times because the sample processing location differs between centrifugation and other processes. However, there is a problem that it takes a long time to process the sample.

  A sample processing apparatus according to one embodiment of the present invention includes a centrifuge for centrifuging a sample in a sample container, a pump for sucking and discharging a solution, a stage for moving the pump, and a disposable pipette tip attached to a tip of the pump. Pipette tip rack for storing reagent bottles, a reagent bottle rack for storing reagent bottles, a housing in which a centrifuge, pump, stage, pipette tip rack, and reagent bottle rack are installed to form a closed space, A temperature controller for controlling the temperature of the pump, and a drive control device for driving the centrifuge, the pump and the stage. The pump is housed in a disposable pipette tip stored in a pipette tip rack and a reagent bottle rack by the stage. The reagent bottle is selectively moved to a position for accessing a sample container in the centrifuge.

  A sample processing apparatus according to another aspect of the present invention includes a centrifuge for centrifuging a sample in a sample container, a pump for sucking and discharging a solution, a stage for moving the pump, and a tip mounted on the pump. A pipette tip rack that stores a disposable pipette tip, a reagent bottle rack that stores a reagent bottle, a temperature controller that controls the temperature in the centrifuge, and a drive control device that drives the centrifuge, the pump, and the stage. The stage selectively moves the disposable pipette tip in the pipette tip rack, the reagent bottle in the reagent bottle rack, and the position to access the sample container in the centrifuge. An opening / closing mechanism for inserting the mounted disposable pipette tip therein is provided at the upper part.

  Also, a sample processing method according to another aspect of the present invention includes a step of centrifuging a sample contained in a sample container with a centrifuge having a sealed upper part, a step of opening a part of the upper part of the centrifuge, and a pump. Driving the stage, moving the stage, inserting the tip of the pipette tip attached to the pump into the sample container in the centrifuge, driving the pump to aspirate the supernatant in the sample container, and driving the stage. Removing the pipette tip to the outside of the centrifuge, and sealing the upper portion of the centrifuge again.

ADVANTAGE OF THE INVENTION According to this invention, since the conveyance mechanism of a sample container becomes unnecessary, the size reduction of an apparatus and reduction of the number of parts are attained. Further, since it is not necessary to transport the sample container between the processes, the sample processing time can be reduced.
Problems, configurations, and effects other than those described above will be apparent from the following description of the embodiments.

FIG. 2 is a schematic diagram illustrating an example of a sample processing apparatus. 9 is a flowchart illustrating an example of a procedure of centrifugation and removal of a supernatant. 7 is a flowchart showing an example of the procedure of reagent dispensing and dispensing, stirring, and reaction. FIG. 4 is an explanatory diagram illustrating an example of a sample processing protocol. The figure which shows the example of the drug sensitivity test result after a sample process. FIG. 2 is a schematic diagram illustrating a configuration example of a sample processing apparatus. FIG. 2 is a schematic diagram illustrating an example of a centrifuge of a sample processing apparatus. The schematic diagram which looked at the centrifuge which installed the fixed lid and the movable lid from the top. The schematic diagram which looked at the centrifuge which installed the fixed lid and the movable lid from the top. The schematic diagram which shows the cross section of the centrifuge which has a fixed lid and a movable lid. The schematic diagram which shows the cross section of the centrifuge which has a fixed lid and a movable lid. 9 is a flowchart illustrating an example of a procedure of centrifugation and removal of a supernatant. FIG. 6 is a schematic cross-sectional view showing another example of the opening and closing mechanism of the movable lid of the centrifuge. FIG. 6 is a schematic cross-sectional view showing another example of the opening and closing mechanism of the movable lid of the centrifuge. FIG. 2 is a schematic cross-sectional view illustrating a configuration example of a sample processing apparatus. The elements on larger scale of FIG. FIG. 4 is a schematic diagram illustrating another configuration example of the sample processing apparatus. 7 is a flowchart showing an example of a procedure of a drug sensitivity test using ATP.

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

[Example 1]
In this embodiment, an example of a sample processing apparatus in which a sample container is directly installed in a centrifuge and a sample is automatically processed will be described.

  FIG. 1 is a schematic diagram illustrating an example of the sample processing apparatus according to the present embodiment. The sample processing apparatus of the present embodiment includes an XZ automatic stages 110 and 111, a pump 120, a centrifuge 130, a pipette tip rack 141, a reagent bottle rack 143, and a waste box 145 in a housing 105 capable of forming a closed space. Have. The pipette tip rack 141 stores the disposable pipette tips 140. The reagent bottle 142 is stored in the reagent bottle rack 143. The disposal box 145 holds the used pipette tip 140. The pump 120 is moved inside the housing 105 by the XZ automatic stages 110 and 111. More specifically, the pump 120 uses the XZ automatic stages 110 and 111 to dispose the disposable pipette tip 140 stored in the pipette tip rack 141, the reagent bottle 142 stored in the reagent bottle rack 143, and the centrifuge 130. The sample is selectively moved to an access position for the sample container 150.

  A temperature controller 160 is connected to the inside of the housing 105 via a temperature control pipe 161 to adjust the temperature inside the housing 105. The temperature control pipe 161 is provided with a filter 162 for removing impurities, airborne bacteria, and the like. A sample container 150 for storing a sample is installed in the centrifuge 130. The XZ automatic stages 110 and 111 are installed orthogonally, and the pump 120 is fixed. The pump 120 can perform an operation of sucking the solution and an operation of discharging the sucked solution. The XZ automatic stage moves the pump 120 in the horizontal and vertical directions to position the pump 120 at a desired location, and performs various sample processing (pre-processing) steps by performing reagent dispensing, dispensing, stirring, and the like. The sample processing is executed according to an algorithm stored in the control PC 170, and the drive and control of the XZ automatic stages 110 and 111, the pump 120, the centrifuge 130, and the temperature controller 160 are executed by the drive control device 171.

  FIG. 2 is a flowchart illustrating an example of a procedure for performing centrifugation and supernatant removal as an example of a sample processing method performed using the above-described sample processing apparatus. It is assumed that the sample is placed in a sample container 150 and set at a predetermined position in the centrifuge 130. First, the set temperature at the time of work is compared with the current temperature in the housing 105 (S11). If the set temperature is reached, the process proceeds to step S13, where the conditions for centrifugation set in advance are set. Perform centrifugation at rotation speed and time. If the current temperature is different from the set temperature, the process proceeds to step S12, in which the temperature controller 160 is operated to wait until the temperature reaches the set temperature, and then the process of step S13 is performed. After the centrifugation, the X stage 110 is driven to move the pump 120 to an access position for the pipette tip on the pipette tip rack 141. Next, the Z stage 111 is driven to lower the pump 120, and a predetermined pipette tip 140 is mounted on the tip of the nozzle of the pump 120 (S14).

  Next, the centrifuge 130 is rotated, and among the samples in the centrifuge, the sample container 150 of the sample to be subjected to supernatant removal is moved to the working position, that is, the position in the centrifuge accessed by the pump 120 (S15). ). Subsequently, the X stage 110 is driven to move the pump 120 to the working position on the centrifuge 130, that is, the access position for the sample container in the centrifuge (S16), and the Z stage 111 is driven to drive the sample in the sample container 150. The pipette tip 140 is immersed in the sample, and a set amount of supernatant is sucked by the pump 120 (S17). Next, after the pump 120 is moved upward by the Z stage 111, the X stage 110 is driven to move the pump 120 to the access position on the waste box 145, the pipette chip 140 is removed together with the supernatant, and the waste box 145 is removed. (S18). In step S19, it is determined whether or not the sample to be processed remains. If the sample remains, the process returns to step S14 to process the next sample.

  FIG. 3 is a flowchart showing an example of a procedure for executing reagent dispensing and dispensing, stirring, and reaction as an example of another sample processing method using the above-described sample processing apparatus.

  As in FIG. 2, the set temperature is compared with the current temperature (S21). If the set temperature is different, the process waits until the set temperature is reached using the temperature controller 160 (S22). Thereafter, the pump 120 is moved from the mechanical origin to the access position above the pipette tip rack 141 on the X stage 110, and the Z stage 111 is driven to mount a predetermined pipette tip 140 on the tip of the pump 120 (S23). If it is determined in step S21 that the temperature has reached the set temperature, the process immediately proceeds to step S23, where the pipette tip 140 is attached to the tip of the pump 120.

  Subsequently, the X stage 110 is driven to move the pump 120 to the access position for the reagent bottle above the reagent bottle rack 143, and the pipette chip 140 is immersed in the reagent in the predetermined reagent bottle 142 on the Z stage 111, and the setting is performed. An amount of the reagent is collected by the pump 120 (S24). Next, the centrifuge 130 is rotated, and among the sample containers 150 in the centrifuge 130, the container containing the sample to be dispensed with the reagent is moved to the working position (S25). Subsequently, the pump 120 is moved to a work position above the centrifuge 130 on the X stage 110 (S26). Subsequently, the Z stage 111 is driven to lower the pipette tip 140 into the sample container 150, and a set amount of reagent is dispensed by the pump 120 (S27).

  Here, it is determined whether stirring is necessary (S28), and when stirring is necessary, the sample is stirred by repeating the suction and discharge of the sample by the pump 120 (S29). At this time, by changing the suction position and the discharge position on the Z stage 111 as needed, it is possible to improve the stirring efficiency and prevent the sample from scattering from the sample container 150. After the stirring, the Z stage 111 is driven to move the pump 120 upward. Then, the X stage 110 is driven to move the pump 120 onto the waste box 145, and the pipette tip 140 is removed (S30). It is determined whether or not the processing for all the samples has been completed (S31). If the processing has been completed, the process proceeds to step S32, and if the reaction time of the reagent is necessary, the process waits for a set time. If there is an unprocessed sample, the process returns to step S23 to process the next sample.

  By using the sample processing apparatus of the present embodiment, centrifugation and removal of the supernatant can be performed without transporting the sample container during sample processing. It is possible to prevent the bacteria from being moved to the supernatant side and decreasing the bacterial recovery rate.

  A sample processing protocol is created and executed by combining the above operations of centrifugation, supernatant removal, reagent dispensing, stirring, and the like, whereby sample processing is automatically completed. FIG. 4 is an explanatory diagram illustrating an example of the sample processing protocol. In the example of FIG. 4, a sample container containing 1 mL of plasma as a sample is set in a centrifuge, centrifuged at 1800 g for 10 minutes, and the supernatant is removed. Thereafter, 1 mL of a surfactant is added, and the mixture is left standing for 15 minutes after stirring. Subsequently, centrifugation is performed at 1800 g for 5 minutes, and the supernatant is removed. Thereafter, 1 mL of the medium is added and stirred, and then centrifuged at 1800 g for 5 minutes to remove the supernatant. Next, 300 μL of a medium is added and stirred, and then cultured at 37 ° C. to perform AST. In this example, a reagent in which sodium dodecyl sulfate 0.15% and saponin 0.2% were mixed as a surfactant, and a Mueller Hinton medium was used as a medium.

  FIG. 5 is a diagram showing the time-dependent changes in the ATP luminescence of Staphylococcus aureus resistant strains and susceptible strains to cefoxitin (CFX) 4 μg / mL as an antibacterial agent. The time after completion of the sample treatment was set to 0 hour, the cells were cultured at 37 ° C., and the amount of ATP luminescence was measured every hour. In the resistant strain, since the amount of ATP luminescence has increased after 2 hours of culture from 0 hour immediately after the sample treatment, it can be determined that the strain has proliferated. On the other hand, in the susceptible strain, since the amount of ATP emission immediately after the sample treatment is reduced after 2 hours, it can be determined that the ATP emission is inhibited.

[Example 2]
In the present embodiment, an example of a sample processing apparatus in which a centrifuge is sealed and temperature control efficiency is improved will be described.

  FIG. 6 is a schematic diagram illustrating a configuration example of the sample processing apparatus according to the present embodiment. For the parts denoted by the same reference numerals as those in FIG.

  The centrifuge 130 has a fixed lid 600 and a movable lid 601 on the upper part. The temperature controller 160 is connected to the inside of the centrifuge 130 via a temperature control pipe 161. The temperature inside the centrifuge 130 is measured by a temperature sensor 652 provided inside the centrifuge 130. The reagent bottle rack 143 is provided with a reagent bottle temperature controller 610 for adjusting the temperature of the reagent bottle 142. In this embodiment, a position sensor 650 for detecting whether or not the sample container exists at the working position in the centrifuge 130 is provided. As the position sensor 650, for example, an optical sensor using reflected light, an ultrasonic sensor, or the like is used. By confirming that the sample container 150 is installed at a position in the centrifuge 130 accessed by the pump 120 by the position sensor 650, when a user forgets to install the sample container 150, reagent dispensing or the like can be performed. The operation prevents the inside of the centrifuge 130 from being contaminated.

  The fixed lid 600 has a detachable structure, and the fixed lid 600 can be removed when the sample container 150 is installed or removed from the centrifuge 130. During sample processing, the fixing lid 600 is fixed on the upper part of the centrifuge 130. FIG. 7 is a schematic diagram illustrating an example of the centrifuge of the sample processing apparatus, and is a view of the centrifuge 130 with the fixed lid 600 removed, as viewed from above. A temperature control pipe 161 is connected inside the centrifuge 130, and the temperature inside the centrifuge 130 is adjusted by the temperature controller 160. The temperature control pipe 161 is provided with a filter 162, which can prevent airborne bacteria, impurities, and the like from being mixed into the sample container 150.

  8 and 9 are schematic views of the centrifuge 130 in which the fixed lid 600 and the movable lid 601 are installed, as viewed from above. The movable lid 601 is slid by an automatic stage 603 and can be opened and closed. FIG. 8 shows a state where the movable lid 601 is closed, and FIG. 9 shows a state where the movable lid 601 is opened. The fixed lid 600 does not cover the entire upper part of the centrifuge 130 but has a shape in which a part is cut out so as to access the sample container 150 placed at the working position in the centrifuge 130 from above. On the other hand, the movable lid 601 has a shape capable of closing the notched opening of the fixed lid 600 and sealing the upper part of the centrifuge 130 in cooperation with the fixed lid 600. Therefore, when the movable lid 601 is closed, the upper part of the centrifuge is sealed as shown in FIG. 8, and when the movable lid 601 is opened, as shown in FIG. Work position can be accessed.

  10 and 11 are schematic views showing a cross section of a centrifuge having a fixed lid and a movable lid. FIG. 10 shows a state where the movable lid 601 is opened, and FIG. 11 shows a state where the movable lid 601 is closed. As shown in FIG. 10, the movable lid 601 is opened only when processing using the pump 120 is performed on the sample container 150 in the centrifuge 130, and when the processing is completed, the movable lid 601 is closed. When performing sample processing such as centrifugation, the movable lid 601 is closed and the centrifuge 130 is sealed as shown in FIG.

  FIG. 12 is a flowchart illustrating an example of a procedure when centrifugation and supernatant removal are performed by the sample processing apparatus according to the present embodiment.

  If the movable lid 601 is open after the work such as the sample exchange, the movable lid 601 is closed, and the upper part of the centrifuge 130 is sealed (S41). The set temperature at the time of the operation is compared with the current temperature (S42). If the set temperature is reached, the process proceeds to step S44. If the set temperature is different, the temperature controller 160 is used to wait until the set temperature is reached. (S43). In step S44, centrifugation is performed at a predetermined number of revolutions / time which is a preset centrifugation condition. After the centrifugation, the pump 120 is moved to the access position on the pipette tip rack 141 by the X stage 110. Subsequently, the Z stage 111 is driven to lower the pump 120, and a predetermined pipette tip 140 is mounted on the tip of the pump 120 (S45). The centrifuge 130 is rotated, and among the sample containers 150 in the centrifuge 130, the sample container containing the sample to be subjected to supernatant removal is moved to the working position (S46).

  Subsequently, the X stage 110 is moved to a working position on the centrifuge 130, that is, an access position for a sample container in the centrifuge (S47). Next, after opening the movable lid 601 of the centrifuge 130 and partially opening the upper part of the centrifuge 130, the Z stage 111 is driven to lower the pump 120, and the specimen container is passed through the cutout opening of the fixed lid 600. The pipette tip 140 is immersed in the sample in 150, and a set amount of supernatant is aspirated by the pump 120 (S48). When the suction is completed, the Z stage 111 is driven to move the pump 120 upward, the pipette tip 140 is taken out of the centrifuge, the movable lid 601 is closed, and the upper part of the centrifuge is sealed again (S49). Next, the X stage 110 is driven to move the pump 120 onto the waste box 145, and the pipette tip 140 is removed together with the supernatant (S50). It is determined whether the processing has been completed for all the samples (S51). If any unprocessed samples remain, the process returns to step S45 to process the next sample. As described above, by restricting the opening and closing of the movable lid 601 when the pump 120 performs processing on the sample in the sample container 150, the temperature fluctuation in the centrifuge 130 is reduced, and the temperature is stabilized. In addition, the risk of contamination such as impurities can be reduced.

  As shown in FIG. 10, the size of the movable lid 601, in other words, the size of the opening of the fixed lid 600, is such that the outer diameter of the pipette tip 140 and the pump 120 can be inserted so that the pipette tip 140 can be inserted into the sample container 150. Is preferably larger than the outer diameter of the nozzle and as small as possible. In practice, it is desirable that the opening has an area of about 1 to 4 times the area of the opening of the sample container 150. By reducing the opening area of the fixed lid 600, it is possible to suppress the temperature fluctuation in the centrifuge 130, and to obtain a stable sample processing result. In addition, since the time for opening the inside of the centrifuge 130 is shortened, the incorporation of airborne bacteria and the like can be prevented.

  The opening and closing mechanism of the movable lid 601 is not limited to a sliding type. FIGS. 13 and 14 are schematic cross-sectional views showing another example of the opening and closing mechanism of the movable lid of the centrifuge. The movable lid may be opened and closed vertically, for example, as in the example shown in FIG. Further, as shown in FIG. 14, a structure in which two left and right movable lids open and close vertically may be employed. The movable lid 601 is driven by the drive unit 605 to open and close the opening of the fixed lid 600.

[Example 3]
In the present embodiment, an example of a sample processing apparatus capable of measuring the amount of pellet after centrifugation in a centrifuge and improving the efficiency of supernatant removal will be described.

  FIG. 15 is a schematic cross-sectional view illustrating a configuration example of the sample processing apparatus of the present embodiment. FIG. 16 is a partially enlarged view of FIG. 1 and FIG. 6 are denoted by the same reference numerals, and redundant description is omitted.

  The sample processing apparatus of this embodiment has a transparent window 1201 on the outer wall facing the working position of the centrifuge 130, and a light source 1202 that illuminates the sample container 150 that has come to the working position in the centrifuge 130. . An interface detection sensor 1203 is provided outside the centrifuge 130 so as to face the transparent window 1201. As shown in FIG. 16, the interface detection sensor 1203 passes through the transparent window 1201, and / or the position of the gas-liquid interface 1205 of the sample in the sample container 150 located at the position in the centrifuge 130 accessed by the pump 120. The position of the interface 1207 between the pellet after centrifugation and the supernatant is detected. The transparent window 1201 and the interface detection sensor 1203 are installed near the working position in the centrifuge 130.

  The position information of the gas-liquid interface 1205 and the pellet interface 1207 obtained by the interface detection sensor 1203 is converted into a distance from the bottom surface of the sample container 150 and recorded in the control PC 170, and the position information of the pipette tip 140 attached to the pump 120 is recorded. Used to control the tip position. For example, when removing the supernatant after centrifugation, it is necessary to aspirate only the supernatant without winding up the pellet. Therefore, it is desirable that the tip of the pipette tip 140 be sucked up as far as possible from the pellet. Therefore, the control PC 170 monitors the height of the gas-liquid interface 1205 at the time of removing the supernatant with the interface detection sensor 1203, and based on the information, the drive control device 171 drives the Z stage 111 and aspirates the supernatant. By constantly adjusting the height of the gas-liquid interface 1205, which is decreasing at the time, and the height of the tip of the pipette tip 140 so as to be equal to each other, the supernatant can be removed without winding up the pellet. Further, by restricting the height of the tip of the pipette tip 140 to a position higher than the interface 1207 between the pellet and the supernatant, it is possible to avoid aspirating the pellet. Since the amount of the sample and the amount of the pellet are different for each sample, by detecting the gas-liquid interface 1205 and the interface 1207 between the pellet and the supernatant for each sample, the sample processing efficiency can be increased and a low ATP background can be obtained. .

  The interface detection sensor 1203 captures an image of the sample in the sample container 150 using an imaging device such as a CCD or a CMOS. By imaging the state of the sample after each step, the sample processing effect can be visually recognized. The interface detection sensor 1203 may perform interface detection using reflected light or transmitted light of a laser. Further, a liquid level detection technology using an ultrasonic wave or a radio wave, or a capacitance type liquid level detection technology may be used. The interface detection sensor 1203 may be installed inside the centrifuge 130. In that case, there is an advantage that the transparent window 1201 becomes unnecessary. When the interface detection sensor 1203 is installed inside, the volume inside the centrifuge 130 is reduced, and the effect of improving the temperature control efficiency is obtained.

[Example 4]
In the present embodiment, an example of a sample processing apparatus including a luminescence measurement container and capable of performing a ATP elimination / extraction process by collecting a part of a sample at each incubation time will be described.

  FIG. 17 is a schematic diagram illustrating another configuration example of the sample processing apparatus of the present embodiment. 1 and FIG. 6 are denoted by the same reference numerals, and redundant description is omitted.

  The sample processing apparatus of this embodiment includes a luminescence measurement container rack 1301 that stores a plurality of luminescence measurement containers 1303 in the housing 105. When performing the ATP emission measurement, an ATP elimination process for eliminating floating ATP not derived from bacteria existing in the sample and an ATP extraction process for destroying viable bacteria and extracting ATP contained therein are performed. Only ATP derived from bacteria is measured.

  FIG. 18 is a flowchart illustrating an example of a procedure for performing a drug sensitivity test using ATP using the sample processing apparatus of the present embodiment. The sample container 150 containing the sample is set in the centrifuge 130 (S61). At this time, necessary reagents and pipette tips are also installed in the sample processing apparatus. A sample processing protocol is designated by the control PC 170, and sample processing is executed (S62). After completion of the sample processing, a predetermined antibacterial agent is dispensed into each sample container 150 by the pump 120. The antibacterial agent is stored in the reagent bottle 142 in the reagent bottle rack 143. The temperature in the centrifuge 130 is set to 37 ° C., and the culture is performed (S63). When the time for measuring the sensitivity is reached (for example, every 2 hours up to 6 hours), a part of the sample in the sample container 150 is dispensed by the pump 120 into the luminescence measurement container 1303 in the luminescence measurement container rack 1301 (S64). . Subsequently, the ATP elimination liquid in the reagent bottle 142 is dispensed into the luminescence measurement container 1303 to eliminate the floating ATP in the sample (S65). Further, the ATP extract is dispensed into the luminescence measurement container 1303 to extract ATP derived from viable bacteria (S66). In step S67, it is determined whether or not all measurement preparations have been completed. If not, the operations in steps S64 to S66 are repeated for the antibacterial agent type and concentration whose sensitivity is to be measured. The measurement is repeated every measurement time. After that, the luminescence measurement container rack 1301 is taken out of the sample processing apparatus and installed in a known luminescence measurement apparatus (S68). The ATP light emission amount is measured by a known method in the light emission measuring device (S69). Finally, the growth or inhibition of bacteria is determined from the change in the amount of ATP at each measurement time (S70).

  Note that the present invention is not limited to the above-described embodiment, and includes various modifications. For example, the above-described embodiments have been described in detail in order to explain the present invention in an easy-to-understand manner, and are not necessarily limited to those having all the configurations described above. Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of one embodiment can be added to the configuration of another embodiment. Also, for a part of the configuration of each embodiment, it is possible to add, delete, or replace another configuration.

120 Pump 130 Centrifuge 150 Sample container 160 Temperature controller 170 Control PC
600 Fixed lid 601 Movable lid 650 Position sensor 1203 Interface detection sensor

Claims (8)

A centrifuge for centrifuging the sample in the sample container;
A pump for sucking and discharging the solution,
A stage for moving the pump,
A pipette tip rack for storing a disposable pipette tip attached to the tip of the pump,
A reagent bottle rack for storing reagent bottles,
Inside the centrifuge, the pump, the stage, the pipette tip rack, and the reagent bottle rack are installed, a housing capable of forming a closed space,
A temperature controller for adjusting the temperature in the housing,
A drive control device that drives the centrifuge, the pump and the stage ,
A sensor for detecting the position of the liquid level in the sample container and the interface of the pellet, which is arranged at a position in the centrifuge accessed by the pump,
With
The drive control device controls the stage based on the detected liquid level and position information of the interface of the pellet,
The stage is selectively moved by the stage to a position for accessing a disposable pipette tip stored in the pipette tip rack, a reagent bottle stored in the reagent bottle rack, and a sample container in the centrifuge. Sample processing device.   The sample processing apparatus according to claim 1, further comprising a sensor that detects whether a sample container is present at a position in the centrifuge accessed by the pump. A centrifuge for centrifuging the sample in the sample container;
A pump for sucking and discharging the solution,
A stage for moving the pump,
A pipette tip rack for storing a disposable pipette tip attached to the tip of the pump,
A reagent bottle rack for storing reagent bottles,
A temperature controller for adjusting the temperature in the centrifuge,
A drive control device that drives the centrifuge, the pump and the stage ,
A sensor for detecting the position of the liquid level in the sample container and the interface of the pellet, which is arranged at a position in the centrifuge accessed by the pump,
With
The drive control device controls the stage based on the detected liquid level and position information of the interface of the pellet,
The stage is selectively moved by the stage to a position for accessing a disposable pipette tip stored in the pipette tip rack, a reagent bottle stored in the reagent bottle rack, and a sample container in the centrifuge. ,
A sample processing apparatus, wherein the centrifuge has an opening / closing mechanism for inserting the disposable pipette tip mounted on the tip of the pump into the upper part thereof. 4. The sample processing apparatus according to claim 3 , wherein the centrifuge includes a fixed lid having an opening and a movable lid capable of closing the opening at an upper part, and the opening and closing mechanism opens and closes the movable lid. 5. The sample processing apparatus according to claim 4 , wherein the opening of the fixed lid has an area of 1 to 4 times the area of the opening of the sample container. 4. The sample processing apparatus according to claim 3 , further comprising a sensor that detects whether a sample container is present at a position in the centrifuge accessed by the pump. A step of centrifuging the sample in the sample container with a centrifuge having a closed top,
Partially opening the upper part of the centrifuge,
Driving a stage that moves a pump, and inserting the tip of a pipette tip attached to the pump into the sample container in the centrifuge,
A step of detecting the position of the interface between the liquid surface and the pellet in the sample container after centrifugation,
A step of driving the pump to aspirate the supernatant in the sample container, interlocking the height of the decreasing liquid level with the height of the tip of the pipette tip, and the tip of the pipette tip Limiting the height of the pellet to a position higher than the height of the pellet, aspirating the supernatant ,
Driving the stage to take out the pipette tip outside the centrifuge;
Re-sealing the top of the centrifuge;
A sample processing method comprising: The upper part of the centrifuge is covered with a fixed lid and a movable lid,
The sample processing method according to claim 7 , wherein the step of partially opening the upper part of the centrifuge is performed by opening the movable lid.

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