Electrophoresis apparatus and control method thereof

This application is based upon Japanese Patent Application No. 2010-179741 filed on Aug. 10, 2010, and Japanese Patent Application No. 2010-187503 filed on Aug. 24, 2010. The entire disclosure of Japanese Patent Application No. 2010-179741 and Japanese Patent Application No. 2010-187503 are incorporated in this specification.

This application relates generally to an electrophoresis apparatus that causes component separation by a capillary electrophoresis method, and to a control method for that electrophoresis apparatus.

Conventionally, a capillary electrophoresis apparatus has been used as an apparatus to analyze the density and amount of certain components contained in a specimen. In this capillary electrophoresis apparatus, after a migration solution has been filled into a capillary flow channel, a specimen is inserted at one end of the capillary flow channel. Next, by applying a voltage to electrodes that are provided at both ends of the capillary flow channel, electric current flows between the electrodes, and a certain component contained in the specimen moves to the other end of the capillary flow channel by the respective electrophoretic mobility. Due to this movement, the certain component of the specimen is separated from the other components, and by detecting the component using an optical method for example, the density and amount of the certain component can be analyzed.

Examples of capillary electrophoresis apparatuses are disclosed in Unexamined Japanese Patent Application KOKAI Publication No. 2007-107915 and Unexamined Japanese Patent Application KOKAI Publication No. H10-246721. In these electrophoresis apparatuses, whether or not migration solution has been filled in the capillary flow channel is constantly determined, so that after filling with migration solution, and before inserting the specimen, a voltage is applied to the electrodes on both ends of the capillary flow channel, and the value of the current flowing between the electrodes is measured.

By inserting the specimen into the capillary flow channel, the fluid inside the capillary flow channel becomes a mixed state of the migration solution and specimen. In other words, the character of the fluid inside the capillary flow channel changes from before and after the specimen is inserted. Therefore, under conditions of applying the same voltage from the electrodes, the current flowing between the electrodes differs. Consequently, when performing electrophoresis after the specimen has been inserted, it is necessary to set the value of the applied voltage separately from before the specimen was inserted.

Moreover, due to the work of inserting the specimen into the capillary flow channel, air bubbles occur in the fluid inside the capillary flow channel, and foreign matter becomes mixed therein. Therefore, even though the value of the current flowing between electrodes before the specimen is inserted is measured as in the inventions of Unexamined Japanese Patent Application KOKAI Publication No. 2007-107915 and Unexamined Japanese Patent Application KOKAI Publication No. H10-246721, when voltage is applied to the electrodes after the specimen has been inserted in order to perform electrophoretic separation, the current that is expected from the value of the voltage does not flow between the electrodes.

Furthermore, after the specimen has been inserted inside the capillary flow channel, the temperature of the component members of the capillary flow channel changes due to the Joule heat that occurs when voltage is applied. Due to this as well, there is a possibility that the expected current will not flow between the electrodes. There is a high possibility that this problem will occur when voltage is repeatedly applied in order to analyze a plurality of specimens. Moreover, there is also a possibility that, due to changes in the temperature of the environment where the components of the capillary flow channel are located, the expected electric current will not flow between the electrodes.

Taking the above situation into consideration, the object of the present invention is to provide an electrophoresis apparatus that is capable of detecting abnormalities in the capillary flow channel during separation of components during electrophoresis, and a control method for that electrophoresis apparatus.

The electrophoresis apparatus of a first aspect of the present invention is an electrophoresis apparatus that applies voltage from electrodes that are provided in a capillary flow channel and causes component separation by performing electrophoresis on a specimen that is injected into the capillary flow channel, and is characterized by comprising:

a physical quantity acquisition unit that, with migration solution and specimen injected inside the capillary flow channel, acquires an electrical quantity that occurs in the capillary flow channel at a specified time when voltage is being applied to the electrodes; and

a physical quantity determination unit that determines whether or not the electrical quantity is within a specified range.

A control method for an electrophoresis apparatus of a second aspect of the present invention is a control method for an electrophoresis apparatus that applies voltage from electrodes that are provided in a capillary flow channel in order to separate components of a specimen injected inside the capillary flow channel by electrophoresis is characterized by comprising:

a physical quantity acquisition step that, with migration solution and specimen injected inside the capillary flow channel, acquires an electrical quantity that occurs in the capillary flow channel at a specified time when voltage is being applied to the electrodes; and

a physical quantity determination step of determining whether or not the electrical quantity is within a specified range.

A more complete understanding of this application can be obtained when the following detailed description is considered in conjunction with the following drawings, in which:

FIG. 1 is a diagram illustrating the construction of an electrophoresis apparatus according to a first embodiment of the present invention;

FIG. 2 is a circuit diagram illustrating the construction of the electric power supply of the electrophoresis apparatus of the first embodiment;

FIG. 3 is a flowchart illustrating the processing that is executed by the electrophoresis apparatus of the first embodiment;

FIG. 4 is a diagram illustrating threshold values (range of electric current values) used in determination of the electric current value in the determination process at the start of voltage application;

FIG. 5 is a diagram illustrating threshold values (differences in electric current values) used in determination of the difference between electric current values in the determination process during voltage application;

FIG. 6 is a flowchart illustrating the determination process at the start of voltage application;

FIG. 7 is a flowchart illustrating the determination process during voltage application;

FIG. 8 is a diagram illustrating a table wherein electric current values that are obtained in the determination process during voltage application are recorded;

FIG. 9 is a diagram illustrating the construction of the electrophoresis apparatus of a second embodiment of the present invention;

FIG. 10A is a top view illustrating a microchip of the second embodiment;

FIG. 10B is a cross-sectional view of section X-X in FIG. 10A of the microchip of the second embodiment;

FIG. 10C is a cross-sectional view of section Y-Y in FIG. 10 A of the microchip of the second embodiment;

FIG. 11 is a partial view that includes the microchip of the electrophoresis apparatus of the second embodiment;

FIG. 12 is a flowchart illustrating the processing executed by the electrophoresis apparatus of the second embodiment;

FIG. 13 is a flowchart illustrating part of the cleaning process in pre-processing that is executed by the electrophoresis apparatus of the second embodiment;

FIG. 14 is a diagram illustrating the construction of an electrophoresis apparatus of a variation of the second embodiment;

FIG. 15 is a partial view that includes a microchip of the electrophoresis apparatus of a variation of the second embodiment;

FIG. 16 is a diagram illustrating the construction of an electrophoresis apparatus of a third embodiment of the present invention;

FIG. 17 is partial view that includes a microchip of the electrophoresis apparatus of the third embodiment; and

FIG. 18 is a flowchart illustrating part of the cleaning process of the pre-processing that is executed by the electrophoresis apparatus of the third embodiment.

(Embodiment 1)

FIG. 1 is a diagram illustrating the construction of an electrophoresis apparatus of a first embodiment of the present invention. FIG. 2 is a circuit diagram illustrating the construction of the electric power supply of the electrophoresis apparatus of the first embodiment.

The electrophoresis apparatus 1 comprises a storage tank 2 , a dispensing unit 3 , a detection unit 5 , a temperature adjustment unit 6 , a controller 7 , a power supply 8 , a voltmeter 9 and an ammeter 10 . In this embodiment, the electrophoresis apparatus 1 performs component separation by a capillary electrophoresis method. In FIG. 1 , in order to simplify the explanation, the power supply 8 , voltmeter 9 and ammeter 10 are omitted.

The storage tank 2 comprises a migration solution tank 11 , a purified water tank 12 and a cleaning solution tank 13 . Migration solution L 1 is stored in the migration solution tank 11 . The migration solution L 1 is a fluid that functions as a so-called buffer in the capillary electrophoresis method, and, for example, is a 100 mM malic acid arginine buffer (pH 5.0)+1.5% chondroitin sulfate C sodium. Purified water L 2 is stored in the purified water tank 12 . Cleaning solution L 3 is stored in the cleaning solution tank 13 .

The dispensing unit 3 inserts a specimen Sp into a capillary flow channel 47 for which capillary electrophoresis is performed, and further has the function of diluting the specimen to a state appropriate for analysis. The dispensing unit 3 comprises a specimen container 14 , a dilution tank 15 , a syringe 16 and a nozzle 17 .

The specimen container 14 comprises a glass blood-collection tube 18 , and a cover 60 that is attached to the opening of the blood-collection tube 18 . A whole-blood specimen Sp is housed in the blood-collection tube 18 . The dilution tank 15 is provided for diluting the specimen Sp to a density suitable for analysis. The nozzle 17 is connected to the syringe 16 . The tip end of the nozzle 17 is cut diagonally so that it has a sharp shape in order that it can easily pass through the cover 60 . The nozzle 17 can take in and discharge the specimen by the intake or discharge operation of the syringe 16 . The nozzle 17 is supported by a drive mechanism that is not illustrated in the figure. Through the action of this drive mechanism, the nozzle 17 can be inserted to or removed from the specimen container 14 , can be inserted into or removed from the dilution tank 15 , and can be inserted into or removed from the capillary flow channel 47 .

The microchip 4 is a member that forms the capillary flow channel 47 , and for example, is made of silica. Preferably, the cross-section of the capillary flow channel 47 is round having a 25 to 100 μm diameter, or is rectangular with side lengths being 25 to 100 μm; however, the shape is not limited to this as long as the shape and dimensions are suitable for performing the capillary electrophoresis method.

An inlet hole 19 is formed on one end of the capillary flow channel 47 , and a discharge hole 20 is formed on the other end of the capillary flow channel 47 . The specimen Sp, migration solution L 1 , purified water L 2 and cleaning solution L 3 are filled into the capillary flow channel 47 from the inlet hole 19 . The specimen Sp, migration solution L 1 , purified water L 2 and cleaning solution L 3 that are filled into the capillary flow channel 47 are discharged from the discharge hole 20 .

An electrode 21 is formed on one end of the capillary flow channel 47 , and an electrode 22 is formed on the other end. The electrode 21 is exposed from the inlet hole 19 , and the electrode 22 is exposed from the discharge hole 20 .

The detection unit 5 is provided in order to analyze a certain component that is separated from the specimen inside the capillary flow channel 47 , and is located closer to the side of the discharge hole 20 of the capillary flow channel 47 than the inlet hole 19 . The detection unit 5 comprises a light source (omitted in the figure) and a light-receiving unit (omitted in the figure), and irradiates the specimen Sp with the light from the light source, and receives reflected light from the specimen Sp by way of the light receiving unit. In doing so, the light absorbance of the specimen Sp is measured.

The controller 7 is provided in order to control all of the parts of the electrophoresis apparatus 1 . The controller 7 comprises a control unit 23 , an external memory unit 24 , main memory unit 25 and an input/output unit 26 .

The control unit 23 comprises a CPU (Central Processing Unit) and the like, and executes processing related to electrophoresis component separation according to a program that is stored in the external memory unit 24 .

The external memory unit 24 comprises a non-volatile memory such as a flash memory, hard disk, DVD-RAM (Digital Versatile Disc Random-Access Memory), DVD-RW (Digital Versatile Disc ReWritable). The external memory unit 24 stores in advance a program for causing the control unit 23 to perform processing, and stores data supplied from the control unit 23 , or supplies stored data to the control unit 23 according to instructions from the control unit 23 .

The main memory unit 25 comprises a RAM (Random-Access Memory) or the like. The main memory unit 25 loads the program that is stored in the external memory 24 and is used as a work area for the control unit 23 .

The input/output unit 26 comprises an input/output interface, and makes it possible to transmit and receive signals between each part of the electrophoresis apparatus 1 and a PC (Personal Computer) 27 as the information display unit illustrated in FIG. 2 .

The temperature adjustment unit 6 is able to adjust the temperature of the microchip 4 by cooling or heating the microchip 4 according to control from the controller 7 .

Three-way valves 28 , 29 , 30 , 31 are provided in the electrophoresis apparatus 1 . The three-way valves 28 , 29 , 30 , 31 each have three connection ports (omitted in the figure), and the controller 7 controls the connected or disconnected state between these connection ports.

The migration solution tank 11 is connected to the three-way valve 28 via the flow channel 32 . The purified water tank 12 and cleaning solution tank 13 are connected to the three-way valve 30 via the flow channels 33 and 34 . The dilution tank 15 is connected to the three-way valve 28 via the flow channel 35 , and is connected to the three-way valve 31 via the flow channel 36 . The three-way valve 28 is connected to the three-way valve 29 via the flow channel 37 . The three-way valve 30 is connected to the three-way valves 29 and 31 via the branched flow channel 38 .

The inlet hole 19 of the capillary flow channel 47 is connected to the three-way valve 29 via the flow channel 39 . A pinch valve 40 is provided in the downstream portion of the flow channel 39 that is connected to the inlet hole 19 of the capillary flow channel 47 . The opening and closing of the pinch valve 40 is controlled by the controller 7 , which makes it possible to allow or block the flow of fluid into the capillary flow channel 47 .

The discharge hole 20 of the capillary flow channel 47 is connected to the three-way valve 31 via the flow channel 41 . A pinch valve 56 is provided in the upstream portion of the flow channel 41 that is connected to the discharge hole 20 of the capillary flow channel 47 . The opening and closing of the pinch valve 56 is controlled by the controller 7 , which makes it possible to allow or block discharge of fluid from the capillary flow channel 47 .

A flow channel 42 is provided on the downstream side of the three-way valve 31 . The discharge port of the flow channel 42 is located inside a waste fluid bottle 43 . The waste fluid bottle 43 is provided in order to store used fluid. A suction pump 44 is connected to the waste fluid bottle 43 . The suction pump 44 generates negative pressure according to control from the controller 7 . This negative pressure acts on the capillary flow channel 47 from the three-way valve 31 via the branched flow channel 38 and flow channel 41 .

As illustrated in FIG. 2 , the electrodes 21 and 22 are connected to the power supply 8 via power line 45 . A switch 46 is provided between the power supply 8 and electrode 21 . Turning ON and OFF of the switch 46 is controlled by the controller 7 , and through this control, voltage can be applied from the power supply 8 to the electrodes 21 , 22 . In the explanation below, an example of a power supply 8 is explained where voltage is applied so that the electrode 21 is a positive electrode and electrode 22 is a negative electrode; however, the power supply 8 can also have the function of applying voltage so that the electrodes are opposite of this.

The voltmeter 9 measures the value of the voltage applied from the power supply 8 to the electrodes 21 , 22 . The ammeter 10 measures the value of the electric current that flows between the electrodes 21 , 22 . The measured values from the voltmeter 9 and ammeter 10 are outputted to the controller 7 .

Next, processing that is executed by the electrophoresis apparatus 1 will be explained. FIG. 3 is a flowchart illustrating the processing that is executed by the electrophoresis apparatus 1 . The flow of this processing is mainly divided into a cleaning process S 11 , filling process S 12 , dispensing process S 13 , separation process S 14 and analysis process S 15 .

The cleaning process S 11 is a process of cleaning the capillary flow channel 47 . More specifically, according to a signal from the controller 7 , the three-way valve 30 is switched to a state wherein the flow channels 33 and 34 are opened up to the branched flow channel 38 . The three-way valve 29 is switched to a state where the branched flow channel 38 is opened up to the flow channel 39 . The pinch valve 40 is in the open state, and the pinch valve 56 is in the closed state. The three-way valve 31 is switched to a state wherein the branched flow channel 38 is opened up to the waste fluid bottle 43 . In the state above, the controller 7 causes the suction pump 44 to operate and create a negative pressure. As a result of generating this negative pressure, purified water L 2 and cleaning solution L 3 fill into the capillary flow channel 47 , and the filled purified water L 2 and cleaning solution L 3 are discharged into the waste fluid bottle 43 . This cleaning process S 11 can also be performed so that purified water L 2 is caused to flow through the capillary flow channel 47 after the cleaning solution L 3 has flowed through.

The filling process S 12 is a process of filling the capillary flow channel 47 with migration solution L 1 in order to perform electrophoresis. More specifically, according to a signal from the controller 7 , the three-way valve 28 is switched to a state wherein the flow channel 32 is opened up to the flow channel 37 , and so that flow channels 32 and 37 are cut off from flow channel 35 . The three-way valve 29 is switched to a state wherein the flow channel 37 is opened up to the flow channel 39 , and the flow channels 37 and 39 are cut off from the branched channel 38 . The pinch valves 40 , 56 and the three-way valve 31 are maintained in the same state as in the cleaning process S 11 . In the state above, by the controller 7 causing the suction pump 44 to operate, the migration solution L 1 is filled into the capillary flow channel 47 through the inlet hole 19 .

The dispensing process S 13 is a process of injecting the specimen Sp into the capillary flow channel 47 from the inlet hole 19 .

More specifically, according to a signal from the controller 7 , the drive mechanism described above (omitted from the figure) operates and causes the nozzle 17 to penetrate through the cover 60 , and the tip end of the nozzle 17 is inserted into the specimen Sp inside the blood-collection tube 18 . Then, by the controller 7 causing the syringe 16 to perform the intake operation, the specimen Sp is drawn into the nozzle 17 .

On the other hand, by the controller 7 switching the three-way valve 28 to a state wherein the flow channel 32 is opened up to the flow channel 35 and causing the pump (not illustrated in the figure) to generate pressure, migration solution L 1 is introduced into the dilution tank 15 . Next, by the controller 7 causing the drive mechanism described above to operate, the nozzle 17 is removed from the cover 60 , and the tip end of the nozzle 17 is placed into the migration solution L 1 in the dilution tank 15 . Then, by the controller 7 causing the syringe 16 to perform the discharge operation, the specimen Sp is introduced into the dilution tank 15 . At this time, in order to promote mixing of the specimen Sp and the migration solution L 1 , it is preferred that the intake operation and discharge operation of the syringe 16 be performed repeatedly. The specimen Sp is whole blood that contains hemoglobin, for example. The migration solution L 1 contains a hemolytic component that promotes a hemolytic action that breaks down the blood cell membrane, and by mixing the migration solution L 1 with the specimen Sp inside the dilution tank 15 , the blood cells in the specimen Sp undergo hemolysis.

Next, by the controller 7 causing the syringe 16 to perform the intake operation, the specimen Sp that was diluted in the dilution tank 15 is drawn into the nozzle 17 . Then, by causing the drive mechanism described above to operate, the tip end of the nozzle 17 enters into the inlet hole 19 of the capillary flow channel 47 . In this state, by the controller 7 causing the syringe 16 to perform the discharge operation, the diluted specimen Sp is introduced into the inlet hole 19 . When there is no need for the specimen Sp that is being analyzed to be diluted, it is possible to perform the dispensing process S 13 without going through the dilution process.

The separation process S 14 is a process of separating out the hemoglobin that is a specified component included in the specimen Sp that is filled into the capillary flow channel 47 .

More specifically, in the circuit illustrated in FIG. 2 , according to a signal from the controller 7 , switch 46 is switched to the ON state, and voltage is applied from the power supply 8 to the electrodes 21 , 22 (step S 101 : FIG. 3 ). When doing this, the output value from the power supply 8 is adjusted so that the measured value from the voltmeter 9 becomes a specified value. By voltage being applied to the electrodes 21 , 22 , electric current flows between the electrodes 21 , 22 , and electroosmotic flow occurs in the fluid inside the capillary flow channel 47 (mixed migration solution L 1 and specimen Sp) going from electrode 21 toward electrode 22 . As a result, movement occurs in the hemoglobin according to a unique amount of electrophoretic mobility. The electrophoretic mobility differs depending on the substance, so the hemoglobin moves from electrode 21 toward electrode 22 at a different speed than the other components included in the specimen Sp.

The analysis process S 15 is a process of detecting the amount or density of hemoglobin, which is a specified component that has been separated out. More specifically, according to a signal from the controller 7 , the detection unit 5 irradiates light having a wavelength of 415 nm from the light source described above (omitted in the figure), and then receives the reflected light by way of the light-receiving unit described above. When the hemoglobin that is separated from the specimen Sp passes through the portion of irradiated light from the light source above (black circle portion in FIG. 1 ), the light absorbance that is found from the state of received light by the light-receiving unit above changes. The amount or density of the hemoglobin is detected by the controller 7 processing this change. The detected amount is stored in the external memory unit 24 of the controller 7 as the analysis result of component separation by electrophoresis.

The electrophoresis apparatus 1 of this embodiment repeats the processing illustrated in FIG. 3 , and performs electrophoretic separation of the specimen Sp a plurality of times, so it is possible to put migration solution L 1 and specimen Sp into the capillary flow channel 47 and apply voltage to the electrodes 21 , 22 a plurality of times.

Here, during the process of repeatedly executing the processing in FIG. 3 , by mixing the migration solution L 1 and specimen Sp inside the capillary flow channel 47 in each dispensing process S 13 , the electrical resistance of the fluid inside the capillary flow channel 47 changes.

In the dispensing process S 13 , due to the work of injecting the specimen Sp into the capillary flow channel 47 , or in other words, due to the work of inserting the nozzle 17 into the inlet hole 19 and discharging specimen Sp from the nozzle 17 , air bubbles occur and foreign matter mixes in with the fluid inside the capillary flow channel 47 . This also causes the electrical resistance of the fluid inside the capillary flow channel 47 to change.

In the separation process S 14 , by voltage being applied to the electrodes 21 , 22 (step S 101 ), Joule heat is stored in the microchip 4 , and the temperature of the microchip 4 rises. Due to this rise in temperature, the fluid (mixture of migration solution L 1 and specimen Sp) inside the capillary flow channel 47 is heated and the electrical resistance changes. Moreover, as the temperature of the environment where the microchip 4 is located changes, the temperature of the fluid inside the capillary flow channel 47 changes, and thus the electrical resistance also changes.

Due to the change in the electrical resistance described above, the expected electric current does not flow between the electrodes 21 , 22 , and in order to prevent electrophoretic separation from being performed in this state, the determination process of steps S 102 to S 112 is executed in the separation process S 14 . In the determination process of steps S 102 to S 112 , an electrical quantity that occurs in the capillary flow channel 47 , or in other words, the value of the electric current that flows between the electrodes 21 , 22 (value measured by the ammeter 10 ) is used.

As illustrated in FIG. 2 , in order to execute the determination process in steps S 102 to S 112 , the controller 7 comprises a physical quantity acquisition unit 71 , physical quantity determination unit 72 , memory unit 73 , cleaning determination unit 74 , replacement unit 75 , temperature adjustment unit 76 , voltage change unit 77 and voltage calculation unit 78 .

The physical quantity acquisition unit 71 , physical quantity determination unit 72 , memory unit 73 , cleaning determination unit 74 , replacement unit 75 , temperature adjustment unit 76 , voltage change unit 77 and voltage calculation unit 78 are realized by the control unit 23 executing processing according to a program stored in the external memory unit 24 . The memory unit 73 is maintained as a structural element of the memory area in part of the main memory unit 25 .

The determination processing of steps S 102 to S 112 includes a determination process that is executed at the point in time when the voltage begins to be applied in step S 101 (steps S 102 to S 106 : hereafter referred to as the determination process at the start of voltage application), and a determination process that is executed during the time between when voltage application is started until analysis of the specimen Sp (detection of the amount and density of hemoglobin) is complete (steps S 107 to S 112 : hereafter referred to as the determination process during voltage application).

In the determination process at the start of voltage application, whether or not the electric current value that was measured by the ammeter 10 at the start of voltage application is within a specified range is determined (step S 102 ). When it is determined that the value of the electric current is not within a specified range (step S 102 : NG), the application of voltage to the electrodes 21 , 22 is stopped (step S 103 ). After that, a cleaning signal for cleaning the capillary flow channel 47 is outputted (step S 105 ), and the cleaning process S 11 is executed. The object of this process is to stop the separation process S 14 in the case where the expected electric current does not flow between the electrodes 21 , 22 due to air bubbles being generated or foreign matter being mixed in the fluid inside the capillary flow channel 47 , a rise in temperature of the microchip 4 , or a change in the temperature of the environment. Furthermore, the object of this process is to remove air bubbles or foreign matter from within the capillary flow channel 47 by cleaning the inside of the capillary flow channel 47 .

The determination of step S 102 is executed every time voltage is applied in step S 101 . Moreover, every time NG is determined in step S 102 , voltage application is stopped (step S 103 ), and a cleaning signal is outputted (step S 105 ).

When determining NG in step S 102 continues and determination is repeatedly performed a first set number of times (hereafter this will be taken to be N 1 times), after the application of voltage has been stopped, YES is determined in step S 104 . In this case, a cleaning signal is not outputted; however a replacement signal to replace the microchip 4 is outputted (step S 106 ). The object of this process is to replace the microchip 4 when it is not possible to remove foreign matter that is mixed in the capillary flow channel 47 during cleaning in step S 105 , or when it is the end of the life of the microchip 4 .

In the following, a detailed example of control by the determination process at the start of voltage application will be explained using FIG. 4 . In the explanation below, it is presumed that in the case where a NG determination occurs in step S 102 continuously and determination is repeated four times (if N 1 is four times), YES will be determined in step S 104 .

FIG. 4 is a diagram illustrating the threshold values that are used in the determination in step S 102 . The values of electric current I 1 to I 10 that are indicated by black dots are electric current values that are obtained from the ammeter 10 on the first to tenth times when repeating the processing in FIG. 3 . The threshold values are set within a range of electric current values of no less than Ik and no greater than Ij. The threshold values above are values that result in desired values of electrophoretic mobility of hemoglobin when electric current within this range flows between the electrodes 21 , 22 .

The electric currents I 1 , I 2 that are acquired the first and second times are within the range of threshold values. Therefore, in the first and second processing, OK is determined in step S 102 ( FIG. 3 ), and processing advances to step S 107 that will be described later.

The electric current I 3 that is acquired the third time is not within the range of threshold values. Therefore, in the third processing, NG is determined in step S 102 , and application of voltage is stopped (step S 103 ).

Up to the third time, the number of times that it has been determined that the value of the electric current is not within the range of threshold values (NG in step S 102 ) is only one time (NG on the third time), so that processing does not continue a fourth time. Therefore, in the third time, NO is determined in step S 104 , and a cleaning signal is outputted (step S 105 ).

The electric currents I 4 , I 5 , I 6 that are acquired in the fourth, fifth and sixth times are within the range of threshold values. Therefore, in the fourth, fifth and sixth processing, OK is determined in step S 102 as in the first and second times, and processing advances to step S 107 .

The electric currents I 7 , I 8 , I 9 acquired in the seventh, eighth and ninth times are not within the range of threshold values. Therefore, in the seventh, eighth and ninth times, NG is determined in step S 102 , and application of voltage is stopped (step S 103 ).

Up to the ninth time, the number of times that it has been determined that the value of the electric current is not within the range of threshold values (NG in step S 102 ) is three times (NG on the seventh, eighth and ninth times), and processing does not advance to a fourth time. Therefore, in the seventh, eighth and ninth times, NO is determined in step S 104 , and a cleaning signal is outputted (step S 105 ).

The electric current I 10 that is acquired in the tenth time is also not within the range of threshold values. Therefore, in the tenth time as well, NG is determined in step S 102 , and application of voltage is stopped (step S 103 ).

Up to the tenth time, the number of times that NG has been continuously determined in step S 102 is four times (NG in the seventh, eighth, ninth and tenth times). Therefore, YES is determined in step S 104 , and a replacement signal to replace the microchip 4 is outputted (step S 106 ).

Next, the determination process during voltage application (steps S 107 to S 112 ) will be explained. In steps S 107 to S 112 , the electric current that is measured by the ammeter 10 is acquired at specified intervals of time. Each time the electric current value is acquired, the difference between that electric current and the electric current measured in the past is calculated, and it is determined whether that difference exceeds a specified value (step S 107 ).

When the difference between electric current values exceeds a specified value (NG in step S 107 ), a temperature adjustment signal for adjusting the temperature of the microchip 4 is outputted (step S 109 ). The size of the voltage applied to the electrodes 21 , 22 is also changed to a corrected value (step S 110 ). The object of this process is to stabilize the electric current near a target value by adjusting the temperature of the microchip 4 , or changing the voltage value, when a large change occurs in the electric current that flows between the electrodes 21 , 22 due to fluctuation in temperature of the microchip 4 or the like.

When, due to large fluctuation continuously occurring in the electric current values acquired from the ammeter 10 , the number of times that NG is continuously determined in step S 107 reaches a second specified number of times (hereafter referred to as N 2 ), YES is determined in step S 108 . In this case, the application of voltage is stopped without outputting a temperature adjustment signal or changing the voltage value (step S 111 ), and a replacement signal for replacing the microchip 4 is outputted (step S 112 ). The object of this process is to stop the separation process S 14 and replace the microchip 4 when fluctuation in the temperature of the microchip 4 cannot be suppressed by adjusting the temperature or changing the voltage value.

In the following, a detailed example of control by the determination processing during voltage application will be explained using FIG. 5 . In the explanation below, when NG is continuously determined four times in step S 107 (N 2 is four times), YES is determined in step S 108 .

FIG. 5 is a diagram illustrating the threshold value ΔI s that is used in the determination of step S 107 in the determination process during voltage application.

In the determination process during voltage application, the electric current is acquired from the ammeter 10 at specified intervals as described above. The threshold values ΔI 1 to ΔI 10 illustrated in FIG. 5 indicate the differences calculated based on the electric currents acquired in the first to tenth times. The dashed line illustrated in FIG. 5 indicates the fluctuation in the voltage value applied to the electrodes 21 , 22 .

The differences ΔI 1 and ΔI 2 that were calculated the first and second times do not exceed the threshold value ΔI s . Therefore, in the first and second times, control such as adjusting the temperature or changing the voltage value in steps S 109 , S 110 is not performed, and the voltage value V1 that is applied in step S 101 is maintained.

In the third time, the difference ΔI 3 exceeds the threshold value ΔI s , so NG is determined in step S 107 . Up to the third time, the number of times NG is determined is one time (NG in the third time), so that NO is determined in step S 108 . Therefore, in the third time, a temperature adjustment signal is outputted (step S 109 ), and the voltage value V2 is changed (step S 110 ).

The difference ΔI 4 in the fourth time was calculated with the voltage value being V2, and did not exceed the threshold value ΔI s . Therefore, in the fourth time, control such as temperature adjustment and changing the voltage value are not performed, and the voltage value V2 is maintained. In the fifth and sixth times as well, the differences ΔI 5 , ΔI 6 did not exceed the threshold value ΔI s , so the voltage value V2 is maintained.

In the seventh, eighth and ninth times, differences ΔI 7 , ΔI 7 and ΔI 9 that exceeded the threshold value ΔI s were calculated. Therefore, in the seventh, eighth and ninth times, NG is determined in step S 107 . Up to the ninth time, the number of times that NG was continuously determined in step S 107 was 3 times (NG in the seventh, eighth and ninth times). Therefore, in the seventh, eighth and ninth times, by determining NO in step S 108 , a temperature adjustment signal is outputted (step S 109 ), and in step S 110 in the seventh, eighth and ninth times, the voltage value is changed to V3, V4 and V5. The differences ΔI 8 and ΔI 9 in the eighth and ninth times are calculated with the voltage values being V3 and V4.

In the tenth time, the difference ΔI 10 is calculated with the voltage value being V5, and the difference ΔI 10 exceeds the threshold value ΔI s . Therefore, in the tenth time as well, NG is determined in step S 107 . Moreover, the number of times that NG was continuously determined in step S 107 is four times (NG in the seventh, eighth, ninth and tenth times). Therefore, in the tenth time, YES is determined in step S 108 . As a result, application of voltage is stopped (step S 111 ), and a replacement signal to replace the microchip 4 is outputted (step S 112 ).

In the following, the determination processes at the start of voltage application and during voltage application are explained in detail. FIG. 6 is a flowchart illustrating the determination process at the start of voltage application. The processing illustrated in FIG. 6 is started according to the voltage applied in step S 101 . The processing in FIG. 6 is executed by the physical quantity acquisition unit 71 , the physical quantity determination unit 72 , memory unit 73 , cleaning determination unit 74 and replacement unit 75 . In order to execute the processing in FIG. 6 , the lower threshold limit Ik and upper threshold value limit Ij illustrated in FIG. 4 are stored in the memory unit 73 .

In FIG. 3 and FIG. 6 , steps S 102 and S 203 correspond, steps S 103 and S 207 correspond, steps S 104 and S 210 correspond, steps S 105 and S 211 correspond and steps S 106 and S 212 correspond.

First, variable i that is stored in the memory unit 73 is read (step S 201 ).

Next, the physical quantity acquisition unit 71 acquires the value of the electric current that is measured by the ammeter 10 at the start of voltage application (step S 202 ).

The physical quantity acquisition unit then determines whether or not the value of the electric current is within the threshold value range (range of no less than electric current Ik and no greater than electric current Ij) (step S 203 ).

When it is determined that the value of the electric current is within the threshold value range (YES in step S 203 ), the variable i is reset to “0” (step S 204 ).

Next, variable i and the electric current value that was acquired in step S 202 are stored in the memory unit 73 (steps S 205 , S 206 ), after which processing advances to the determination process during voltage application (step S 107 in FIG. 3 ).

On the other hand, in step S 203 , when it is determined that the value of the electric current is not within the threshold value range (NO in step S 203 ), application of voltage to the electrodes 21 , 22 is stopped (step S 207 ). More specifically, switch 46 in FIG. 2 is turned OFF.

Next, 1 is added to the variable i (step S 208 ), and variable i is written over and stored in the memory unit 73 (step S 209 ).

Next, whether or not variable i is a specified value N 1 is determined (step S 210 ).

When it is determined that variable i is not a specified value N 1 (NO in step S 210 ), the cleaning determination unit 74 outputs a cleaning signal (step 211 ) and the cleaning process S 11 ( FIG. 3 ) is executed.

On the other hand, when it is determined that variable i is a specified value N 1 (YES is step S 210 ), the replacement unit 75 outputs a replacement signal to the PC 27 ( FIG. 2 ) to replace the microchip 4 (step S 212 ). As a result, an image is displayed on the screen of the PC 27 prompting to replace the microchip 4 , and the user is notified that the microchip 4 requires replacement. After the microchip 4 has been replaced, the user operates the electrophoresis apparatus 1 , which causes the variable i to be reset to “0”, and then causes the cleaning process S 11 to begin.

When the processing in FIG. 6 is executed again by repeating the processing in FIG. 3 , variable i that was stored in the previous steps S 205 and S 209 is read in step S 201 . Depending on the determination result in step S 203 , either “0” or “1” is added to variable i and the result is stored in steps S 205 and S 209 . In the process of repeating the process in FIG. 3 by reading and storing variable i above, the number of times that NO is continuously determined in step S 203 is counted. Each time the processing in FIG. 6 is performed, the determination in step S 210 is performed according to the count value above.

Next, the determination process during voltage application will be explained in detail. FIG. 7 is a flowchart illustrating the determination process during voltage application. The processing in FIG. 7 is started when the electric current value is stored in the memory unit 73 in step S 206 in FIG. 6 . The processing in FIG. 7 is executed by the physical quantity acquisition unit 71 , physical quantity determination unit 72 , memory unit 73 , replacement unit 75 , temperature adjustment unit 76 , voltage change unit 77 and voltage value calculation unit 78 . In order to execute the processing in FIG. 7 , the threshold value ΔI s illustrated in FIG. 5 is stored in the memory unit 73 .

In FIG. 3 and FIG. 7 , steps S 107 and S 305 correspond, steps S 108 and S 309 correspond, steps S 109 and S 310 correspond, steps S 110 and S 312 correspond, steps S 111 and S 313 correspond and steps S 112 and S 314 correspond.

First, variable j is set to “0” (step S 301 ).

Next, the physical quantity acquisition unit 71 acquires the measured value from the ammeter 10 (step S 302 ). Step S 302 is executed at specified intervals, and the processing from step S 303 on is executed each time the electric current value is acquired in step S 302 .

The physical quantity determination unit 72 then reads the electric current value that was stored in the past step S 306 (or S 206 in FIG. 6 ) (step S 303 ). In the first time of performing step S 303 , the electric current value I 1 that was stored in step S 206 is read.

Next, the physical quantity determination unit 72 calculates the difference between the electric current value acquired in step S 302 and the electric current value that was read in step S 303 (step S 304 ). When a large change occurred in the electric current that flows between the electrodes 21 , 22 , a large value is calculated for the difference between electric current values.

The physical quantity determination unit 72 then determines whether or not the difference calculated in step S 304 exceeds the threshold value ΔI s (step S 305 ).

In step S 305 , when it is determined that the difference does not exceed the threshold value ΔIs (YES in step S 305 ), the electric current value that was acquired in step S 302 is stored in the memory unit 73 (step S 306 ).

FIG. 8 illustrates a table in which the electric current values are recorded in step S 306 .

In the table in FIG. 8 , electric current value I 1 that was stored in step S 206 ( FIG. 6 ) is recorded as the initial value, and the electric current values I 11 , I 12 , I 14 , I 15 , I 16 that were acquired in the first, second, fourth, fifth and sixth time that step S 302 was performed are recorded. These values are electric current values whose difference with the electric current values stored in the previous step S 306 do not exceed the threshold value ΔI s .

In the table in FIG. 8 , the electric current value acquired in the third time that step S 302 was performed is not recorded. This is because the difference ΔI 3 ( FIG. 5 ) between electric current value that was acquired in the third time that step S 302 was performed and the electric current I 12 that was acquired in the second time that step S 302 was performed exceeds the threshold value ΔI s .

Also, for example, the difference ΔI 4 ( FIG. 5 ) between the electric current value I 14 that was acquired the fourth time that step S 302 was performed and the electric current value I 12 that was acquired the second time that step S 302 was performed did not exceed the threshold value ΔIs, so the electric current value I 14 is not recorded in the table in FIG. 8 (stored in step S 306 ).

After step S 306 , whether or not the analysis time has elapsed is determined (step S 307 ). The analysis time is the time required from the point when application of voltage is started in step S 101 until the hemoglobin passes the portion irradiated with light (block dot portion in FIG. 1 ). The analysis time, for example, is calculated from the electric current value that is stored in step S 306 , the electrical mobility of hemoglobin and the length L from the inlet hole 19 to the portion irradiated with light ( FIG. 1 ).

When it is determined that the analysis time has not elapsed (NO in step S 307 ), processing moves to step S 301 , and processing is repeated from step S 301 .

In this repeated process, when it is determined in step S 305 that the difference exceeded the threshold value ΔI s (NO in step S 305 ), processing advances to step S 308 .

In step S 308 , 1 is added to variable j, and then in step S 309 , it is determined whether or not variable j is a specified value N 2 (step S 309 ). In other words, each time the electric current value is acquired in step S 302 , as a result of performing steps S 303 to S 305 , it is determined whether or not the number of times when NO was continuously determined in step S 305 has reached N 2 times.

When it is determined that the number of times that NO was determined above has not reached N 2 (NO in step S 309 ), the temperature adjustment unit 76 outputs a temperature adjustment signal in order to adjust the temperature of the microchip 4 (step S 310 ). By a temperature adjustment signal being input, the temperature regulator 6 ( FIG. 1 ) adjusts the temperature of the microchip 4 by cooling or heating the microchip 4 .

Next, the voltage change unit 77 calculates a correction value for the voltage to be applied to the electrodes 21 , 22 (step S 311 ). In step S 311 , first, of the electric current values recorded in the table in FIG. 8 , the electric current value recorded most recently is read. For example, during the third time that the processing in FIG. 7 is performed, the electric current value I 12 from the second time is read. Then, the voltage value that would cause this value I 12 to flow between the electrodes 21 , 22 is calculated as the correction value above. It is also possible to set a target value for the electric current in advance, and to calculate the voltage value that will generate an electric current of this size as the correction value.

The voltage change unit 77 then outputs a voltage change signal in order to change the size of the voltage applied to the electrodes 21 , 22 to the correction value in step S 313 (step S 312 ). As a result, the value of the voltage that is applied to the electrodes 21 , 22 is changed to the correction value that was calculated in step S 311 .

After that, by moving to step S 302 , the processing is repeated from step S 302 .

Through the previous steps S 310 to S 312 , when there is no longer a large change in the electric current that flows between the electrodes 21 , 22 , in the repeated processing YES is determined in step S 305 , after which processing moves to step S 301 and variable j is reset to “0”.

On the other hand, when the change in electric current is not reduced even through the previous steps S 310 to S 312 , NO is determined again in step S 305 , and 1 is added to variable j (step S 308 ). After that, steps S 310 to S 312 are executed again, then processing moves to step S 302 and the determination in step S 305 is performed.

In step S 305 , when NO is determined repeatedly, 1 is added to variable j each time, and the value of variable j increases.

When the number of times that NO is continuously determined in step S 306 reaches N 2 and the variable j becomes the specified value N 2 (YES in step S 309 ), the switch 46 is switched to OFF, and the application of voltage to the electrodes 21 , 22 is stopped (step S 313 ). As a result, the separation process S 14 is stopped. Next, the replacement unit 75 outputs a replacement signal for replacing the microchip 4 (step S 314 ). By doing so, an image prompting to replace the microchip 4 is displayed on the screen of the PC 27 , and the microchip 4 is replaced. After that, the cleaning process S 11 is executed according to operation from the user.

When the processing in FIG. 7 is repeated until YES is determined in step S 307 without YES being determined in step S 309 , the voltage value calculation unit 78 calculates the value of the voltage to be applied in step S 101 ( FIG. 3 ) the next time (step S 315 ). In step S 315 , the voltage value is calculated based on the electric current value that was stored in step S 306 .

Next, the voltage value that was calculated in step S 315 is stored in the memory unit 73 (step S 316 ). The voltage value that is stored in step S 316 is read from the memory unit 73 in step S 101 the next time, and voltage having this size is applied to the electrodes 21 , 22 .

With this embodiment, the determination of whether or not the value of the electric current that flows between the electrodes 21 , 22 is within a specified range (range of not less than an electric current Ik and no greater than an electric current Ij) (step S 203 in FIG. 6 ) is executed with the migration solution L 1 and specimen Sp injected inside the capillary flow channel 47 . Therefore, by the character of the fluid inside the capillary flow channel changing due to the migration solution L 1 and specimen Sp mixing, by air bubbles being generated in or foreign matter being mixed into the fluid inside the capillary flow channel 47 due to the work of injecting the specimen, by the temperature of the microchip 4 rising, or by the temperature of the environment surrounding the microchip 4 changing, the expected electric current flowing between the electrodes 21 , 22 is not detected at the start of voltage application (NO in step S 203 ). Therefore, it is possible to detect abnormality in the capillary flow channel during electrophoretic component separation.

Furthermore, in step S 203 , when it was determined that the electric current value was not within a specified range (NO in step S 203 ), application of voltage to the electrodes 21 , 22 was stopped (step S 207 ), and a cleaning signal was outputted (step S 211 ). Therefore, performing electrophoretic separation with unexpected current flowing is prevented, and fluid inside the capillary flow channel 47 in which air bubbles or the like occurred is replaced.

Moreover, when the temperature of the microchip 4 became high, the electrical resistance of the fluid inside the capillary flow channel 47 changes, and the value of the electric current flowing between the electrodes 21 , 22 becomes large. In this case, in the process of repeating the processing in FIG. 6 , when the number of times NO is continuously determined in step S 203 reaches N 1 (YES in step S 210 ), a replacement signal to replace the microchip 4 is outputted (step S 212 ). Therefore, continuously using a hot microchip 4 for electrophoretic separation is avoided.

When the temperature of the microchip 4 greatly changes while voltage is applied to the electrodes 21 , 22 , in step S 305 if FIG. 7 it is determined that the difference between electric current values exceeded the threshold value ΔIs (NO in step S 305 ), and a temperature adjustment signal for adjusting the temperature of the microchip 4 is outputted (step S 310 ). As a result, temperature adjustment of the microchip 4 is performed, so it useful for stabilizing the current flowing between the electrodes 21 , 22 .

Similar to as described above, when the temperature of the microchip 4 greatly changes while voltage is applied, a voltage change signal is outputted (step S 312 ), and the value of the voltage applied to the electrodes 21 , 22 is changed. As a result, even though the temperature of the microchip 4 greatly changes, change in the electric current that flows between the electrodes 21 , 22 is kept small.

Moreover, only when it is determined in step S 305 that the difference in electric current values does not exceed the threshold value ΔIs (YES in step S 305 ) is the electric current value stored in step S 306 . In step S 312 , according to the outputted voltage change signal, the value of the electric current flowing between electrodes 21 , 22 is changed to the value stored in the most recent step S 306 . Therefore, the electric current flowing between the electrodes 21 , 22 is controlled to be the value when the difference in step S 305 is determined to not exceed the threshold value ΔIs. As a result, the electric current flowing between the electrodes 21 , 22 can be controlled to near a target value.

When a large temperature change repeatedly occurs in the microchip 4 while voltage is applied between the electrodes 21 , 22 , by changing the electric current that flows between the electrodes 21 , 22 each time, the difference between the electric current values that is calculated in step S 305 becomes large. In this case, when the number of times that NO is continuously determined in step S 305 reaches N 2 times (YES in step S 309 ), application of voltage is stopped (step S 313 ). Therefore, when it is not possible to suppress temperature fluctuation in the microchip 4 during the temperature adjustment and changing of the voltage value in steps S 310 to S 312 , it is possible to stop the separation process S 14 (process that causes electrophoretic separation).

After application of voltage has been stopped in step S 313 , a replacement signal to replace the microchip 4 is outputted (step S 314 ), prompting replacement of the microchip 4 . As a result, continuous use of a microchip 4 in which there was a large temperature change is prevented.

The next time step S 101 is performed, the value of the voltage applied to the electrodes 21 , 22 is set based on the electric current value that is stored in step S 306 (steps S 315 , S 316 ). As a result, this is useful for controlling the electric current that flows between the electrodes 21 , 22 to a value near a target value each time the separation process S 14 is performed.

The first embodiment can undergo various variations as described below.

For example, in step S 202 in FIG. 6 , the instant that the electric current value is acquired is not necessarily limited to being the start of voltage application, and can be set to any arbitrary time while voltage is being applied.

Moreover, in the first embodiment above, the processing in FIG. 6 and FIG. 7 was executed based on the electric current value that was measured by the ammeter 10 ; however, instead of the electric current value, it is also possible to use the value of the voltage (value measured by the voltmeter 9 ) applied to the electrodes 21 , 22 as the electrical quantity. It is also possible to use the electric power, which is the product of the value of the voltage that is applied to the electrodes 21 , 22 and the electric current that flows between the electrodes 21 , 22 . In the construction in FIG. 2 , the measured value from the voltmeter 9 is acquired at the timing that the measured value is acquired from the ammeter 10 , and by taking the product of these measured values from the ammeter 10 and voltmeter 9 , the amount of electric power can be obtained. When the amount of electric power is used, control is possible that also takes into consideration the fluctuation in the output from the power supply 8 .

Furthermore, in the first embodiment above, output of the cleaning signal in step S 211 in FIG. 6 is executed every time that NO is determined in step S 203 ; however, it is possible to not output the cleaning signal when the number of times that NO has been determined in step S 203 reaches a certain value.

In the first embodiment above, output of the replacement signal in step S 212 is executed when the number of times that NO is continuously determined in step S 203 reaches N 1 times; however, the replacement signal can be outputted when the total number of times that NO is determined in step S 203 reaches a certain value.

Moreover, in the first embodiment above, output of the temperature adjustment signal in step S 310 in FIG. 7 , or output of the voltage correction value calculation and voltage change signal in steps S 311 and S 312 is executed every time that the difference between electric current values in step S 305 was determined to exceed a threshold value (NO in step S 305 ); however, output can also be executed when the number of times that NO is determined in step S 306 reaches a certain value.

When NO is determined in step S 305 , it is possible to execute just one of the output of the temperature adjustment signal in step S 310 , and the voltage correction value calculation and voltage change signal in steps S 311 and S 312 .

Furthermore, in the first embodiment above, stopping voltage application and outputting a replacement signal in steps S 313 and S 314 are executed when the number of times that NO is continuously determined in step S 305 reaches N 2 times; however, this can be executed when the total number of times that NO is determined in step S 305 reaches a certain value.

Moreover, the number of capillary flow channels 47 can be set to an arbitrary number. In the case of a plurality of capillary flow channels 47 , the processing in FIGS. 3 , 6 and 7 is executed for each capillary flow channel 47 . The construction of the capillary flow channel 47 is not limited to being a so-called straight type, and could, for example, be a cross-junction type in which two flow channels cross. The specimen Sp is not limited to containing hemoglobin, which is representative of whole blood, and could include, for example, DNA, RNA (rebonucleic acid) or protein.

(Embodiment 2)

FIG. 9 is a diagram illustrating the construction of an electrophoresis apparatus 80 of a second embodiment of the present invention. The electrophoresis apparatus 80 of this second embodiment comprises: a fluid storage tank 81 , specimen tank 82 , waste fluid tank 83 , dispensing unit 84 , microchip 85 , electrodes 86 , 87 , detection unit 88 , pump (pressure generation unit) 89 , suction pump 90 , three-way valves 91 to 93 , flow channel 94 to flow channel 96 , control unit 97 and power supply 98 . The microchip 85 comprises a capillary flow channel 99 , inlet hole 100 and discharge hole 101 .

Stored fluid L, for example, migration solution, purified water, cleaning solution and the like are stored in the stored fluid tank 81 . Specimen fluid K is stored in the specimen tank 82 . Specimen fluid K is a sample containing a certain component for which analysis is to be performed by the electrophoresis apparatus 80 , and is in a form of being processed in a state suitable for measurement, for example, a diluted or mixed state. Used fluid is stored in the waste fluid tank 83 .

The dispensing unit 84 injects the specimen fluid K that is in the specimen tank 82 into the capillary flow channel 99 of the microchip 85 .

The pump 89 generates pressure. The pressure that the pump 89 generates is applied to the flow channels 95 , 96 via the three-way valve 93 . The pump 89 can feed solution into the electrophoresis apparatus 80 that includes the flow channels and functional units.

FIG. 10A is a top view illustrating the microchip 85 of this second embodiment. FIG. 10B is a cross-sectional view of section X-X in FIG. 10A of the microchip 85 of this second embodiment. FIG. 10C is a cross-sectional view of section Y-Y in FIG. 10A of the microchip 85 of this second embodiment.

The microchip 85 has a minute flow channel formed in the substrate thereof that is made of a resin material, and functions as the capillary flow channel 99 . The microchip 85 is formed by joining together a substrate 85 a and a substrate 85 b . The substrate 85 a functions as a base where the capillary flow channel 99 is formed. The inlet hole 100 and the discharge hole 101 are formed in the substrate 85 b at a position that corresponds to the capillary flow channel 99 .

In this second embodiment, the cross section of the capillary flow channel 99 is set as a square with each side being 40 μm, and the length of the capillary flow channel 99 is set at about 30 mm. The cross section and length of the capillary flow channel 99 is not limited to the values above.

An inlet hole 100 and discharge hole 101 are formed in the capillary flow channel 99 . The inlet hole 100 is provided on one end of the capillary flow channel 99 and the specimen fluid K is input through the inlet hole 100 from the dispensing unit 84 . In this second embodiment, in addition to the specimen fluid K, it is possible to input stored fluid L such as migration solution, purified water, cleaning solution and the like to through the inlet hole 100 . The discharge hole 101 is provided on the other end of the capillary flow channel 99 , and the specimen fluid K and stored fluid L that were filled into the capillary flow channel 99 are discharged from the discharge hole 101 .

The spatial portion of the inlet hole 100 that passes through the substrate 85 a and connects to the capillary flow channel 99 is called reservoir R 1 . Similarly, the spatial portion on the discharge hole 101 side (the spatial portion of the discharge hole 101 that passes through the substrate 85 a and the comes in contact with the capillary flow channel 99 ) is called reservoir R 2 .

An electrode 86 and electrode 87 are provided on both ends of the capillary flow channel 99 . In this second embodiment, the electrode 86 is exposed in the inlet hole 100 , and the electrode 87 is exposed in the discharge hole 101 .

The detection unit 88 analyzes a specified component that is separated out from the specimen fluid K in the capillary flow channel 99 . The detection unit 88 is provided in the portion of the capillary flow channel 99 that is closer to the discharge hole 101 than the inlet hole 100 . The detection unit 88 comprises, for example, a light source and a light receiving unit. The detection unit 88 irradiates light from the light source onto the specimen fluid K, and by the light receiving unit receiving the light that passes through, it is possible to measure the light absorption and analyze a specified component.

FIG. 11 is a partial view that includes the microchip 85 of the electrophoresis apparatus of this second embodiment. FIG. 11 , similar to FIG. 10B , illustrates the state wherein the microchip 85 has been cut along section line X-X in FIG. 10A .

The suction pump 90 can draw in solution that is in the capillary flow channel 99 from the flow channel 95 side by the suction force P 1 . When the suction pump 90 is operated, the solution inside the capillary flow channel 99 is drawn toward the flow channel 95 by the suction force P 1 , and discharged to the waste fluid tank 83 .

Suction force P 1 is applied by the suction pump 90 and sucks the solution inside the capillary flow channel 99 . When doing this, force is applied such that it pulls both the substrate 85 a and substrate 85 b of the microchip 85 against each other, and the direction of this force is the same as the direction of the force applied when applying pressure to the substrate 85 a and substrate 85 b in order to join together the substrate 85 a and substrate 85 b . Therefore, by generating a suction force P 1 in the suction pump 90 , it is possible to reduce the possibility that the substrate 85 a and substrate 85 b will come apart.

It is also possible to have the pump 89 that feeds solution function as the suction pump 90 , or in other words, have the pump 89 draw in the solution that is in the capillary flow channel 99 . In this case, by controlling the opening and closing of the three-way valve 93 , and by generated a suction force P 1 in the pump 89 while the flow channel 95 is opened up to the pump 89 , the pump 89 functions the same as the suction pump 90 . By doing so, it is possible to eliminate the suction pump 90 when designing the electrophoresis apparatus 80 .

In order to remove the solution inside the capillary flow channel 99 , it is possible to perform purging of the solution instead of suction. Supposing the case of purging the solution inside the capillary flow channel 99 , a force applies pressure to the solution in the capillary flow channel 99 from the inside toward the outside. In other words, a force is applied in the direction that promotes the joined surfaces of the substrate 85 a and substrate 85 b to come apart, and the load on the microchip 85 becomes large. When sucking out instead of purging the solution inside the capillary flow channel 99 , a force is applied that pulls the substrate 85 a and the substrate 85 b together, eliminating the possibility of the substrates 85 a , 85 b coming apart. Therefore, in order to remove the solution inside the capillary flow channel 99 , performing suction instead of purging is preferred.

However, when the solution in the capillary flow channel 99 is sucked from one side and purged from the other side, and the suction force is greater than the purging pressure, a force is applied that pulls the substrate 85 a and substrate 85 b together. Purging pressure can be used together with the suction force only when purging pressure is applied as an aid when performing this kind of suction.

The operation of the parts of the electrophoresis apparatus 80 described above is controlled by the control unit 97 . The control unit 97 comprises a CPU, memory, input/output interface and the like.

Three-way valves 91 , 92 are provided in the electrophoresis apparatus 80 . The three-way valves 91 , 92 each have three connection ports, and the connected state and blocked state of these connection ports are independently controlled by the control unit 97 .

The fluid storage tank 81 and specimen tank 82 are connected to flow channel 94 or flow channel 96 via the three-way valves 91 , 92 . The opening and closing of the three-way valves 91 , 92 is controlled by the control unit 97 , and the connected state and blocked state with the capillary flow channel 99 are independently controlled. The flow channel 94 is connected to the capillary flow channel 99 of the microchip 85 , and the flow channel 96 is connected to the waste fluid tank 83 .

As illustrated in FIG. 11 , fluid that is input from flow channel 94 to inlet hole 100 (or in other words, the reservoir R 1 portion) flows through the capillary flow channel 99 and to the flow channel 95 via the discharge hole 101 (or in other words reservoir R 2 ).

The power supply 98 is connected to electrode 86 and electrode 87 , and applies a 1.5 kV voltage to the electrodes 86 , 87 . For example, the power supply 98 applies a voltage such that the electrode 86 is a positive electrode and electrode 87 is a negative electrode; however, may also have the function to apply voltage so that the polarity is opposite this.

In the following, FIG. 9 to FIG. 13 will be used to explain the processing that is executed by the electrophoresis apparatus 80 of this second embodiment. FIG. 12 is a flowchart illustrating the processing executed by the electrophoresis apparatus 80 . This flow is mainly divided into a pre-processing process (step S 1 ) and an analysis process (step S 2 ).

A cleaning process of the pre-processing equipment (step S 11 ) is a process that is performed first in the pre-processing process (step S 1 ), and when the electrophoresis apparatus 80 is used continuously, is a process that is performed to clean each of the parts of the electrophoresis apparatus 80 . After that, the dispensing process for inserting the specimen (step S 12 ) is performed.

More specifically, the cleaning process (step S 11 ) is divided into filling the pre-processing fluid (step S 111 ) and discharging the pre-processing fluid (step S 112 ), and cleaning is performed by causing pre-processing fluid such as cleaning solution or purified water to flow through the inside of the capillary flow channel 99 .

In this second embodiment of the present invention, the pre-processing fluid is filled by the following method. FIG. 13 is a flowchart illustrating the process of filling the pre-processing fluid, which is part of the cleaning process of the pre-processing process that is executed by the electrophoresis apparatus 80 of this second embodiment. Filling of the pre-processing fluid (step S 111 ) is explained as filling 1 of pre-processing fluid (step J 1 ).

First, by discharging pre-processing fluid to the flow channel 112 via the discharge hole 101 at the same time that the pre-processing fluid is introduced into the capillary flow channel 99 by way of the flow channel 94 and inlet hole 100 , the pre-processing fluid flows through the capillary flow channel 99 (step J 11 ).

Then, the suction pump 90 is used to suck out the pre-processing fluid that is passing through the capillary flow channel 99 with a suction force P 1 (step J 12 ). As a result, the pre-processing fluid in the capillary flow channel 99 flows toward the discharge hole 101 with much energy, and by flowing into the reservoir R 2 , can fill the reservoir R 2 with pre-processing fluid. With this passing fluid, the capillary flow channel 99 is filled with the pre-processing fluid, and the reservoir R 2 is also filled with pre-processing fluid (step J 13 ). Here, the capillary flow channel 99 can be cleaned by the pre-processing fluid flowing through the capillary flow channel 99 . Moreover, with a sufficient amount of pre-processing fluid flowing into the reservoir R 2 of the discharge hole 101 , the reservoir R 2 can be cleaned.

Filling with pre-processing fluid (step S 111 ) ends and again the suction pump 90 is used to apply suction to the capillary flow channel 99 with a suction force P 1 . The pre-processing fluid in the capillary flow channel 99 cleans away impurities such as specimen K that was used in the previous analysis, and is discharged to the waste fluid tank 83 via the flow channel 112 (step S 112 ). By removing the pre-processing fluid with suction, it is possible to remove all of the pre-processing fluid that remains in the capillary flow channel 99 . Therefore, there is no fear of the solution that will be filled into the capillary flow channel 99 next mixing with the pre-processing fluid, and cleaning efficiency is improved.

The dispensing process (step S 12 ) is a processing of filling the capillary flow channel 99 with migration solution for enabling electrophoresis and specimen fluid K. First, the migration fluid is filled into the capillary flow channel 99 (step S 121 ). Next, the dispensing unit 84 injects the specimen fluid K into the capillary flow channel 99 , which has been sufficiently filled with migration solution (step S 122 ).

When filling with the migration solution as well (step S 121 ), the suction pump 90 can be used to apply suction as in the case of filling with pre-processing fluid. Even when the capillary flow channel 99 and reservoir R 2 are filled with migration solution, by using the suction pump 90 to apply suction, it is possible to completely fill the capillary flow channel 99 and reservoir R 2 .

After the pre-processing process (step S 1 ) has ended, the analysis process (step S 2 ) is executed. The analysis process (step S 2 ) comprises a separation process (step S 21 ) and a detection process (step S 22 ).

The separation process (step S 21 ) is a process of separating out a specified component contained in the specimen fluid K by electrophoresis. In the separation process (step S 21 ), electrophoresis is performed by putting specimen fluid K into the capillary flow channel 99 that is filled with migration solution and applying voltage to the electrodes 86 , 87 . In the separation process, by filling the capillary flow channel 99 with migration solution in step S 121 , it becomes easier to inject the specimen fluid K, and it is possible to perform the separation process (step S 21 ) with better precision.

More specifically, separation by electrophoresis can be achieved by applying voltage from the power supply 8 to the electrodes 86 , 87 according to an instruction from the control unit 97 so that the electrode 86 becomes a positive electrode and the electrode 87 becomes a negative electrode, and by generating an electroosmotic flow in the migration solution going from the electrode 86 to the electrode 87 . When that happens, movement of the specified component from the electrode 86 to the electrode 87 occurs according to unique electrophoretic mobility.

The detection process (step S 22 ) is a process of detecting the amount or density of a specified component that was been separated out. More specifically, according to an instruction from the control unit 97 , the detection unit 88 irradiates light having a wavelength of 415 nm from the light source onto a specified location of the capillary flow channel 99 , and the light receiving unit receives the light that passes through. When the specified component passes the specified location of the capillary flow channel 99 , the light (light absorbance) received by the light receiving unit changes, and from that change it is possible to detect the density or amount of specified component. The analysis result is stored for example in a memory unit (not illustrated in the figure), and the detection process (step S 22 ) ends. Through the process above, the pre-processing process (step S 1 ) and analysis process (step S 2 ) end, and analysis using the electrophoresis apparatus 80 is completed.

In this second embodiment, the control unit 97 ( FIG. 9 ) functions as the physical quantity acquisition unit 71 , physical quantity determination unit 72 , memory unit 73 , cleaning determination unit 74 , replacement unit 75 , temperature adjustment unit 76 , voltage change unit 77 and voltage value calculation unit 78 illustrated in FIG. 2 , and these units execute the steps S 101 to S 112 in FIG. 3 and the processing in FIG. 6 and FIG. 7 . Step S 101 in FIG. 3 is the separation process (step S 21 ), and is executed according to the voltage that is applied to the electrodes 86 , 87 .

FIG. 14 is a diagram illustrating the construction of an electrophoresis apparatus 140 of a variation of embodiment 2. FIG. 15 is a partial view that includes the microchip 141 of the electrophoresis apparatus 140 of a variation of the second embodiment. In this variation of the second embodiment, a suction pump 113 is provided on the inlet hole 100 side. The other construction is the same as the electrophoresis apparatus 80 illustrated in FIG. 9 and FIG. 11 .

The suction pump 113 is provided in the flow channel 94 . The suction pump 113 removes the stored fluid L and specimen fluid K (collectively referred to as the solution) in the capillary flow channel 99 by sucking out the solution in the capillary flow channel 99 from the inlet hole 100 side with a section force P 2 .

In this second embodiment, with the pre-processing fluid flowing through the capillary flow channel 99 , the pre-processing fluid in the capillary flow channel 99 is sucked out by having the suction pump 113 generate a suction force P 2 when the capillary flow channel 99 is filled to a certain extent with the pre-processing fluid. As a result, by sucking the pre-processing fluid toward the flow channel 94 , it is possible to fill the pre-processing fluid into the reservoir R 1 .

When the suction pump 113 generates a suction force and sucks out the pre-processing fluid in the capillary flow channel 99 , or in other words, when supply of pre-processing fluid from the flow channel 94 to the capillary flow channel 99 is stopped, the three-way valve 92 is switched according to control from the control unit 97 so that flow channels 94 and 96 are connected. As a result, due to the suction of the suction pump 113 , the pre-processing fluid that flowed in the flow channel 94 flows toward the flow channel 96 , and finally flows into the waste-fluid tank 83 . Similar to removing the pre-processing fluid in the capillary flow channel 99 , the three-way valve 92 is switched by the control unit 97 so that the pre-processing fluid flows to the waste-fluid tank 83 . When suction by the suction pump 113 ends, the three-way valve 92 is switched by the control unit 97 , and the pre-processing fluid flows from the flow channel 94 to the capillary flow channel 99 .

It is also possible to have the pump 89 that feeds solution function as the suction pump 113 , or in other words, having the pump 89 perform the function of sucking out solution that is in the capillary flow channel 99 . In this case, opening and closing of the three-way valves 92 , 93 is controlled, and when the flow channels 94 , 96 are connected to the pump 89 and the pump 89 generates a suction force P 2 , the pump 89 functions the same as the suction pump 113 . By doing so, it is possible to eliminate the suction pump 113 when designing the electrophoresis apparatus 140 .

By performing the process (step J 12 ) of sucking the pre-processing fluid in the capillary flow channel 99 by the suction pump 113 in the filling of pre-processing fluid (step S 111 ) in the cleaning process (step S 11 ), it is possible to completely fill the inside of the reservoir R 1 with pre-processing fluid.

Similar to the process of filling with pre-processing fluid, in step S 121 as well, filling with migration solution can also be performed by apply suction from a suction pump 90 . By doing so, it is possible to more reliably perform filling even when filling the capillary flow channel 99 and reservoir R 1 with migration solution.

In this variation of the second embodiment, suction is performed from the inlet hole 100 side via the flow channel 94 ; however, it is also possible to perform suction from the inlet hole 100 side via a flow channel that is separate and different from the flow channel 94 and that is connected to the inlet hole 100 . By doing so, not only is the discharge hole 101 side cleaned, but the inlet hole 100 side is also cleaned, so it is possible to improve the cleaning effect inside the capillary flow channel 99 .

As explained above, with this second embodiment, in the pre-processing process (particularly, the cleaning process), it is possible to reduce mechanical load on the flow channel of the microchip, and to improve the cleaning efficiency.

In cleaning of the capillary flow channel and reservoir, it was easy for filling with solution into minute areas to become inadequate, and there were areas where cleaning was not performed; however, but using suction, filling with solution could be performed reliably. As a result, cleaning became thorough, and the cleaning efficiency was improved.

Moreover, by applying suction to the solution flowing in the capillary flow channel, the cleaning efficiency of the capillary flow channel can be improved. Furthermore, by applying suction to the capillary flow channel, and discharging the solution from the capillary flow channel, there is no mixing with the solution to be used next, and thus it becomes possible to improve the cleaning efficiency.

As described above, by improving the cleaning efficiency, the microchip can be maintained in a clean state. Therefore, repeated use during analysis becomes possible, and the number of times the microchip can be used until it is disposed of can be increased.

Furthermore, by applying suction when performing cleaning, it is possible to reduce the burden on the microchip, there is no fear of the joined surfaces of the substrates of the microchip coming apart, and the durability of the microchip is improved. As a result, the microchip can be used repeatedly during analysis, and the number of times the microchip can be used can be increased.

(Embodiment 3)

FIG. 16 is a diagram illustrating the construction of an electrophoresis apparatus 150 of a third embodiment of the present invention. FIG. 17 is a partial view that includes the microchip 151 of an electrophoresis apparatus 150 of a third embodiment. The electrophoresis apparatus 150 of this third embodiment comprises an auxiliary flow channel for applying suction to the stored fluid L in the capillary flow channel 99 . The other construction is the same as that of the electrophoresis apparatus 80 of the second embodiment illustrated in FIG. 9 and FIG. 11 .

The microchip 151 comprises: an auxiliary channel 120 that connects to the capillary flow channel 99 via the reservoir R 1 and an auxiliary hole 121 that is form on the other end section of the auxiliary channel 120 in addition to the construction of the microchip 85 illustrated in FIG. 9 and FIG. 11 . The auxiliary hole 121 passes through the substrate 85 a , and the spatial section that extends up to the auxiliary channel 120 is called reservoir R 3 .

The reservoir R 3 is connected to the capillary flow channel 99 via the auxiliary channel 120 , and is located in the end section of the auxiliary channel 120 that is far from the capillary flow channel 99 . It is possible to suck solution such as stored fluid L that is in the capillary flow channel from the reservoir R 3 via the auxiliary channel 120 .

By applying suction with a suction force of P 3 using a suction pump 131 that is provided in the end section of the auxiliary channel 120 , pre-processing fluid flows to the reservoir R 3 via the auxiliary channel 120 . When doing this, the pre-processing fluid near the area of the reservoir R 1 that is connected to the auxiliary channel 120 is sucked by the suction force P 3 .

The reservoir R 3 differs from reservoirs R 1 and R 2 in that it does not need to be filled with solution. This is because during analysis, only the stored fluid L flows in the capillary flow channel 99 , so the auxiliary channel 120 and the reservoir R 3 are only used during cleaning.

In the reservoirs R 1 and R 2 , it is difficult for solution to move in the low corner sections, and particularly, the low corner section that is paired with the capillary flow channel 99 side are sections where flow is difficult. In other words, the low corner sections are areas where it is easy for a previous analysis specimen to remain. Especially, it is easy for an analysis specimen to remain in the low corner section that is paired with the capillary flow channel 99 side of the reservoir R 1 , so by providing an auxiliary channel 120 in that location and generating flow of solution, it becomes possible to improve the cleaning efficiency of the reservoir R 1 .

Moreover, it is possible to apply suction to the reservoir R 1 on the side having the auxiliary channel 120 , which has the effect of making it easier to fill the reservoir R 1 with solution.

It becomes easier to remove solution from the capillary flow channel 99 , and there is no fear of mixing with the solution that will be used next, thus it is possible to further improve the cleaning efficiency.

Next, FIG. 12 and FIG. 16 to FIG. 18 will be used to explain the processing executed by the electrophoresis apparatus 150 of this third embodiment. The basic flow of this processing is the same as that of the processing explained in the second embodiment.

FIG. 18 is a flowchart illustrating part of the cleaning process of the pre-processing process that is executed by the electrophoresis apparatus 150 of this third embodiment. In the following, filling with pre-processing fluid (step S 111 ) is explained as filling 2 with pre-processing fluid (J 2 ).

First, pre-processing fluid is caused to flow through the capillary flow channel 99 by introducing pre-processing fluid into the capillary flow channel 99 from the flow channel 94 via the inlet hole 100 , and at the same time, the pre-processing fluid is discharged from the flow channel 112 via the discharge hole 101 (step J 21 ).

Next, the suction pump 90 applies suction having a suction force P 1 to the pre-processing fluid passing through the capillary flow channel 99 (step J 22 ). As a result, pre-processing fluid in the capillary flow channel 99 vigorously flows toward the discharge hole 101 , and the reservoir R 2 can be filled with pre-processing fluid.

Once the flow of pre-processing fluid to the capillary flow channel 99 has stopped (step J 23 ) and the reservoirs R 1 , R 2 and the capillary flow channel 99 are filled with pre-processing fluid, the spatial section on the inlet hole 100 side, or in other words, the reservoir R 1 is covered and sealed from the outside with a sealing member 130 (step J 24 ). Then, the suction pump 131 applies suction having a suction force P 3 to the capillary flow channel 99 via the auxiliary channel 120 , and sucks the pre-processing fluid that is flowing in the capillary flow channel 99 (step J 25 ).

After that, the sealing member 130 that covered and sealed the reservoir R 1 is removed, and pre-processing fluid is again allowed to flow from the flow channel 94 into the capillary flow channel 99 via the inlet hole 100 (step J 26 ).

The suction pump 90 then generates a suction force P 1 and sucks the pre-processing fluid that flows in the capillary flow channel 99 (step J 27 ). From this passing fluid, the capillary flow channel 99 is filled with pre-processing fluid, and the reservoirs R 1 , R 2 are also filled with pre-processing fluid (step J 28 ).

As was explained above, with the electrophoresis apparatus of this third embodiment, in the pre-processing process, and particularly in the cleaning process, it is possible to reduce the mechanical load on the flow channel of the microchip and to improve the cleaning efficiency.

It also becomes possible to adequately fill the capillary flow channel and reservoirs with solution, and to clean the minute areas and improve the cleaning efficiency, and as result, the microchip can be used repeatedly during analysis and the number of times the microchip can be repeatedly used also increases. Moreover, by applying suction during cleaning, the burden on the microchip can be reduced, the fear of the joined surfaces of the substrates of the microchip coming apart is eliminated, and the durability of the microchip is improved.

Furthermore, by providing a flow channel (auxiliary channel) that is separate from the capillary flow channel, flow of solution is generated at and near the low corner sections of the reservoir, so it becomes possible to further improve the cleaning efficiency. The solution remaining in the capillary flow channel can be removed and mixing with the next solution to be used can be prevented, so the cleaning efficiency can be further improved.

In this third embodiment, an example of providing an auxiliary channel on the inlet hole side was explained; however it is also possible to provide the auxiliary channel on the discharge hole side, or on both sides. By removing the pre-processing fluid from the auxiliary channel side during cleaning, it is possible to prevent impurities from adhering again during cleaning.

The electrophoresis apparatus of the embodiments is not limited to the examples given above. The detailed design of the construction of the electrophoresis apparatus of the present invention can undergo various changes. For example, the design of the flow channel or the number of storage tanks, the positions of each of the features, the shapes of the features, and the like can be designed to correspond to the usage.

Moreover, in the embodiments above, for convenience of explanation, the number suction pumps used was one; however, a suction pump can be provided on both the inlet side and discharge side of the capillary flow channel of the microchip. Also, an auxiliary channel can be connected to the reservoirs on both ends of the capillary flow channel, and can be arbitrarily set.

The number of capillary channels is not limited to one and could be more than one. The construction of the capillary flow channel is not limited to a so-called straight form, and could, for example, be a cross-junction type in which two flow channels cross.

Analysis is performed using a capillary electrophoresis method, and for the data to be detected, data for a chromatogram can be analyzed as an electropherogram, and data for the dissolution time can be analyzed as the movement time, and the calculated parameter can be used as indices. The measurement object of the electropherogram is a reference specimen and proximate specimen, and cleaning and replacement of the microchip can be managed according to the parameters obtained by acquiring this electropherogram. Peak identification calculation such as fitting calculation can be used for the calculation, and the peak separation, retention time or half value width can be used as indices.

Furthermore, a cleaning unit provided in the electrophoresis apparatus for cleaning the capillary flow channel, as shown in Embodiments 1 to 3, is not limited to a unit that reserves the cleaning solution and fills the capillary flow channel with the cleaning solution according to the output of the cleaning signal. For example, a cleaning unit that is capable of filling the capillary flow channel with tap water may be provided in the electrophoresis apparatus. In this case, the cleaning unit fills the capillary flow channel with tap water according to the output of the cleaning signal to clean the capillary flow channel.

In addition, the following construction is included as preferred forms of the present invention.

The electrophoresis apparatus of a first aspect of the present invention is preferably characterized by comprising:

a physical quantity acquisition unit ( 71 ) that acquires an electrical quantity amount at the time that voltage applied to electrodes is started.

The electrophoresis apparatus is preferably characterized by further comprising:

a cleaning determination unit ( 74 ) that, when it is determined that the electrical quantity is not within a specified range by the physical quantity determination unit ( 72 ), outputs a cleaning signal in order to clean the capillary flow channel ( 47 , 99 ).

The electrophoresis apparatus is preferably characterized by further comprising:

a replacement unit ( 75 ) that outputs a replacement signal for replacing a component of the capillary flow channel ( 47 , 99 ); wherein the physical quantity acquisition unit ( 71 ) acquires the electrical quantity at every specified time when voltage is applied to the electrodes ( 21 , 22 , 86 , 87 );

the physical quantity determination unit ( 72 ) determines whether or not the electrical quantity is within the specified range every time the electrical quantity is acquired by the physical acquisition unit ( 71 );

the cleaning determination unit ( 74 ) outputs the cleaning signal every times the physical quantity determination unit ( 72 ) determines that the electrical quantity is not within the specified range; and

the replacement unit ( 75 ) outputs the replacement signal without the cleaning signal being outputted, when the number of times that the physical quantity determination unit ( 72 ) continuously determined that the electrical quantity was not within the specified range has reached a first specified number of times.

The electrophoresis apparatus is preferably characterized by further comprising:

a memory unit ( 73 ) that stores the electrical quantity that the physical quantity acquisition unit ( 71 ) acquires; and

a temperature adjustment unit ( 76 ) that outputs a temperature adjustment signal in order to adjust the temperature of the components of the capillary flow channel ( 47 , 99 ); wherein the physical quantity acquisition unit ( 71 ) acquires at specified time intervals an electrical quantity that occurs in the capillary flow channel ( 47 , 99 ) while voltage is being applied to the electrodes ( 21 , 22 , 86 , 87 );

the physical quantity determination unit ( 72 ), every time the physical quantity acquisition unit ( 71 ) acquires the electrical quantity, calculates the difference between that electrical quantity and the electrical quantity that is stored in the past in the memory unit ( 73 ), and determines whether or not that difference exceeds a specified value; and

the temperature adjustment unit ( 76 ) outputs a temperature adjustment signal when the physical quantity determination unit ( 72 ) determines that the difference exceeds the specified value.

The electrophoresis apparatus is preferably characterized by further comprising:

a replacement unit ( 75 ) that outputs a replacement signal for replacing a component of the capillary flow channel ( 47 , 99 ); wherein

the temperature adjustment unit ( 76 ) outputs a temperature adjustment signal every time the physical quantity determination unit ( 72 ) determines that the difference between the electrical quantities exceeds a specified value; and

the replacement unit ( 75 ) outputs the replacement signal without a temperature adjustment signal being outputted when the number of times that the physical quantity determination unit ( 72 ) determined that the difference between the electrical quantities exceeded the specified value reaches a second specified number of times.

The electrophoresis apparatus is preferably characterized by further comprising:

a memory unit ( 73 ) that stores the electrical quantity that the physical quantity acquisition unit ( 71 ) acquires; and

a voltage change unit ( 77 ) that changes the size of the voltage that is applied to the electrodes ( 21 , 22 , 86 , 87 ); wherein

the physical quantity acquisition unit ( 71 ) acquires at specified time intervals an electrical quantity that occurs in the capillary flow channel ( 47 , 99 ) while voltage is being applied to the electrodes;

the physical quantity determination unit ( 72 ), every time the physical quantity acquisition unit ( 71 ) acquires the electrical quantity, calculates the difference between that electrical quantity and the electrical quantity that is stored in the past in the memory unit ( 73 ), and determines whether or not that difference exceeds a specified value; and

the voltage change unit ( 77 ) calculates a correction value for the voltage applied to the electrodes ( 21 , 22 , 86 , 87 ) and changes the size of the voltage applied to the electrodes ( 21 , 22 , 86 , 87 ) to the correction value when the physical quantity determination unit ( 72 ) determines that the difference exceeds the specified value.

The voltage change unit ( 77 ) is preferably characterized by calculating the correction value based on the electrical quantity whose difference with the electrical quantity that is stored in the past does not exceed the specified value.

The voltage change unit ( 77 ) is preferably characterized by calculating the correction value based on a preset target value for the electrical quantity.

The electrophoresis apparatus is preferably characterized by further comprising:

a replacement unit ( 75 ) that outputs a replacement signal for replacing a component of the capillary flow channel ( 47 , 99 ); wherein

the voltage change unit ( 77 ) changes the voltage applied to the electrodes ( 21 , 22 , 86 , 87 ) every time the physical quantity determination unit ( 72 ) determines that the difference between electrical quantities exceeds a specified value; and

the replacement unit ( 75 ) outputs the replacement signal without the voltage applied to the electrodes ( 21 , 22 , 86 , 87 ) being changed when the number of times that the physical quantity determination unit ( 72 ) has determined that the difference in electrical quantities has exceeded the specified value has reached a second specified number of times.

The electrophoresis apparatus is preferably characterized by further comprising:

a voltage value calculation unit ( 78 ) that calculates the value of the voltage to be applied to the electrodes the next time based on the electrical quantity stored in the memory unit ( 73 ); wherein

the electrophoresis apparatus ( 1 , 80 , 140 , 150 ) applies the voltage calculated by the voltage calculation unit ( 78 ) to the electrodes ( 21 , 22 , 86 , 87 ).

The electrophoresis apparatus is preferably characterized in that the electrical quantity is the electric current that flows between the electrodes ( 21 , 22 , 86 , 87 ) according to the voltage that is applied to the electrodes ( 21 , 22 , 86 , 87 ).

The electrophoresis apparatus is characterized by preferably further comprising:

a microchip ( 85 , 141 , 151 ) that has the capillary flow channel ( 99 ), and reservoirs (R 1 , R 2 ) that connect to the ends of the capillary flow channel ( 99 ) and that can store solution;

a dispensing unit ( 84 ) that dispenses solution to the capillary flow channel ( 99 ); and

a suction unit that applies suction to the solution inside the reservoirs (R 1 , R 2 ) and inside the capillary flow channel ( 99 ) from outside of the reservoirs (R 1 , R 2 ).

The electrophoresis apparatus is preferably characterized in that the dispensing unit ( 84 ) also functions as the suction unit that applies suction to the solution inside the reservoirs (R 1 , R 2 ) and inside the capillary flow channel ( 99 ).

The electrophoresis apparatus is preferably characterized by comprising:

an auxiliary channel ( 120 ) that connects to the capillary flow channel ( 99 ) via the reservoir (R 1 ), and is a different channel than the capillary flow channel ( 99 );

a sealing unit ( 130 ) that seals the reservoir (R 1 ), which connects to the auxiliary channel ( 120 ), from outside; and

a second suction unit ( 131 ) that applies suction to the solution inside the reservoir (R 1 ) and inside the capillary flow channel ( 99 ) from the other end section of the auxiliary channel ( 120 ).

The control method for an electrophoresis apparatus of a second aspect of the present invention is preferably characterized in that:

a microchip ( 85 , 141 , 151 ) having the capillary flow channel ( 99 ), and reservoirs (R 1 , R 2 ) that are connected to the ends of the capillary flow channel ( 99 ) and that are capable of storing solution are provided in the electrophoresis apparatus ( 80 , 140 , 150 ), and the control method comprises:

a cleaning process that includes at least one time each of a filling process that fills the reservoirs (R 1 , R 2 ) and the capillary flow channel ( 99 ) with pre-processing fluid, and a discharge process that applies suction from the outside of the reservoir (R 1 ) on one of the ends of the capillary flow channel ( 99 ) to the pre-processing fluid that was filled in the reservoirs (R 1 , R 2 ) and capillary flow channel ( 99 ) and removes the pre-processing fluid from the reservoirs (R 1 , R 2 ) and capillary flow channel ( 99 );

a dispensing process of filling buffer solution into the capillary flow channel ( 99 ) and dispensing the specimen that is the object of measurement into the capillary flow channel ( 99 );

a process of applying voltage to both ends of the capillary flow channel ( 99 ) and performing electrophoresis; and

a process of detecting the measurement results of electrophoresis.

The control method for the electrophoresis apparatus is preferably characterized in that in the discharge process the dispensing unit ( 84 ), which is used when dispensing the specimen in the dispensing process, applies suction to the pre-processing fluid from the outside of the reservoir (R 1 ) on the side where the specimen is dispensed.

The control method for the electrophoresis apparatus is preferably characterized in that the discharge process seals the reservoir (R 1 ) from the outside, and applies suction to the pre-processing fluid inside the capillary flow channel ( 99 ) from the outside on the far end from the capillary flow channel ( 99 ) of an auxiliary channel ( 120 ) that is a flow channel that is different from the capillary flow channel ( 99 ) and that connects to the capillary flow channel ( 99 ) via the reservoir (R 1 ).

Having described and illustrated the principles of this application by reference to one or more preferred embodiments, it should be apparent that the preferred embodiments may be modified in arrangement and detail without departing from the principles disclosed herein and that it is intended that the application be construed as including all such modifications and variations insofar as they come within the spirit and scope of the subject matter disclosed herein.