Sample analyzing apparatus

Provided is a sample analyzing apparatus with which multiple analyses can be performed at the same time in a rapid and accurate manner using a small quantity of a liquid to be measured. This biochemical analyzing apparatus (50) is provided with a chip holder (53) into which an analysis chip (10) can be installed, a chip holder rotation unit (54) for rotating the chip holder (53), a pipetting unit (90) for injecting a candidate liquid into injection ports (22) in the analysis chip (10), and a measurement unit (80) capable of collectively measuring the respective reactions of the candidate liquid and multiple types of antigens (30). The chip holder (53) is rotated by the chip holder rotation unit (54), and injection of the candidate liquid is performed by the pipetting unit (90).

TECHNICAL FIELD

The present invention relates to a sample analysis device used for analyzing target liquid.

BACKGROUND ART

Some sample analysis devices conventionally known analyze liquid itself. Other sample analysis devices conventionally known analyze target liquid prepared by dispersing or dissolving an analysis target, for example, with at least one or more reactants to react with the target liquid being stored in a plurality of storage parts of one reaction container. Patent document 1 discloses a container of this type. The reaction container disclosed in patent document 1 is configured integrally with a plurality of storage parts opened at the upper surface of a substrate and allowing storage of a reagent. Further, at least two of the storage parts are formed independently and configured so as to be capable of communicating with each other.

A sample analysis device requires a constant amount of target liquid for analysis. Meanwhile, if the target liquid is body fluid or blood, etc. to be taken from a living being including a human body, it is preferable that the target liquid be as little as possible in consideration of a burden on a biological body. According to an existing method of conducting analysis using a small amount of target liquid, reaction between a reactant and the target liquid is measured using a micro-flow path into which the target liquid is introduced by means of capillary action. Patent documents 2 and 3 disclose a method or a device using such a micro-flow path. Patent document 2 discloses a nozzle cartridge functioning as a container storing a reagent or an analyte. This nozzle cartridge includes a storage part for a reagent or an analyte, a discharge nozzle, and a flow path through which the reagent or the analyte stored in the storage part is supplied to the discharge nozzle. Patent document 3 discloses a micro chemical chip formed of a first substrate having a sample inlet, a second substrate having a sample flow path, and a third substrate having a sample outlet. The sample inlet is formed as a hole penetrating the first substrate from front to back. The sample flow path is formed as a slit penetrating the second substrate from front to back. The sample outlet is formed as a hole penetrating the third substrate from front to back. The second substrate is arranged between the first and third substrates. The sample inlet and the sample outlet communicate with each other through the sample flow path. The sample flow path is opened on at least one end thereof.

A sample analysis device is required to pipette target liquid into an analysis chip. Patent documents 4 and 5 disclose mechanisms of pipetting of this type. Patent document 4 discloses a pipetting device that discharges liquid into the inside of a well having an opening at one end and allowing storage of liquid therein. The well is formed in a microchip in which a micro-flow path communicating with an opposite end of the well is formed. The well has a well bottom formed of an annular stepped part projecting inwardly toward the opposite end. This pipetting device includes: a pipetting nozzle with a tip opening and a rear end to which a pipe is connected, the pipetting nozzle sucking and discharging liquid through the tip opening; movement means that moves pump means and the pipetting nozzle relative to each other at least in the depth direction of the well, the pump means being connected to the pipe and supplying suction pressure and discharge pressure to the pipetting nozzle; and control means that makes the movement means move the pipetting nozzle until the tip opening is located at the well bottom and then discharges liquid first through the tip opening while making the tip opening contact the bottom surface and/or inner peripheral surface of the well bottom. Patent document 5 discloses a method of pipetting a minute amount of liquid into a container through a pipette. According to this method, a given amount of the liquid is dripped into the container while abutting contact is made between the tip of the pipette and a peripheral wall inside the container.

Patent Document 3: PCT International Publication No. WO2012/001972

DISCLOSURE OF THE INVENTION

Problems to be Solved by the Invention

For measuring a plurality of components in target liquid, reactants corresponding to these components should be stored in a container. In this regard, the configurations disclosed in patent documents 2 and 3 are expected to achieve the effect of restricting the amount of target liquid. However, these configurations still find it difficult to analyze items such as tens of types of items by one measurement.

It is preferable that, if an analysis chip with a micro-flow path to be used has a configuration where a plurality of micro-flow paths is connected to an injection port, liquid be introduced uniformly into all of these micro-flow paths. If the aforementioned method of using an analysis chip with a micro-flow path employs the ELISA (enzyme linked immunosorbent assay) process, for example, target liquid should be injected several times into the micro-flow path during the course of measurement for example of a reaction result. Injecting target liquid several times accurately and rapidly leads to reduction in measurement time. However, further improvement has still been desired for a conventional sample analysis device such as those disclosed in patent documents 4 and 5 in terms of introducing liquid uniformly and rapidly into micro-flow paths.

The present invention is intended to provide a sample analysis device capable of conducting analysis of a plurality of items rapidly and accurately using a small amount of liquid as a measurement target.

Means for Solving the Problems

The present invention relates to a sample analysis device comprising: a chip holder that allows installation of an analysis chip on the chip holder, the analysis chip comprising a substrate, an injection port formed at the substrate and through which target liquid as a measurement target is injected, and a flow path connected to the injection port and allowing introduction of the target liquid into the flow path by means of capillary action, a plurality of reactants capable of selectively reacting with a component in the target liquid being fixed to the flow path; a chip holder rotation mechanism that rotates the chip holder; a pipetting mechanism that injects the target liquid into the injection port of the analysis chip; and a measurement device that allows measurement of reactions between the target liquid and the plurality of reactants, wherein the pipetting mechanism injects the target liquid while the chip holder rotation mechanism rotates the chip holder.

Preferably, the pipetting mechanism has a tip portion of a tapered shape, and the pipetting mechanism injects the target liquid with the tip portion being inserted into the injection port.

Preferably, the injection port of the analysis chip is formed at the center of the substrate.

Preferably, the flow path of the analysis chip includes a plurality of flow paths arranged in a radial pattern to extend from the injection port to an outer edge of the substrate, and the plurality of reactants capable of selectively reacting with a component in the target liquid is fixed to each of the flow paths.

Preferably, the analysis chip is formed in such a manner that the flow path surrounds the injection port.

Preferably, the sample analysis device further comprises an air injection mechanism that injects air into the injection port of the analysis chip.

Preferably, the air injection mechanism injects air into the analysis chip while the chip holder is rotated.

Preferably, the analysis chip further comprises a housing in which the substrate is arranged and housed, and the housing includes: an opening part where an upper surface of the substrate is exposed at least partially; liquid trapping space provided inside the housing and on an outer peripheral side of the substrate; and a communication opening formed around the opening part and between the upper surface of the substrate and the housing.

Preferably, the communication opening is arranged inwardly in a radial direction from the outer periphery of the substrate.

Effects of the Invention

Analysis of a plurality of items about liquid as a measurement target can be conducted rapidly and accurately by the sample analysis device according to the present invention.

PREFERRED MODE FOR CARRYING OUT THE INVENTION

A preferred embodiment of a biochemical analysis device as a sample analysis device of the present invention and a preferred embodiment of an analysis chip of the present invention are described below by referring to the drawings.

In this embodiment, a biochemical analysis device50that determines an allergy of an analyte as target liquid by means of chemiluminescence resulting from antigen-antibody reaction by employing the ELISA process and an analysis chip10used in the biochemical analysis device50are described as an example of a sample analysis device and an example of an analysis chip of the present invention respectively.

The analysis chip10of this embodiment is described.FIG. 1is a perspective view of the analysis chip10according to the embodiment of the present invention.FIG. 2is a perspective view illustrating the configuration of the analysis chip10.FIG. 3is a plan view of the analysis chip10.FIG. 4is a sectional view taken along a line A-A ofFIG. 3.FIG. 5illustrates a part B (an area surrounded by a dashed line ofFIG. 1) in an enlarged manner.FIG. 6is a plan view of a substrate schematically illustrating an antigen30as a reactant fixed to a micro-flow path23.FIG. 7is an enlarged view schematically illustrating antigens30as reactants adjacent to each other in the micro-flow path23.

As illustrated inFIG. 1, the analysis chip10of this embodiment has an outer shape formed into a substantially disc shape. As illustrated inFIGS. 2 to 4, the analysis chip10includes a substrate20, a film14, a lower housing12, an upper housing13, an absorber15, liquid trapping space16, and an air communication opening17.

The substrate20is formed into a substantially disc shape using a light-transmitting material such as cyclic polyolefin. As illustrated inFIG. 6, the antigen30to specifically react with a target substance contained in an analyte (target liquid) as a measurement target is fixed to the substrate20.

The substrate20of this embodiment includes an injection port22and a micro-flow path23. The antigen30as a reactant is fixed to the substrate20.

The substrate20is formed into a disc shape. The configuration of the substrate20is described. The substrate20has a through hole to become the injection port22. The substrate20has a lower surface provided with a plurality of slits equiangularly spaced in a radial pattern with respect to the injection port22. Each of these slits has one end portion connected to the injection port22and an opposite end portion connected to an opening part at an outer edge surface of the substrate20. The antigen30is fixed to the bottom surface of each slit. The film14described later is attached to a surface of the substrate20provided with the slit. In this way, in this embodiment, the slit formed in the substrate20is closed by the film14and the slit in the substrate20and the film14form the micro-flow path23.

The injection port22is used for introducing target liquid such as an analyte or a reagent solution into the micro-flow path23. The injection port22is located at a substantially central position of the substrate20formed into a substantially disc shape. The injection port22communicates with each of a plurality of micro-flow paths23inside the substrate20.

The micro-flow path23is a capillary having one end communicating with the injection port22inside the substrate20and an opposite end penetrating the substrate20to reach as far as an outer edge of the substrate20in a radial direction. As illustrated inFIG. 6, the micro-flow path23includes a plurality of micro-flow paths23extending from the injection port22and being equiangularly spaced in a radial pattern. The substrate20of this embodiment includes eight micro-flow paths23.

The micro-flow path23is configured in such a manner that liquid is introduced into space inside the micro-flow path23by means of capillary action. For example, in this embodiment, based on the viscosity of a blood analyte as target liquid and a result of verification, the micro-flow path23is set to have a width of 0.1 mm or more and 3 mm or less and a height of 0.1 mm or more and 0.5 mm or less.

As described above, the antigen30is fixed to the inner wall of the micro-flow path23. The antigen30includes a plurality of antigens30fixed so as to be aligned linearly in a lengthwise direction of each micro-flow path23. As illustrated inFIG. 6, the antigens30are each fixed in the form of a spot having a diameter smaller than a width between wall surfaces of the micro-flow path23. The antigens30fixed to the wall surfaces of the micro-flow path23do not extend over the wall surfaces entirely but they exist as spots on the wall surfaces. By doing so, an area occupied by the fixed antigens30can be controlled at a minimum required area. This reduces the probability of contamination or reaction nonuniformity to occur if a large area is occupied by the fixed antigens30. During measurement of light-emitting reaction described later, fixing the antigens30in the form of small-diameter spots as in this embodiment also effectively reduces the probability of interference between light beams resulting from light-emitting reactions generated in adjacent micro-flow paths23, compared to fixing antigens to the entire region of the micro-flow path23. In this embodiment, as will also be described later, a camera unit83captures an image of an antigen30from above where light-emitting reaction is generated, thereby acquiring image information. Thus, light-emitting reaction at one antigen30in the form of a small-diameter spot30should be assured in a sufficient condition with in-plane uniformity for distinguishing this antigen30from a different light-emitting antigen30and preventing interference between light beams from these antigens30. For this purpose, to direct light resulting from light-emitting reaction and to travel toward an image-capturing element mainly in a direction substantially perpendicular to the micro-flow path23, the upper surface of the antigen30in the form of a spot is formed as a substantially smooth surface. This is achieved by controlling the antigen30in terms of its viscosity, etc. or forming the antigen30by pressing into a smooth shape with a tool such as a stamp, for example.

The antigens30are arranged at given intervals. As illustrated inFIG. 7, a distance d between adjacent antigens30is set in such a manner that light beams emitted from antigens30in adjacent positions do not interfere with each other during measurement of light-emitting reaction. In this embodiment, the adjacent antigens30should be formed at positions separated from each other by the distance d that is 60% or more of the diameter of an antigen30having a smallest diameter of those of the antigens30fixed to the micro-flow path23.

The antigens30are various types of allergens to specifically react with a selected component (target substance) in an analyte. In this embodiment, eight micro-flow paths23are formed in the substrate20. Five antigens30are aligned substantially linearly while being separated by the aforementioned given distance d in each of the micro-flow paths23. To reliably measure reactions of a plurality of antigens30fixed to the substrate20, antigens of the same type may be arranged at a plurality of micro-flow paths or at different positions. Alternatively, antigens of types different from each other may be used. In this case, many pieces of analysis information can be acquired collectively.

The substrate20of this embodiment has the aforementioned configuration. The configuration of the substrate20is not limited to the aforementioned configuration but can be changed, if appropriate, in a manner that depends on the purpose of the substrate20. For example, the number of the micro-flow paths23may be changed or the micro-flow paths23may be arranged at unequal angles. Further, the antigen30is described as an example of a reactant fixed to the substrate20. Alternatively, an antibody may be fixed.

The film14is formed into a substantially circular thin-film shape and attached to the lower surface of the substrate20as described above. The substrate20is arranged over the upper surface of the lower housing12through the film14.

The lower housing12is arranged on a lower surface (one surface) side of the substrate20and formed into a substantially circular shape having an outer periphery of a larger diameter than the substrate20. The lower housing12is provided with a wall part extending along the outer periphery of the lower housing12to form a lower part of the peripheral surface of the analysis chip10.

The upper housing13is arranged on an upper surface (opposite surface) side of the substrate20. The upper housing13is formed into a substantially ring-like shape having an outer periphery of a larger diameter than the substrate20. The upper housing13has an opening part18formed at the center of the upper housing13and having a circular shape of a smaller diameter than the substrate20. The upper housing13is provided with a wall part extending along the outer periphery of the upper housing13to form an upper part of the peripheral surface of the analysis chip10. A housing of the analysis chip10of this embodiment is formed of the lower housing12and the upper housing13.

The absorber15is formed of a member having moisture-retaining properties. The absorber15is formed into a ring-like shape of a smaller diameter than the lower housing12and the upper housing13and arranged in the liquid trapping space16. Liquid having been discharged from the micro-flow path23is absorbed by the absorber15. In the case of biochemical analysis, for example, discharge of liquid targeted for analysis from an analysis device to the outside of a system should strictly be avoided. For this reason, the absorber15is provided along the outer periphery of the substrate20.

As illustrated inFIG. 4, the liquid trapping space16is defined by the lower housing12and the upper housing13into ring-like space surrounding the outer periphery of the substrate20. An opening part of the micro-flow path23on an outer edge side formed in the peripheral surface of the substrate20is opened to the liquid trapping space16. Thus, as will be described later, target liquid discharged from the opening part of the micro-flow path23is discharged to the liquid trapping space16. The target liquid having been discharged to the liquid trapping space16is absorbed by the absorber15arranged in the liquid trapping space16. Further, the discharged target liquid achieves the action of moisturizing the liquid trapping space16and the micro-flow path23in the substrate20.

As illustrated inFIG. 5, the air communication opening17is defined at an inner opening wall of the upper housing13by the upper surface of the substrate20and the upper housing13. The air communication opening17includes a plurality of air communication openings17arranged at substantially regular intervals. As illustrated inFIG. 3, in the radial direction of the substrate20, the air communication opening17is formed slightly inwardly from an opening of the micro-flow path23provided at the outer edge of the substrate20and close to the liquid trapping space16. By the presence of the air communication opening17, the injection port22of the substrate20and external space communicate with each other through the micro-flow path23. Thus, air having been injected through the injection port22by an air nozzle unit100in an air injecting process described later is discharged from the air communication opening17to external space through the micro-flow path23. In the radial direction of the substrate20, the air communication opening17is arranged inwardly from the opening as a liquid discharge opening of the micro-flow path23close to the liquid trapping space16. This prevents liquid discharged from the micro-flow path23from being discharged to the outside of the system of the analysis chip10through the air communication opening17.

The analysis chip10of this embodiment has the aforementioned configuration. The following description is about the biochemical analysis device50that analyzes target liquid using the analysis chip10of this embodiment.FIG. 8is a perspective view of the biochemical analysis device50according to the embodiment of the present invention.FIG. 9is a perspective view illustrating the inside of the biochemical analysis device50in outline.FIG. 10is a plan view illustrating the inside of the biochemical analysis device50in outline.FIG. 11is a plan view of a chip holder53illustrating a state where a pipetting unit90is injecting target liquid into the analysis chip10.FIG. 12is a block diagram schematically illustrating a relationship between a control unit110and each structure.FIG. 13illustrates an example of analysis image information acquired by a measurement unit80.

As illustrated fromFIGS. 8 to 12, the biochemical analysis device50includes a housing51, a touch panel52, a chip holder rotation unit54, the measurement unit80, the pipetting unit90, the air nozzle unit100, a reagent holder unit58, and the control unit110.

The housing51houses each structure of the biochemical analysis device50and separates internal mechanisms for analysis and external space. The housing51is provided with a door55.

The touch panel52functions both as operation means and display means of the biochemical analysis device50. The touch panel52is used for making various settings and performing various operations, and for displaying a measurement result and an analysis result, for example.

The chip holder rotation unit54rotates the analysis chip10. In this embodiment, an injecting process of injecting target liquid into the analysis chip10and a discharging process for liquid having been introduced into the micro-flow path23are performed by making the chip holder rotation unit54rotate the analysis chip10. The configuration of the chip holder rotation unit54is described below.

The chip holder rotation unit54of this embodiment includes the chip holder53, a chip holder drive motor, a temperature adjustment unit, and a temperature sensor.

The chip holder53is installed at an upper part of the chip holder rotation unit54. The chip holder53includes a fitting part531to make a fit with the analysis chip10. The fitting part531is formed at the upper surface of the chip holder53and functions as a frame part to contact a portion of the peripheral surface of the analysis chip10. As illustrated inFIG. 11, with the analysis chip10placed at the chip holder53, the fitting part531holds a portion of the outer periphery of the analysis chip10to prevent falling off of the analysis chip10from the chip holder53to be caused by centrifugal force.

The fitting part531is configured to make a fit with the analysis chip10in such a manner that the center of the injection port22of the analysis chip10and the center of rotation of the chip holder53substantially agree with each other. The analysis chip10is configured to be placed in a substantially horizontal posture while being installed at the chip holder53.

The analysis chip10and the fitting part531can also be configured as follows. An analysis chip fitting part with a protrusion, a recess, or a protrusion and a recess is formed at the lower surface of the analysis chip10(lower surface of the lower housing12). Then, a shape conforming to the shape of the analysis chip fitting part is formed at a surface of the fitting part531to contact the lower surface of the analysis chip10. This can make a fit between the analysis chip10and the fitting part531more reliably, while making it possible to adjust the rotation speed of the analysis chip10more properly. Additionally, as a result of increase in the area of contact between the analysis chip10and the fitting part531, heat of the analysis chip10can be adjusted more easily by the temperature adjustment unit through the chip holder53in an incubation process described later, thereby achieving efficient temperature adjustment. In consideration of expansion or compression of the chip holder53by heat during incubation, the shapes formed at the analysis chip fitting part and the fitting part531may be shapes that can be detached from each other easily such as a mountain shape and a valley shape, teeth-like shapes, conical shapes, or corrugated shapes, for example.

The chip holder drive motor is arranged inside the chip holder rotation unit54and has a drive shaft coupled to the rotary shaft of the chip holder53(not illustrated in the drawings). The chip holder drive motor is configured to rotate at a frequency that can be adjusted at any value. The chip holder rotation unit54is electrically connected to the control unit110. Based on a signal from the control unit110, the chip holder rotation unit54adjusts the rotation frequency of the chip holder drive motor to rotate the chip holder53at a given speed. In this embodiment, the chip holder53is configured to rotate at a speed that can be switched between an injection rotation speed described later and a liquid discharge speed described later.

The injection rotation speed is a rotation speed of the chip holder53employed when the pipetting unit90injects liquid into the injection port22of the analysis chip10.

The liquid discharge speed is a rotation speed employed when liquid having been introduced into the micro-flow path23of the analysis chip10is discharged from the micro-flow path23to the liquid trapping space16. To discharge liquid from the micro-flow path23by means of centrifugal force, the liquid discharge speed of this embodiment is set so as to rotate the chip holder53at a speed higher than the injection rotation speed that does not cause discharge of liquid having been introduced into the micro-flow path23.

The temperature adjustment unit is arranged inside the chip holder rotation unit54and configured to achieve temperature adjustment of the analysis chip10installed at the chip holder53(not illustrated in the drawings). By the presence of the temperature adjustment unit, pre-incubation and incubation for generating reaction between the antigen30and target liquid proceed properly.

The temperature sensor is arranged inside the chip holder rotation unit54(not illustrated in the drawings). Temperature information acquired by the temperature sensor is transmitted to the control unit110. The control unit110is configured in such a manner that the control unit110can adjust warming by the temperature adjustment unit based on the acquired temperature information.

The measurement unit80is described next. The measurement unit80measures light-emitting reaction. The measurement unit80includes a dark box81, a chip holder movement mechanism82, the camera unit83, and an LED unit.

The dark box81is configured as a hermetically-sealed rectangular parallelepiped. The dark box81functions as a dark box for shielding light from the outside of the system during measurement and as a temperature adjusting chamber for heat retention during pre-incubation and incubation. The dark box81has an opening part at one side surface.

The chip holder movement mechanism82includes drive means (not illustrated in the drawings) arranged at the opening part of the dark box81and used for moving the chip holder rotation unit54. The chip holder movement mechanism82allows the chip holder rotation unit54to move between a liquid injection position, an air injection position, and a measurement position.

The liquid injection position of the chip holder rotation unit54is a position employed when the pipetting unit90injects liquid into the analysis chip10. The chip holder rotation unit54at the liquid injection position is arranged outside the dark box81(in the state ofFIGS. 9 and 10). The air injection position of the chip holder rotation unit54is a position employed when the air nozzle unit100injects air into the analysis chip10.

The measurement position of the chip holder rotation unit54is a position employed when the measurement unit80measures the analysis chip10inside the dark box81. The measurement position is such that the opening part of the dark box81is closed in response to movement of the chip holder rotation unit54to hermetically seal the dark box81.

The camera unit83is arranged above the dark box81. The camera unit83is a measurement unit (image capturing unit) to capture an image of the analysis chip10from above at the measurement position. Various determinations are made based on image information resulting from image capturing by the camera unit83. The exposure time of the camera unit83of this embodiment is adjusted based on an experimental result, etc., so as to allow detection of emission of very weak light. A member for reducing influence of reflected light such as a polarizing plate may be arranged inside the dark box81.

The measurement unit80makes the camera unit83capture an image of the analysis chip10at the measurement position where light-emitting reaction is generated, thereby acquiring image information as measurement information. As illustrated inFIG. 13, the camera unit83acquires information about an image with a resolution by which the position of light-emitting reaction can be identified clearly. The camera unit83includes the LED unit.

The LED unit is an illumination device for illuminating the inside of the dark box81during image capturing by the camera unit83.

The measurement unit80is electrically connected to the control unit110. The chip holder movement mechanism82, the camera unit83, the LED unit, and the temperature sensor of the measurement unit80are configured in such a manner as to allow transmission and receipt of various signals to and from the control unit110. Based on a signal from the control unit110, the measurement unit80drives the drive means of the chip holder movement mechanism82so as to move the chip holder rotation unit54to the liquid injection position, the air injection position, or the measurement position. A signal from the control unit110is also used for making the camera unit83capture an image or for control over luminosity adjustment by the LED unit, etc.

The pipetting unit90is described next. The pipetting unit90pipettes liquid (target liquid) into the injection port22of the analysis chip10placed at the chip holder53. Liquid to be injected into the analysis chip10by the pipetting unit90includes a blocking solution, an analyte, a cleaning liquid, and a luminescent substrate, for example.

The pipetting unit90includes a pipetting casing91, a pipetting nozzle92, a pipetting nozzle movement mechanism93, and a pipetting unit movement mechanism94.

A detachable pipette chip95is attached to the pipetting nozzle92. Liquid is pipetted into the analysis chip10using the pipette chip95as a tip portion of the pipetting nozzle92. The pipetting nozzle movement mechanism93moves the pipetting nozzle92in a vertical direction. The pipetting unit movement mechanism94moves the pipetting unit90. The pipetting unit90can be moved in a horizontal direction by the pipetting unit movement mechanism94. The pipetting unit90can move between a liquid injection position illustrated inFIG. 11where the pipetting unit90is close to the chip holder53, and a standby position illustrated inFIG. 10where the pipetting unit90is separated from the chip holder53.

The pipetting unit90moves the pipetting nozzle92between a pipette chip attachment position, a pipette chip detachment position, the standby position, and the liquid injection position by using the pipetting nozzle movement mechanism93and the pipetting unit movement mechanism94. In the pipetting unit90, based on a signal from the control unit110, drive means of each of the pipetting nozzle movement mechanism93and the pipetting unit movement mechanism94is driven so as to move the pipetting nozzle92to the liquid injection position, the pipette chip attachment position, the pipette chip detachment position, or the standby position.

The pipette chip attachment position of the pipetting unit90is a position employed for attaching an unused pipette chip95to be placed in the reagent holder unit58described later. The pipette chip detachment position of the pipetting unit90is a position employed when a used pipette chip95is detached from the pipetting nozzle92by a pipette chip detachment mechanism (not illustrated in the drawings) of the reagent holder unit58. The standby position is the position of the pipetting nozzle92employed while the pipetting unit90is moving. The standby position is higher than any of the liquid injection position, the pipette chip attachment position, and the pipette chip detachment position. The pipetting nozzle92is at the standby position while the pipetting unit90is moving to cause no interference with movement of the pipetting nozzle92.

The liquid injection position of the pipetting unit90is a position employed for injection of liquid into the analysis chip10. The liquid injection position of this embodiment is set in such a manner that the tip of the pipette chip95installed at the tip of the pipetting nozzle92substantially agrees with the center of rotation of the chip holder53in a plan view.

The liquid injection position of this embodiment is set in such a manner that the tip of the pipette chip95is placed at a position below the upper surface of the substrate20and not contacting the bottom surface of the injection port22.

An injecting process at the liquid injection position is performed while the chip holder53rotates at the injection rotation speed. The pipetting unit90injects liquid into the analysis chip10continuously at a constant speed or in stages. The tip of the pipette chip95is placed below the upper surface of the substrate20. This prevents flying-off of liquid over the upper surface of the substrate20or blockage of the injection port22with droplets of target liquid. As a result, the target liquid of a minute amount can be introduced rapidly and properly into the micro-flow path23through the injection port22.

As a result of pipetting while rotating the chip holder53, even if a tip portion of the pipette chip95deviates from the center of rotation, distances from the tip portion of the pipette chip95to a plurality of the micro-flow paths23can be substantially equal. Thus, liquid is introduced into these micro-flow paths23with substantially equal probability. This prevents the occurrence of a problem such as failing to introduce liquid properly into some of these micro-flow paths23. This can effectively reduce influence on the injecting process to be exerted by the accuracy of the shape or attachment condition of the tip portion of the pipetting nozzle92, particularly in the case where the tip portion of the pipetting nozzle92is formed of a disposable pipette chip95, for example.

A method of injecting liquid into the analysis chip10using the pipetting unit90can be determined properly in a manner that depends on the amount of the liquid to be injected. For example, to reduce time of the injection, without injecting the liquid in stages, a given amount of the liquid may be injected at a time. Alternatively, a speed of the injection may be changed.

The air nozzle unit100is described next. The air nozzle unit100is for auxiliary discharge of liquid with air to the liquid trapping space16remaining in the micro-flow path23of the analysis chip10without having been discharged only by centrifugal force resulting from rotation. The air nozzle unit100is arranged above the chip holder rotation unit54.

The air nozzle unit100includes an air nozzle101and an air nozzle movement mechanism102. In this embodiment, the air nozzle unit100injects air while the chip holder53is rotated at the liquid discharge speed.

The air nozzle movement mechanism102moves the air nozzle101between an air injection position and a standby position. The air nozzle101is moved between the air injection position and the standby position by the air nozzle movement mechanism102.

The air injection position is a position employed for injection of air into the injection port22of the analysis chip10. A tip portion of the air nozzle101at the air injection position faces the injection port22of the analysis chip10. In this embodiment, the standby position is a position employed when the air nozzle unit100does not inject air. When the air nozzle101is at the standby position, the tip portion of the air nozzle101is placed above the air injection position and does not face the injection port22.

At the air injection position, air is injected while the chip holder53rotates at the liquid discharge speed. Inside the analysis chip10, liquid remaining in the micro-flow path23is discharged to the liquid trapping space16with air injected through the injection port22. Even if liquid remains in the micro-flow path23by means of capillary action, such remaining liquid can reliably be removed from the micro-flow path23with the air injected from the air nozzle unit100. The liquid having been discharged to the liquid trapping space16is absorbed by the absorber15. The air having exited the micro-flow path23passes through the air communication opening17to be discharged to the outside the system of the analysis chip10. As described above, in the analysis chip10, the air communication opening17is arranged inwardly in the radial direction from the exit of the micro-flow path23, as illustrated inFIG. 3. This prevents the liquid discharged from the micro-flow path23from being discharged to the outside of the system of the analysis chip10through the air communication opening17, while allowing discharge of the air to the outside of the system of the analysis chip10.

In this embodiment, air is injected after rotation of the chip holder53is started. By doing so, most of liquid is discharged in advance by centrifugal force from the micro-flow path23and thereafter, air is injected. If liquid is discharged only by means of air injection, discharge of the liquid from a particular micro-flow path23may be finished first. In this case, air may exist intensively only in a discharge channel in this micro-flow path23, thus possibly failing to discharge the liquid from remaining micro-flow paths. Such a problem can be avoided by discharging most of the liquid in advance by means of centrifugal force resulting from rotation of the chip holder53. In this way, according to the configuration of this embodiment, every liquid in the plurality of micro-flow paths23can efficiently be discharged.

The reagent holder unit58is described next. The reagent holder unit58is for installation of a reagent cartridge96and the pipette chip95on the reagent holder unit58.

The reagent cartridge96stores multiple types of target liquid to be injected into the analysis chip10including a blocking solution, an analyte, a luminescent substrate, a cleaning liquid, etc. A plurality of unused pipette chips95is placed in the reagent cartridge96. The reagent holder unit58of this embodiment includes an installation part (not illustrated in the drawings) with which the reagent cartridge96can be attached and detached. The reagent cartridge96is fixed to the installation part.

The pipette chip95is attached to the pipetting nozzle92of the pipetting unit90. The pipette chip95is a disposable chip to be changed for each liquid to be injected. The reagent holder unit58of this embodiment includes a disposal housing part97for housing a used pipette chip95and the pipette chip detachment mechanism (not illustrated in the drawings). The pipette chip detachment mechanism detaches a used pipette chip95from the pipetting nozzle92.

The control unit110is described next. The control unit110is a computer formed of a CPU, a memory as a storage, etc. As illustrated inFIG. 12, the control unit110is electrically connected to the touch panel52, the chip holder rotation unit54, the measurement unit80, the pipetting unit90, the air nozzle unit100, etc. As described above, each unit performs all of or some of its operations in response to a signal from the control unit110. Specifically, a signal from the control unit110is used for controlling a sequence of the biochemical analysis device50, etc. that includes control over rotation speed of the chip holder53, movement of the chip holder rotation unit54, movement of the pipetting unit90and a pipetting process by the pipetting unit90, air injection by the air nozzle unit100, image capturing by the measurement unit80, and warming by the temperature adjustment unit, for example. The control unit110is further responsible for image processing, setting and storage of a test condition, output of analysis data, etc. Exerting control over the measurement unit80by the control unit110includes exerting control over all the structures of the measurement unit80including the camera unit83, the chip holder movement mechanism82, and the LED unit. Additionally, exerting control over the chip holder rotation unit54, the pipetting unit90, the air nozzle unit100, and the reagent holder unit58includes exerting control over the movement mechanism of each of these structures.

In this embodiment, as described above, antigen-antibody reaction is measured based on image information acquired as a result of capturing of an image by the camera unit83about light-emitting reaction generated at the measurement position.

Specificity of reaction with a selected substance is acquired from an antigen30exhibiting this light-emitting reaction in the acquired image information. Information for example about the intensity of the reaction specificity is acquired based on the intensity of the emitted light.

The biochemical analysis device50of this embodiment has the aforementioned configuration. A flow of measurement by the biochemical analysis device50of this embodiment is described next.FIG. 14is a flowchart of measurement and analysis conducted by the biochemical analysis device50according to the embodiment of the present invention.

A user of the biochemical analysis device50is placed the analysis chip10at the chip holder53. Further, the user places the reagent cartridge94storing an analyte, a reagent solution, a cleaning liquid, the pipette chip95, etc. at the reagent holder unit58. Next, the user operates the touch panel52to start measurement at the biochemical analysis device50. In response to receipt of a signal indicating start of the measurement from the touch panel52, the control unit110starts control over sequential steps from blocking solution injection in step S101.

First, the blocking solution injection (S101) is performed to prevent non-specific adsorption of an antibody, etc. to a part in the micro-flow path23other than the antigen30. The blocking solution injection (S101) is performed by making the pipetting unit90inject a blocking solution through the injection port22of the analysis chip10while the chip holder53is rotated at the injection rotation speed. The blocking solution having been injected through the injection port22is introduced into the plurality of micro-flow paths23formed in a radial pattern with respect to the injection port22to extend over the micro-flow paths23entirely by means of the aforementioned capillary action. After the pipette chip95is detached, a pre-incubation process (S102) is performed to fix the injected blocking solution sufficiently to a part in the micro-flow path23other than the antigen30.

The pre-incubation process (S102) is performed with the chip holder53having been moved to the inside of the dark box81functioning as a temperature adjusting chamber. After the pre-incubation process (S102) is performed for a given period of time, the chip holder53is returned to a position outside the dark box81. Then, for analyte injection (S104), a liquid discharging process (S103) is performed to discharge the blocking solution to the outside of the micro-flow path23to release the inside of the micro-flow path23.

The liquid discharging process (S103) is performed by making the chip holder rotation unit54rotate the chip holder53at the liquid discharge speed and making the air nozzle unit100inject air through the injection port22of the analysis chip10.

The micro-flow path23is formed to extend in a direction toward its outer edge from the center of rotation. The remaining blocking solution is moved and discharged to the liquid trapping space16outside the outer edge of the micro-flow path23by centrifugal force, while being discharged further with air substantially reliably to the liquid trapping space16. As described above, even in the micro-flow path23where strong surface tension is generated by capillary action, the liquid discharging process can still be performed rapidly and effectively.

The blocking solution having been discharged from the micro-flow path23is absorbed by the absorber15in the liquid trapping space16. According to the analysis chip10of this embodiment, liquid having been discharged from the micro-flow path23is absorbed by the absorber15provided in the liquid trapping space16. This can reliably prevent discharge of target liquid to the outside of the system of the analysis chip10. The target liquid having been discharged to the liquid trapping space16is absorbed by the absorber15. This prevents the target liquid having been discharged from the micro-flow path23from flowing back into the micro-flow path23, so that subsequent processes are performed properly.

The analyte injection (S104) is performed by injecting an analyte into the analysis chip10while the chip holder53is rotated at the injection rotation speed. Like in the blocking solution injection (S101), the analyte having been injected through the injection port22is introduced uniformly into the plurality of micro-flow paths23by means of capillary action. After the analyte injection (S104), an incubation process (S105) is performed to prompt antigen-antibody reaction between the antigen30and the analyte.

Like the pre-incubation process (S102), the incubation process (S105) is performed with the chip holder53having been moved to the inside of the dark box81functioning as a temperature adjusting chamber. The incubation is performed by making temperature adjustment for a given period of time using the temperature adjustment unit.

The absorber15of the analysis chip10contains the blocking solution already absorbed as a result of the liquid discharging process for the blocking solution (S103), so that the inside of the analysis chip10has already been humidified. This prevents drying of the inside of the micro-flow path23during the incubation (S105). Then, the chip holder53is taken out of the dark box81to proceed to a liquid discharging process for the analyte (S106).

Like the liquid discharging process for the blocking solution (S103), the liquid discharging process for the analyte (S106) is performed by rotating the chip holder53at the liquid discharge speed and making the air nozzle unit100inject air. As a result of this liquid discharging process (S106), the analyte in the micro-flow path23is discharged to the liquid trapping space16and absorbed by the absorber15. After the inside of the micro-flow path23is released by this liquid discharging process for the analyte, a cleaning process (S107) is performed.

Like the blocking solution injection (S101), the cleaning process (S107) is performed by rotating the chip holder53at the injection rotation speed and injecting a cleaning liquid through the injection port22of the analysis chip10and introducing the cleaning liquid into the plurality of micro-flow paths23formed in a radial pattern with respect to the injection port22. Next, like the liquid discharging process for the blocking solution (S103), a liquid discharging process for the cleaning liquid is performed by making the chip holder rotation unit54rotate the chip holder53at the liquid discharge speed and making the air nozzle unit100inject air. By performing the aforementioned cleaning process of injecting and discharging the cleaning liquid, the liquid remaining in the plurality of micro-flow paths23of the substrate20is discharged together with the cleaning liquid. The cleaning liquid is also absorbed by the absorber15provided in the liquid trapping space16. After the cleaning process (S107), labeled antibody injection (S108) of deriving a luminescent substrate by means of enzyme reaction is performed. The luminescent substrate is used for a final process of measuring light emission and to be added to the antigen30where the antigen-antibody reaction is generated by the incubation (S105).

Like the blocking solution injection (S101), the analyte injection (S104), or the cleaning liquid injection (S107), the labeled antibody injection (S108) is performed by injecting a labeled antibody and rotating the chip holder53at the injection rotation speed. Like the incubation (S105) performed to prompt antigen-antibody reaction, incubation (S109) is performed after the injection of the labeled antibody to add the labeled antibody reliably to the antigen30where the antigen-antibody reaction is generated. Next, a liquid discharging process for the labeled antibody (S110) is performed.

A cleaning process for the labeled antibody (S111) is similar to the cleaning process in step S107and is performed by injecting and discharging a cleaning liquid. The cleaning process (S111) including injection and discharge of the cleaning liquid is repeated several times, where necessary, thereby obtaining reliable cleaning effect. After the cleaning process (S111), a process of luminescent substrate injection (S112) is performed.

Like the blocking solution injection (S101), the analyte injection (S104), or the cleaning liquid injection (S107), the luminescent substrate injection (S112) is performed by injecting the luminescent substrate into the chip holder53rotated at the injection rotation speed. After the luminescent substrate injection (S112), a measuring process (S113) is performed.

The measuring process (S113) is performed by making the camera unit83of the measurement unit80capture an image of the analysis chip10. The presence or absence of light emission and the intensity of the emitted light at each antigen30indicating a result of the measurement can be displayed for example on the touch panel52, stored in the storage of the control unit110, transmitted to an external computer connected through wired or wireless communication, or output from an output device such as a printer.

A determining process (S114) is performed on all types of antigens30(in this embodiment, 40 types). In the determining process (S114), based on the type of the antigen30generating light-emitting reaction understood from a result of the measurement obtained in the measuring process (S113), specificity of reaction of the analyte with each antigen30is determined and the intensity of the reaction specificity is determined based on the intensity of the emitted light. As described above, the analysis chip10and the biochemical analysis device50according to this embodiment achieve measurement of a large number of items of as many as 40 types collectively and simultaneously within a short length of time.

The analysis chip10of this embodiment described above achieves the following effects.

The analysis chip10of this embodiment includes: the substrate20formed into a substantially disc shape; the injection port22formed at the center of the substrate20and through which target liquid as a measurement target is injected; and the plurality of micro-flow paths23formed in a radial pattern to extend from the injection port22to the outer edge of the substrate20and allowing introduction of the target liquid into the micro-flow paths23by means of capillary action. Multiple types of antigens30to selectively react with a component in the target liquid are fixed to each of the micro-flow paths23to be spaced from each other. In this way, multiple types of antigens30are fixed to one micro-flow path23. This makes it possible to make measurement of a plurality of items at a time, while restricting a required amount of the target liquid. Additionally, by forming the micro-flow paths23in a radial pattern, the target liquid remaining in the micro-flow paths23can be discharged from the micro-flow paths23by means of centrifugal force. This works effectively, particularly in sample analysis of repeating processes of injecting and discharging multiple types of liquid several times during the course of measurement, like in this embodiment.

In the analysis chip10, the antigen30is fixed in the form of a spot to the micro-flow path23. This makes it possible to arrange a large number of antigens30in a limited area.

In the analysis chip10, the antigen30fixed to the micro-flow path23has a shape like a thin film having a flat upper surface. By doing so, for acquiring image information by making the camera unit83capture an image of the analysis chip10from above, the upper surface of the antigen30is formed so as to direct light (optical axis) resulting from light-emitting reaction mainly in a direction substantially perpendicular to the micro-flow path23. This prevents interference with a different light-emitting antigen30, so that an image of light-emitting reaction can favorably be captured.

The analysis chip10further includes a housing in which the substrate20is arranged and housed and formed of the lower housing12and the upper housing13. The housing includes the opening part18where the upper surface of the substrate20is exposed at least partially, and the liquid trapping space16provided inside the housing and on an outer peripheral side of the substrate20. This prevents target liquid having been discharged from the micro-flow path23from being discharged to the outside of the system of the analysis chip10at the liquid trapping space16inside the housing, while allowing injection of liquid through the opening part18from above the substrate20and allowing image capturing by the camera unit83. The forgoing can be rephrased as follows. The analysis chip10of this embodiment further includes: the lower housing12formed into a larger diameter than the substrate20; the upper housing13having the opening part18and being formed into a larger diameter than the substrate20; and the liquid trapping space16formed on the outer peripheral side of the substrate20using the lower housing12and the upper housing13. Thus, target liquid having been discharged from the micro-flow path23is trapped in the liquid trapping space16, so that the target liquid can be prevented from flowing out of the analysis chip10. This works effectively, particularly in the biochemical analysis device50required to avoid diffusion or leakage of an analyte taken from a biological body into and out of the biochemical analysis device50.

The analysis chip10further includes the absorber15arranged in the liquid trapping space16and formed of a member having moisture-retaining properties. Thus, target liquid having been discharged to the liquid trapping space16is absorbed by the absorber15. This achieves the action of moisturizing the liquid trapping space16and the micro-flow path23in the substrate20, while preventing the target liquid having been discharged from the micro-flow path23from flowing back into the micro-flow path23.

The analysis chip10includes the air communication opening17formed around the opening part18and between the upper surface (surface close to the opening part18) of the substrate20and the upper housing13. This establishes a passage extending from the injection port22to the air communication opening17through the micro-flow path23for air from the air nozzle unit100, so that liquid in the micro-flow path23can effectively be discharged to the outside of the micro-flow path23by injection of air into the injection port22.

The injection port22of the analysis chip10is formed at a substantially central position of the substrate20. This makes it possible to introduce liquid substantially uniformly into the plurality of micro-flow paths23connected to the injection port22.

The micro-flow paths23of the analysis chip10are formed in a radial pattern to extend from the injection port22to the outer edge of the substrate20. This makes it possible to effectively discharge liquid in the micro-flow paths23by means of centrifugal force resulting from rotation of the chip holder53.

The air communication opening17of the analysis chip10is arranged inwardly in the radial direction from the opening of the micro-flow path23formed at the outer edge of the substrate20and where liquid is discharged to the liquid trapping space16. Specifically, the air communication opening17is located inwardly in the radial direction from the exit of the micro-flow path23(outer opening part in the radial direction). As a result, liquid having been discharged to the outside of the radial direction from the micro-flow path23is prevented from leaking to the outside of the analysis chip10through the air communication opening17.

The biochemical analysis device50of this embodiment described above achieves the following effects.

The biochemical analysis device50includes: the chip holder53that allows installation of the analysis chip10on the chip holder53; the chip holder rotation unit54that rotates the chip holder53; the pipetting unit90that injects target liquid into the injection port22of the analysis chip10; and the measurement unit80that allows measurement of reactions between the target liquid and multiple types of antigens30collectively. By making the chip holder rotation unit54rotate the chip holder53, the target liquid having been introduced into the micro-flow path23is discharged. Thus, in an analysis device that analyzes target liquid having strong surface tension using the micro-flow paths23, the target liquid can be discharged rapidly and reliably.

In the biochemical analysis device50, the chip holder53includes the fitting part531to make a fit with the analysis chip10. Thus, the analysis chip10can reliably be fixed to the chip holder53, thereby preventing falling off of the analysis chip10from the chip holder53to be caused by centrifugal force during rotation.

Further, the analysis chip10placed at the chip holder53can be rotated properly at a given speed. Additionally, the analysis chip10is installed on the chip holder53with temperature adjusting means. Thus, in an analysis device such as that of this embodiment requiring incubation under a constant temperature, an increased area of contact between the analysis chip10and the chip holder53achieves more reliable temperature adjusting control.

In the biochemical analysis device50, the pipetting unit90injects target liquid while the chip holder rotation unit54rotates the chip holder53. Thus, the liquid can be introduced uniformly into the plurality of micro-flow paths23connected to the injection port22. This can prevent the occurrence of a situation where the liquid is introduced unevenly into some of the micro-flow paths23or target liquid of a necessary amount cannot be introduced into some of the micro-flow paths23. As a result, even if the tip portion of the pipetting nozzle92(tip of the pipette chip95) at the liquid injection position deviates from the center of rotation or even if the analysis chip10is not placed in a horizontal posture, distances to respective liquid inlets of the micro-flow paths23can be substantially equal in response to rotation during the injecting process. This reduces influence on the injecting process by an error of accuracy of the shape of the pipette chip95or attachment condition of the pipette chip95, so that the injecting process can be performed properly.

In the biochemical analysis device50, the pipetting unit90has the pipette chip95of a tapered shape. With the pipette chip95being inserted into the injection port22, the pipetting unit90injects target liquid. This prevents flying-off of the target liquid over the upper surface of the substrate20or its periphery or blockage of the injection port22with droplets of the target liquid. As a result, the target liquid can be introduced rapidly into the micro-flow path23through the injection port22.

The biochemical analysis device50includes the air nozzle unit100that injects air into the injection port22. This air and rotation of the chip holder53work in combination to reliably discharge target liquid in the micro-flow path23formed in the analysis chip10.

The biochemical analysis device50makes the air nozzle unit100inject air into the analysis chip10while rotating the chip holder53. Thus, even if target liquid is left unremoved in the micro-flow path23by the presence of strong surface tension in the micro-flow path23, such target liquid can reliably be discharged from the micro-flow path23with air injected from the air nozzle unit100.

The present invention is not limited to each aspect of the preferred embodiment of the analysis chip10and that of the preferred embodiment of the biochemical analysis device50of the present invention described above. Various changes can certainly be devised based on the principles of the present invention.

According to the configuration of this invention, the liquid injection position is set in such a manner that the tip of the pipette chip95substantially agrees with the center of rotation of the chip holder53. However, the liquid injection position can be set in different appropriate ways. According to a modification described next, the liquid injection position is set in such a manner that the tip of the pipette chip95from which target liquid is injected deviates from the center of rotation of the chip holder53.FIG. 15is a schematic view illustrating a state in outline where the pipetting unit90of a biochemical analysis device according to the modification is injecting target liquid into the analysis chip10. Illustrations of structures of the analysis chip10except the substrate20are omitted fromFIG. 15. Illustrations of the structures of the biochemical analysis device50including the chip holder53are also omitted.

As illustrated inFIG. 15, according to the modification, the tip side of the pipette chip95from which liquid is pipetted is set at a position deviating from the center of rotation of the chip holder53. This can be rephrased as follows. As described above, the substrate20provided in the analysis chip10of this embodiment includes a plurality of micro-flow paths23arranged in a radial pattern with respect to the injection port22. Respective entrances of the micro-flow paths23are located at equally-spaced positions from the center of the injection port22. A liquid injection position of this modification is set at a position deviating from these equally-spaced positions. The pipette chip95at the liquid injection position is arranged adjacent to the injection port22so as to make liquid pipetted from the tip of the pipette chip95contact the inner side surface of the injection port22. The tip of the pipette chip95at the liquid injection position is set so as to be placed below the upper surface of the substrate20and so as to form a gap between the tip of the pipette chip95and the bottom surface of the injection port22. Liquid is pipetted toward the chip holder53being rotated while the tip of the pipette chip95is placed at the liquid injection position. The tip side of the pipette chip95at the liquid injection position is approximated in advance to the inner side surface of the injection port22. Thus, liquid can be injected uniformly and properly into the entrances of the plurality of micro-flow paths23formed at the inner side surface of the injection port22.

A modification using an analysis chip210having a different configuration from the analysis chip10of the aforementioned embodiment is described next.FIG. 16is a plan view illustrating the analysis chip210according to the modification.FIG. 17is a side sectional view schematically illustrating the configuration of the inside of the analysis chip210according to the modification. A biochemical analysis device50using the analysis chip210has the same configuration as that of the aforementioned embodiment.

The analysis chip210of the modification includes a first substrate220, a second substrate230, an absorber215, liquid trapping space216, an air communication opening217, and a rotation position reference mark250.

The first substrate220is formed into a disc shape. A circular columnar stage part241is formed at the center of the first substrate220. A wall part242is formed to extend over the entire periphery of an end surface of the first substrate220.

The second substrate230is formed into a disc shape using a light-transmitting material. The second substrate230is bonded to an upper part of the first substrate220. A circular injection port222for injection of various types of liquid is formed at the center of the second substrate230. The injection port222is formed into a smaller diameter than the stage part241. Thus, the injection port222is accommodated inside the stage part241in a plan view. A lower part of the injection port222of the second substrate230is formed into a tapered shape in a side view that expands further radially at a position closer to the stage part241of the first substrate220.

The upper surface of the stage part241of the first substrate220and the lower surface of the second substrate230form a gap therebetween. The liquid having been injected through the injection port222is introduced to the gap by means of capillary action. This gap is formed to extend over the entire outer periphery of the injection port222. This gap functions as a flow path255of the analysis chip210. In this way, the flow path255of the analysis chip210is formed into a ring-like shape surrounding the outer periphery of the injection port222. Thus, the flow path255of the analysis chip210of this modification can be expressed as a single flow path255.

In this modification, multiple types of antigens30are fixed to the flow path255to be close to the stage part241. The multiple types of antigens30are arranged at given intervals in a concentric circular pattern surrounding the injection port222. The antigens30are aligned so as not to overlap each other at least at their centers in a radial direction. By doing so, a distance between the antigens30is maintained properly, so that an image of light-emitting reaction can be captured with a high resolution.

Aligning the antigens30in the concentric circular pattern is not the only method of fixing the antigens30. For example, multiple types of antigens30may also be arranged irregularly in the flow path255of the analysis chip210according the modification. Alternatively, a partition may be provided to a part of the flow path255to divide the flow path255into sector forms. Still alternatively, the antigens30may be fixed to the flow path255to be close to the second substrate230. As described above, the method of arranging the antigens30can also be changed in this modification.

The absorber215is formed of a member having moisture-retaining properties. The absorber215is formed into a ring-like shape of a larger diameter than the stage part241. The liquid trapping space216is formed inside the analysis chip210to surround the outer peripheral surface of the stage part241. The absorber215is arranged in the liquid trapping space216so as to surround the outer peripheral surface of the stage part241. Target liquid having been discharged from the flow path255by means of centrifugal force resulting from rotation of the analysis chip210or injection of air by the air nozzle unit100is discharged to the liquid trapping space216and absorbed by the absorber215.

The air communication opening217includes a plurality of air communication openings217formed outside the stage part241in a plan view. Air having been injected by the air nozzle unit100and having passed through the air communication openings217is discharged from the inside of the analysis chip210to the outside of the analysis chip210. An air communication opening217abelonging to the plurality of air communication openings217lies on a virtual straight line connecting the center of the analysis chip210and the rotation position reference mark250to be placed at a position adjacent to the rotation position reference mark250.

The rotation position reference mark250is an indication used for detecting the orientation of the analysis chip210and is provided to the first substrate220. The rotation position reference mark250of this modification is provided at one position at the edge of the stage part241and has a semicircular shape. The number of the rotation position reference marks250, and the location and the shape of the rotation position reference mark250can be changed, if appropriate. For example, the rotation position reference mark250can be provided to the second substrate230.

The rotation position reference mark250is stored in advance in the storage of the control unit110as arrangement state determination information corresponding to information about the shape of the analysis chip210to be used for identifying a rotation position. Based on the position of the rotation position reference mark250in image information acquired by the measurement unit80and the arrangement state determination information, the control unit110determines the orientation of the rotated analysis chip210.

In this modification, a positioning notch280is formed in each of the first substrate220and the second substrate230. The positioning notch280is used for determining the positions of the first substrate220and the second substrate230when the first substrate220and the second substrate230are adhesively joined during a step of manufacturing the analysis chip210. The positioning notches280of this modification are formed at positions facing each other across the center of the analysis chip210. The first substrate220and the second substrate230are adhesively joined at proper positions determined by the respective positioning notches280formed in the first substrate220and the second substrate230. Further, the air communication opening217aformed in the second substrate230is adjacent to the rotation position reference mark250. Thus, whether or not the first substrate220and the second substrate230are in their proper positions can also be determined by using the air communication opening217a.

The analysis chip210of this modification has the aforementioned configuration. The biochemical analysis device50analyzes target liquid using the analysis chip210. Target liquid such as an analyte enters the flow path255through the injection port222and is introduced into the flow path255from an inner side toward an outer side by means of surface tension.

A method of injecting target liquid such as an analyte into the analysis chip210and a method of measuring reaction with the antigen30are the same as the aforementioned methods. In this modification, the orientation of the rotated analysis chip210can be determined accurately based on the rotation position reference mark250. The type of each reaction is measured based on position information about the multiple types of antigens30fixed to the analysis chip210. The position information about the antigens30is information set in advance.

As described above, the analysis chip210is formed in such a manner that the flow path255surrounds the outer periphery of the injection port222. By doing so, space around the injection port222can be used for arrangement of many types of antigens30. Further, manufacturing cost can be reduced as a result of a simple configuration of forming the flow path255around the injection port222.

The configuration of the analysis chip210according to the modification can be changed, if appropriate. For example, the analysis chip210may include a housing to hold the first substrate220and the second substrate230. In this case, the wall part242can be omitted from the first substrate220and liquid trapping space can be arranged inside the housing and on the outer peripheries of the first substrate and the second substrate. Alternatively, the analysis chip210of the modification may include a housing same as the housing of the aforementioned embodiment (including the lower housing12and the upper housing13) and may include an air communication opening in a gap between the housing and the second substrate.

In the biochemical analysis device50of this embodiment, the chip holder rotation unit54includes the temperature adjustment unit inside the chip holder rotation unit54. However, the location of a temperature adjustment unit can be changed, if appropriate. For example, a temperature adjustment unit may be provided inside the dark box81. Additionally, a temperature adjustment unit may be arranged in the dark box81in addition to the temperature adjustment unit arranged in the chip holder rotation unit54. By doing so, the temperature of the analysis chip10may be adjusted using a plurality of temperature adjustment units.

The biochemical analysis device50of this embodiment can employ an appropriate method of measuring the antigen30placed in the micro-flow path23of the analysis chip10at the measurement position. For example, based on the frequency of rotation of the drive motor for rotating the chip holder53, reaction may be measured by estimating and determining the arrangement state of the antigen30after operation of rotating the analysis chip10.

In the biochemical analysis device50of this embodiment, the amount of suction of target liquid by the pipetting unit90is set in a manner that depends on the type of the target liquid. However, this configuration can be changed, if appropriate. For example, the concentration of a reagent solution may be adjusted and the amount of suction (or the amount of injection into the analysis chip10) may be kept at a constant amount.

The biochemical analysis device50of this embodiment is configured to inject air using the air nozzle unit100in the liquid discharging process. However, this air injecting process can be omitted in a manner that depends on an analysis target such as an analyte.

The configuration of the analysis chip10of this embodiment is such that the antigen30as a reactant to react with target liquid is fixed to the substrate20. Alternatively, an antibody may be fixed. In this way, a reactant to be fixed to the substrate of the analysis chip can be changed, if appropriate, as long as the reactant is a substance to react with target liquid.

The configuration of the analysis chip10of this embodiment is not limited to that described in this embodiment but can be changed, if appropriate. For example, the micro-flow paths23can be arranged at positions not symmetric with each other.

The configuration of the analysis chip10of this embodiment is such that the absorber15is arranged in the liquid trapping space16. However, this configuration can be changed, if appropriate. For example, the analysis chip10may also be configured in such a manner that the liquid trapping space16is given a structure of trapping liquid and this trapping structure functions to prevent liquid having been discharged from the micro-flow path23from returning back into the micro-flow path23. The analysis chip10may also be configured in such a manner that numerous slits are formed in the bottom surface of the liquid trapping space16and liquid having been discharged from the micro-flow path23is caused to stay in the liquid trapping space16by these slits. Alternatively, the absorber15may be omitted from the configuration of the analysis chip10. As described above, a structure for trapping liquid in the liquid trapping space16can be changed, if appropriate.

The configuration of the substrate20provided in the analysis chip10of this embodiment is not limited to the configuration described in this embodiment. The substrate can be formed of a plurality of members. For example, the configuration of the substrate20may be such that the micro-flow path23is formed by fixing a substrate of a substantially disc shape instead of arranging the film14on the lower surface of the substrate20. As described above, an appropriate configuration can be employed for the substrate20.

In the description of this embodiment given above, the biochemical analysis device50is described as an example of a sample analysis device. However, the present invention is not limited to the biochemical analysis device50but is applicable to various types of sample analysis devices. For example, the present invention is also applicable to a sample analysis device to detect trace metal, for example.

EXPLANATION OF REFERENCE NUMERALS