JP6638303B2 - Analyzer chip holder and analyzer - Google Patents

Description

  The present invention is mounted on an analyzer that prepares a liquid to be measured using kinematic action such as inertial force in a microchip and irradiates the liquid to be measured with light to measure the concentration of a specific component. The present invention relates to a chip holder for holding a microchip, and an analyzer provided with the chip holder.

In recent years, it is referred to as “μ-TAS (μ-Total Analysis System)” or “Lab on a chip”, which can perform chemical analysis and the like more minutely than conventional devices by applying micromachine technology. An analysis method using a microchip has attracted attention.
An analysis system using such a microchip performs all steps of analysis including mixing, reaction, separation, extraction, and detection of reagents in a fine flow path formed on a small substrate by a micromachining technology. It is aimed at that. Such an analysis system is used, for example, for analyzing blood in the medical field, and analyzing biomolecules such as ultra-trace proteins and nucleic acids.

  Conventionally, as an analyzer that uses a microchip to measure the concentration or substance amount of a specific component in a sample, a centrifugal rotor that is driven by rotation and has a tip holder that holds the microchip, and a tip holder There has been proposed a device including a light source unit that irradiates light to a measurement unit of a held microchip and a light receiving unit that receives light transmitted through the measurement unit (see Patent Document 1).

  In the above-described analyzer, the sample in the microchip is centrifuged by rotating the centrifugal rotor in a state where the microchip is held by the chip holder, so that a liquid to be measured is prepared. Thereafter, a mixed reaction process of mixing and reacting the obtained liquid to be measured and the reagent is performed, and further, the liquid to be measured is sent to the measuring section of the microchip. Then, when the rotation of the centrifugal rotor stops, the measurement unit of the microchip held by the chip holder is located in the measurement area between the light source unit and the light receiving unit. Then, the light from the light source unit is irradiated to the measuring unit of the microchip, and the light from the measuring unit is received by the light receiving unit, so that the concentration and the amount of the specific component in the liquid to be measured in the measuring unit are measured. You.

JP 2007-322208 A

However, the above-described analyzer has the following problems.
In the above-described analyzer, the microchip is held by the chip holder in a posture in which, for example, each measurement cell is arranged at a position concentric with the center of the rotation axis of the centrifugal rotor.
However, when the microchip is set on the chip holder, a slight displacement may occur or the microchip may float on the chip holder. In addition, if the centrifugal rotor is rotated in such a state, the displacement or lifting of the microchip may increase. Then, when such a displacement or floating occurs, when the light from the light source unit is applied to the measurement unit of the microchip, the amount of light applied to the measurement unit varies. For this reason, it is difficult to perform highly reproducible and highly accurate measurement of the concentration and the amount of a specific component in the liquid to be measured.
In particular, when the amount of the sample to be injected into the microchip is smaller, the amount of the test target liquid contained in the measurement unit is also smaller, so a microchip having a finer measurement unit is required. When a suitable microchip is used, the above-mentioned problem becomes remarkable.

Therefore, an object of the present invention is to provide a chip holder that can eliminate the displacement of the microchip, which is caused when the microchip is set.
Another object of the present invention is to increase the required measurement of the test liquid stored in the measurement unit of the microchip even when the microchip is displaced when the microchip is set. An object of the present invention is to provide an analyzer that can perform the analysis with high accuracy.

The chip holder for an analyzer according to the present invention is mounted on an analyzer that analyzes the liquid to be measured by irradiating the liquid to be measured contained in the measurement unit of the microchip with the light, for holding the microchip. Chip holder,
A bottom support for supporting the bottom surface of the microchip, a first side support, a second side support, a third side support and a first side support arranged to surround the side surface of the microchip and support the side surface of the microchip ; With four side supports,
Both side edges of the third side support are integrally connected to one side edge of each of the first side support and the second side support via a connection portion. The upper edge is configured as a cantilever spring that is displaced in a direction of coming and going with respect to the third side support,
At least one side support of the first side support and the second side support elastically holds the microchip in a direction intersecting a reference plane including a surface of the bottom support in contact with the microchip. It is characterized in that a pressing portion for pressing is provided.

The analyzer of the present invention is an analyzer that analyzes the liquid to be measured by irradiating the liquid to be measured contained in the measurement unit of the microchip with light,
A centrifugal rotor arranged in a measurement processing chamber where the measurement process is performed, and provided in the centrifugal rotor, including a chip holder for holding the microchip,
The chip holder has a bottom support that supports the bottom surface of the microchip, and four side supports that are arranged to surround the side surfaces of the microchip and support the side surfaces of the microchip,
In the chip holder, at least one of the side supports arranged along a radial direction of a circular orbit about the rotation axis of the centrifugal rotor includes a reference surface including a surface of the bottom support that contacts the microchip. A pressing portion for elastically pressing the microchip is provided in a direction intersecting the surface .

According to the chip holder for an analyzer of the present invention, the kinematic action and the pressing force of the pressing portion provided on the side support work on the microchip when preparing the test liquid. For this reason, it is possible to eliminate the displacement of the microchip, which is caused when the microchip is set.
According to the analyzer of the present invention, since the analyzer has the above-described chip holder for the analyzer, even when the microchip is displaced when the microchip is set, the measurement unit of the microchip is used. The required measurement can be performed with high accuracy on the stored test liquid.

It is an explanatory view showing the outline of composition in an example of an analyzer provided with a tip holder for analyzers of the present invention. It is a six-view figure showing an example of a microchip held by a tip holder for analyzers of the present invention. FIG. 2 is a perspective view showing an example of an analyzer chip holder of the present invention mounted on the analyzer shown in FIG. 1. FIG. 4 is a side view of the chip holder for the analyzer shown in FIG. 3. FIG. 2 is an explanatory diagram showing a part of a centrifugal rotor in the analyzer shown in FIG. 1 in an enlarged manner. FIG. 2 is an explanatory diagram schematically showing a direction of a pressing force acting on a microchip by a pressing portion of a chip holder for an analyzer of the present invention in the analyzer shown in FIG. 1. FIG. 2 is an explanatory diagram schematically showing a direction of a pressing force acting on a microchip when rotation of a centrifugal rotor starts in the analyzer shown in FIG. 1.

Hereinafter, embodiments of the present invention will be described.
FIG. 1 is an explanatory view schematically showing a configuration of an example of an analyzer provided with a chip holder for an analyzer of the present invention (hereinafter, simply referred to as “tip holder”). This analyzer uses the light emitted from the specific component to determine the concentration and the amount of a specific component in a liquid to be measured obtained by centrifuging a sample such as blood, which is put into a microchip, for example. Measurement.

  The analyzer includes a measurement processing mechanism 10 that prepares a liquid to be measured by centrifuging a sample put into a microchip, and executes a measurement process on the liquid to be measured. The control mechanism 50 is configured to control and calculate the concentration and physical quantity of a specific component in the liquid to be measured based on the light intensity signal from the measurement processing mechanism 10.

  The measurement processing mechanism 10 has a plurality of chip holders 11 according to the present invention, each holding a microchip. In FIG. 1, one tip holder 11 is shown for convenience, and the other tip holders are omitted.

FIG. 2 is a six-view drawing showing an example of a microchip held by a chip holder.
This microchip 1 has a flat rectangular parallelepiped shape. More specifically, the microchip 1 includes a long rectangular top surface 2 and a bottom surface 3 and two large side surfaces 4 formed between the long side of the top surface 2 and the long side of the bottom surface 3. 5 and small side surfaces 6 and 7 formed between the short side of the top surface 2 and the short side of the bottom surface 3. Further, between the bottom surface 3 of the microchip 1 and the two side surfaces 6 and 7 having a small width, an R-shaped curved surface C is formed.
On the upper surface 2 of the microchip 1, a sample inlet 8 into which a sample is injected is formed. In addition, a measurement unit 9 for accommodating a test target liquid is formed near the bottom surface 3 in the microchip 1.

  FIG. 3 is a perspective view showing an example of the chip holder according to the present invention, which is mounted on the analyzer shown in FIG. The chip holder 11 has a housing space S for housing the microchip 1 having a rectangular parallelepiped shape, and a plate-shaped bottom support 12 for supporting the bottom surface 3 of the microchip 1 housed in the housing space S; The first side support 13, the second side support 14, the third side support 15, and the fourth side support respectively supporting the side surfaces 4, 5, 6, and 7 of the microchip 1, which are arranged so as to surround the side surfaces of the microchip 1. And a body 16.

  In the illustrated example, the bottom support 12 is configured by two divided plate-shaped support elements 12a and 12b. These support elements 12a and 12b are arranged apart from each other in the longitudinal direction of the microchip 1 (the long side direction of the upper surface 2).

  The first side support 13 and the second side support 14 supporting the side surfaces 4 and 5 of the microchip 1 face each other along each side edge of the support elements 12a and 12b in the bottom support 12. It is arranged in. The lower edge of each of the first side support 13 and the second side support 14 is integrally connected to the side edges of the support elements 12 a and 12 b of the bottom support 12. A holding portion 14 a for holding the microchip 1 between the first side support 13 and the second side support 14 is provided at the upper end of the second side support 14. The holding portion 14a is formed of a curved plate-shaped cantilever spring. Further, each of the first side support 13 and the second side support 14 is provided with fixed support portions 13b and 14b for fixing to the centrifugal rotor 20 described later.

  The third side support 15 and the fourth side support 16 supporting the side surfaces 6 and 7 of the microchip 1 face each other along the edge of each of the support elements 12a and 12b on the bottom support 12. It is arranged in. Both side edges of the third side support 15 are integrally connected to one side edge of each of the first side support 13 and the second side support 14 via a connection portion 15a. The lower edge of the fourth side support 16 is integrally connected to the edge of the support element 12 b of the bottom support 12. As a result, the fourth side support 16 is displaced in a direction in which the upper end edge of the fourth side support 16 is separated from the third side support 15 with the lower edge connected to the support element 12b as a support point. It is configured as a cantilever spring.

  The first side support 13 is provided with a pressing portion 17 that elastically presses the microchip 1 in a direction obliquely intersecting with a reference plane F including a surface of the bottom support 12 that contacts the bottom surface 2 of the microchip 1. Have been. As shown in FIG. 4, the pressing portion 17 in this example is configured by an L-shaped leaf spring, and elastically presses the microchip 1 in a direction obliquely intersecting the reference plane F. The angle θ of the direction of the pressing force by the pressing unit 17 with respect to the reference plane F (see FIG. 6) is, for example, 10 to 50 °. If the angle θ is smaller than 10 °, the effect of the pressing force of the pressing unit 17 on the reference plane F may be weak. On the other hand, if the angle θ is larger than 50 °, there is a possibility that the work of inserting and removing the chip holder 11 from the microchip 1 becomes difficult.

  Such a plurality of tip holders 11 are spaced apart from each other at equal intervals along the circumferential direction of a disk-shaped centrifugal rotor 20 arranged in a measurement processing chamber (not shown) in which a measurement process is performed. Is provided. As shown in FIG. 5, the centrifugal rotor 20 includes a circular ring-shaped outer peripheral portion 21, a center portion 22 where the rotation axis R is located, and a spoke portion 23 connecting the outer peripheral portion 21 and the center portion 22. It is configured. The spoke portion 23 of the centrifugal rotor 20 has a long rectangular opening 24 extending in the radial direction of the centrifugal rotor 20, and the tip holder 11 is fixed to the opening 24. The central portion 22 of the centrifugal rotor 20 is fixed to the distal end of the drive shaft 26 of the centrifugal motor 25, and is driven to rotate by the centrifugal motor 25 using the drive shaft 26 as the rotation axis R. The centrifugal rotor 20 prepares a liquid to be measured by performing a process such as a centrifugal separation process on a sample in the microchip 1 held by the chip holder 11 and measures the liquid to be measured by the microchip 1 It has a function of sending liquid to the section 9.

  The measurement unit 9 of the microchip 1 held by the chip holder 11 is moved along a circular orbit S about the rotation axis R of the centrifugal rotor 20 when the centrifugal rotor 20 is driven to rotate. On the circular orbit of the measurement unit 9 in the microchip 1, a measurement region M for measuring the concentration or the amount of a specific component in the liquid to be measured is provided.

  Below the centrifugal rotor 20, a light source unit 30 that irradiates light to the measurement area M is provided immediately below the measurement area M. As the light source unit 30, a solid light emitting element such as an LED, or a lamp such as a flash lamp or a halogen lamp can be used. The wavelength of the light emitted from the light source unit 30 is appropriately selected according to a specific component in the liquid to be measured. For example, when a specific component in the liquid to be measured is marked with resorufin, a green LED having a light emission peak at a wavelength of 525 nm can be used as the light source unit 30.

  Above the centrifugal rotor 20, a light receiving unit 40 that receives light emitted from the liquid to be measured in the measuring unit 9 that passes through the measuring region M is provided just above the measuring region M. As the light receiving unit 40, for example, a high-sensitivity photodetector such as a photomultiplier tube (photomultiplier), a photodiode, a photoresistor made of CdS, or the like can be used.

  The control mechanism 50 includes a central control unit 51, a light source unit control unit 52 that controls the light source unit 30, a light receiving unit control unit 53 that controls the light receiving unit 40, and a motor control unit 54 that controls the centrifugal motor 25. Have. The central control unit 51 includes an information reading unit 55 provided on the microchip for reading information by an identifier such as a barcode or a QR code (registered trademark), an input unit 56 for inputting data to the control mechanism 50, and a measurement result. A display unit 57 for displaying, an output unit 58 for outputting data such as measurement results, and an external storage medium 59 for storing data such as measurement results are connected.

In the above-described analyzer, the measurement process for the liquid to be measured is performed as follows.
First, a sample is injected into the sample inlet 8 of the microchip 1. Further, the information reading unit 55 reads information based on the identifier provided on the microchip 1. The identifier provided on the microchip includes information such as the rotation speed and rotation pattern of the centrifugal rotor 20 and calibration curve data indicating the relationship between the measured light intensity and the concentration or substance amount of a specific component in the liquid to be measured. The central control unit 51 initializes a control program such as the rotation speed and the rotation pattern of the centrifugal rotor 20 based on the information recorded in the identifier.

  Next, the required number of microchips 1 into which the sample has been loaded are set in the chip holder 11. The number of microchips 1 held is determined in consideration of the rotational balance when the centrifugal rotor 20 is rotationally driven. Specifically, on one surface of the centrifugal rotor 20, the positional relationship of the held microchips is point symmetry with the center of the centrifugal rotor 20 as a point of symmetry, or a straight line passing through the center of the centrifugal rotor 20 as a symmetry axis. The number of microchips 1 is selected so as to be line-symmetric. For example, in the analyzer shown in FIG. 1, the number of the chip holders 11 is six, and thus the number of the microchips 1 held is preferably two, three, four, or six.

  Thereafter, the preprocessing of the sample in the microchip 1 is performed by operating the analyzer by pressing a start button provided on the analyzer. Specifically, the light source unit 30 is turned on, and the centrifugal rotor 20 is rotationally driven by the centrifugal motor 25. The rotation speed of the centrifugal rotor 20 and the processing time by the centrifugal rotor 20 are controlled based on information by an identifier provided on the microchip 1. A specific rotation speed of the centrifugal rotor 20 in the pretreatment step is, for example, 5000 rotations / minute. The centrifugal rotor 20 may be controlled to rotate at a constant rotation speed, or may be controlled to switch to a different rotation speed every time a predetermined time elapses.

  The above-mentioned pretreatment process is performed by utilizing the centrifugal force applied to the microchip 1 when the centrifugal rotor 20 is rotationally driven. The pretreatment process includes a separation process for separating a measurement target solution from a sample, a weighing process for dispensing a certain amount of a measurement target solution, a mixing reaction process for mixing and reacting a measurement target solution and a reagent, and a measurement process. A process of feeding the target liquid to the measuring unit 9.

  By performing the pretreatment process in this way, the sample in the microchip 1 is subjected to the centrifugal separation process to prepare the liquid to be measured, and the liquid to be specified is sent to the measuring unit 9. In the pre-processing step, the light source unit 30 is turned on, so that the output of light emitted from the light source unit 30 is stabilized.

  Then, after the pre-processing step is completed, a measurement process is performed on the liquid to be measured held in the measurement unit 9 of the microchip 1. Specifically, in the measurement region M, light from the light source unit 30 is irradiated to the measurement unit 9 of the microchip 1, and the intensity of light emitted from the measurement unit 9 of the microchip 1 is measured by the light receiving unit 40. In the central control unit 51 of the control mechanism 50, based on the calibration curve data recorded on the identifier provided on the microchip 1, from the obtained measurement data, the concentration and the substance amount of the specific component in the liquid to be measured are obtained. Is calculated.

  As described above, when the microchip 1 is set on the chip holder 11, the pressing portion 17 exerts a pressing force P1 on the microchip 1 in a direction obliquely intersecting the reference plane F as shown in FIG. When the rotation of the centrifugal rotor 20 starts, the action of the inertial force P2 acts on the microchip 1, as shown in FIG. At this time, the microchip 1 is pressed against the pressing portion 17 by the inertial force P2, and as a reaction of the component P2-1 of the inertial force P2 perpendicular to the contact surface of the pressing portion 17 with the microchip 1, the microchip 1 , The action of the elastic pressing force P3 by the pressing portion 17 acts. As a result, the action of the resultant force P4 of the pressing force P3 and the component P2-2 of the inertia force P2, which is horizontal to the contact surface of the pressing portion 17 with the microchip 1, acts on the microchip 1. Of the resultant force P4, the component P4-1 perpendicular to the bottom surface of the microchip 1 pushes the microchip 1 toward the bottom surface of the chip holder 11, that is, the reference surface F, and the microchip 1 is positioned.

According to such a chip holder 11, the microchip 1 has a kinematic action to be exerted when preparing the test liquid, specifically, an inertia force P 2 when the rotation of the centrifugal rotor 20 starts, and The operation of the pressing force P3 by the pressing portion 17 provided on the one side support 13 works. For this reason, it is possible to eliminate the displacement of the microchip 1 that occurs when the microchip 1 is set.
Further, according to the above-described analyzer, since the chip holder 11 is provided, even when the microchip 1 is displaced when the microchip 1 is set, the measuring unit 9 of the microchip 1 can be used. The required measurement can be performed with high accuracy on the liquid to be inspected stored in the container.

DESCRIPTION OF SYMBOLS 1 Microchip 2 Top surface 3 Bottom surface 4, 5, 6, 7 Side surface 8 Sample inlet 9 Measurement unit 10 Measurement processing mechanism 11 Chip holder 12 Bottom support 12a, 12b Support element 13 First side support 13b Fixed support 14 Second side support 14a Nipping portion 14b Fixed support 15 Third side support 15a Connecting portion 16 Fourth side support 17 Pressing portion 20 Centrifugal rotor 21 Outer peripheral portion 22 Central portion 23 Spoke 24 Opening 25 Centrifugal motor 26 Drive shaft Reference Signs List 30 light source unit 40 light receiving unit 50 control mechanism 51 central control unit 52 light source unit control unit 53 light receiving unit control unit 54 motor control unit 55 information reading unit 56 input unit 57 display unit 58 output unit 59 external storage medium C curved surface F reference surface M Measurement area R Rotation axis S Housing space

Claims (2)

A chip holder for holding the microchip, which is mounted on an analyzer that analyzes the measurement target liquid by irradiating light to the measurement target liquid contained in the measurement unit of the microchip,
A bottom support for supporting the bottom surface of the microchip, a first side support, a second side support, a third side support and a first side support arranged to surround the side surface of the microchip and support the side surface of the microchip ; With four side supports,
Both side edges of the third side support are integrally connected to one side edge of each of the first side support and the second side support via a connection portion. The upper edge is configured as a cantilever spring that is displaced in a direction of coming and going with respect to the third side support,
At least one side support of the first side support and the second side support elastically holds the microchip in a direction intersecting a reference plane including a surface of the bottom support in contact with the microchip. A chip holder for an analyzer, wherein a pressing portion for pressing is provided. An analyzer that analyzes the measurement target liquid by irradiating light to the measurement target liquid contained in the measurement unit of the microchip,
A centrifugal rotor arranged in a measurement processing chamber where the measurement process is performed, and provided in the centrifugal rotor, including a chip holder for holding the microchip,
The chip holder has a bottom support that supports the bottom surface of the microchip, and four side supports that are arranged to surround the side surfaces of the microchip and support the side surfaces of the microchip,
In the chip holder, at least one of the side supports arranged along a radial direction of a circular orbit about the rotation axis of the centrifugal rotor includes a reference surface including a surface of the bottom support that contacts the microchip. An analyzer characterized by comprising a pressing portion for elastically pressing the microchip in a direction intersecting with the surface .

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