JP4880419B2 - Chip having measuring unit and method for measuring liquid sample using the same - Google Patents

Description

  The present invention is useful for measuring liquid samples useful as biochips used for biochemical tests of DNA, proteins, cells, blood, etc., and μ-TAS (Micro Total Analysis System) used for chemical synthesis or environmental analysis. More specifically, the present invention relates to a chip having a weighing unit capable of weighing different liquid amounts.

  A small chip (hereinafter simply referred to as a chip) having a fluid circuit inside performs a series of experimental operations performed in a laboratory in a chip of several cm square and a thickness of several millimeters. There are many advantages such as a small amount of reagent, low cost, high reaction rate, high throughput testing, and the ability to obtain test results immediately at the site where the sample is collected. It is suitably used for chemical testing.

  Here, an example of a conventional chip is shown. FIG. 8 is a plan view of the sample processor card disclosed in Patent Document 1. In FIG. In FIG. 8, the blood sample is introduced from the opening 28, is held in the sample holding chamber 36 by applying a centrifugal force in an appropriate direction, and then is carried to the sample separation chamber 50. The sample separation chamber 50 is for separating solid particulate matter in blood. Next, the blood sample from which the solid particulate matter has been separated is held in the sample holding chamber 61 under a centrifugal force in an appropriate direction and then weighed in the sample measuring chamber 63. An excessive blood sample at the time of measurement overflows into the overflow chamber 65. Next, the weighed blood sample is mixed and reacted in the mixing chamber 60 with the reaction reagent weighed in the reaction reagent measuring chamber 54, and the reaction solution is transferred to the cuvette chamber 62 and analyzed using a light source and a detector. Inspected. As described above, by having a measuring unit such as the sample measuring chamber 63 and the reaction reagent measuring chamber 54, accurate analysis can be performed.

  However, like the chip disclosed in Patent Document 1, the conventional chip can usually only measure a certain amount of liquid corresponding to the internal volume of the measuring unit included in the chip. On the other hand, the required amount of sample is not always constant, for example, the required amount of blood sample varies depending on the blood test item. Therefore, if you want to weigh a different amount of sample, you must redesign a new tip for the amount you want to weigh, and each time you want to weigh a different amount of sample There was a complication of having to replace the tip with a volumetric meter.

Patent Document 2 proposes a micro liquid control device that is small enough to be mounted on a microchip and capable of quantitatively measuring an arbitrary amount of liquid. However, passive valves and gas pumps are used in this apparatus, and the system is very complicated. In addition, the micro liquid control device described in Patent Document 2 is used by being mounted on a microchip and is an apparatus independent of the microchip, so the microchip itself has a measuring function. Do not mean.
U.S. Pat. No. 4,883,763 JP 2006-23209 A

  The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a chip having a measuring unit capable of measuring liquid samples of different liquid amounts and a method of measuring a liquid sample using the chip. Is to provide.

  The present invention measures a liquid sample introduced by utilizing a centrifugal force caused by rotation about a first rotation axis, and rotates about at least one rotation axis different from the first rotation axis. A chip having a weighing unit that discharges a liquid sample that is weighed using centrifugal force by the centrifugal force used to introduce the liquid sample or to discharge the liquid sample Provided is a chip characterized by having a structure capable of measuring liquid samples of different volumes according to the strength or direction of centrifugal force applied.

  The present invention also measures the liquid sample introduced by utilizing the centrifugal force caused by the rotation about the first rotation axis, and the centrifugal force caused by the rotation about the second rotation axis or the third rotation axis. A chip having a metering unit for discharging the metered liquid sample, the metering unit introducing at least one metering unit body for metering the liquid sample, and / or introducing the liquid sample A first opening and a second opening for discharging, and the same number of waste liquid reservoirs connected to at least one of the measuring unit main bodies via a flow path, The volume of the measured liquid sample is discharged using the centrifugal force generated by the rotation about the rotation axis 2 and the centrifugal force generated by the rotation about the third rotation axis. A chip characterized by a different volume from the weighed liquid sample Subjected to.

  Here, in the chip of the present invention, the measuring unit includes a measuring unit main body for measuring the liquid sample, a first opening connected to one end of the measuring unit main body, and the other end of the measuring unit main body. And a waste liquid reservoir connected to the measuring unit main body through a flow path, and the inner wall of the measuring unit main body on the first opening side or the second opening side It is preferable that the inner wall has a structure having one or more recesses having a constant volume.

  Further, according to the present invention, the weighing unit is connected to the first weighing unit main body and the second weighing unit main body, which are connected to each other, and the first weighing unit main body and the second weighing unit main body through a flow path. The first and second waste liquid reservoirs, and the first and second metering unit main bodies, the first waste liquid reservoir and the second waste liquid reservoir are the following (i): And (ii) a chip characterized in that it is arranged.

  (I) When the measured liquid sample is discharged from the measuring unit by rotation about the second rotation axis, only the liquid sample measured by the first measuring unit main body is discharged.

  (Ii) When the measured liquid sample is discharged from the measuring unit by rotation about the third rotation axis, the liquid measured by the first measuring unit main body and the second measuring unit main body The sample is discharged.

  Here, the liquid sample measured by the first measuring unit main body by the rotation about the second rotation axis is discharged from the first opening, and at the second measuring unit main body. The measured liquid sample is transferred to the first waste liquid reservoir, and the liquid measured by the first measuring unit main body and the second measuring unit main body by rotation about the third rotating shaft. It is preferable that the sample is discharged from the second opening.

  Further, according to the present invention, the weighing unit has a first weighing unit main body, one end of which is a first opening, a second flow channel having a second weighing unit main body, A third channel whose one end is the second opening, a fourth channel whose one end is connected to the first waste liquid reservoir, and a fifth channel whose one end is connected to the second waste liquid reservoir The other end of the first channel, the one end of the second channel, and the other end of the fourth channel are connected to each other at the first junction, and the second channel The other end of the first flow path, the other end of the third flow path, and the other end of the fifth flow path are connected to each other at the second merge portion, and the second flow path and the fourth flow path of the first merge portion. The wall surface I at the portion where the flow path intersects is orthogonal to the line connecting the second rotation axis and the point a closest to the first rotation axis on the wall surface I, and the first 2 has an inclination in a direction away from the rotation axis, The wall surface II at the portion where the second flow path and the third flow path or the fifth flow path intersect at the second merging portion is farthest from the third rotation axis and the first rotation axis on the wall surface II. Orthogonal to a line connecting the point b and having a slope in a direction away from the third rotation axis with respect to a straight line passing through the point b, and the first weighing unit body and the first rotation axis The tip is characterized by being shorter than the distance between the second measuring unit main body and the first rotating shaft.

  Here, it is preferable that the first flow path and the second flow path are inclined in a direction away from the first rotation axis as they go from the first opening to the second opening. .

  Furthermore, the present invention includes a first weighing unit body and a second weighing unit body having different internal volumes, the weighing units being arranged vertically on a substantially straight line, and the bottom of the first weighing unit body A chip is provided, wherein a flow path having an opening directed in the direction of the second measuring unit main body is connected.

  Here, it is preferable that the internal volume of the second measuring unit body is smaller than the internal volume of the first measuring unit body.

Furthermore, the liquid sample measuring method of the present invention is a liquid sample measuring method using the above chip, and includes the following steps (a) and (b). To do.
(A) a step of introducing a liquid sample into the measuring unit in the chip using a centrifugal force by rotation about the first rotation axis;
(B) Using the centrifugal force caused by rotation about the second rotation axis or the third rotation axis selected according to the volume of the liquid sample to be weighed, The process of discharging from the measuring unit.

The liquid sample weighing method of the present invention is a liquid sample weighing method using the above chip, and includes the following steps (c) and (d).
(C) The liquid sample is introduced into the measuring unit in the chip by using the centrifugal force generated by the rotation about the first rotation axis, the strength of which is adjusted according to the volume of the liquid sample to be measured. Process,
(D) A step of discharging the weighed liquid sample from the measuring unit using a centrifugal force generated by rotation about a rotation axis different from the first rotation axis.

  According to the chip and the liquid sample weighing method of the present invention, different liquid amounts can be weighed with one chip, so there is no need to redesign a new chip according to the amount to be weighed, Each time a different amount of sample is to be weighed, the trouble of having to replace the tip with a metering portion with a different volume is eliminated.

  The chip of the present invention is not particularly limited, but is, for example, a plate shape of about several cm square and a thickness of several mm, and has a fluid circuit therein. In addition to a measuring part for measuring a liquid sample and a reaction reagent used for reaction with the liquid sample, the fluid circuit usually includes a sample introduction part for introducing the liquid sample into the fluid circuit, and a reaction reagent for storing the reaction reagent. Each unit arranged at an appropriate position, such as a holding unit, a mixing unit that mixes and reacts a liquid sample with a reaction reagent, and a detection unit that performs detection of a target component in the mixed solution, and a flow connecting them It is mainly composed of roads. However, in the chip of the present invention, it is not necessary to include all the above-described parts other than the measuring part, and there may be cases where one or a plurality of parts are not provided.

  The target component in the liquid mixture is detected by, for example, irradiating the detection unit with light and detecting the intensity of the emitted light. Typically, the chip of the present invention is formed by laminating a plate-like substrate on which the fluid circuit is formed and another plate-like substrate of the same size.

  A major feature of the chip according to the present invention is that the measuring unit is configured to measure a plurality of different liquid amounts. Specifically, a liquid sample that is measured using a centrifugal force generated by rotation about a certain rotation axis, and that is measured using a centrifugal force generated by rotation about another rotation axis. In the metering unit for discharging the liquid, the metering unit has different volumes of liquid depending on the centrifugal force used for introducing the liquid sample or the strength or direction of the centrifugal force used for discharging the liquid sample. It has a structure capable of weighing a sample.

  Here, as a relatively simple means for measuring different amounts using one measuring unit, a method of changing the direction of centrifugal force at the time of introducing a liquid sample as shown in FIG. 1 can be mentioned. FIG. 1 is a schematic diagram showing the relationship between the direction of centrifugal force applied to the measuring unit main body having a U-shaped structure and the volume of the liquid sample to be measured when the liquid sample is introduced. As shown in FIG. 1A, when the centrifugal force F is applied substantially perpendicular to the measuring unit main body, the measuring unit main body having a U-shaped structure is almost completely filled with the liquid sample. . On the other hand, as shown in FIG. 1B, when an oblique centrifugal force F is applied to the measuring unit main body, the measuring unit main body having a U-shaped structure is completely filled with the liquid sample. In other words, the volume of the liquid sample to be weighed is smaller than in the case of FIG. In this way, it is possible to control the volume of the liquid sample to be weighed by adjusting the application direction of the centrifugal force. Usually, the centrifugal force is applied by placing the chip on the rotating device and rotating the chip. However, the adjustment of the direction in which the centrifugal force is applied is performed by placing the chip on the rotating device. This can be done by adjusting the setting angle. That is, the position (angle) of the chip with respect to the rotation axis of the rotating device is adjusted so that a centrifugal force in a desired direction is applied.

  The present invention provides a chip capable of weighing liquid samples of different volumes, as in the above example, and the weighing unit discharges centrifugal force or liquid sample used for introducing the liquid sample. It is characterized in that liquid samples of different volumes can be weighed according to the direction and strength of the centrifugal force used in the above. In the above example, when measuring a liquid sample of a desired volume, precise control of the direction of centrifugal force is required, while the tip of the present invention employs a direction of centrifugal force with a relatively high degree of freedom. In addition, due to the structure of the metering unit that it has, it is possible to weigh liquid samples of different volumes with high accuracy and reproducibility. Hereinafter, the present invention will be described in detail with reference to embodiments.

<First Embodiment>
FIG. 2 is a plan view schematically showing the measuring unit in the chip according to the first embodiment of the present invention. The weighing unit 201 shown in FIG. 2 is connected to the weighing unit body 202 for weighing a liquid sample, the first opening 203 connected to one end of the weighing unit body 202, and the other end of the weighing unit body 202. And a waste liquid reservoir 206 connected to the measuring unit main body 202 through the flow path 205, and the inner wall of the measuring unit main body 202 on the first opening 203 side has a constant volume. One recess 207 is provided. In the metering unit shown in FIG. 2, the first opening 203 is an opening for introducing a liquid sample, but can also serve as a discharge port for discharging the weighed liquid sample. The second opening 204 functions as a liquid sample discharge port. The waste liquid reservoir 206 is for storing an excessive liquid sample that overflows from the measuring unit main body 202 when the liquid sample is introduced.

  A major feature of the weighing unit included in the chip of the present embodiment is that the inner wall of the weighing unit main body 202 on the first opening 203 side has one recess 207. With such a configuration, the liquid sample to be weighed is changed by changing the direction of the centrifugal force used to discharge the liquid sample, that is, by changing the position of the rotation axis that is the center of rotation when the chip is rotated. The volume of can be changed.

  Here, the shape of the measuring unit main body 202 is not particularly limited, and is appropriately selected in consideration of the amount to be measured. Further, the shape of the recess 207 is not particularly limited, and may be a U-shaped recess, or may be a recess having another shape such as a square shape. The number of the recesses may be one for a single weighing unit main body 202, or may be a plurality. In FIG. 2, the recess 207 is provided on the inner wall on the first opening 203 side, but may be provided on the inner wall on the second opening 204 side instead of or together with this. However, when one recess 207 is provided on each of the inner walls on the first opening 203 side and the second opening 204 side, they need to have different volumes. In addition, the internal diameter of the flow path 205 is not specifically limited, For example, it is about 50-1000 micrometers.

Next, a method for measuring a liquid sample using the chip of the present embodiment will be described with reference to FIG. The measurement method basically includes the following steps (a) and (b).
(A) a step of introducing a liquid sample into the measuring unit in the chip using a centrifugal force generated by rotation about the first rotation axis;
(B) Liquid measured using a centrifugal force generated by rotation about either the second rotating shaft or the third rotating shaft selected according to the volume of the liquid sample to be measured The process of discharging the sample from the measuring unit.

  Hereinafter, each step will be described in detail. First, a liquid sample is introduced from the first opening 203 into the measuring unit main body 202 using centrifugal force generated by rotation about the first rotation axis (step (a)). The first rotating shaft is, for example, a liquid sample introduced from an opening (not shown) for introducing a liquid sample into the fluid circuit of the chip, such as the rotating shaft A shown in FIG. It is a rotating shaft that provides a centrifugal force that allows it to flow into the body 202. Application of centrifugal force to the chip is typically performed by placing the chip on a rotating device and rotating the chip. At this time, the excess liquid sample is stored in the waste liquid reservoir 206 through the flow path 205. Thereby, the measuring unit main body 202 is filled with the liquid sample.

  In the subsequent step, the first opening 203 is utilized by utilizing the centrifugal force generated by the rotation about the second rotation axis or the third rotation axis selected according to the volume of the liquid sample to be weighed. Alternatively, the weighed liquid sample is discharged from the weighing unit through the second opening 204 (step (b)). In the chip of this embodiment, the volume of the liquid sample to be discharged differs depending on whether the liquid sample is discharged from the first opening 203 or the second opening 204, and the selection of the opening for discharging the liquid sample is selected. Depends on whether the second rotation axis or the third rotation axis is selected. Here, the second rotation shaft is, for example, the rotation shaft B shown in FIG. 2, and allows the liquid sample to be discharged from the measuring unit main body 202 through the second opening 204. It is a rotating shaft that provides centrifugal force. Further, the third rotation axis is a centrifuge that allows the liquid sample to be discharged from the measuring unit main body 202 through the first opening 203, for example, as the rotation axis C shown in FIG. A rotating shaft that provides force.

  For example, when the chip is rotated around the rotation axis B shown in FIG. 2, the liquid sample is discharged from the second opening 204, and the volume of the liquid sample discharged at this time is within the measuring unit main body 202. The volume of the liquid sample present in On the other hand, when the liquid sample is discharged by rotation about the rotation axis C, the liquid sample is discharged from the first opening 203. At this time, since the liquid sample remains in the recess 207, the first opening 203 is discharged. The volume of the liquid sample discharged from is smaller by the volume of the recess 207 than when discharged from the second opening 204. As described above, the volume of the liquid sample discharged from the measuring unit main body 202 can be changed by selecting the rotation axis, that is, by changing the direction of the centrifugal force. When the liquid sample is discharged, the liquid sample stored in the waste liquid reservoir 206 remains in the waste liquid reservoir 206 even by rotation around the second rotation shaft or the third rotation shaft. The liquid sample discharged from the measuring unit main body 202 is subjected to necessary processing in a portion different from the measuring unit in the chip. For example, a weighed liquid sample is mixed with a reaction reagent in a mixing section.

<Second Embodiment>
FIG. 3 is a plan view schematically showing the measuring unit in the chip according to the second embodiment of the present invention. The weighing unit 301 shown in FIG. 3 has a first weighing unit main body 302, one end of which is a first flow path 304 having a first opening 303, and a second weighing unit main body 305. , A third channel 308 whose one end is the second opening 307, a fourth channel 310 whose one end is connected to the first waste liquid reservoir 309, and one end thereof which is the second channel 308. And a fifth channel 312 connected to the waste liquid reservoir 311. The other end of the first channel 304, one end of the second channel 306, and the other end of the fourth channel 310 are connected to each other at the first junction 313, and the second channel The other end of the first flow path 306, the other end of the third flow path 308, and the other end of the fifth flow path 312 are connected to each other at the second junction 314. Thus, the measuring unit of the chip of this embodiment has a structure in which two measuring unit main bodies and two waste liquid reservoirs are connected via a plurality of flow paths. Further, the measuring unit main body 302 and the measuring unit main body 305 are not located at the same height, but the measuring unit main body 302 is arranged at a higher position. Here, “high” means that the distance from the first rotating shaft used for introducing the liquid sample into the measuring unit 301 is short. In addition, it is preferable that the internal diameter of each said flow path is thin enough, specifically, it is preferable that it is about 50-1000 micrometers, and it is more preferable that it is about 100-300 micrometers. Further, the first flow path 304 and the second flow path 306 are separated from the first rotation axis (for example, the rotation axis A in FIG. 3) as they go from the first opening 303 to the second opening 307. It is preferable that it inclines to.

  The structure of the measuring unit shown in FIG. 3 will be described in more detail. FIG. 4 is an enlarged plan view showing the first junction 313 in the present embodiment. As shown in FIG. 4, the first merging portion 313 is configured such that the wall surface I at the portion where the second flow path 306 and the fourth flow path 310 intersect is the first rotation axis and the first surface on the wall surface I. The straight line X is perpendicular to a line connecting the point a closest to the rotation axis, and is inclined in a direction away from the second rotation axis with respect to the straight line X passing through the point a. Here, the first rotating shaft is exemplified as the rotating shaft A in FIG. 3, for example, and the second rotating shaft is exemplified as the rotating shaft B in FIGS. 3 and 4, for example.

  FIG. 5 is an enlarged plan view showing the second junction 314 in the present embodiment. As shown in FIG. 5, the second merging portion 314 has a wall surface II where the second flow path 306 and the third flow path 308 or the fifth flow path 312 intersect with the third rotation axis. Is perpendicular to a line connecting the point b farthest from the first rotation axis on the wall surface II, and is inclined with respect to a straight line Y passing through the point b in a direction away from the third rotation axis. The Here, the first rotating shaft is exemplified as the rotating shaft A in FIG. 3, for example, and the third rotating shaft is exemplified as the rotating shaft C in FIGS. 3 and 5, for example. 5A, a wall surface II is a wall surface at a portion where the second flow path 306 and the fifth flow path 312 intersect. In FIG. 5B, the wall surface II is a second flow path. It is regarded as a wall surface at a portion where the path 306 and the third flow path 308 intersect.

  Here, the angle formed by the straight line X or Y and the wall surface I or II varies depending on where the second rotation axis or the third rotation axis is taken. In this embodiment, each rotation axis When at least one point is adopted, the above-described requirements regarding the wall surface I and the wall surface II may be satisfied. This is because the object of the present invention can be achieved if at least the rotating shaft is employed.

  According to the measuring section according to the present invention having the above-described configuration, the position of the rotation shaft with respect to the tip that changes the direction of the centrifugal force used for discharging the liquid sample, that is, the rotation center when the tip is rotated By changing the volume of the liquid sample to be weighed.

  Next, a method for measuring a liquid sample using the chip of the present embodiment will be described with reference to FIG. First, a liquid sample is introduced from the first opening 303 into the weighing unit main bodies 302 and 305 by using a centrifugal force generated by rotation about the first rotation axis (step (a)). The first rotating shaft is, for example, the rotating sample A as shown in FIG. 3, where the liquid sample introduced from an opening (not shown) for introducing the liquid sample into the fluid circuit of the chip is the measuring unit. A rotating shaft that provides a centrifugal force that allows it to flow into the bodies 302 and 305. Application of centrifugal force to the chip is typically performed by placing the chip on a rotating device and rotating the chip. At this time, the excess liquid sample is stored in the waste liquid reservoir 311 through the fifth channel 312. Thereby, the measurement part main bodies 302 and 305 are filled with the liquid sample.

  In the subsequent step, the first opening 303 is utilized by utilizing the centrifugal force generated by rotation about the second rotation axis or the third rotation axis selected according to the volume of the liquid sample to be weighed. Alternatively, the weighed liquid sample is discharged from the weighing unit through the second opening 307 (step (b)). In the chip of this embodiment, the volume of the liquid sample to be discharged differs depending on whether the liquid sample is discharged from the first opening 303 or the second opening 307, and the selection of the opening for discharging the liquid sample is selected. Depends on whether the second rotation axis or the third rotation axis is selected. Here, the second rotation axis is a rotation that causes a centrifugal force to allow the liquid sample to be discharged through the first opening 303, for example, the rotation axis B shown in FIG. Is the axis. Also, the third rotation axis is a rotation axis that provides a centrifugal force that allows the liquid sample to be discharged through the second opening 307, such as the rotation axis C shown in FIG. It is.

  For example, when the chip is rotated around the rotation axis B shown in FIG. 3, only the liquid sample weighed by the first weighing unit body 304 is discharged from the first opening 303, while the second weighing is performed. The liquid sample measured by the main body 305 is transferred to the first waste liquid reservoir 309 and is not discharged from the first opening 303. Therefore, the volume of the liquid sample that is substantially weighed and discharged is the volume of the liquid sample that is weighed by the first weighing unit body 302. On the other hand, when the tip is rotated around the rotation axis C, the liquid sample measured by the first measuring unit main body 302 and the second measuring unit main body 305 is discharged from the second opening 307. Become. As described above, the volume of the liquid sample discharged from the measuring unit can be changed by selecting the rotation axis, that is, by changing the direction of the centrifugal force.

<Third Embodiment>
FIG. 6 is a plan view schematically showing the measuring unit in the chip according to the third embodiment of the present invention. The weighing unit shown in FIG. 6 includes a first weighing unit main body 601 and a second weighing unit main body 602 with different internal volumes, which are vertically aligned on a substantially straight line. A flow path 604 having an opening 603 oriented in the direction of the second measuring unit main body 602 is connected to the bottom. Here, “substantially on a straight line” means that the second measuring unit main body 602 is disposed almost directly below the first measuring unit main body 601, and thereby the liquid sample that has flowed out from the opening 603 of the channel 604. To enter the second measuring unit main body 602. According to such a structure, liquid samples having different volumes can be measured according to the strength of the centrifugal force used for introducing the liquid sample.

  Here, the shapes of the first measuring unit main body 601 and the second measuring unit main body 602 are not particularly limited, and are appropriately selected in consideration of the amount to be measured. For example, it can be U-shaped as shown in FIG. Further, the internal volume of the first measuring unit main body 601 is preferably larger than the internal volume of the second measuring unit main body 602. The cross-sectional shape of the channel 604 is not particularly limited, and examples thereof include a square shape or a circular shape. The inner diameter of the flow path 604 is not particularly limited, and is about 50 to 1000 μm, for example.

Next, with reference to FIG. 6 as well, a method for measuring a liquid sample using the chip of this embodiment will be described. In FIG. 6, it is assumed that the internal volume of the first measuring unit main body 601 is larger than the internal volume of the second measuring unit main body 602. The measurement method basically includes the following steps (c) and (d).
(C) The liquid sample is introduced into the measuring unit in the chip by using the centrifugal force generated by the rotation about the first rotation axis, the strength of which is adjusted according to the volume of the liquid sample to be measured. Process,
(D) A step of discharging the weighed liquid sample from the weighing unit by using a centrifugal force caused by rotation about a rotation axis different from the first rotation axis.

  Hereinafter, each step will be described in detail. First, the liquid sample is introduced into the measuring unit in the chip by using the centrifugal force generated by the rotation about the first rotation axis, the strength of which is adjusted according to the volume of the liquid sample to be measured ( Step (c)). The introduced liquid sample is weighed by either the first weighing unit body 601 or the second weighing unit body 602. The first rotating shaft is, for example, a liquid sample introduced from an opening (not shown) for introducing the liquid sample into the fluid circuit of the chip, as in the rotating shaft A shown in FIG. This is a rotating shaft that provides a centrifugal force that allows the flow into the measuring unit main body 601. Application of centrifugal force to the chip is typically performed by placing the chip on a rotating device and rotating the chip.

  At this time, the strength of the centrifugal force caused by the rotation about the first rotation axis is selected according to whether the liquid sample is measured by the first measuring unit main body 601 or the second measuring unit main body 602. The That is, the flow path 604 is provided at the bottom of the first measuring unit main body 601, and the opening 603 is directed toward the second measuring unit main body 602, but the centrifugal force is relatively small. In other words, the liquid sample introduced into the first measuring unit main body 601 cannot pass through the flow path 604, remains in the first measuring unit main body 601, and is measured by the first measuring unit main body 601. On the other hand, when the centrifugal force is relatively large, the liquid sample passes through the flow path 604 to reach the second measuring unit main body 602 and is measured by the second measuring unit main body 602. Of the liquid sample transferred from the first measuring unit main body 601 to the second measuring unit main body 602, an excess amount exceeding the internal volume of the second measuring unit main body 602 is stored in a waste liquid reservoir (not shown). The

Here, the strength of the centrifugal force necessary for introducing the liquid sample into the second measuring unit main body 602 depends on the type of the liquid sample, the inner diameter of the flow path 604, and the like, and is appropriately determined depending on these. Adjusted. As a specific example, when the liquid sample is water, the channel 604 has a cross-sectional shape of 300 μm × 200 μm square, and the distance between the channel 504 and the rotation axis is 60 mm, the liquid sample The number of revolutions required to pass through the flow path 604 and be introduced into the second measuring unit main body 602 is about 500 to 700 rpm or more.
In the subsequent step, the weighed liquid sample is discharged from the weighing unit using a centrifugal force caused by rotation about a rotation axis different from the first rotation axis (step (d)). At this time, when the liquid sample has been weighed by the first measuring unit main body 601, a larger volume of the liquid sample has been discharged, and when the liquid sample has been weighed by the second measuring unit main body 602, A smaller volume of liquid sample is discharged. Thus, the volume of the liquid sample discharged from the measuring unit can be changed by changing the strength of the centrifugal force used for introducing the liquid sample.

  As described above, the chip of the present invention is characterized by the measuring section, but a conventionally known structure can be adopted for the structure other than the measuring section of the fluid circuit. FIG. 7 is a plan view schematically showing an example of the chip of the present invention. Hereinafter, with reference to FIG. 7, a blood sample testing method using the chip of the present invention will be briefly described. First, a blood sample such as whole blood, plasma, or serum is introduced into the fluid circuit from the sample introduction unit 701. The introduced blood sample is carried to the measuring unit 702 and weighed, for example, by a centrifugal force caused by rotation about the rotation axis D. The structure of the measuring unit 702 shown in FIG. 7 is merely conceptually described, and actually has a structure as shown in FIG. 2, FIG. 3, or FIG. In the chip of the present invention, as described above, different volumes of liquid are used depending on the centrifugal force used for introducing the liquid sample or the strength or direction of the centrifugal force used for discharging the liquid sample. It is possible to weigh the sample. Next, the weighed sample is carried to the first mixing unit 704 by, for example, centrifugal force caused by rotation about the rotation axis E, and is carried from the first reaction reagent holding unit 705 by centrifugal force in another direction. Mixed with reaction reagent 1. Next, the mixed solution is conveyed to the second mixing unit 706 and further mixed with the reaction reagent 2 conveyed from the first reaction reagent holding unit 707 by centrifugal force in another direction. The mixed liquid obtained in the second mixing unit 706 in this way is introduced into the detection unit 708, irradiated with light to the detection unit 708, and detected by the method of detecting the intensity of the emitted light, etc. The target component in the liquid mixture is detected. Note that another operation may be performed during the above series of operations. For example, a blood separation unit may be provided between the sample introduction unit 701 and the measurement unit 702, or a measurement unit may be provided between the reaction reagent holding unit 705 and the first mixing unit 704.

  The embodiment disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

It is a schematic diagram which shows the relationship between the direction of the centrifugal force applied to the measurement part main body which has a U-shaped structure at the time of liquid sample introduction, and the volume of the liquid sample measured. It is a top view which shows typically the measurement part in the chip | tip of the 1st Embodiment of this invention. It is a top view which shows typically the measurement part in the chip | tip of the 2nd Embodiment of this invention. It is a top view which expands and shows the 1st confluence | merging part in the 2nd Embodiment of this invention. It is a top view which expands and shows the 2nd junction part in the 2nd Embodiment of this invention. It is a top view which shows typically the measurement part in the chip | tip of the 3rd Embodiment of this invention. It is a top view which shows typically an example of the chip | tip of this invention. It is a top view which shows an example of the conventional chip | tip.

Explanation of symbols

  201, 301 Weighing unit, 202 Weighing unit main body, 203, 303 First opening, 204, 307 Second opening, 205, 604 Flow path, 206 Waste liquid reservoir, 207 Recess, 302, 601 First weighing unit main body, 304 1st flow path, 305, 602 2nd measuring part main body, 306 2nd flow path, 308 3rd flow path, 309 1st waste liquid reservoir, 310 4th flow path, 311 2nd waste liquid Reservoir, 312 5th flow path, 313 1st merge part, 314 2nd merge part, 603 opening.

Claims (9)

A liquid sample introduced by utilizing a centrifugal force caused by rotation about the first rotation axis is weighed , and the second rotation axis or the third rotation axis , which is different from the first rotation axis, is centered. A chip having a measuring section for discharging the measured liquid sample using centrifugal force generated by rotation,
The weighing unit is
One or more weighing unit bodies for weighing a liquid sample;
A first opening and a second opening for introducing and / or discharging a liquid sample;
A waste liquid reservoir of the same number as the measuring unit main body, connected to at least one of the measuring unit main body via a flow path,
Discharged using the volume of the weighed liquid sample discharged using the centrifugal force caused by rotation about the second rotation axis and the centrifugal force caused by rotation about the third rotation axis is the, and wherein different from the volume of metered liquid sample, Chi-up. The weighing unit is
A main body for measuring a liquid sample;
A first opening connected to one end of the weighing unit body;
A second opening connected to the other end of the weighing unit body;
A waste liquid reservoir connected to the measuring unit main body through a flow path,
2. The chip according to claim 1 , wherein an inner wall on the first opening side or an inner wall on the second opening side of the measuring unit main body has one or more concave portions having a constant volume. The weighing unit is
A first weighing unit body and a second weighing unit body coupled to each other;
A first waste liquid reservoir and a second waste liquid reservoir connected to the first measurement unit main body and the second measurement unit main body via a flow path,
The first metering unit main body and the second metering unit main body, and the first waste liquid reservoir and the second waste liquid reservoir are arranged to satisfy the following (i) and (ii). The chip according to claim 1 .
(I) When the measured liquid sample is discharged from the measuring unit by rotation about the second rotation axis, only the liquid sample measured by the first measuring unit main body is discharged.
(Ii) When the measured liquid sample is discharged from the measuring unit by rotation about the third rotation axis, the liquid measured by the first measuring unit main body and the second measuring unit main body The sample is discharged. The liquid sample measured by the first measuring unit main body is discharged from the first opening and measured by the second measuring unit main body by the rotation about the second rotation axis. A liquid sample is transferred to the first waste reservoir;
By rotation around the third rotation axis, said first liquid sample is weighed in the weighing unit body and the second metering body is discharged from said second opening, to claim 3 The chip described. The weighing unit is
A first flow path having the first metering unit body, one end of which is the first opening;
A second flow path having the second measuring unit body;
A third channel whose one end is the second opening;
A fourth flow path having one end connected to the first waste liquid reservoir;
A first flow path having one end connected to the second waste liquid reservoir,
The other end of the first flow path, one end of the second flow path, and the other end of the fourth flow path are connected to each other at a first junction.
The other end of the second flow path, the other end of the third flow path, and the other end of the fifth flow path are connected to each other at a second junction.
The wall surface I in the portion where the second flow path and the fourth flow path intersect in the first merge portion is the most similar to the second rotation axis and the first rotation axis on the wall surface I. Orthogonal to a line connecting the near point a and having a slope in a direction away from the second rotation axis with respect to a straight line passing through the point a,
A wall surface II at a portion where the second flow path and the third flow path or the fifth flow path of the second merge portion intersect the third rotation shaft and the wall surface II. Orthogonal to a line connecting the point b furthest to the first rotation axis and having a slope in a direction away from the third rotation axis with respect to a straight line passing through the point b, and
Wherein the first metering section body distance between the first axis of rotation, characterized in that less than the distance between the second measuring body and said first axis of rotation, according to claim 4 Chip. The first flow path and the second flow path are inclined in a direction away from the first rotation axis as they go from the first opening to the second opening, The chip according to claim 5 . A method for measuring a liquid sample using the chip according to any one of claims 1 to 6 , comprising the following steps (a) and (b):
(A) a step of introducing a liquid sample into the measuring unit in the chip using a centrifugal force generated by rotation about the first rotation axis;
(B) Liquid measured using a centrifugal force generated by rotation about either the second rotating shaft or the third rotating shaft selected according to the volume of the liquid sample to be measured The process of discharging the sample from the measuring unit. The introduced liquid sample is weighed using the centrifugal force caused by the rotation about the first rotation axis, and the centrifugal force caused by the rotation about the at least one rotation axis, which is different from the first rotation axis, is measured. A chip having a measuring unit for discharging the measured liquid sample by using the first measuring unit main body and the second measuring unit, which are vertically arranged on a substantially straight line and have different internal volumes. And a liquid sample using a chip having a flow path having an opening directed in the direction of the second measuring unit main body at the bottom of the first measuring unit main body . A method for weighing a liquid sample, comprising the following steps (c) and (d):
(C) The liquid sample is introduced into the measuring unit in the chip by using the centrifugal force generated by the rotation about the first rotation axis, the strength of which is adjusted according to the volume of the liquid sample to be measured. Process,
(D) A step of discharging the weighed liquid sample from the measuring unit using a centrifugal force generated by rotation about a rotation axis different from the first rotation axis. 9. The method for measuring a liquid sample according to claim 8, wherein the internal volume of the second measuring unit main body is smaller than the internal volume of the first measuring unit main body .

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