Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system

• US 10,309,976 B2
• Filed: 06/29/2015
• Issued: 06/04/2019
• Est. Priority Date: 06/30/2014
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: PHC Holdings Corporation
• Inventors: Johno, Masahiro, Okamoto, Fusatoshi
• Primary Examiner(s): White, Dennis
• Application Number:
  US15/322,910
• Publication Number:
  US 20170131304A1
• Time in Patent Office: 1,436 Days
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 33/487 of liquid biological material
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 35/00069 whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: G01N 35/00584 Control arrangements for automatic analysers

Abstract

A substrate for sample analysis has a rotation axis, a first chamber having a first space for retaining a liquid, a second chamber having a second space for retaining the liquid to be discharged from the first chamber, and a first channel having a path connecting the first chamber and the second chamber. The first space includes a first portion and a second portion, and a coupling portion located between the first and second portions. The substrate includes a wall portion partitioning the first and second portions from each other. The second chamber is more distant from the rotation axis than is the first portion. The coupling portion is closer to the rotation axis than is the wall portion. The second portion at least includes a portion which is more distant from the rotation axis than is the first portion.

Claims

1. A substrate for sample analysis on which transfer of a liquid is to occur with rotational motion, the substrate for sample analysis comprising:

a substrate having a rotation axis;

a first chamber being located in the substrate and having a first space for retaining a liquid;

a second chamber being located in the substrate and having a second space for retaining the liquid to be discharged from the first chamber; and

a first channel being located in the substrate and having a path connecting the first chamber and the second chamber, the first channel being capable of being filled via capillary action with the liquid retained in the first space, wherein,

the first space of the first chamber includes a first portion and a second portion, and a coupling portion being located between the first portion and the second portion and coupling the first portion and the second portion;

the substrate has a wall portion partitioning the first portion and the second portion of the first space from each other;

the second chamber is more distant from the rotation axis than is the first portion of the first chamber;

the coupling portion of the first space is closer to the rotation axis than is the wall portion of the substrate;

a portion of the first portion of the first space that is, as viewed from a direction which is parallel to the rotation axis, located outward of a circle which is centered around the rotation axis and whose radius is segment connecting the rotation axis and a point on the wall portion that is the closest to the rotation axis is ½

or less in volumetric capacity to that of the first space; and

the first channel is connected to the first portion of the first space.

2. The substrate for sample analysis of claim 1, wherein a distance from the rotation axis to a position on the first portion at which the first channel is connected is longer than a distance from the rotation axis to a point on the wall portion that is the closest to the rotation axis.

3. The substrate for sample analysis of claim 1, wherein the first portion of the first space includes a portion located outward of a circular arc which is centered around the rotation axis and whose radius is a line segment connecting the rotation axis and a point on the wall portion that is the closest to the rotation axis.

4. The substrate for sample analysis of claim 1, wherein the second portion of the first space includes a portion located outward of a circular arc which is centered around the rotation axis and whose radius is a line segment connecting the rotation axis and a point on the wall portion that is the closest to the rotation axis.

5. The substrate for sample analysis of claim 3, wherein the second portion of the first space includes a portion which is more distant from the rotation axis than is the first portion.

6. The substrate for sample analysis of claim 1, wherein the second space is greater in volumetric capacity than a portion of the first portion of the first space that is, as viewed from a direction which is parallel to the rotation axis, located outward of a circle which is centered around the rotation axis and whose radius is a line segment connecting the rotation axis and a point on the wall portion that is the closest to the rotation axis.

7. The substrate for sample analysis of claim 1, further comprising:

a third chamber being in the substrate located more distant from the rotation axis than is the second chamber and having a third space for retaining of the liquid to be discharged from the second chamber; and

a second channel being located in the substrate and having a path connecting the second chamber and the third chamber, the second channel capable of being filled via capillary action with the liquid that is retained in the second space.

8. The substrate for sample analysis of claim 7, wherein,

the second channel includes a first bent portion which is convex toward an opposite side from the rotation axis and a second bent portion which is convex toward the rotation axis, the first bent portion being located between the second bent portion and the second chamber;

a distance from the rotation axis to the third chamber is longer than a distance from the rotation axis to an apex of the first bent portion; and

a distance from the rotation axis to a liquid surface of the liquid that is retained in the third chamber as created by a centrifugal force due to rotation of the substrate is longer than a distance from the rotation axis to an apex of the second bent portion.

9. The substrate for sample analysis of claim 8, wherein,

the first channel includes a first bent portion which is convex toward an opposite side from the rotation axis and a second bent portion which is convex toward the rotation axis, the first bent portion being located between the second bent portion and the first chamber;

a distance from the rotation axis to the second chamber is longer than a distance from the rotation axis to an apex of the first bent portion; and

a distance from the rotation axis to a liquid surface of the liquid that is retained in the first chamber as created by a centrifugal force due to rotation of the substrate is longer than a distance from the rotation axis to an apex of the second bent portion.

10. The substrate for sample analysis of claim 1, further comprising a magnet located near the second chamber.

11. A sample analysis system comprising:

the substrate for sample analysis of claim 10; and

a sample analysis device, including

a motor to rotate the substrate for sample analysis around the rotation axis in a state where the rotation axis is inclined at an angle which is greater than 0°

but not more than 90°

with respect to the direction of gravity,

a rotation angle detection circuit to detect an angle of a shaft of the motor,

a drive circuit to control rotation and a stopping angle of the motor based on a result of detection by the rotation angle detection circuit, and

a control circuit including an arithmetic unit, a memory, and a program which is stored in the memory and executable by the arithmetic unit, to control based on the program an operation of the motor, the rotation angle detection circuit, the origin detector, and the drive circuit,

wherein,

when the substrate for sample analysis with the first chamber being filled with the liquid is placed on a turntable of the sample analysis device,

the program comprises the processes of;

(a) stopping the substrate for sample analysis at a predetermined first angle to allow a portion of the liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the liquid, and transfer another portion of the liquid to the first channel via capillary action,

(b) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the liquid in the first portion, move excess liquid to the second portion to thereby allow the remaining liquid to be retained in the second portion, and move the measured portion of the liquid in the first portion to the second chamber through the first channel,

(c) stopping the substrate for sample analysis at a predetermined second angle to allow a portion of the remaining liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the remaining liquid, and transfer another portion of the remaining liquid to the first channel via capillary action, and

(d) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the remaining liquid in the first portion, move excess liquid to the second portion to thereby allow the superfluous liquid to be retained in the second portion, and move the measured portion of the remaining liquid in the first portion to the second chamber through the first channel.

12. The sample analysis system of claim 11, further comprising, between the process (b) and the process (c), the processes of:

(e) stopping the substrate for sample analysis at a predetermined third angle to transfer a portion of the liquid in the second chamber to the second channel via capillary action; and

(f) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the second channel to, with a centrifugal force due to rotation of the substrate, move the liquid in the second chamber to the third chamber through the second channel.

13. The sample analysis system of claim 12, further comprising, after the process (d), the processes of:

(g) stopping the substrate for sample analysis at a predetermined fourth angle to transfer a portion of the liquid in the second chamber to the second channel via capillary action; and

(h) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the second channel to, with a centrifugal force due to rotation of the substrate, move the liquid in the second chamber to the third chamber through the second channel.

14. The sample analysis system of claim 11, wherein, in at least one of the processes (a) and (b), after stopping rotation of the substrate for sample analysis, the substrate is allowed to alternately rotate clockwise or counterclockwise by a predetermined angle.

15. A sample analysis device comprising:

a motor to rotate the substrate for sample analysis of claim 10 around the rotation axis in a state where the rotation axis is inclined at an angle which is greater than 0°

but not more than 90°

with respect to the direction of gravity,

a rotation angle detection circuit to detect an angle of a shaft of the motor,

a drive circuit to control rotation and a stopping angle of the motor based on a result of detection by the rotation angle detection circuit, and

a control circuit including an arithmetic unit, a memory, and a program which is stored in the memory and executable by the arithmetic unit, to control based on the program an operation of the motor, the rotation angle detection circuit, and the drive circuit,

wherein,

when the substrate for sample analysis with the first chamber being filled with the liquid is placed on a turntable of the sample analysis device,

the program comprises the processes of;

(a) stopping the substrate for sample analysis at a predetermined first angle to allow a portion of the liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the liquid, and transfer another portion of the liquid to the first channel via capillary action,

(b) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the liquid in the first portion, move excess liquid to the second portion to thereby allow the remaining liquid to be retained in the second portion, and move the measured portion of the liquid in the first portion to the second chamber through the first channel,

(c) stopping the substrate for sample analysis at a predetermined second angle to allow a portion of the remaining liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the remaining liquid, and transfer another portion of the remaining liquid to the first channel via capillary action, and

(d) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the remaining liquid in the first portion, move excess liquid to the second portion to thereby allow the superfluous liquid to be retained in the second portion, and move the measured portion of the remaining liquid in the first portion to the second chamber through the first channel.

16. A non-transitory computer-readable storage medium storing a program for a sample analysis system comprising:

the substrate for sample analysis of claim 7; and

a sample analysis device, including

a motor to rotate the substrate for sample analysis around the rotation axis in a state where the rotation axis is inclined at an angle which is greater than 0°

but not more than 90°

with respect to the direction of gravity,

a rotation angle detection circuit to detect an angle of a shaft of the motor,

a drive circuit to control rotation and a stopping angle of the motor based on a result of detection by the rotation angle detection circuit, and

a control circuit including an arithmetic unit, a memory, and a program which is stored in the memory and executable by the arithmetic unit, to control based on the program an operation of the motor, the rotation angle detection circuit, the origin detector, and the drive circuit,

wherein,

when the substrate for sample analysis with the first chamber being filled with the liquid is placed on a turntable of the sample analysis device,

the program comprises the processes of;

(a) stopping the substrate for sample analysis at a predetermined first angle to allow a portion of the liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the liquid, and transfer another portion of the liquid to the first channel via capillary action,

(b) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the liquid in the first portion, move excess liquid to the second portion to thereby allow the remaining liquid to be retained in the second portion, and move the measured portion of the liquid in the first portion to the second chamber through the first channel,

(c) stopping the substrate for sample analysis at a predetermined second angle to allow a portion of the remaining liquid to move within the first chamber based on gravity, fill at least a part of the first portion of the first chamber with the portion of the remaining liquid, and transfer another portion of the remaining liquid to the first channel via capillary action, and

(d) rotating the sample analysis substrate at a rate causing a centrifugal force which is stronger than a capillary force acting on the liquid filling the first channel to, with a centrifugal force due to rotation of the substrate, measure out a portion of the remaining liquid in the first portion, move excess liquid to the second portion to thereby allow the superfluous liquid to be retained in the second portion, and move the measured portion of the remaining liquid in the first portion to the second chamber through the first channel.