JP5224961B2 - Analytical devices and methods - Google Patents

Description

  The present invention relates to a rotationally driven analytical device, and more particularly to biological fluid metering in an analytical device used to measure biological fluids.

  Conventionally, as a method of analyzing a biological fluid, a method of analyzing using a microdevice having a liquid flow path is known. Microdevices can control fluids using a rotating device, and can use centrifugal force to measure samples, separate cytoplasmic materials, transfer and distribute separated fluids, etc. Biochemical analysis can be performed.

As shown in FIGS. 9A and 9B, the analytical device described in Patent Document 1 that uses centrifugal force to transfer a solution causes the sample liquid to flow into the inflow path 114 from the inlet 116 using an insertion instrument such as a pipette. The sample liquid is injected and transferred to the measurement cell 115 by the rotation of the analysis device, the sample liquid is sucked up by the capillary force acting on the flow path 117 by the rotation reduction or stop, and the rotation is accelerated again to measure the sample liquid. The sample liquid and the reagent 118 can be stirred by returning to the cell 115.
JP 2006-145451 A

  However, in Patent Document 1, since the measurement cell 115 is arranged at a right angle to the centrifugal direction, when the sample liquid in the measurement cell 115 is optically measured, there is no sample liquid for filling the measurement cell 115. A large amount is required and it is difficult to reduce the amount of the sample solution.

  Further, if the amount of the sample solution in the measurement cell 115, the volume of the flow channel 117, and the application position of the reagent 118 in the flow channel 117 are not accurately controlled, uneven stirring occurs, and if the specific gravity of the reagent is large, the measurement cell There is a possibility that the reagent is precipitated on the outer peripheral side of 115 and the measurement accuracy is lowered.

  Further, since the configuration of the stirring mechanism including the inflow path 114 for stirring the sample solution and the reagent, the measurement cell 115, and the flow path 117 is U-shaped, it is formed between the inflow path 114 and the flow path 117. Area is formed as a useless space, and there is a problem that it is not suitable for downsizing of the analysis device.

  SUMMARY OF THE INVENTION An object of the present invention is to solve the conventional problems, and to provide a device for analysis that can reduce the amount of a sample solution, eliminate uneven stirring between the sample solution and a reagent, and is suitable for downsizing.

  The analysis device according to claim 1 of the present invention has a microchannel structure for transferring a sample solution toward a measurement spot by centrifugal force generated by rotation driving, and is used for reading to access a reaction solution at the measurement spot. A first holding cavity that holds the sample liquid transferred by the centrifugal force, and is arranged adjacent to the first holding cavity in the circumferential direction of the rotational drive. An operation cavity, a connecting portion that is provided on a side wall of the first holding cavity and sucks the sample liquid held by the first holding cavity by capillary force and transfers the sample liquid to the operation cavity; Arranged in the outer peripheral direction of the rotational drive, communicated with the outermost peripheral position of the operation cavity via a connecting passage, and the operation cavity And a second holding cavity for holding the sample liquid transferred by centrifugal force, and the connecting portion of the operation cavity is held in the first holding cavity with respect to the rotational axis that generates the centrifugal force. It is characterized by being formed to extend in the outer peripheral direction from the liquid surface of the liquid.

  The analyzing device according to claim 2 of the present invention is characterized in that, in claim 1, the cross-sectional dimensions in the thickness direction of the operation cavity and the connecting portion are limited to a size on which a capillary force acts.

According to a third aspect of the present invention, there is provided the analytical device according to the first aspect, wherein a cavity opened to the atmosphere is formed on the inner peripheral side of the operation cavity.
The analysis device according to claim 4 of the present invention is characterized in that, in claim 3, the cavity is formed to be connected to the first holding cavity.

  The analysis device according to claim 5 of the present invention is the analysis device according to claim 1, wherein the cross-sectional dimension in the thickness direction of the connection passage is limited so that the capillary force of the connection passage is larger than the capillary force acting on the operation cavity. It is characterized by that.

  The analysis device according to claim 6 of the present invention is the analysis device according to claim 1, wherein a reagent is carried in the operation cavity, and a stirring rib extending in the radial direction is formed around the reagent. Features.

  In the analysis method according to claim 7 of the present invention, when the sample liquid is transferred toward the measurement spot of the analytical device by the centrifugal force generated by the rotation drive, the centrifugal force is transmitted by the centrifugal force via the communication path on which the capillary force acts. The sample liquid is transferred to the first holding cavity, and the rotation drive is stopped or decelerated so that the sample liquid in the first holding cavity is adjacent to the first holding cavity in the circumferential direction of the rotation drive. The sample is transferred to the arranged operation cavity via a connecting portion on the side wall of the first holding cavity, on which capillary force acts, and is quantified. The reagent disposed in the operation cavity is dissolved by rocking and stirring, and the sample solution in the operation cavity in which the reagent is dissolved is generated by centrifugal force generated by the rotation drive. Towards the measurement spot in the subsequent stage arranged in the outer circumferential direction of the rotary drive with respect to the operating cavity, the capillary force and wherein the transferring via a connecting passage to act.

  According to this configuration, by controlling the centrifugal force generated by the rotation drive, even a small amount of sample liquid moves between the first holding cavity and the operation cavity via the connecting portion, and is carried on the operation cavity. The reagent that has been added can be sufficiently stirred with the sample solution. The sample liquid in the operation cavity after stirring the reagent and the sample liquid is transferred to the second holding cavity through the connecting passage by controlling the centrifugal force generated by the rotation drive, and the permeability is measured here. Can be analyzed. Further, the analysis device can be miniaturized by arranging the first holding cavity and the operation cavity in the circumferential direction.

Hereinafter, embodiments of the present invention will be described with reference to FIGS.
(Embodiment 1)
1 to 6 show Embodiment 1 of the present invention.

  The external shape of the analyzing device 100 is a disk shape as shown in FIG. 3, and is driven to rotate about the rotation axis O. The posture of the analytical device 100 during the rotation is such that the rotation axis O is inclined so as to be inclined at a predetermined angle of 0 ° to 45 ° with respect to the horizontal. The predetermined angle is preferably in the range of 10 ° to 45 °.

  As shown in FIG. 4, the analysis device 100 includes a base substrate 1 having a microchannel liquid storage chamber 4, a first holding cavity 6, an operation cavity 9, second holding cavities 17 and 18, and the like. The cover substrate 2 that closes the opening is bonded to the adhesive layer 3.

FIG. 1 shows a perspective view of the main part of the base substrate 1, and FIG. 2 shows a plan view thereof. FIG. 5 shows an AA sectional view, a BB sectional view, and a CC sectional view in FIG.
A liquid storage chamber 4 is formed between the rotation center O and the first holding cavity 6 of the base substrate 1. A sample solution is injected into the liquid storage chamber 4 from the through hole 7. The liquid storage chamber 4 and the first holding cavity 6 are connected by a communication passage 5. A gap between the communication passage 5 and the cover substrate 2 is formed in a gap where a capillary force acts as shown in FIG.

  An operation cavity 9 is formed adjacent to the rotation center O in the circumferential direction of the first holding cavity 6 of the base substrate 1. A gap between the operation cavity 9 and the cover substrate 2 is formed in a gap where a capillary force acts, and the first reagents 10 and 11 are supported. In the operation cavity 9, a stirring rib 12 extending in the radial direction is formed around the first reagent 10, 11, specifically between the first reagent 10, 11. The cross-sectional dimension in the thickness direction of the stirring rib 12 and the cover substrate 2 is smaller than the cross-sectional dimension in the thickness direction of the operation cavity 9 with the cover substrate 2. A cavity 13 is formed on the inner peripheral side of the operation cavity 9, and the cavity 13 is connected to the first holding cavity 6 through the communication portion 14. A gap between the cavity 13 and the cover substrate 2 is formed in a gap where no capillary force acts. The cavity 13 communicates with the atmosphere via a through hole 15 formed in the first holding cavity 6.

  The first holding cavity 6 and the operation cavity 9 are connected via a connecting part 16 that extends from the side wall of the first holding cavity 6 through the communication part 14. As shown in FIG. 5B, the gap between the connecting portion 16 and the cover substrate 2 is formed in a gap where a capillary force acts. Here, the distal end of the connecting portion 16 is formed so as to extend in the outer peripheral direction with respect to the rotation axis from the liquid surface of the sample liquid held in the first holding cavity 6. More specifically, the leading end of the connecting portion 16 extends to the outermost peripheral portion of the first holding cavity 6.

On the outer peripheral side of the operation cavity 9, second holding cavities 17 and 18 are formed.
Of the second holding cavities 17, 18, the second holding cavity 17 on the inner peripheral side is deeper than the second holding cavity 18 on the outer peripheral side, and the second holding cavity 17 is connected via the connecting passage 19. Has been. The cross-sectional dimension in the thickness direction between the connecting passage 19 and the cover substrate 2 is limited to be larger than the capillary force acting on the operation cavity 9 in the gap where the capillary force acts as shown in FIG. ing. A communication hole 20 communicates with the atmosphere. A second reagent 21 is carried in the second holding cavity 18.

6A to 6D show the process of transferring the reagent.
After injecting the sample solution 50 into the liquid storage chamber 4 as shown in FIG. 6A, when the analysis device 100 is driven to rotate about the rotation axis O, the sample solution 50 passes through the communication passage 5 by centrifugal force. Then, it is transferred to the first holding cavity 6.

  With the sample solution 50 moved to the first holding cavity 6, the rotational drive of the analyzing device 100 is decelerated, or the outermost peripheral portion of the first holding cavity 6 is directed downward as shown in FIG. 6B. When the analysis device 100 is stopped in this state, the sample solution 50 in the first holding cavity 6 is transferred to the operation cavity 9 having a capillary force larger than that of the connecting portion 16 via the connecting portion 16 by the capillary force. It is transferred as shown in (c). In the state where the sample liquid 50 is sucked into the operation cavity 9, the space filled with the sample liquid 50 and the size of the gap are the same in the operation cavity 9, but a little not filled with the sample liquid 50. Space 9a remains.

  In the state shown in FIG. 6C, the sample solution 50 and the first reagents 10 and 11 come into contact with each other, and the first reagents 10 and 11 are dissolved in the sample solution. When the analyzing device 100 is swung by a predetermined angle around the rotation axis O in this state, the sample liquid 50 in the operation cavity 9 moves in the operation cavity 9 because of the space 9a, and this stirring is performed. At this time, it collides with the stirring rib 12 and is stirred more reliably. Thus, even when the specific gravity of the reagent is large, it acts more effectively so that the reagent does not precipitate.

  After sufficient stirring is performed in FIG. 6C, when the analytical device 100 is driven to rotate about the rotation axis O, the sample liquid in the operation cavity 9 passes through the connection passage 19 and passes through the second holding cavity. 17 and 18 and is held in the second holding cavity 18 on the outer peripheral side as shown in FIG. Since the second reagent 21 is carried in the second holding cavity 18 on the outer peripheral side, the analytical device 100 is swung at a predetermined angle around the rotation axis O in the state shown in FIG. Then, the second reagent 21 further dissolves in the sample solution.

  After the second reagent 21 is completely dissolved, the light 23 projected from the light source 22 onto the sample liquid in the second holding cavity 18 as a measurement spot on the outer peripheral side as shown in FIG. And is read by the photodetector 24 to perform analysis.

  Since it comprised in this way, even if it is a small amount of sample solutions, a sample solution can be reliably moved between the 1st holding | maintenance cavity 6 and the operation cavity 9, and the 1st reagents 10 and 11 can be dissolved. . In addition, the sample solution in the operation cavity 7 is transferred to the second holding cavities 17 and 18 and the second reagent 21 is dissolved to realize accurate measurement.

(Embodiment 2)
In the first embodiment, the case where the sample liquid is injected into the liquid storage chamber 2 and detected in the second holding cavity 18 at the end of the transfer of the sample liquid has been described as an example. However, FIGS. Embodiment 2 shown in FIG. 1 shows an analysis device in which a first holding cavity 6, an operation cavity 9, and second holding cavities 17 and 18 are provided during transfer.

In addition, the same code | symbol is attached | subjected and demonstrated to what comprises the effect | action similar to Embodiment 1. FIG.
In the case of the second embodiment, the base substrate 1 and the cover substrate 2 are bonded together as in the case of the first embodiment, and FIGS. 7 and 8 show the base substrate 1 of the second embodiment. .

  This analytical device dilutes blood as a sample liquid spotted on the blood spotting section 25 with a diluent set in the diluent storage section 26 to measure the measuring sections 27, 28, 29, 30, 31, The light 23 that has been transferred to the light source 22 and passed through the measuring units 27 to 32 from the light source 22 is appropriately read by the photodetector 24 to perform analysis.

  The blood spotted on the blood spotting part 25 is sucked up by the blood holding part 34 via the microchannel 33 formed between the cover substrate 2 and the blood. In this state, when the analysis device is driven to rotate about the central axis O, the blood is quantified in the blood quantification chamber 36 via the blood separation unit 35. Excess blood is collected in the blood discharge unit 37. The diluent is quantified in the diluent quantification chamber 38. Excess diluted solution is collected in the discharge unit 40 via the mixing unit 39.

The blood quantified in the blood quantification chamber 36 and the diluent quantified in the diluent quantification chamber 38 are mixed in the mixing unit 39 and transferred toward the liquid storage chamber 4.
The diluted blood serving as the sample liquid transferred toward the liquid storage chamber 4 is quantified in the diluted blood quantification chambers 41, 42, 43, and 44 where the capillary force acts.

  By rotating the analysis device again, the diluted blood quantified in the diluted blood quantification chambers 41 to 44 is transferred to the measuring units 27 to 30. The diluted blood quantified in the liquid storage chamber 4 where the capillary force acts passes through the connecting passage 5 and is transferred to the first holding cavity 6. The diluted blood in the first holding cavity 6 is sucked into the operation cavity 9 through the connecting portion 16.

Although not shown in the figure, the operation cavity 9 carries a reagent as in the first embodiment. Reagents are also carried on the measurement units 27 to 29 and 31.
By shaking the analytical device in this state, each reagent is dissolved by stirring, and the absorbance is measured while the analytical device is rotating. By rotating the analytical device, the diluted blood in the operation cavity 9 passes through the connecting passage 19 and is transferred to the second holding cavity 17. A part of the diluted blood in the second holding cavity 17 moves to the measurement unit 31 and is transferred to the measurement unit 32 through the siphon-shaped passage 45, and the absorbance is measured during the rotation of the analytical device.

  The present invention is useful as a weighing means for an analytical device used for component analysis of a liquid collected from a living organism or the like.

FIG. 3 is a perspective view showing a main part of the microchannel configuration of the base substrate of the analytical device according to the first embodiment of the present invention. The principal part top view which shows the microchannel structure of the base substrate of the device for analysis in the embodiment Plan view of the analyzing device of the embodiment Sectional drawing of the principal part of the analytical device of the embodiment AA, BB, CC sectional view of FIG. Process diagram of transfer process of the embodiment The perspective view which shows the microchannel structure of the base substrate of the device for analysis in Embodiment 2 of this invention The top view which shows the microchannel structure of the base substrate of the device for analysis in the embodiment Plan view and sectional view of conventional example

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 Analytical device O Rotational axis 1 Base substrate 2 Cover substrate 3 Adhesive layer 4 Liquid storage chamber 5 Communication passage 6 First holding cavity 7 Through hole 9 Operation cavity 10, 11 First reagent 12 Stirring rib 13 Cavity 14 Communication Unit 16 connection unit 19 connection channel 17, 18 second holding cavity 21 second reagent 25 blood spotting unit 27-30 measuring unit 33 microchannel 34 blood holding unit 35 blood separation unit 36 blood quantification chamber 37 blood discharge unit 38 Diluent determination chamber 39 Mixing section 41, 42, 43, 44 Dilution blood determination chamber

Claims (7)

An analytical device having a microchannel structure for transferring a sample solution toward a measurement spot by a centrifugal force generated by rotation driving, and used for reading to access a reaction solution at the measurement spot,
A first holding cavity for holding a sample liquid transferred by the centrifugal force;
An operation cavity disposed adjacent to the first holding cavity in the circumferential direction of the rotational drive;
A connecting portion that is provided on a side wall of the first holding cavity and sucks up the sample liquid held in the first holding cavity with a capillary force and transfers the sample liquid to the operation cavity;
A second arrangement is provided in the outer peripheral direction of the rotational drive with respect to the operation cavity, communicates with the outermost peripheral position of the operation cavity via a connection passage, and holds a sample liquid transferred from the operation cavity by centrifugal force. A holding cavity, and a connecting portion between the operation cavity and the first holding cavity is arranged in a more peripheral direction than a liquid surface of the sample liquid held in the first holding cavity with respect to a rotation axis that generates the centrifugal force. Analytical device that is formed by stretching. The analytical device according to claim 1, wherein a cross-sectional dimension of the operation cavity and the connecting portion in a thickness direction is limited to a size on which a capillary force acts. The analytical device according to claim 1, wherein a cavity opened to the atmosphere is formed on a side of an inner peripheral side of the operation cavity. The analytical device according to claim 3, wherein the cavity is formed so as to be connected to the first holding cavity. The analytical device according to claim 1, wherein a cross-sectional dimension in a thickness direction of the connection passage is limited so that a capillary force of the connection passage is larger than a capillary force acting on the operation cavity. The analytical device according to claim 1, wherein a reagent is supported in the operation cavity, and a stirring rib extending in a radial direction is formed around the reagent. When the sample liquid is transferred toward the measurement spot of the analytical device by the centrifugal force generated by the rotation drive,
The sample solution is transferred to the first holding cavity by the centrifugal force through the communication path on which the capillary force acts,
The rotary drive is stopped or decelerated, and the sample liquid in the first holding cavity is held in the operation cavity disposed adjacent to the first holding cavity in the circumferential direction of the rotary drive. Transfer through the connecting portion where the capillary force acts on the side wall of the cavity and quantify,
The analytical device is swung to agitate and stir the sample solution in the operation cavity to dissolve the reagent arranged in the operation cavity,
Capillary force acts toward the measurement spot at the subsequent stage arranged in the outer circumferential direction of the rotation drive with respect to the operation cavity by the centrifugal force generated by the rotation drive of the sample solution in the operation cavity in which the reagent is dissolved. Analysis method for transporting through a connecting passage.

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