One or more embodiments of the present invention relate to a micro liquid transfer structure utilizing a capillary action as a propulsive force to transfer a liquid, and more particularly, it relates to a micro liquid transfer structure in which a transfer direction of the liquid is optionally controllable, and an analysis device comprising such a micro liquid transfer structure.
In Patent Literature 1, a micro structure constituting a liquid flow system has been suggested in which a plurality of micro projections are arranged at intervals to cause a capillary action, thereby utilizing the capillary action as a propulsive force for transfer of a liquid.
Furthermore, in Non Patent Literature 1, there is investigated control of fluidity of a liquid in a flow system (a capillary pump) in which such a capillary action is utilized.
Patent Literature 1: Jpn. PCT National Publication No. 2005-532151
Non Patent Literature 1: Capillary pumps for autonomous capillary systems; Lab on a Chip, 2007, 7, 119 to 125
However, according to research by the present inventors, even a flow system of Non Patent Literature 1 is insufficient to control fluidity of a liquid with good reproducibility. For example,
The present inventors have earnestly repeated investigation, and in consequence, a reason for the deviation occurrence in the liquid transfer direction may be that, when the liquid flows between respective adjacent micro projections, there is not any difference in flow resistance of the liquid and hence the liquid transfer direction is not determined.
One or more embodiments of the present invention have been developed in view of the above circumstances to provide a micro liquid transfer structure which is constituted by arranging a plurality of micro projections at intervals to cause a capillary action, and in the micro liquid transfer structure, a difference is made in flow resistances of liquid transfer paths formed between the micro projections, thereby making it possible to optionally control a liquid transfer direction. One or more embodiments of the present invention provide an analysis device comprising such a micro liquid transfer structure.
A micro liquid transfer structure according to one or more embodiments of the present invention is directed to a micro liquid transfer structure which comprises a plurality of micro projections arranged at intervals which cause a capillary action and which has a constitution where there are periodically arranged unit rows in which the micro projections are arranged in one row and in which spaces between the adjacent micro projections are formed as liquid transfer paths, and in each of the unit rows, at least one of the liquid transfer paths is formed as a low flow resistance liquid transfer path in which a flow resistance is relatively lowered than in the other liquid transfer paths, and the low flow resistance liquid transfer path is disposed along a predetermined liquid transfer direction.
An analysis device according to one or more embodiments of the present invention comprises such a micro liquid transfer structure as described above, and has a constitution where a propulsive force is obtained by the micro liquid transfer structure to transfer a prepared liquid including an analysis target.
According to one or more embodiments of the present invention, when a propulsive force of liquid transfer is obtained by a micro liquid transfer structure in which a plurality of micro projections are arranged at intervals to cause, a capillary action, a liquid transfer direction is optionally controllable with good reproducibility and without causing any deviation in the liquid transfer direction.
Hereinafter, one or more embodiments of the present invention will be described with reference to the drawings.
[Analysis Device]
As shown in these drawings, an analysis device 1 is constituted as an influenza diagnostic kit by an immunochromatography method, and comprises a substrate 2, a cover 3 that covers the surface of the substrate 2, a conjugate pad 4 impregnated with a gold colloid labelled antibody that combines with an influenza antigen, and an absorbent pad 5 that absorbs a residual liquid after analysis.
In the surface of the substrate 2, there are formed a conjugate pad abutment portion 4a, a first capillary pump portion 6a, a liquid transfer flow path portion 7, a detecting section 8, a second capillary pump portion 6b, and an absorbent pad abutment portion 5a.
The detecting section 8 is provided with a test flow path 8a coated with a capture antibody that captures the influenza antigen combined with the gold colloid labelled antibody, and a control flow path 8b coated with a capture antibody that captures the gold colloid labelled antibody that is not combined with the influenza antigen. In one or more embodiments, as shown in
It is to be noted that
Furthermore, the first capillary pump portion 6a and the second capillary pump portion 6b are constituted in a micro liquid transfer structure that utilizes a capillary action as a propulsive force to transfer a prepared liquid including an analysis target, and such a micro liquid transfer structure will be described later.
The cover 3 can be made of a resin or a glass, and the cover 3 may be transparent to such an extent that the detecting section 8 formed on the surface of the substrate 2 can be seen through the cover 3. The cover 3 is joined to the substrate 2 so as to seal the first capillary pump portion 6a, the liquid transfer flow path portion 7, the detecting section 8 (the test flow path 8a and the control flow path 8b), and the second capillary pump portion 6b, while the conjugate pad 4 and the absorbent pad 5 are held in cutout portions 4b and 5b formed on one end side, respectively.
At this time, the conjugate pad abutment portion 4a is formed to be as deep as or slightly deeper than the bottom surface of the first capillary pump portion 6a so that the first capillary pump portion 6a sealed with the cover 3 opens on the side of the conjugate pad abutment portion 4a. Consequently, via this opening, the conjugate pad 4 is connected to the first capillary pump portion 6a.
Similarly, the absorbent pad abutment portion 5a is formed to be as deep as or slightly deeper than the bottom surface of the second capillary pump portion 6b so that the second capillary pump portion 6b sealed with the cover 3 opens on the side of the absorbent pad abutment portion 5a Consequently, via this opening, the absorbent pad 5 is connected to the second capillary pump portion 6b.
To diagnose whether or not a test subject is infected with influenza by use of the analysis device 1, a prepared specimen liquid including a specimen (an analysis target) suchas nasal mucus sampled from the test subject is first dropped to the conjugate pad 4.
The prepared specimen liquid dropped to the conjugate pad 4 exudes from the conjugate pad 4 and enters the first capillary pump portion 6a. Then, the prepared specimen liquid advances in the first capillary pump portion 6a by the capillary action as the propulsive force, and is transferred to the liquid transfer flow path portion 7. The prepared specimen liquid transferred to the liquid transfer flow path portion 7 flows in the liquid transfer flow path portion 7 by the capillary action, and is transferred to the detecting section 8 formed on the flow path.
A residual liquid of the prepared specimen liquid passed through the detecting section 8 reaches the second capillary pump portion 6h, and advances in the second capillary pump portion 6b by the capillary action as the propulsive force.
At this time, a flow length of the prepared specimen liquid increases, and as a result, a flow resistance also increases in a cumulative manner, so that a liquid transfer speed of the prepared specimen liquid decreases. However, the second capillary pump portion 6b is formed to be widened toward its end as shown in the drawing, and the number of liquid transfer paths 61 formed between micro projections 60 in the micro liquid transfer structure which will be described later increases toward a flow direction, thereby making it possible to inhibit the decrease of the liquid transfer speed due to the flow resistance. Consequently, the prepared specimen liquid can be transferred at a constant flow rate without using any external pump, thereby enabling analysis (diagnosis) with high reproducibility,
The residual liquid of the prepared specimen liquid advances in the second capillary pump portion 6b and is then absorbed in the absorbent pad 5.
When the prepared specimen liquid is dropped to the conjugate pad 4, the gold colloid labelled antibody impregnated into the conjugate pad 4 dissolves in the prepared specimen liquid. Then, if a patient is infected with influenza, the influenza antigen is contained in the prepared specimen liquid. Consequently, a part of the gold colloid labelled antibody dissolved in the prepared specimen liquid combines with the influenza antigen, and is transferred to the detecting section 8 formed on the flow path of the liquid transfer flow path portion 7, together with the residual gold colloid labelled antibody that is not combined with the influenza antigen.
As described above, the detecting section 8 is provided with the test flow path 8a coated with the capture antibody that captures the influenza antigen combined with the gold colloid labelled antibody, and the control flow path 8b coated with the capture antibody that captures the gold colloid labelled antibody that is not combined with the influenza antigen. Therefore, when the prepared specimen liquid is passed through the detecting section 8 and then a color generated by gold colloidal particles is visually recognized only in the control flow path 8b, it can be diagnosed that the test subject is not infected with influenza. On the other hand, when the color generated by the gold colloidal particles are visually recognized also in the test flow path 8a, it can be diagnosed that the test subject is infected with influenza.
[Micro Liquid Transfer Structure]
Next, there will be described the micro liquid transfer structure in which the capillary action is utilized as the propulsive force of the liquid transfer to transfer the prepared liquid including the analysis target in the analysis device 1 mentioned above.
As shown in
Furthermore, in one or more embodiments, the micro projections 60 are uniformly arranged so that the liquid transfer paths 61 formed into one unit row and the liquid transfer paths 61 formed into a unit row adjacent to this one unit row are positioned alternately as shown in the drawing. Consequently, when the liquid passes through the liquid transfer paths 61 formed into the one unit row by the capillary action and the liquid surface comes in contact with the micro projections 60 of the adjacent unit row, the liquid spreads between these unit rows by the capillary action, and then these are repeated. Then, due to the above arrangement, the liquid transfer paths of the liquid by the capillary action are formed as in a parallel circuit, and the flow resistance can be decreased as compared with a case where the liquid transfer paths are formed as in a series circuit, so that the propulsive force of the liquid transfer in which the capillary action is utilized can efficiently be obtained.
Furthermore, as shown in
Here, as shown in
As shown in
That is, the pinning angle of an edge portion 62b formed on the outlet side of the liquid transfer path 61b of adjacent micro projections 60b and 60c which form the other liquid transfer paths 61b exclusive of the low flow resistance liquid transfer path 61a is decreased than the pinning angle of an edge portion 62a formed on the outlet side of the low flow resistance liquid transfer path 61a of adjacent micro projections 60a and 60b which form the low flow resistance liquid transfer path 61a, whereby the flow resistance of the low flow resistance liquid transfer path 61a is relatively lowered than flow resistances of the other liquid transfer paths 61b.
As shown in
Furthermore, in
Thus, as shown in
Consequently, according to one or more embodiments, the capillary action can be utilized to transfer the liquid, so that it is possible to suitably control fluidity with good reproducibility and without causing any deviation in the liquid transfer direction.
Furthermore, in the analysis device 1 mentioned above, each of the first capillary pump portion 6a and the second capillary pump portion 6b is formed into an isosceles triangular shape, and the low flow resistance liquid transfer portion 61a is arranged along a perpendicular line drawn from a vertex of the triangle to a base thereof, whereby the propulsive force of the liquid transfer by utilizing the capillary action in the micro liquid transfer structure can efficiently be obtained. However, the arrangement of the low flow resistance liquid transfer portion 61a can suitably be set in accordance with a desirable liquid transfer direction.
In one or more embodiments, when it is desired to curve the liquid transfer direction as shown in
Thus, according to one or more embodiments, in obtaining the propulsive force of the liquid transfer by the micro liquid transfer structure comprising the plurality of micro projections arranged at the intervals which causes the capillary action, the liquid transfer direction can optionally be controlled with good reproducibility and without causing any deviation in the liquid transfer direction.
In the above, the present invention has been described with reference to one or more embodiments. However, the present invention is not limited to the above-mentioned embodiments, and various changes and operations can be carried out in the scope of the present invention.
In one or more embodiments concerned with the micro liquid transfer structure, to relatively lower the flow resistance of the low flow resistance liquid transfer path 61a than the flow resistances of the other liquid transfer paths 61b, the edge portions 62 which develop the pinning effect are formed on the outlet side of the liquid transfer path 61 of the adjacent micro projections 60 which form the liquid transfer path 61, and the pinning angle of the edge portion 62 is suitably set, thereby relatively decreasing the flow resistance of the low flow resistance liquid transfer path 61a than the flow resistances of the other liquid transfer paths 61b, but the present invention is not limited to this embodiment.
The flow resistance of the low flow resistance liquid transfer path 61a may relatively be lowered than the flow resistances of the other liquid transfer paths 61b in one or more embodiments, as follows.
1) The edge portions 62 which develop the pinning effect are formed on the outlet side of the liquid transfer paths 61b only in the adjacent micro projections 60 which form the other liquid transfer paths 61b, and in one or more embodiments, a shape on the outlet side of the liquid transfer path 61a of the adjacent micro projections which form the low flow resistance liquid transfer path 61a is adjusted into a rounded shape that does not develop any pinning effect, thereby relatively lowering the flow resistance of the low flow resistance liquid transfer path 61a than the flow resistances of the other liquid transfer paths 61b.
2) A region on the other liquid transfer path 61b side of the adjacent micro projections 60 which form the other liquid transfer paths 61b is subjected to a hydrophobic treatment to increase the flow resistance, thereby relatively lowering the flow resistance of the low flow resistance liquid transfer path 61a than the flow resistances of the other liquid transfer paths 61b.
3) A sectional area of the low flow resistance liquid transfer path 61a is increased, thereby relatively lowering the flow resistance of the low flow resistance liquid transfer path 61a than the flow resistance of the other liquid transfer path 61b.
Furthermore, in one or more embodiments, the intervals between the adjacent unit rows are suitably adjusted to relatively lower the flow resistance of the inter-row liquid transfer path 61c formed between the unit rows than the flow resistance of the low flow resistance liquid transfer path 61a, but the present invention is not limited to this embodiment. By use of a technique shown in each of the above 1) to 3) or the like, the flow resistance of the inter-row liquid transfer path 61c may relatively be lowered than the flow resistance of the low flow resistance liquid transfer path 61a.
Furthermore, the shape of the micro projection 60 is not limited to that of the above-mentioned embodiments, and can suitably be designed in such a range that does not obstruct the effect of the present invention.
Additionally, in one or more embodiments concerned with the analysis device, the test flow path 8a and the control flow path 8b provided in the detecting section 8 are formed into the wide and shallow bottom, and their bottom surfaces are coated with the capture antibody, but the present invention is not limited to this embodiment. As shown in
It is to be noted that
Furthermore, in one or more embodiments concerned with the analysis device, the influenza diagnostic kit has been described, but the present invention is not limited to this embodiment. One or more embodiments of the present invention are applicable to various analysis devices in each of which the capillary action is utilized for acquirement of the propulsive force to transfer a prepared liquid including an analysis target without using any external pump as liquid transfer means.
Next, one or more embodiments of the present invention will be described in more detail with reference to specific examples.
In a mold prepared by performing micro processing in accordance with a photolithography method, polydimethylsiloxane (SILPOT184 manufactured by Dow Corning Toray and having a weight ratio of 10:1 to a hardener) was cast, and a substrate was formed so that a capiliary pump (a micro liquid transfer structure) of the same arrangement as shown in
The procedure of Example 1 was repeated except that a capillary pump having all micro projections arranged in the same manner as in micro projections 60a shown in
The procedure of Example 1 was repeated except that a capillary pump having all micro projections arranged in the same manner as in micro projections 60c of an example shown in
[Evaluation]
As a prepared liquid, 3% TRITON-X100 (manufactured by The Dow Chemical Company) was used, and dropped at a drop rate of 5 μL into an input port provided in a cover. The prepared liquid flowing in a capillary pump by a capillary force was photographed with a digital microscope (VHK-1000 manufactured by Keyence Corporation), and a time for which the prepared liquid passed through the capillary pump was measured, whereby a variability of the flow rate (coefficient of variation; CV) was calculate. The measurement was carried out five times, and Table 1 shows the average value. Table 1 also shows that evaluation of a micro liquid transfer structure having a CV of 5% or less is represented by “o”, which indicates the good structure capable of stably transferring a liquid, and shows that evaluation of a micro liquid transfer structure having a CV in excess of 5% is represented by “x”.
One or more embodiments of the present invention are applicable and utilizable not only to analysis devices in medical fields as influenza diagnostic kits and others but also to analysis devices in various fields.
There are herein referred to all contents of the literatures described in this description and the Japanese application based on the Paris convention.
Although the disclosure has been described with respect to only a limited number of embodiments, those skilled in the art, having benefit of this disclosure, will appreciate that various other embodiments may be devised without departing from the scope of the present invention. Accordingly, the scope of the invention should be limited only by the attached claims.
1 analysis device
60 (60a, 60b and 60c) micro projections
61 liquid transfer path
61
a low flow resistance liquid transfer path
61
b another liquid transfer path
61
c inter-row liquid transfer path
62 (62a and 62b) edge portion
Number | Date | Country | Kind |
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2014-242226 | Nov 2014 | JP | national |
Number | Date | Country | |
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Parent | PCT/JP2015/005904 | Nov 2015 | US |
Child | 15606014 | US |