The present invention relates to an analytical tool used for analyzing a particular component contained in a sample liquid (such as blood or urine, for example).
In an analysis method, reaction liquid obtained upon reaction of a sample and a reagent is analyzed by an optical technique, for example. In such a method for analyzing a sample, use is made of an analytical tool for providing a reaction field. For example, there exist analytical tools which are designed to remove solid components in the sample liquid before the sample liquid is supplied to reagent portions. Examples of such analytical tools include one shown in
The analytical tool 9A shown in
The analytical tool 9B shown in
In the analytical tools 9A and 9B, the removal of solid components at the filters 92, 98 is performed mainly when the sample liquid moves in the plane direction of the filters 92, 98. Therefore, in the analytical tools 9A and 9B, a large filtration length can be attained, so that efficient removal of solid components is expected. On the other hand, however, there is a fear that the removal of solid components takes long time and the measurement time becomes long due to the large filtration length and a long retention time of the sample liquid in the filters 92, 98. Such a fear is serious in an analytical tool designed to move a sample liquid by utilizing capillary action. Moreover, in such an analytical tool as a microdevice which has a flow path of a small sectional area, the movement of a sample liquid through the small flow path by capillary action becomes difficult when the sample liquid has a high viscosity. In such a case again, the above fear is serious.
When a sample liquid is moved by utilizing motive power of a pump as is in the analytical tool 9B, the sample liquid can be moved relatively easily, so that the above fear relating to the measurement time is not serious. However, since the apparatus for performing analysis by using the analytical tool 9B need be provided with a pump, the cost for the apparatus increases correspondingly. Moreover, the use of the pump increases the cost required for a single time of measurement.
An object of the present invention is to provide an analytical tool which is capable of removing solid components contained in a sample liquid without increasing the measurement time and which is advantageous in terms of cost.
According to the present invention, there is provided an analytical tool comprising a liquid introduction port, one or a plurality of flow paths for moving a sample liquid introduced through the liquid introduction port, and a separation film for filtering the sample liquid supplied to the liquid introduction port and then introducing the sample liquid to the one or a plurality of flow paths. The sample liquid is caused to move through the separation film in the thickness direction of the separation film for filtration.
In the analytical tool, the sample liquid is moved in the thickness direction of the separation film for removal of solid components contained in the sample liquid. Therefore, as compared with the structure in which the sample liquid is moved in the plane direction of the separation film, the retention time of the sample liquid in the separation film becomes shorter. As a result, the sample liquid does not receive so high resistance in the separation film and can pass through the separation film in a relatively short period of time. Thus, the time necessary for the removal of solid components and the measurement time can be shortened. Since the resistance in the movement of the sample liquid is low, the sample liquid can be moved by capillary action. Therefore, the sample liquid need not be moved by utilizing the motive power of a pump, so that the apparatus for performing measurement by using the analytical tool can be manufactured at a relatively low cost. Moreover, since the motive power of a pump need not be utilized, the measurement cost can be reduced correspondingly.
Since the movement resistance in the separation film can be reduced, the analytical tool can be structured as a microdevice which utilizes capillary action in a small flow path. In this case, one or a plurality of flow paths may have a principal, rectangular cross section which has a width of 10˜500 μm and a depth of 5˜500 μm and which satisfies depth/width 0.5. The “principal cross section” herein indicates a vertical section extending perpendicularly to the travel direction of the sample liquid, and indicates the vertical section of a portion which is mainly utilized for traveling the sample liquid when the sectional configuration is not uniform.
Preferably, to promote the movement of the sample liquid through the flow path, one or plurality of flow paths may have a hydrophilically-treated inner surface. The hydrophilization may be so performed that the contact angle of pure water at the inner surface becomes 0˜80 degrees, and preferably 0˜60 degrees.
As the sample liquid, a biochemical sample such as urine or blood may be used, and typically, blood may be used.
For example, the separation film is positioned higher than one or plurality of flow paths. With such an arrangement, the sample liquid can be moved in the thickness direction of the separation film so that solid components can be removed at the separation film. For example, the analytical tool may further comprise a liquid receiving portion for retaining the sample liquid passed through the separation film, and the liquid receiving portion communicates with the liquid introduction port and one or plurality of flow paths. Preferably, in this case, the separation film is spaced from the bottom surface of the liquid receiving portion.
For example, the analytical tool of the present invention may comprise a substrate in which the liquid receiving portion is formed, a cover in which the liquid introduction port is formed, and an adhesive layer interposed between the substrate and the cover and including a through-hole for fitting the separation film.
When the analytical tool includes a plurality of flow paths, it is preferable that the flow paths extend radially from the liquid receiving portion.
The separation film may be selected depending on the size of a solid component to be removed, and for example, a porous material may be used. Examples of porous material which is usable as the separation film include paper, foam (expanded material), a woven material, a non-woven material, a knitted material, a membrane filter, a glass filter, or a gel material. When the sample liquid is blood and blood cells in the blood are to be separated at the separation film, it is preferable to use, as the separation film, a material whose minimum pore diameter (pore size) is 0.1˜3.0 μm.
For example, the analytical tool may comprise reagent portions for reaction with the sample liquid, and a plurality of flow paths for moving the sample liquid. In this case, the reagent portions provided in at least two of the flow paths are different from each other in reagent included therein. In this case, the tool is adapted to measure a plurality of items from a single kind of sample liquid. Preferably, the reagent portions of the at least two flow paths are arranged on a common circle.
Preferably, each of the flow paths is structured to temporarily retain the sample liquid upstream from the reagent portion before the sample liquid is introduced to the reagent portion. Specifically, the analytical tool further comprises a branching flow path branched from a channel set in the flow path. The sample liquid is temporarily retained at the channel in the flow path by bringing the branching flow path into communication with the outside through a portion other than the liquid introduction port, and the sample liquid is caused to move through the flow path beyond the channel by bringing the flow path into communication with the outside through a portion other than the liquid introduction port. Preferably, the flow path is connected to a gas discharge port for discharging gas from the flow path, and the sample liquid is caused to move beyond the channel by opening the gas discharge port.
As better shown in
The substrate 5 comprises a transparent circular disk having a circumferential edge which is stepped downwardly. As shown in
The liquid receiving portion 50 serves to retain a sample liquid supplied to the microdevice Y for introduction to each of the flow paths 51. The liquid receiving portion 50 comprises a circular recess formed on an upper surface 5A of the substrate 5.
Each of the flow paths 51 serves to move the sample liquid and is formed on the upper surface 5A of the substrate 5 so as to communicate with the liquid receiving portion 50. As shown in
As shown in
Each of the reaction portions 51B has a sectional area which is larger than that of the principal cross section of the flow path 51. The reaction portions 51B are arranged on a common circle. As shown in
The reagent portion 54 comprises a solid which dissolves when a sample liquid is supplied thereto and exhibits a color upon reacting with a particular component contained in the sample liquid. In this embodiment, a plurality of kinds of reagent portions 54 which differ from each other in components or composition are prepared so that a plurality of items can be measured in the microdevice Y.
Each of the recesses 52 serves to emit a light toward the lower surface 5B side of the substrate 5 when the reaction portion 51B is irradiated with light from the upper surface 5A side of the substrate 5 and the light is transmitted to the recess, as will be described later (See
For example, the substrate 5 is made by molding a transparent resin material such as acrylic resin such as polymethyl methacrylate (PMMA), or polystyrene (PS), polycarbonate (PC) or polyethylene terephthalate (PET). The liquid receiving portion 50, the flow paths 51, the recesses 52 and the branching flow paths 53 can be made at the same time in the resin-molding process by appropriately designing the configuration of the mold.
Preferably, the inner surfaces of the liquid receiving portion 50, the flow paths 51, the recesses 52 and the branching flow paths 53 are hydrophilically treated. Although various known techniques for hydrophilization can be employed, it is preferable that hydrophilization is performed by bringing a mixed gas containing fluorine gas and oxygen gas into contact with each inner surface and then bringing water or water vapor into contact with the inner surface. Unlike a prior art hydrophilization technique such as ultraviolet irradiation, this method is capable of hydrophilically treating a standing surface (side surface of a flow path, for example) as well, because this method utilizes gas and water for hydrophilization. The hydrophilization with respect to each inner surface is so performed that the contact angle of pure water at the inner surface becomes 0˜80 degrees, and preferably 0˜60 degrees.
The cover 6 is in the form of a circular disk having a downwardly projecting circumferential edge. The projection 60 of the cover 6 serves to engage the stepped, smaller-thickness portion of the substrate 5. As shown in
The sample introduction port 61, which is used for introducing a sample liquid, comprises a through-hole. As better shown in
Each of the first gas discharge ports 62, which are used for discharging gas from the flow paths 51, comprises a through-hole. As better shown in
The recesses 63 are utilized for irradiating the reaction portions 51B with light from the upper surface 6A side of the cover 6, as will be described later (See
The common flow path 64 serves to guide gas to the second gas discharge port 65 in discharging gas in the fluid paths 51 to the outside. As shown in
As shown in
Similarly to the substrate 5, the cover 6 may be made by resin-molding using a transparent resin material. The sample introduction port 61, the first gas discharge ports 62, the recesses 63, the common flow path 64 and the second gas discharge port 65 can be made at the same time in the resin-molding process. It is preferable that the cover 6 as well is hydrophilically treated at least at the portion facing the flow paths 51 of the substrate 5. The hydrophilization can be performed by the same technique as that for the substrate 5.
As better shown in
The separation film 8 serves to separate solid components contained in a sample liquid such as blood cells in blood. As shown in
As the separation film 8, a porous material may be used, for example. Examples of porous material used as the separation film 8 includes paper, foam (expanded material), an woven material, a non-woven material, a knitted material, a membrane filter, a glass filter, or a gel material. When the sample liquid is blood and blood cells in the blood are to be separated in the separation film 8, it is preferable to use, as the separation film 8, a material whose minimum pore diameter (pore size) is 0.1˜3.0 μm.
The mount portion 1 shown in
The light source 2 serves to irradiate the reaction portions 51B of the microdevice Y with light and is fixed at a position for facing the recesses 63 of the cover 6. The light source 2 may comprise a mercury lamp or a white LED, for example. Though not illustrated, when such a light source is used, the light from the light source 2 is caused to pass through a filter before reaching the reaction portions 51B. By using such a filter, it is possible to select a light of an appropriate wavelength in accordance with the light absorption characteristics of the substance as an object to be analyzed contained in the reaction liquid.
The light receiving portion 3 serves to receive light passed through the reaction portion 51B and is fixed at a position for facing the recesses 52 of the substrate 5. The amount of light received by the light receiving portion 3 is used as the base for the analysis of the sample liquid (for the concentration computation, for example). The light receiving portion 3 may comprise a photodiode, for example.
The opening mechanism 4 includes a first hole-making member 41 for making a hole in the seal portion 62a, and a second hole-making member 42 for making a hole in the seal portion 65a. The hole-making members 41 and 42 are reciprocally movable up and down by the operation of a non-illustrated actuator.
The first hole-making member 41 includes a substrate 41a in the form of a circular disk, and a plurality of needles 41b projecting downward from the lower surface of the substrate. As shown in
As shown in
The method for opening the first and the second gas discharge ports 62, 65 is not limited to those described above. For example, the first and the second gas discharge ports 62, 65 may be opened by melting or deforming the sealing members 62a, 65a by applying energy to the sealing members 62a, 65a. The energy application may be performed by using a light source such as a laser, an ultrasonic generator or a heating element, for example. Alternatively, the gas discharge ports 62, 65 may be opened by peeling off the sealing members 62a, 65a.
For analyzing a sample liquid, the sample liquid S is supplied to the microdevice Y through the sample introduction port 61. The supply of the sample liquid S may be performed after the microdevice Y is mounted to the analytical apparatus X. However, it is preferable that the microdevice Y is mounted to the analytical apparatus X after the sample liquid S is supplied to the microdevice Y.
As will be understood from
In this embodiment, solid components are removed by moving the sample liquid in the thickness direction of the separation film 8. Therefore, as compared with the structure in which solid components are removed by moving the sample liquid in the plane direction of the separation film 8, the retention time of the sample liquid in the separation film 8 becomes shorter. Therefore, the time necessary for removing solid components becomes shorter.
To introduce the sample liquid S to the flow paths 51, holes are made simultaneously with respect to the plurality of seal portions 62a. As shown in
When the holes are made at the seal portions 62a, the interior of the flow paths 51 are brought into communication with the outside through the first gas discharge ports 62 and the branching flow paths 53. Therefore, the sample liquid S retained in the liquid receiving portion 50 moves through the flow paths 51 by capillary action. As indicated by arrows in
To guide the sample liquid s to the reaction portion 51B, a hole is made at the seal portion 65a. As shown in
When the hole is made at the seal portion 65a, the interior of each flow path 51 is brought into communication with the outside through the second gas discharge port 65 and the common flow path 64. Therefore, the sample liquid S, which has stopped upstream from the reaction portion 51B, moves again through the flow path 51 by capillary action. Thus, as shown in
At each of the reaction portions 51B, the reagent portion 54 is dissolved by the sample liquid to establish a liquid phase reaction system. As the sample liquid S reacts with the reagent, the liquid phase reaction system exhibits a color depending on the amount of the substance to be detected in the sample or a reaction product is produced in accordance with the amount of the substance to be detected. As a result, the liquid phase reaction system of the reaction portion 51B exhibits light transmission characteristics (light absorption characteristics) depending on the amount of the substance to be detected. When a predetermined time period has elapsed from the sample supply to the reaction portion 51B, the reaction portion 51B is irradiated with light from the light source 2 shown in
In the above-described analysis method, after the sample liquid S is guided to a portion (each channel 51A) close to the reaction portion 51B, the sample liquid S is supplied from the channel 51A to the reaction portion 51B by opening the seal portion 65a. Thus, the sample liquid S can be supplied to the reaction portions 51B of the plurality of flow paths 51 just by opening a single gas discharge port. Therefore, the time taken from when the operation to supply the sample liquid S is performed (the seal portion 65a is opened) until when the sample liquid reaches the reaction portions 51B can be shortened. Accordingly, variation of the time taken from the sample supply starting operation to the completion of the sample supply among the flow paths 51 and among each measurement (among analytical tools) can be reduced. Thus, the timing at which the reaction starts at the reaction portions 51 can be properly controlled by the operation of opening the seal portion 65a. Particularly, in this embodiment, the sample liquid can be supplied simultaneously to the plurality of reaction portions 51B just by opening a single gas discharge port. Therefore, it is possible to make the reaction time uniform among the reaction portions 51B and among a plurality of microdevices Y, whereby the measurement error can be reduced.
The present invention is not limited to the foregoing embodiments and may be modified in various ways. For example, the present invention is applicable to such a microdevice as shown in
In the analytical tool Y′, the sample liquid and the reagent liquid respectively supplied through the sample introduction port 61A and the reagent introduction port 61B move in the thickness direction of the separation film 8′ to reach the liquid receiving portions 50A and 60B. Thereafter, the sample liquid and the reagent liquid move to the reaction portion 51B′ by capillary action and undergo reaction at the reaction portion 51B′. The reaction product is analyzed by an optical method.
In the analytical tool Y′ shown in
Although the analysis based on the light which is transmitted when the reaction portion is irradiated with light is described in the foregoing embodiments, the present invention is also applicable to the sample analysis based on the light reflected from the reaction portion. The irradiation of the reaction portion and the measurement of the transmitted light need not necessarily be performed individually with respect to each reaction portion but may be performed collectively with respect to the plurality of reaction portions.
The present invention is applicable to an analytical tool which is designed to move a mobile component by capillary action. Therefore, the invention is applicable to a tool for performing analysis by an electrochemical method as well as that for performing analysis by an optical method. Moreover, the invention is applicable not only to an analysis method in which a sample is moved but also to an analysis method in which a reagent is moved instead of a sample and a method in which a sample and a reagent are moved together with a carrier liquid. The application of the present invention is not limited to microdevices, and the invention is also applicable to other types of analytical tools.
Number | Date | Country | Kind |
---|---|---|---|
2002-281101 | Sep 2002 | JP | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/JP03/12295 | 9/25/2003 | WO | 00 | 3/25/2005 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2004/029619 | 4/8/2004 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
4753776 | Hillman et al. | Jun 1988 | A |
4868129 | Gibbons et al. | Sep 1989 | A |
5460974 | Kozak et al. | Oct 1995 | A |
6315738 | Nishikawa et al. | Nov 2001 | B1 |
6383452 | Miyake et al. | May 2002 | B1 |
6615856 | McNeely et al. | Sep 2003 | B2 |
6632399 | Kellogg et al. | Oct 2003 | B1 |
20010028862 | Iwata et al. | Oct 2001 | A1 |
20040121356 | Yamagata et al. | Jun 2004 | A1 |
20060008381 | Taguchi et al. | Jan 2006 | A1 |
Number | Date | Country |
---|---|---|
0 698 413 | Aug 1995 | EP |
0 806 666 | Feb 1997 | EP |
1 329 717 | Oct 2001 | EP |
63-177059 | Jul 1988 | JP |
1-257268 | Oct 1989 | JP |
3-59457 | Mar 1991 | JP |
6-201704 | Jul 1994 | JP |
8-105901 | Apr 1996 | JP |
8-114539 | May 1996 | JP |
10-2875 | Jan 1998 | JP |
10-10125 | Jan 1998 | JP |
10-501340 | Feb 1998 | JP |
10-197526 | Jul 1998 | JP |
10-206417 | Aug 1998 | JP |
10-513259 | Dec 1998 | JP |
2000-199761 | Jul 2000 | JP |
2000-266759 | Sep 2000 | JP |
2001-50952 | Feb 2001 | JP |
2002-71684 | Mar 2002 | JP |
2002-202310 | Jul 2002 | JP |
2002-243726 | Aug 2002 | JP |
2002-243734 | Aug 2002 | JP |
WO 9533986 | Dec 1995 | WO |
WO 9623223 | Aug 1996 | WO |
WO 9808606 | Mar 1998 | WO |
Number | Date | Country | |
---|---|---|---|
20060045799 A1 | Mar 2006 | US |