JP4339200B2 - Sample supply element for immunochromatography equipment - Google Patents

Description

  The present invention relates to a sample supply element for an immunochromatography apparatus, and a housing for an immunochromatography apparatus including the same and an immunochromatography apparatus.

  The immunochromatographic apparatus is an immunochromatographic method, that is, a sample is brought into contact with a sample development start position on an immunochromatographic development film made of a water-absorbing material, and then developed in a predetermined direction by capillary action, and the development direction of the immunochromatographic development film It is an apparatus used in a method for analyzing a substance to be analyzed in a sample by observing a change in a detection zone (region where an antigen or antibody is immobilized) provided downstream (Patent Documents 1 to 9).

A lateral flow immunochromatography apparatus for developing a sample in a predetermined direction of an immunochromatographic development membrane by a capillary phenomenon is a type in which a pad portion is provided directly below a sample dropping port [hereinafter referred to as (A) type], and a pad portion. Type [hereinafter referred to as (B) type] (see FIG. 12).
In the (A) type, a pad portion 93 is disposed between the sample dropping port 92 derived from the housing 91a and the immunochromatographic development film 99, and the sample dropping port 92 contacts the pad portion 93, and the pad portion 93 is The structure is in contact with the immunochromatographic development film 99. The main role of the pad part is (1) after temporarily absorbing and holding the supplied sample, and (2) using the surface area to gradually supply the sample over a wide area of the immunochromatographic development membrane. (3) Protection of the exposed immunochromatographic development membrane, but there are many commercially available products that simplify the reagent and simplify the operation by preliminarily immobilizing the analyte detection reagent on the pad. Yes.

  In the (B) type (for example, Patent Document 1), the sample dripping port 92 is in direct contact with the immunochromatographic development film 99, and the advantage of the pad portion as in the (A) type cannot be utilized. Simplification of the production that does not include the pad portion is expected. However, none are commercially available.

  In the case of the conventional type (A), the detection sensitivity decreases due to a part of the sample remaining in the pad portion, the background of the immunochromatographic development film increases due to the resupply of the residual sample to the immunochromatographic development film, and the pad Problems such as non-specific staining that occur from the contact portion between the immunochromatographic development membrane and the immunochromatography membrane frequently occur, which hinders result determination. In particular, in an immunochromatography method in which a substrate solution and a washing solution are additionally supplied after sample supply, the development is disturbed due to the additional solution flowing into the pad portion, and the above problem is further aggravated.

  In the case of the conventional (B) type, since there is no pad part, the sample concentrates on the opening just below the sample dropping port, so that the sample accumulates and clogs the immunochromatographic development film, or the sample is not absorbed immediately. In other words, problems such as surface tension flow on the immunochromatographic development film occur, which greatly impedes chromatographic development. As a result, the sample remains in the portion held by the sample dripping port and the immunochromatographic development film, and the background of the immunochromatographic developing film increases due to the decrease in detection sensitivity and the resupply of the sample, and the sample dripping port and the immunochromatography Problems such as non-specific staining generated from the developed membrane contact portion frequently occur, which hinders result determination. In particular, in the immunochromatography method in which a substrate solution and a washing solution are additionally supplied after sample supply, the above problem is further aggravated due to blocking and development disturbance due to the sample on which the additional solution is deposited and the sample dropping port in contact. End up.

Japanese Patent No. 2702498 Japanese Patent No. 3284896 Japanese Patent No. 3248436 JP-A-10-104236 Japanese Patent Laid-Open No. 10-300750 JP-A-11-153600 JP 2000-329767 A Japanese Patent No. 2890384 Japanese Patent No. 3021380

  The problem of the present invention is that the immunochromatography apparatus can simplify the production by not including the pad part, and further, the function of the pad part, that is, the sample is gradually spread over a wide range of the immunochromatographic development film. An object of the present invention is to provide a sample supply element having a function of supplying, a housing for an immunochromatography apparatus including the same, and an immunochromatography apparatus.

  As a result of diligent research, this researcher found that the pad portion and the sample dripping port contacted the immunochromatographic development membrane due to a decrease in detection sensitivity, background increase and non-specific staining from the conventional pad unit and sample dripping port. I found out that this is due to Furthermore, it has been found that these problems can be solved by incorporating the function of the pad portion into the sample dropping port structure of the housing instead of eliminating the pad portion, thereby completing the present invention.

The subject is a sample supply element for an immunochromatography apparatus including an immunochromatographic development film inside according to the present invention,
(A) a sample introduction portion having an upper opening for sample addition and a discharge port provided at the bottom;
(B) a sample guiding channel communicating with the outlet;
(C) A sample extension provided in communication with the sample guiding channel and having a bottom opening, and (d) a sample extension provided in communication with the bottom opening of the sample drawing and facing the immunochromatographic development film. A sample supply means including a sample extension having a wall surface, and the supplied sample flows in the order described above;
The sample guide path has an inner diameter that allows the sample introduced into the sample introduction part to be guided to the next sample drawing part after being retained in the sample introduction part;
The bottom opening of the sample pull-in portion has an inner diameter wider than the inner diameter of the sample guiding channel;
The edge of the bottom opening of the sample pull-in portion is not in contact with the immunochromatographic development membrane;
After the sample droplet that has reached the edge of the bottom opening of the sample drawing portion comes into contact with the immunochromatographic development film, a sample expansion space in which the sample can be expanded on the immunochromatographic development film along the sample expansion wall surface , Formed between the surface of the immunochromatographic development film;
This can be solved by the sample supply element described above.
The present invention also relates to an immunochromatographic apparatus housing including the sample supply element.
Furthermore, the present invention relates to an immunochromatographic apparatus including the sample supply element.

  According to the sample supply element of the present invention, since the pad portion is not included, the function of the pad portion, that is, the sample is gradually supplied to a wide range of the immunochromatographic development film even though the manufacturing can be simplified. Therefore, for example, a decrease in detection sensitivity, an increase in background, and nonspecific staining can be suppressed.

Hereinafter, the sample supply element, the housing, and the immunochromatography apparatus of the present invention will be described mainly with reference to the accompanying drawings.
The housing and the immunochromatography apparatus of the present invention are improvements of the conventionally known housing and immunochromatography apparatus, except that the sample supply element of the present invention is provided as a sample supply element. It can consist of the same composition as a graph device.

For example, one embodiment of the immunochromatography apparatus 10 of the present invention shown in FIG. 1 includes a housing (housing upper lid 1a and housing substrate 1b), an immunochromatographic developing film 9 made of an absorbent material and housed in the housing, and the immunochromatography. It includes a liquid developing material 7 (upstream side) and a liquid suction material 8 (downstream side) as means for determining the flow direction of chromatographic development on the graph developing film.
The immunochromatography apparatus 10 includes a sample supply means 2 for introducing a sample into the apparatus, and a determination window 3 through which a capture zone 95 on the immunochromatographic development film can be observed. An opening 4 as a means and an additional liquid storage container (for example, the liquid storage container 11 and the liquid storage preliminary container 12) can be included.

  The housing in the immunochromatographic apparatus of the present invention can have an appropriate shape and size according to the assay to be performed. The housing can also be fabricated from any material suitable for the assay being performed. The material used to fabricate the housing can be selected from materials that do not interfere with all reagents used in performing the assay, including the sample, sample medium, or components of the signal generating system. Preferably, the housing is made from a thermoplastic material or the like. Generally, the housing has a means (for example, judgment window 3) for visually checking the capture zone 95 (or plural) of the surface of the immunochromatographic development membrane, from which the result of the assay can be measured. .

  Further, the immunochromatographic apparatus of the present invention is an immunochromatographic developing film made of an absorbent material, which is housed in a housing, for capturing a member of a specific binding pair in a certain zone and moving the liquid from the zone by capillary action including. For example, in one embodiment shown in FIG. 1 or 2, the immunochromatographic development film includes an absorbent material piece having one or more capture zones, that is, an absorbent immunochromatographic development film 9. The immunochromatographic development film 9, the liquid suction material 8 and the liquid development material 7 are in a liquid receiving relationship, and the immunochromatographic development film 9 overlaps the liquid development material 7 on the upstream end side and the liquid suction material 8 on the downstream end side. (Regions 71 and 81, respectively). By using the adhesive substrate 96 as necessary, the connection between the liquid developing material 7, the immunochromatographic developing film 9, and the liquid suction material 8 can be strengthened. The material of the substrate is preferably made of paper or plastic, and the pressure-sensitive adhesive can be selected from those that do not interfere with all the reagents used for performing the assay. These are housed in the immunochromatography apparatus 10 and preferably can be confined in an immovable state in the immunochromatography apparatus 10.

The immunochromatography apparatus of the present invention includes a sample supply means for introducing a sample into the apparatus on the housing. The sample includes not only a test sample containing a substance to be analyzed or a processed product thereof (for example, a diluted product) but also various reagents (for example, a signal generating component, an antigen, etc.) on the test sample or the processed product. , Antibodies and the like) are also included.
The sample supply means in the present invention, for example, as schematically shown in FIG.
(A) a sample introduction part 21 having an upper opening 21a for sample addition and a discharge port 21b provided at the bottom;
(B) a sample guiding channel 22 communicating with the discharge port 21b;
(C) communicating with the sample guiding channel 22 and having a sample drawing part 23 having a bottom opening 23a; and (d) communicating with the bottom opening 23a of the sample drawing part 23 and facing the immunochromatographic developing film 9. The sample extension 24 having the sample extension wall surface 24a provided
Are included in the above order along the flow direction of the supplied sample. In addition, the up-down direction in this specification means the direction along the gravity direction.

The shape of the sample introduction part in the present invention is, for example, hemispherical (for example, FIG. 7), conical, pyramid (for example, quadrangular pyramid, triangular pyramid, polygonal pyramid), cylindrical, or prismatic (for example, four A hemispherical shape is particularly preferable in that the sample remains little.
The size of the upper opening of the sample introduction part can be appropriately determined according to its shape, and is not particularly limited. For example, when the opening shape is circular, the diameter is, for example, It can be 2 mm to 15 mm, preferably 2.5 mm to 12 mm, more preferably 3 mm to 10 mm. Further, the shape and size of the bottom outlet can be determined so as to coincide with the shape and size of the next sample guiding channel.

  The shape and size of the sample guiding channel in the present invention are particularly limited as long as the sample introduced into the sample introducing unit can be guided to the next sample drawing unit after being retained in the sample introducing unit. It is not a thing. The shape of the sample guiding channel may be, for example, the inner diameter may be constant along the vertical direction or expanded downward (ie, the inner diameter on the outlet side is larger than the inner diameter on the inlet side). Big). The cross-sectional shape of the sample guide channel can be, for example, a circle (for example, FIG. 7), a quadrangle, a triangle, or a polygon, and a circle is preferable in that no residual liquid is left in the sample guide channel. . The ease of flow of the sample in the sample guide channel is affected by, for example, the channel shape or the concentration of the surfactant contained in the sample. Therefore, the inner diameter of the sample guide channel depends on these conditions. For example, when the cross-sectional shape is circular, the inner diameter is, for example, 0.1 mm to 5 mm, preferably 0.5 mm to 4 mm, more preferably 1 mm to 4 mm. Can be. Further, since the inner diameter of the sample guide channel is smaller than the inner diameter of the sample introduction part and the sample drawing part, it plays a role of protecting the exposed immunochromatographic development film. One sample guiding channel may be provided between the sample introduction unit and the sample drawing unit, or a plurality of sample guiding channels may be provided.

  The sample guide channel can be provided with ribs (for example, ribs 25 in FIG. 7) as desired. If a rib is provided in the sample guiding channel, the flow of the sample from the sample introduction part to the sample drawing part can be enhanced. The shape of the rib can be, for example, a semi-cylinder (for example, FIG. 7), a triangular column, or a quadrangular column, and a semi-cylinder is preferable. Further, the number of ribs provided in one sample guiding channel is not particularly limited, and may be one or plural.

The shape of the sample lead-in portion in the present invention is not particularly limited as long as the bottom opening has an inner diameter wider than the inner diameter of the sample guiding channel. For example, a hemispherical shape (for example, FIG. 7), Cone, pyramid (for example, quadrangular pyramid, triangular pyramid, polygonal pyramid), cylindrical, or prismatic (for example, quadrangular, triangular, polygonal pyramid) can be mentioned, and hemisphere in that the sample remains little The shape is particularly preferred. Further, the size of the bottom opening of the sample drawing portion can be appropriately determined according to the shape of the sample drawing portion, and is not particularly limited, for example, when the opening shape is circular, The diameter can be, for example, 1 mm to 10 mm, preferably 2 mm to 8 mm, more preferably 3 mm to 6 mm.
The bottom opening and the immunochromatographic development membrane are not in direct contact, and the distance is, for example, 0.05 mm to 5 mm, preferably 0.05 mm to 4 mm, more preferably 0.1 mm to 3 mm. be able to.

The sample extension part in the present invention has a sample extension wall surface. As schematically shown in FIG. 8, as long as the sample expansion wall surface 24a can form the sample expansion space 24b together with the surface of the immunochromatographic development film 9, its shape, size, or arrangement The position is not particularly limited.
As the shape of the sample expanding portion, as shown in FIG. 9, for example, a semi-cylindrical shape [FIG. 9 (a)], a prismatic shape [FIG. 9 (b)], a pyramid shape, or a pyramid shape lacking the top of the head [ FIG. 9C can be cited. In addition, the shape shown in FIG. 9 is a schematic perspective view seen from the bottom surface side of the housing upper lid, and an arrow A indicates the chromatographic development direction. If the shape of the sample extension is semi-cylindrical (the chromatographic development direction and the cylindrical axis direction match), the sample does not spread in the short axis direction of the immunochromatographic development film, and the sample is collected at the center of the immunochromatographic development film This is preferable.

  The size of the sample extension portion can be appropriately determined according to the shape or the arrangement position. For example, as shown in FIG. 7, when the semi-cylindrical sample extension is arranged in the downstream direction of the chromatographic development, the length along the major axis direction of the chromatographic development film is, for example, 2 mm to 30 mm. , Preferably 3 mm to 20 mm, more preferably 3 mm to 15 mm. The length along the minor axis direction of the chromatographic development film can be, for example, 2 mm to 20 mm, preferably 3 mm to 15 mm, more preferably 3 mm to 10 mm.

The sample expansion wall surface of the sample expansion portion can be arranged in a non-contact state with the immunochromatographic development film, or can be arranged in contact with each other, but is preferably arranged in a non-contact state. In the case of non-contact, a partition wall (for example, partition walls 26a and 26b in FIG. 7) is used to prevent the sample from being absorbed by the immunochromatographic development film and flowing in the downstream direction on the immunochromatography development film. Is preferably provided. The partition also has a function of fixing the immunochromatographic development film.
Also, the angle of the sample expansion wall can be parallel to the immunochromatographic development film, or can be arranged with an inclination. For example, as shown in FIG. 10, it can be arranged with an inclination so that the downstream side of the sample expansion wall is closest to or in contact with the immunochromatographic development film [FIG. 10 (a)] and is arranged horizontally. [Fig. 10 (b)] and can be inclined so that the upstream side of the sample expansion wall is closest to or in contact with the immunochromatographic development membrane [Fig. 10 (c)]. As in the embodiment shown in FIG. 10A, when the downstream side is closest or brought into contact, the sample is accumulated on the downstream side when the sample holding amount decreases, which is advantageous from the viewpoint of sample supply.

  In the present invention, the sample extension portion can be arranged in any direction with respect to the sample drawing portion, for example, the downstream direction or the upstream direction of the chromatographic development direction, or the direction orthogonal or deflected thereto. It is preferable to arrange in the downstream direction of the chromatographic development direction in that it can be rapidly developed in the detection zone.

The housing in the immunochromatography apparatus of the present invention can be provided with additional liquid supply means for introducing an additional liquid into the apparatus as desired.
For example, in one aspect shown in FIG. 1 or 2, the additional liquid supply means includes an opening 4 that can be used to supply additional liquid onto the liquid spreading material 7. The opening 4 can be, for example, cylindrical, conical, prismatic, or pyramidal (eg, FIG. 1 or 2), with a pyramidal shape being preferred.

  Further, for example, as shown in FIG. 2, the housing may include a liquid storage container 11 and a liquid storage preliminary container 12 that store the additional liquid after the additional liquid is introduced into the additional liquid supply means. In the embodiment shown in FIG. 2, the additional liquid amount is supplied with an optimal amount for performing the test, and the liquid storage container 11 has a capacity capable of storing the optimal amount. The liquid storage container 11 and the liquid storage preliminary container 12 are connected through the opening 13 (a plurality can be provided) so that an increment when an additional liquid amount more than the optimum amount is supplied due to a supply error or the like flows into the liquid storage preliminary container 12. Furthermore, the pulling of the sample can be strengthened by adding ribs 14 (a plurality of ribs are possible) as required. The opening 13 may be, for example, a circle, a triangle, a quadrangle, etc., but a quadrangle (for example, FIG. 2) is preferable. The cross-sectional shape of the rib 14 can be, for example, a circle, a triangle, a quadrangle, etc., but a quadrangle (for example, FIG. 4) is preferable.

In the sample supply element of the present invention, the behavior until the sample introduced from the sample introduction part reaches the immunochromatographic development film will be described with reference to FIG.
When the sample 6 is introduced into the sample introduction part 21, the sample 6 is stored in the sample introduction part 21 because the inner diameter of the sample guide channel 22 is narrow [FIG. 11 (a)]. However, since gravity acts on the sample 6, the sample 6 is gradually drawn into the sample drawing portion 23 through the sample guide channel 22 [FIG. 11 (b)]. In the present invention, the size of the sample drawing portion and the distance from the immunochromatographic development film are such that when the entire amount of the sample 6 is drawn into the sample drawing portion 23, the lower end of the sample droplet 6a is It sets so that it may contact [FIG.11 (c)]. The size of the sample pull-in portion can be determined based on, for example, the sample volume. For example, when the sample is 10 μL to 100 μL, the depth of the sample pull-in portion in the gravity direction is, for example, 0.5 mm to It can be 15 mm, preferably 1 mm to 10 mm, more preferably 1 mm to 8 mm. The sample droplet 6a in contact with the immunochromatographic developing film 9 quickly flows into the sample expansion space 24b due to the surface tension, and then gradually supplied to the immunochromatographic developing film 9 [FIGS. 11 (d) and (e). ].

  Thus, in the sample supply element of the present invention, since the sample introduced into the sample introduction part does not concentrate on the immunochromatographic development film at once, the sample concentrates in the immunochromatography as in the known (B) type apparatus. Does not clog the graph expansion membrane. In addition, the sample expansion space allows the sample to be gradually supplied over a wide area of the immunochromatographic development film, but does not require the pad part essential for the known (A) type apparatus, and the manufacturing is simple. Is possible.

  The sample supply element of the present invention can be applied to a sample supply application in an immunochromatography apparatus.

It is a perspective view of one mode of the immunochromatograph device of the present invention. It is a perspective view which shows the one aspect | mode of the immunochromatography apparatus of this invention shown in FIG. 1 in the state decomposed | disassembled into the housing upper cover, the immunochromatography expansion | deployment film | membrane, and the housing board | substrate. It is a top view of the housing upper cover in the one aspect | mode of the immunochromatography apparatus of this invention shown in FIG. It is a bottom view of the housing upper cover in the one aspect | mode of the immunochromatography apparatus of this invention shown in FIG. In the one aspect | mode of the immunochromatography apparatus of this invention shown in FIG. 1, it is a top view which shows the state which removed the housing upper cover. It is sectional drawing of the one aspect | mode of the immunochromatography apparatus of this invention shown in FIG. (A) enlarged partial plan view, (b) enlarged partial sectional view, and (c) enlarged partial bottom view showing the sample supply means and its peripheral part of the housing upper lid in one embodiment of the immunochromatographic apparatus of the present invention shown in FIG. It is. It is an expanded fragmentary sectional view which shows typically the structure of the sample supply means in the one aspect | mode of the sample supply element of this invention, and its peripheral part. It is a perspective view which shows typically the shape of the sample expansion part which can be used with the sample supply element of this invention. It is an expanded partial sectional view which shows arrangement | positioning with the sample expansion wall surface and immunochromatography expansion | deployment film | membrane in the sample supply element of this invention. It is explanatory drawing which shows typically the state of the movement of the sample in the one aspect | mode of the sample supply element of this invention shown in FIG. It is an expanded partial sectional view which shows typically the sample supply part structure in the conventional immunochromatography apparatus.

Explanation of symbols

10: Immunochromatography apparatus;
DESCRIPTION OF SYMBOLS 1 ... Housing; 2 ... Sample supply means; 3 ... Judgment window; 4 ... Opening part;
5 ... evaporation window; 6 ... sample; 7 ... liquid spreading material; 8 ... liquid suction material;
9: Immunochromatographic development membrane;
DESCRIPTION OF SYMBOLS 11 ... Liquid storage container; 12 ... Liquid storage preliminary container; 13 ... Opening;
14 ... ribs;
21 ... Sample introduction part; 22 ... Sample guide channel; 23 ... Sample drawing part;
24 ... sample expansion part; 25 ... rib; 26 ... partition wall;
95 ... capture zone; 96 ... adhesive substrate.

Claims (3)

A sample supply element for an immunochromatographic apparatus including an immunochromatographic developing film inside,
(A) a sample introduction portion having an upper opening for sample addition and a discharge port provided at the bottom;
(B) a sample guiding channel communicating with the outlet;
(C) A sample extension provided in communication with the sample guiding channel and having a bottom opening, and (d) a sample extension provided in communication with the bottom opening of the sample drawing and facing the immunochromatographic development film. A sample supply means including a sample extension having a wall surface, and the supplied sample flows in the order described above;
The sample guide path has an inner diameter that allows the sample introduced into the sample introduction part to be guided to the next sample drawing part after being retained in the sample introduction part;
The bottom opening of the sample pull-in portion has an inner diameter wider than the inner diameter of the sample guiding channel;
The edge of the bottom opening of the sample pull-in portion is not in contact with the immunochromatographic development membrane;
After the sample droplet that has reached the edge of the bottom opening of the sample drawing portion comes into contact with the immunochromatographic development film, a sample expansion space in which the sample can be expanded on the immunochromatographic development film along the sample expansion wall surface , Formed between the surface of the immunochromatographic development film;
A sample supply element as described above.   A housing for an immunochromatographic apparatus, comprising the sample supply element according to claim 1.   An immunochromatographic apparatus including the sample supply element according to claim 1.

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