CA1129498A - Structural configuration and method for transport of a liquid drop through an ingress aperture - Google Patents

Abstract

IMPROVED STRUCTURAL CONFIGURATION AND METHOD FOR TRANSPORT
OF A LIQUID DROP THROUGH AN INGRESS APERTURE
Abstract A device is disclosed that includes an ingress aperture which provides improved transport of a drop of liquid, from an exterior surface of the device to the device interior. Means, such as a corner, are provided at the inter-section of the aperture sidewall and the exterior surface for urging a drop deposited thereon to move into contact with the aperture sidewall and thus into the aperture.

Description

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IMPROVE3 STRUC~URAL CONFIGURATION AND METHOD FOR TRANSPORT
OF A LIQ~ID DROP THRO~GH AN INGRESS APERTURE
Background of the Invention 1) Field of the Invention This invention is dlrected to a device and method for transport of a llquid drop through an ingress aperture, e.g., into a transport zone prior to processing of the liquid. In a prererred embodiment, such aperture cooperates with opposed surfaces located within the device whlch provide for capillary flow of liquid within a transport zone. One of the surfaces can include a reagent-containing layer suitable for a radiometric analysis of the liquid.

2) State of the Prior Art A number of liquid transport devices rely upon capillary flow Or liquid between two spaced-apart surfaces to spread the liquid. For example, an enclosed capillary chamber can be provided by sealing a cover sheet, e.g., around its perimeter to a reagent layer laminated to a support so that the cover sheet ls left spaced away from the 20reagent layer a distance suitable for capillary flow. At least two apertures are then provided in the chamber. One aperture provides for the introduction Or drops or liquid, and the other for the venting of air as the capillary cham-ber is filled. Such a device is shown, e.g., in U.S. Patent 25N- 3,690,836, issued on September 12, 1972.
Prior to this invention, the lngress aperture for introduction Or liquid lnto a devlce Or the type described above has featured a smooth, curved sidewall, such as a cyllndrical wall. Such apertures sufrer the disadvantage 30that a drop of liquid that is not accurately placed on the cover sheet, i.e., is placed wlth its center outside the sidewall Or the aperture, tends to stay outside the aperture rather than move into it. It is only when the center Or the drop ls deposlted well wlthin the aperture 35 that the surface tension of the llquld drop forces the drop into the aperture in full contact with the sidewall. Parti-cularly this has been a problem ror cover sheets formed from materials that tend to be hydrophoblc, i.e., that form with 4~

the liquid in question a liquid-vapor contact angle that is greater than 90. For example, certain plastlcs are suf-ficiently hydrophobic that drops of liquid such as blood serum are more likely to remain on the cover sheet than to 5 flow into a cylindrical aperture in the sheet.

3) Related Applications -Canadian Application Serial No. 338,320, filed on October 24, 1979, entitled "Electrode-Containing Device with Capillary Transport Between Electrodes" discloses liquid trans-port devices that function as a bridge between two electrodes, the liquid access apertures in one embodiment being a hexagon.
U.S. Patent No. 4,233,029, issued November 11, 1980, entitled "Liquid Transport Device and Method", discloses such a hexagonal aperture for use in a llquid transport device in general.
S~MMARY OF THE INVENTION
This invention concerns the discovery that the ingress aperture of such devices ca~ be predeterminedly shaped to be more effective in urging applied drops into lt 20 than previous apertures of the type having a sidewall com-prising a smooth, curved surface, e.g., a cylinder.
More specifically, there is provided an lmproved liquid transport device comprising an exterior, drop-receiving surface, means interior of said surface for transporting the 25 liquid through a zone, and an ingress aperture comprising an internal sidewall fluidly connecting the surface and the interior transporting means. The improvement features, in at ].east the intersection of the exterior surface and the sidewall, at a predetermined location, means for substantlally 3 urging a portion of a drop of liquid deposited on the sur-face to move lnto contact wlth the sldewall.
Such a device is particularly useful in intro-ducing liquid into a transport zone between two opposed transport surfaces spaced apart a distance effective to 35 induce capillary flow of the liquid between the transport surfaces.
Thus, in accordance with the present inventlon, there is provided a device having a drop-centering aperture ~z~

for the improved conveyance of a drop of llquid from an exterior surface to an interior liquid transport zone of the device.
It is a significant aspect of the inventlon that aperture geometry facilitates such drop-centerlng.
In yet another related aspect of the inventlon, a test device for radiometric detection of an analyte ls provided with a self-centering aperture.
Other features and advantages will become apparent 10 upon reference to the following Description of the Preferred Embodiments when read ln llght of the attached drawlngs.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is an enlarged dimetric view of a device pre-pared in accordance with the lnvention;
Fig. 2 is an elevational vlew in section through the aperture of the cover sheet, demonstratlng the operation Or the device;
Fig. 3 is a fragmentary, diagrammatic plan view illustrating an effect of the invention;
Fig. 4 is a plan view Or a preferred embodiment of the invention,^and Fig. 5 is a sectional view taken generally along the plane of line V-V of Fig. 4.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The device and method of this invention ls described in connectlon wlth preferred embodlments featurlng the capillary transport of biological liquids and particularly blood serum, between two opposed surfaces. In addltion, the devlce and rnethod can be applled to any llquld a drop of 3 whlch ls to be carrled through an lngress aperture from an exterlor surface to a transport means for transportlng the llquld for any end use. For example, lndustrlal liquids can be so transported.
A device 10 constructed in accordance wlth one 35 embodiment of the invention comprises, Fig. 1, two members 12 and 14 each havlng an exterior surface 16 and lô, re-spectlvely, and interlor, opposed surfaces 20 and 22, re-spectively. Edge surfaces 24 define the limits of extenslon .

of the members. Surfaces 20 and 22 are spaced apart a distance "x", Fig. 2, that is effective to induce capillary flow of liquid between the surfaces, as is described in the aforesaid commonly-owned application and patent. In this manner the spaced-apart surfaces 20 and 22 define a transport zone 26 and act as means for transporting introduced liquid between the surfaces. As will be readily apparent, a range of values for "x" is permissible, and the exact value depends upon the liquid being transported.
Surfaces 20 and 22 can each be smooth, Figs. 1 and 2, or provided with a variety of surface configurations such as parallel grooves, the grooves of one surface being aligned or at a positive angle with respect to the grooves of the other.
A preferred means for introducing a drop of liquid into zone 26 is an aperture 30 extending from surface 16 to surface 20, through member 12. The aperture comprises a sidewall 32 extending between the surfaces. The preferred largest flow-through dimension of aperture 30, measured as an outside diameter, is one which is about equal to the greatest diameter of the expected drop. The drop diameter in turn is dictated by the volume and surface tension of the drop. The volume of the drop should be adequate to fill transport zone 26 to the extent desi.red. For uses such as clinical analysis as herein described, a convenient drop volume is about 10 ~1. Thus, slnce a 10 ~1 drop of fluld having 70 dynes/cm surface tension has a diameter of about 0.26 cm, the largest flow-through dimension, measured as an outside diameter, Fig. 1, is preferably about 0.26 cm.
3 In accordance with one aspect of the lnventlon, the intersection of surface 16 and sldewall 32 ls provlded with means that encourage the selected drop of liquid deposited or received on surface 16 generally at aperture 30 to move into contact with the entire perlmeter of sldewall 32. More specifically, sidewall 32 is shaped so as to comprise a plurality of surfaces that intersect, at least with surface 16, at predetermined locations to form a plurality of interior corners 34. As used herein, "prede-~2~

termined location" or "locations" means locatlons dellber-ately chosen, and distinguishes the clalmed lnventlon from cylindrical apertures which lnadvertently or accldentally have imperfections, such as microscopic corners, ln the sidewall. Such accidental constructs are not capable of providing substantial urging of the drop lnto the aperture.
As shown in Fig. 1, sidewall 32 comprises throughout lts length, six sidewall surfaces and six such predetermlned corners 34. Equal angles of such corners and equal wldths of the intersecting surfaces are selected to provlde a transverse, cross-sectlonal shape that ls a regular hexagon, the preferred configuration.
In operation, Fig. 2, device 10 is placed in a drop-displacing zone ad~acent to a source of drops, and a drop A
cf liquid such as blood serum or whole blood is dropped onto the device as a free-form drop or is touched off from a pendant surface, arrow 35, onto surface 16 generally at aperture 30. The surface 16 preferably ls maintalned ln a generally horizontal orientation during thls step. Corners 34 act to center the drop and urge lt into contact with the surfaces of sidewall 32. It then moves down lnto zone 26 and into contact with surface 22, where capillary attraction further causes the llquid to spread throughout zone 26, arrows 36, to the posltion shown in phantom. Assumlng sufflcient volume in the drop, the spreadlng ceases at edge surfaces 24 which define an energy barrler to further cap-lllary flow. Once the drop of llquld is so distrlbuted, a varlety of processing can be done to the liquld, as wlll be appreciated.
Thus the drop ls applied to aperture 30 so as to contact one of the corners, to lnsure effectlve filllng of the aperture. The effect is most pronounced when the center of gravity of the drop is positioned over the aperture, rather than the solid surface 16.
To vent air as the llquid advances within zone 26, means are provided withln the devlce, such as the open space between members 12 and 14 along all or a portion of any one of edge surfaces 24. Alternatively, a second aperture, not l~ Z~

shown, can be formed in either member 12 or 14.
The corners of the aperture, at the surface 16 where the drop is first applied, appear to act as centers of force whlch induce the drop to move into contact with sidewall 32 along its entire perimeter or clrcumference. That ls, re-ferring to Fig. 3, it ls believed that the centering force F3 of a drop A applied at one of the corners 34 is signifl-cantly greater than the corresponding centering force Fl or F2 that exists for a drop A' placed at any adJacent location 38 or 39 spaced apart or away from a corner. At least one corner is needed for the effect. However9 at least three corners 34 are preferred, as in Flg. 3, to lnsure a greater likelihood that the drop A will be in contact wlth a corner 34 when it contacts surface 16.
For a predetermlned largest flow-through dlmenslon of the sidewall 32 calculated as described above, the greater the number of corners that are created by the use of a colresponding number of intersecting surfaces, then the greater is the likellhood that the drop wlll contact a corner. However, as the number of corners ls lncreased, so is the value of the interior angle of each corner, untll e~/entually the sidewall 32 approaches a smooth, curved ~urface in shape wherein all the centering forces are equal, and the effect is lost. It has been found, therefore, that a preferred number of corners ls between three and about ten. Highly preferred ls slx corners ln a regular hexagon.
As a matter of practlcallty, the corners 34 wlll have a slight radlus of curvature. For the corners to be effectlve, they each should have a radius of curvature that is no larger than about 0.4 mm.
Although flat or planar surfaces are preferred between the corners, they can also be contlnuously curved as shown, e.g., for surface 39, Flg. 3.
Although the centerlng mechanism of the corners ls not fully understood, it ls belleved that the effect ls due to forces that apply to the compound menlscus when the drop ls located at a corner 34. As is well known, a compound meniscus is one in which the princlpal radil of curvature of the drop surface vary, depending on the locatlon taken on the surface of the drop. If the drop is properly located at a corner, the compound meniscus forms a drop that extends laterally farther out over the aperture than lt does when not located at a corner, and the weight of this extension causes the drop to fall or otherwise move into contact with the perimeter of sidewall 32 and then through the aperture. Or, there is at the corner a greater tendency for the drop to wet the sidewall than would occur in the absence of a cor-ner.
It will be readily appreciated that the centeringforce of corners 34 is needed primarily at the lntersectlon of sidewall 32 and exterlor surface 16. Thus, aperture 30 will function equally as well if sidewall 32 ls smoothed out as it approaches surface 20 to form a cylinder, not shown.
In addition, it will also be appreciated that the presence of a capillary zone below aperture 30, and speciri-cally surface 22 that contacts a drop in aperture 30, assists in metering the drop through aperture 30 and into the zone.
Members 12 and 14 can be formed from any suitable material, such as plastic as shown, or from metal.
In ~igs. 4 and 5, a preferred form of the device is one in which a transport chamber is formed for radio-metric analysis of an analyte of a biologlcal llquid such as blood. Parts similar to those previously described bear the same reference numeral to which the distinguishing suffix "a" is appended. Thus device 10a features a support member 14a, ~ig. 5, a cover member 12a, a spacer member 50 used to adhere members 12a and 14a together, and a radiometrlcally 3 detectable test element 60 disposed on support 14a spaced away from member 12a to define a transport zone 26a. The spacing between surface 20a and the test element ls a cap-illary spacing to lnduce the drop that enters through aperture 30a to spread throughout the zone 26a. Preferably, the test element 60 abuts agalnst the sldewalls of spacer member 50, and is held against member 14a by means such as adhesive.
Thus, the members 12a, 14a and 50 deflne a cap-..2 --8--illary transport chamber contalning the test element 60 and having any convenient shape, such as a rectangular chamber when viewed in plan, Fig. 4.
Any sultable ~oining means can be applied between members 12a and 50, and members 50 and 14a. For example, a variety of adhesives can be used, or if all the members are plastic, ultrasonic welding or heat-sealing can be used.
Member 12a is provided with an access aperture 30a extending through the member from its exterior surface 16a 10 to zone 26a, disposed directly above a portlon of test element 60. At least that portion of the aperture's slde-wall 32a that lntersects with surface 16a is provlded wlth corners 34a as described above. Preferably sldewall 32a ls ln the cross-sectional shape of a regular hexagon. An 15 addltlonal, cyllndrlcally shaped aperture 70 in member 12a acts as a vent for expelled air.
A viewing aperture or port 80 is optionally pro-vided in support member 14a, partlcularly when the latter member is not ltself transparent.
Test element 60 comprlses an optlonal transparent support 62, such as poly(ethylene terephthalate), and at least an absorbent layer 64 disposed on support 62. Such layer can have a varlety of blnder composltlons, for example, gelatin, cellulose acetate butyrate, polyvinyl alcohol, agarose and the llke, the degree Or hydrophlllclty of whlch depends upon the material selected. Gelatin ls partlcuarly preferred as it acts as a wetting agent to pro-vide for unlform llquld flow through zone 26a. Support 62 can be omitted where adequate support for layer 64 can be 3 obtained from support member 14a.
Addltional layers such as a layer 66 can be dls-posed above layer 64 to provlde a varlety of chemlstries or functlons, such as to provlde, either ln layer 66 alone or together with layer 64, a reagent compositlon. Filterlng, registration and mordanting functlons can be provided also by such addltlonal layers, such as are described in U.S.
Patent No. 4,042,335, issued on August 16, 1977. Thus, layer 66 can comprise a reagent, such as an enzyme, and a 2~4~3 g binder Or the same type as is used for layer 64.
As used herein, "reagent" in "reagent composltion"
means a material that is capable of lnteractlon wlth an analyte, a precursor of an analyte, a decomposltlon product of an analyte, or an intermedlate. Thus, one of the re-agents can be a preformed, radiometrically detectable specles that is caused by the analyte of cholce to move out Or a radiometrically opaque portlon or layer of the element, such as layer 66, into a radiometrlcally transparent portlon or layer, such as a reglstration layer.
The noted lnteractlon between the reagents of the reagent composition and the analyte is therefore meant to re~er to chemical reactlon, catalytlc actlvlty as ln the formation o~ an enzyme-substrate complex, or any other form of chemical or physlcal lnteractlon, lncludlng physlcal dlsplacement, that can produce ultlmately a radiometrically detectable slgnal in the element 60. As ls well known, radiometric detection lncludes both colorlmetrlc and fluorl-metric detectlon, dependlng upon the lndlcator reagent selected for the assay. The assay Or the element ls de-signed to produce a signal that ls proportlonal to the amount of analyte that ls present.
A wide variety of radlometrlc assays can be pro-vided by element 60. Preferably, the assays are all oxygen-lndependent, as the flow of blood or blood serum into zone26a tends to seal off element 60 from any addltlonal oxygen.
Typical analytes whlch can be tested lnclude BUN, total proteln, bilirubin and the like. The necessary reagents and binder or vehlcle composltlons ror the layers of element 60, 3 such as layers 64 and 66, ~or these analytes can be those descrlbed ln, respectlvely, U.S. Patent Nos. 4,o66,403, issued on January 3, 1978; 4,132,528, lssued on January 2, 1979; and 4,069,016 or 4,069,017, issued on January 17, 1978;
and the llke.
Quantitatlve detectlon of the change produced in element 60 by reason Or the analyte of the test element ls preferably made by scannlng the element through port 80 with a photometer or fluorimeter. A variety of such instruments ~ ~ Z ~ ~Q ~

can be used, for example the radlometer disclosed ln German OLS 2,755,334, published June 29, 1978, or the photometer descrlbed in ~.S. Patent No. 4,119,381, issued on October 10, 1978.
The following is an illustrative example Or the device shown in Figs. 4 and 5.
Example Members 12a and 14a are formed from polystyrene of a thickness 0.127 and 0.254 mm, respectively, member 50 10 being steel of a thickness 0.38 mm. The three members are sealed together by adhesives such as polybutyl acrylate adhesive obtainable from Franklln Chemical under the trade-mark "Covinax". Apertures 30a and 70 in member 12a are about 8 mm apart on center, the outside dlameter Or the hexagon of 15 aperture 30a belng about 2.6 mm. Vlew port 80 is about 5 mm ln diameter. The capillary spaclng between test element 60 and member 12a ls about 0.05 mm and the width Or element 60 ls about 11.5 mm.
For a test element 60 deslgned to detect total protein, in a lO~ul drop Or blood serum, the following sequential layers are used:
Layer Composition Amount 62 Gelatln-subbed 175 microns poly(ethylene tere- thlck phthalate) oly(acrylamlde-co-N- 16-0 g/m2 ~ vlnyl-2-pyrrolidone 64 ~ Cuso4-5H2o 10.8 g/m ~ LiOH 5.4 g/m 3 ~ tartarlc acid 8.0 g/m The inventlon has been described ln detall wlth particular reference to certain preferred embodlments thereor, but it will be understood that varlatlons and modifications can be effected within the spirit and scope Or the invention.

Claims (19)

What is claimed is:

1. In a liquid transport device comprising an exterior, drop-receiving surface, means interior of said surface for transporting the liquid through a zone, and an ingress aperture comprising an internal sidewall fluidly connecting said surface and said interior transporting means, the improvement wherein at least the intersection of said exterior surface and said sidewall includes at a pre-determined location, means for substantially urging a por-tion of a drop of liquid deposited thereon to move into contact with said sidewall.

2. A device as defined in claim 1, wherein said urging means comprises a surface configuration capable of forming a compound meniscus on a contacting liquid drop.

3. A device as defined in claim 1 or 2, wherein said predetermined location comprises an interior corner in the aperture sidewall at at least said exterior surface.

4. A device as defined in claim 1, wherein said intersection includes from 3 to about 10 of said urging means at spaced-apart locations.

5. A device as defined in claim 1, wherein said aperture has six of said urging means.

6. A device as defined in claim 1, wherein said aperture, at said intersection, has a transverse cross-sectional shape of a regular hexagon.

7. A device as defined in claim 1, wherein said transporting means includes two spaced-apart opposed sur-faces at least one of which includes an absorbent layer containing at least one reagent capable of producing a radiometrically detectable signal when contacted by the liquid of the drop.

8. In a liquid transport device comprising an exterior, drop-receiving surface, a capillary transport zone interior of said surface formed by interior, capillary-spaced surfaces of first and second wall members, one of said wall members including a liquid ingress aperture com-prising a sidewall extending from said exterior surface to said transport zone, the improvement wherein at least the intersection of said exterior surface and said sidewall includes at a predetermined location, means for substantially urging a drop of liquid deposited on said surface to move into con-tact with said sidewall.

9. A device as defined in claim 8, wherein said predetermined location comprises an interior corner in the aperture sidewall at at least said exterior surface.

10. A device as defined in claim 8, wherein said intersection includes said urging means at a plurality Or predetermined, spaced-apart locations numbering from 3 to about 10.

11. A device as defined in claim 8, wherein said intersection includes said urging means at six generally equidistantly spaced locations.

12. A device as defined in claim 8, wherein said aperture has a transverse cross-sectional shape of a regular hexagon.

13. A device as defined in claim 8, wherein one of said interior surfaces includes an absorbent layer con-taining at least one reagent capable of producing a radio-metrically detectable signal when contacted by the liquid of the drop.

14. In a liquid transport device comprising an exterior, drop-receiving surface, a capillary transport zone interior of said surface formed by interior, capillary-spaced surfaces of first and second members, one of said members including an ingress aperture extending from said exterior surface to said transport zone, the improvement wherein said aperture comprises from 3 to about 10 distinct sidewalls extending between said exterior surface and said interior surface of said one member, and intersecting to define from 3 to about 10 interior corners.

15. A device as defined in claim 14, wherein said aperture has six corners defined by six intersecting side-walls.

16. A device as defined in claim 14, wherein said aperture has a transverse cross-sectional shape of a regular hexagon.

17. A device as defined in claim 14, wherein said other member interior surface is the exposed surface of an absorbent layer containing at least one reagent capable of producing a radiometrically detectable signal when contacted by the liquid.

18. A test device for radiometric detection of an analyte of a liquid, comprising a support, a cover member spaced away from the support, one or more layers disposed sequentially on the support and containing at least one reagent composition in at least one of said layers, said composition being capable of producing a radiometrically detectable signal that is proportional to the quantity of the analyte, means for sealing said layers between said support and said cover member with a capillary space between the outermost one of said layers and said cover member, said space being effective to provide capillary flow of liquid between said cover member and said outermost layer, said cover member including a liquid ingress aperture and an air vent aperture spaced away from said access aperture, said ingress aperture having a sidewall extending through said cover member and comprising six surfaces inter-secting to form six corners, whereby a drop of the liquid placed in contact with said cover member at said ingress aperture is urged by said corners to enter the aperture and said capillary space.

19. A method of transporting a drop of liquid through an aperture in a wall member from an exterior surface to an interior surface of that member, said aperture being defined by a sidewall that includes, at a predetermined loca-tion at least at the intersection of said exterior surface and the sidewall, means for urging a drop of deposited liquid to move into contact with the sidewall, the method comprising the steps of:

a) placing said wall member in a drop-displacing zone adjacent to a source of drops of the liquid, and b) applying a drop to said aperture in operative contact with said urging means, whereby the drop fills the aperture and transport is assured.