CA1119834A

CA1119834A - Capillary transport device having connected transport zones

Info

Publication number: CA1119834A
Application number: CA000356506A
Authority: CA
Inventors: Richard L. Columbus
Original assignee: Eastman Kodak Co
Current assignee: Eastman Kodak Co
Priority date: 1979-07-23
Filing date: 1980-07-18
Publication date: 1982-03-16
Also published as: US4271119A

Abstract

CAPILLARY TRANSPORT DEVICE HAVING
CONNECTED TRANSPORT ZONES
Abstract A device is disclosed comprising first and second capillary liquid transport zones provided by first and second pairs of opposing surfaces, the opposing surfaces of the sec-ond zone both extending from the same one of the paired sur-faces of the first zone. The inlet to the second zone is a diverting aperture that is formed in such same surface and configured (i) to insure complete wetting of the second pair of surfaces by the liquid and (ii) to provide a cross-sectional flow-through area greater than about 0.2 mm2.

Description

111~834 CAPlLLARY TRANSPORT DEVICE HAVING
CONNECTED TRANSPORT ZONES
1) Field of the Invention This invention is directed to a device and a method for transporting liquid by capillary attraction into dif-ferent zones.

2) Back~round of the Invention Capillary transport devices have been constructed with two surfaces spaced to cause flow of introduced liquid by capillary action, thus creating between such surfaces a zone of intended liquid transport. When the two surfaces are two opposed sheets sealed around their edges, liquid is introduced through an access aper~ure formed in one of the 5 sheets, and trapped air vented, e.g., by a separate aper-ture. Such capillary transport devices have been used for analyzing liquids; one such device being shown in ~.S. Patent No. 3,6~0,836 wherein one of the opposing surfaces is an - absorbent reagent-containing layer. The transported liquid reacts with the imbibed reagents to produce a visible color indicative of the analyte.
The above-described devices are generally limited to capillary flow between the opposing surfaces. Such flow dis-tributes the liquid to, e.g., two absorbent test areas that define in part the opposing surfaces, as shown for example, in U.S. Patent No. 3,715,192, issued February 6, 1973. How-ever, the number of different test areas that are possible is limited by the number that can fit within the total surface areas of the zone that are to be wetted by the liquid.
In my U.S. Patent No. 4,233,029, issued November 11,

3 lg80, the liquid transport device described therein is capable of diverting flow to individual test areas or zones. Such zones, though separate, are provided by a pair of opposing surfaces that are extensions of the pair of surfaces pro-viding the first transport zone. That is, each separate testzone branch extends from an opening formed by both opposing walls or surfaces providing the first zone.
Although such branching features are highly useful, there is a limit to the number of branches that can extend ~1983 from openings formed by both the opposing walls. lf addi-tional zones could be extended fro~ only one of the surfaces of the first zone, then additional tests could be conducted in such additional zones.
Prior to this invention liquid transport devices did provide additional capillary zones created by relatively small diverting apertures having a cross-sectional flow-through area of 0.2 mm or less. "Cross-sectional flow-through area" is used herein to mean the area measured 10 transverse to liquid flow through that area. This area limitation was necessary, because with preferred hydrostatic heads and prior art aperture configurations liquid would not divert into larger apertures. Examples of such small di-verting apertures, generally circular in shape, can be found 15 in conventional devices.
The problem, however, is that the prior art trans-port zones fed by such small area apertures created sharply-curved menisci that would not wet a solid test element dis-posed at the end of the zone. Thus, one problem has been to 20 devise a diverting aperture that will provide capillary flow in a zone of sufficient cross-sectional area to properly wet a solid test element at the end of the zone.
Still another drawback of apertures of 0.2 mm2 cross-sectional flow-through area or less is that test ele-25 ments that are area dependent, such as ion-selective ele-ments, tend not to develop a useful signal for such small cross-sectional flow-through areas.
3) ~ther Applications My Canadian Application S.N. 356,460, filed July 18, 3 1980, entitled "Multi-Analyte Test Device" is directed to a liquid capillary transport zone that transports a drop of liquid to a multiple number of radiometric test sites.

SUMMARY OF THE INVENTION
This invention is based on the di~covery that a di-verting aperture can be constructed with a flow-through area larger than was possible with prior devices. It is such larger apertures that permit the rsdius of curvature of the . ,.

111~834 meniscus of the cecond zone to be reduced to a value u6eful for wetting solid test elements as described above.
Additionally, larger volumes of liquid are provided for testing.
In accordance with one aspect of the invention, there is provided an improved liquid transport device of the I kind wherein a first zone of intended cspillary liquid trans-I port is formed by a first pair of opposing surfaces 6pacedapart a distance effective to induce capillary flow of intro-I 10 duced liquid. Liquid access means are provided 60 that in-; troduced liquid flows in the first zone from the access means by capillary attraction. This device is improved by the addition of at least a second pair of opposing surfaces spaced apart a distance effective to induce capillary flow of 15 introduced liquid within the second zone and to provide a second zone of intended capillary liquid transport. The ~ec-il ond pair of surfaces extends from only one surface of the first pair of surfaces, and diverting means are included in the one surface for directing a portion of the capillary 20 liquid flow away from the first zone into the ~econd zone ~j while the remainder of the liquid continues flowing in the ; first zone. The diverting means is configured to insure com-plete wetting of the second pair of surfaces by the liquid I moving therepast and to provide a cross-sectional flow-i! 25 through area greater than about 0.2 mm2. As used herein, ' "greater than about 0.2 mm2" means, by an amount that is ,~ statistically significant, e.g., is greater than variations `ji ~produced by experimental error in measuring the area.
Thus, one advantage of the present invention is that 3 subsequent processing of the liquid, such as by analytical tests, need not be limited to a single zone created by the first pair of opposing surfaces, but can be carried out in a multiplicity of zones, all of which are filled by depositing a quantity of liquid into a single access means.
Another advantage of the invention is that the mul-tiple zones can be automatically supplied by liquid all with-out the necessity for active driving elements such as pumps.
Other features and advantages will become apparent upon reference to the following Description of the Preferred Embodiments when read in light of the attached drawing6.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a plan view of a device con6tructed in I accordance with the invention;
Fig. 2 is a frsgmentary 6ection view ta~en generally along the line II-II of Fig. l;
Fig. 3 is a frsgmentary section view ta~en generally along the line III-lII of Fig. 2;
Fig. 4 is a fragmentary 6ection view taken generally along the line IIl-III of Fig. 2;
Figs. 5A-5C are enlarged fragmentary plan views of an embodiment similar to that of Fig. 1, with a portion of top member 14a being broken away to illu6trate the liquid 15 flow pattern in the device ineo the aperture of the second ~ zone;
} Figs. 6A-6C are fragmentary section views taken gen-I erally along the line VIA-VIA through VlC-VlC of Figs. 5A-5C.
Fig. 7 is a section view ~imilar to that of Fig. 2, ~ but illustrating another embodiment;
j! 20 Fig. 8 is a fragmentary section view taken slong the jl line VIII-VIII of Fig. 7;
I Fig. 9A is a fragmentary section view similar to ¦ that of Fig. 3, but illustrating additional embodiments;
~' Fig. 9B is a view 6imilar to that of Fig. 9A, but of ) 25 a comparative example;
Fig. 10 is a plan view of yet another embodiment of t the invention;
Fig. 11 is a fragmentary 6ection view taken gener-O ally along the line XI-XI of Fig. 10; and Figs. 12 and 13 are eection views taken generally ~long the line XII-XII and XIIl-XIII respectively, of Figs.
11 and 10.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The device of the invention is capable of providing from a single first capillary zone, an increased number of processing or test loci for liquid supplied thereto. Thi6 is achieved by the creation of additional cap~llary tran6port zones each of which extends from either one cf the 6urfaces of the first zone. This invention ha~ been rendered possible by the discovery of ~ diverting means that effectively draws off at one of the surfaces defining the first zone 8 new, u6eful capillary stream while allowing the first capillary stream to continue to flow in the first transpor~ zone. A
preferred form of such diverting means is a ~pecially ~haped aperture, as hereinafter described.
The embodiments which follow refer to whole blood or blood serum as the preferred transport liquid. ln addition, 10 other liquids can be processed, including other biological liquids and industrial liquids, such as photographic devel-oper solutions.
A liquid transport device 10 of the invention com-prises, Figs. 1-2, a first transport zone 12 comprising two 15 members 14 and 16 having opposing interior surfaces 18 snd 20, Fig. 2, spaced apart a distance sl, that is effective ¦ to induce liquid to flow between the surfaces by capillary action alone. Sidewalls 22 and 24, Fig. 1, are used to mount members 14 and 16 in this spaced-apart relation, with or 20 without bridging studs (not shown) within the zone. Wàlls 22 and 24 are secured to members 14 and 1~ ~y any conventional means, including water-insoluble adhesives or ultrasonic ~! bonding.
To permit introduction of liquid into zone 12, a 1 25 liquid access aperture 30 is provided in one of members 14 and 16, preferably 14, thereby defining a locus of liquid , introduction. A quantity of liquid is be deposited at aper-¦ ture 30, either in drop form, or as a quantity that is in-jected into the aperture. Because of the capillary 6pacin~
sl, injecting pressure need not be effective to fill zone i 12.
The size of aperture 30 is selected to insure that the volume of liquid introduced will contact both surfaces 18 and 20, to initiate transport of liquid menisci 31 and 33 3 through zone 12 in the direction of arrows 32 and 34, respec-tively, Fig. 2. lf a 10 ~1 sized drop is necessary for-proper liquid flow, sperture 30 can be, e.g., about 1.0 ~m to about 5.0 ~m in diameter. Alternatively, aperture 30 can have cornered 6idewalls, not shown, so as to have the 6hape ; of, e.g., a hexagon instead of a citcle, to insure more po~i-tive movement of the liquid into the aperture.
As the liquid sdvances within zone 12, air i6 en-trapped. To vent the air, st least one vent aperture 4Q i6provided, Fig. 1, preferably at the end of zone 12 that i~
opposite to the locus of liquid introduction defined by aper-ture 30. Alternatively, aperture 40 can be disposed in one or more of the sidewalls ~2 and 24, or in member 16. The l; 10 size of vent aperture 40 i~ not critical. Generally, it is smaller than that of aperture 30.
Yet another variation is to provide grooves, not shown, in surfaces 18 and 2Q to control the shape of the men-~ isci 31 and 33 as they advance. Such grooves preferably ~re 1, 15 mutually parallel within a given surface and the grooves of opposing surface portions are disposed at a finite angle.
lt will be readily appreciated that a number ofareas are available on surfaces 18 and 20 to process or test the liquid that is transported through zone 12. For example, j 20 a portion of zone 12 downstream from meniscus 31 i6 reserved j for microscopic viewing of the liquid, as are a plurality of other portions throughout the zone.
In accordance with one aspect of the invention, a second liquid capillary transport zone 50 is provided, Figs.
2 and 4, which diverges from first zone 12 so as to create additional areas for testing or processing of the liquid.
,i Zone 50 is defined by a second pair of members 52 and 54 having opposed interior surfaces 56 and 58, respectively, spaced apart a capillary distance s2, Fig. 2. Members 52 3 and 54 comprise generally planar sheets mounted in an aper-ture 59 which extends only a portion of the distance between sidewalls 22. Preferably there is a distance z from the aperture edge 69 to each sidewall 22, measuring st least about 2.0 mm. Bridging studs, not shown, can be disposed between members 52 and 54 within the 6econd zone 50 to maintain spacing 52 As shown, s2 equals the aperture width w, but as described hereinafter, 6pacing 82 can be increased a~ zone 50 extends away from zone 12. To vent trapped air from zone 50, part or all of edges 61, Fig. 4, of ~9834 surfaces 56 and 58, are left open ~o the stmQsphere. Sur-faces 56 and 58 can be either grooved or smooth, a8 described for surfaces 18 and 20.
To divert 8 portion of the liquid flowing through zone 12 in the direction of arrow 60 and into capillary flow within zone 50, surfaces 56 and 58 of zone 50 form a prede-termined aperture 70 in surface 20 at a locus downstream from aperture 30. Aperture 70 is configured to hsve two charac-j teristics. First, it has a total cross-sectional area, ! 10 measured transverse to liquid flow therethrough, that i6 greater than 0.2 mm2, to insure that meniscus 80 will wet a test element 71, Fig. 2, when it reaches th~t element.
~ Second, it is configured to insure that the transported j liquid completely wets surfaces 56 and 58 at the vicinity of i 15 aperture 70, as described in greater detail hereinafter.
! Aperture 70 i6 characterized as a simple aperture ij that is, one having only a single flow portion. As used !~ herein, "flow portions" are those parts of the aperture shape that are free of substantial interior corners. Such por-j 20 tions are graphically determinable by sectioning the aperture ~ ` shape along hypothetical lines connecting the 6ubstantial ; interior corners, if any. An interior corner,in turn, is a marked protruding demarcation in the wall curvature (as seen . from inside the aperture) that cannot properly be considered ~! 25 to be an extension of the curvature prior to that temarca-tion. Mathematically, such corners are locations st which !~ the first derivative of the surface changes abruptly in value. For a simple aperture, the entire cross-sectional flow-through area is the "flow portion". In contrast, a 3 compound aperture has more than one flow portion. Examples are described hereinafter.
In accordance with another aspect of the invention, the configuration of aperture 70 provides a length "1", Fig.
3, measured in a plane transverse to the direction of flow 35 through the aperture along arrow 60, that exceeds the width "w" (or s2) of the aperture. Most preferably, the ratio l/w is between about 2.5 and about 10Ø
The corners 72 and 73 of aperture 70 are squared, Fig. 3, or they can be rounded a~ 6hown in Figs. SA-5C.

1.1.19834 Rounded corners are generally preferred. In the embodiment of Fig. 3, dimension "1" extend6 generall~ perpendicularly to the flow direction designated by arrow 32. Alternatively, sperture 70 can be rotated 90 degrees 6uch that "1" i6 par-5 allel to arrow 32. ln such an arrangement, rounded corner~are particularly preferred.
The thickness of member 16 defining the aperture, that is, the dimension "t", Fig. 2, i8 not believed to be a significant f~ctor in determining the relationship of "1" and 10 ~W~
As is indicated in Fig. 1, 8 number of additional transport zones are extended from the single first zone 12, all downstream from access aperture 30 at predetermined loca-tions. These additional zones each have a diverting aperture 15 70~, 70", and 70''', respectively, configured as described for aperture 70.
The dimensions for sl and 82 are selected to maintain capillary flow of the liquid. Actual values will depend of course on the liquid being transported and the 20 materials from which members 14 and 16 and 52 snd 54 are !selected. Preferred values for use with blood setum are 250 microns or less.
Optionally, an additional pair of opposing 6urfsces can be added to zone 50, in the form of opposing 6idewalls i25 87, shown in phantom, Fig. 4. In such an embodiment, menis-cus 80 wets all boundary surfaces and one or more vent aper-itures are provided in walls 52, 54 or 87.
!'The opposing surfaces of the 6econd zone can be sur-faces of one and the 6ame member shaped as a tube, Figs.
30 5A-5C and 6A-6C. Parts similar to those previously described bear the same reference numeral to which the distingui6hing Buf f ix "a" ifi appended. Thus, first capillary zone 12a is formed by opposing surfaces of members 14a and 16a, and side-wall6 22a. Aperture 70a i6 formed in 6urface 20a of member i35 16a, Fig. 5A, to divert liquid flow into the 6econd zone 50a, Fig. SA, in the manner described for the previous embodi-ment. However, aperture 70a is the aperture of a tubular member 82 inserted into an aperture 84 in member 16a. The surface 86 of tube 82 defines the oppo6ing surfaces of zone li19834 g 50a. As in the previous embodiment, the ratio l/w, Fig. 5A, is between about 2.5 and about lOØ
The mechanism that permits the diverting aperture of the invention to operate to direct a portion of the flow into 5 the second zone i8 not completely understoot, nor is it necessary to the practice of the invention. However, the following description of the flow patterns for the embodiment of Figs. 5A-5C and 6A-6C is believed to roughly illustrste the mechanism involved. Member 14a has been broken awsy for 10 this purpose, Figs. 5A-5C, leaving ehe liquid in position as it would be if the member 14a were fully in place.
It is believed that the de6cribed configuration per-mits coalescence of the liquid within the aperture a~ illus-trated in Figs. 5A through 5C (end 6A through 6C). As meni~-15 cus 31, Fig. 5A, reaches aperture 70a, it moves p~st the sides 69a thereof as though to bypass it. However, a portion 31' of the meniscus moves into the aperture at corners 72a, Fig. 6A. As meniscus 31 continues to advsnce, Figs. SB and 6B, it tries to close upon itself in the direction of arrows ~ 20 74. However, because of the shape selected for aperture 70a, j the liquid coalesces and starts to fill aperture 70a and zone;l 50a. Air is pushed out of aperture 70a in the direction of arrow 76. Finally, before meniscus 31 completely closes on I itself, arrows 78, Fig. 5C, aperture 70a fills up and all of ! 25 surface 86 of member 82 located immediately below the ~urface20 of the first zone, e.g., at tbe level of point 79, Fig.
l~ 6C, is completely wetted. It will be appreciated that the jl advancing portion of the new meniscus 80, Fig. 6C, hss al-J ready wrapped itself around most of surface 86 at the point 3 in time depicted, so that when closure of arrows 78 occurs, ¦ coalescence of the liquid in aperture 80 in zone 50a below ~ surface 20a is complete. Point 79 becomes a line of inter-¦ 6ection be~ween the meniscus and 6urface 86, below first zone~urface 20a. A new meniscus 80 has thus formed in zone 50a, ' 35 and continues to advance through that zone.
If aperture 70a were as wide as it is l~ng, e.g., if it were circular, then meniscus 31, Fig. 5B, would tend to close on itself before coalescence occurred and before the liquid filled aperture 70a and completely wetted ~urfaces "~, 111'~83~

86. That is, coalescence would not occur at point 79 before the closure of the meniscus 31. The result would be ~ halt of the new meniscus at the aperture and zone 50a would not be filled.
An advantage in having opposin~ member6 of the ~econd zone extend through to the fir6t zone, Figs. 2 and 6A-6C, is that such members can have ~urfaces with different contact angles compared to the oppo~ing surfaces of the first zone, as an aid to flow within the zone. However, it is not 10 critical to the invention that the opposing 6urface6 of the second zone extend all the way through the ~ne member of the j first zone to which they are attached. Fur-thermore, 6pacing ; between the opposing surface~ of the second zone need not be i maintained constant, but can be increased or decreased. Both 15 of these features are illustrated in the embodiment of Figs.
7 and 8. Parts similar to those previously described bear ~I the same reference numeral to which the di~tinguishing suffix i "b" is appended. Thus, Fig. 7, device 10b comprises zone 12b formed by opposing surfaces 18b and 20b of members 14b and ~j ~ 16b, and aperture 30b permits introduction of liquid. Menis-~i ci 31b and 33b form and flow in directions 32b and 34b a8 in Ij the previous embodiments. However, diverting aperture 70b ¦! that leads to zone 50b is the aperture in member 16b, ~haped substantially the same as aperture 70a, Fig. 5A, with oppo~-25 ing surfaces 86b. Surfaces 86b of zone 50b are continued by - the interior surfaces of a hollow member 91 that is mounted or adhered underneath member 16b. Member 91 features an i aperture 92 formed by interior surface 95, that i8 identical in shape and size to aperture 70b. Interiorly of member 91, 3 surface 95 expands and converts into a cylindrical ~urface, Fig. 8, having a spacing s2b between ~urfaces 95 that is greater than either width w or length 1 of apertures 92 and 70b, Capillary spacing i8 maintained for s2b.
An important feature of ~urface 95 is that the 35 widening of 62a occurs gradually, leaving no exterior cor-ners at locations 94, Fig. 7, ~uch as would comprise energy barrier~ to the flow of meniscus 80b. On the other hand, interior corners such as might occur at surface intersection 96 do not create such barriers.

~1~9834 lt will be appreciated that curved portion 94 by which spacing s2b is gradually widened, can extend for any desired portion of the length of zone 50b.
As is spparent, a portion of the liquid flows via arrow 60b through diverting aperture 70b into zone 50b.
A variety of shape6 are useful for the diverting aperture, Fig. 9A. Parts similar to those previously de-scribed bear the same reference numersl to which the di~tin-guishing suffix "c", "d", and "e" are appended. Thus, cur-10 face 20c features a diverting aperture 70c that has the shapeof two concave surfaces of constant radii of curvature inter-secting at two relatively sharp apexes, as shown in Fig. 9A.
The ratio of "1" to "w" is in the range noted above. Thi~ is jj currently the most preferred shape of the diverting aperture i! 15 because this shape can tolerate greater values of w than can ! apertures such as aperture 70. Specifically, whereas aper-jl ture 70c can have a width up to about 3.0 mm, width w of !1 aperture 70 is preferably less than that, e.g., no greater than about 1 mm. Tubular walls, not shown, extend below sur-;1 20 face 20c as an extension of the zone initiated by aperture l~ 70c.
i~ The above-described diverting apertures have cross-sectional shapes that provide only concave ~urfaces, to the ,' extent they are curved at all. Diverting aperture 70d i8 an )! 25 example of a useful aperture with a convex surface 190. In such a shape, 1 is more properly measured as 9 total length i of the cross-sectional flow-through area. The aperture i6 1~ considered to be a simple aperture as the first derivative of surface 190 does not change abruptly.
3 Ihe diverting aperture can be a compound aperture, aperture 70e, with more than one flow portion. In ~uch a case, each flow portion must be examined to determine if, first, its cro6s-sectional flow-through area is 0.2 mm2 or less. If it is, then flow in that flow portion can be ex-~5 pected to occur, regardless of the ratio of length to width for that portion. If however the flow-throygh area i~ -greater than 0.2 mm2, then the length and width of that portion are designed to provide a ratio l/w that conforms to the range noted above.

The apertures of Fig. 9A demon6trste that, given a total flow-through area greater than 0.2 mm2, ehe 6hapes that work best are those that approximate ~perture 70 of Figs. 1 and 2, that is, are relatively long snd thin when 5 measured transverse to flow. Conversely, those apertures that tend not to work are those thst approximate the 6hape of a square or circle. For example, a regular five-pointed star is unsatisfactory as it approximates more the shape of a square than it does a rectangle having a length at least 2.5 10 times the width. The aperture 70f of Fig. 9B is an addi-tional example of an aperture that i~ inoperative for pur-poses of diverting liquid flow into the second zone. Such aperture has flow portions 200, 202 and 204, as determined by section lines (not shown) that can be drawn to connect the 15 interior corners. Assuming that flow portion 200 has a cross-sectional flow-through area in excess of 0.2 mm2, the ratio l/w for aperture 200 does not conform to ehe range of from about 2.5 to about 10Ø Instead l/w is sbout equal to unity. The presence of elongated portions 202 and 204 ex-! 20 tending from portion 200 does not correct the deficiency, even though if used by themselves, portions 202 or 204 would I be operative. The effect of such aperture 70f is to obtain i' initial flow partway into portions 202 and 204, but not por-j tion 200. For that rea~on, the liquid does not completely ! 25 wet the surfaces of the second zone downstream from aperture 70f, and does not continue to flow within the second zone.
On the other hand, if portion 200 were designed to have a cross-sectional flow-through area no greater than 0.2 mm2, then aperture 70f would be operative.
! 30 Once the liquid flows into any of the transport ~ zones, a variety of functions are performable on the liquid i, at different locations within the zone or zones. For ex-, ample, test elements of various kinds can be disposed at test loci in the zones for contact with the liquid. Figs. 10-13 35 illustrate a highly preferred form of such test elements, comprising ion-selective electrodes 114, hereinafter "ISE'~", for evaluating the activity, and therefore, the concentra-tion, of any electrolytes in the liquid. Parts ~imilar to lll~B34 those previously described bear the sa~e reference numeral to which the distinguishing suffix "g" has been attached.
Thus, device 10g comprises a first transport zone 12g, Fig. 13, that is an ion bridge extending between and 5 connecting matched pairs of ISE's 114I, 114II, 114~
and 114IV. Each of the ISE's is disposed in a second, third, fourth and fifth transport zone extending separately from zone 12g, as described hereinafter.
More specifically, each of the ISE pairs is mounted, 10 as by adhesive, on a frame 122, Fig. 10, and the pairs are connected by the ion bridge formed by the transport device 10g which comprises members 14g and 16g having opposed sur-faces 18g and 20g, Fig. 11, as described for the previous embodiments. Preferably, at least surface 20g is provided 15 with parallel grooves, Figs. 11 and 13. A pair of liquid access apertures 30g and 30g' are formed in member 14g, pref-erably shaped as a hexagon, as shown in Fig. 10. To retard flow of liquid after it is introduced into the access aper-tures, gating walls 110 are formed within zone 12g, each with 20 a gating aperture 112, described and claimed in my Canadian S.N. 354,146, filed July 17, 1980, entitled "~iquid Transport Device Containing Means for Delaying Capillary Flow".
In accordance with another aspect of the invention, 25 the paired ISE's are disposed in second, third, fourth, and fifth transport zones 50g extending from surface apertures 70g, Figs. 11 and 13. In this embodiment, these zones extend only the thickness "t" of member 16g, Fig. 11, because the ISE's are adhered to the undersurface of member 16g with 3 apertures 70g between them and first zone 12g. Thus the op-posing surfaces of zone 50b are the opposing surfaces 86g of aperture 70g.
As with the previous embodiments, aperture 70g has a length 1, Fig. 12, that is greater than the width w, here 35 equal to twice the radius R. Most preferably, the same ratio range described above applies to the ratio~of 1 and 2R.
As described in IJ.S. Patent No. 4,053,381, issued on October 11, 1977, each ISE 114 is a generally flat lil~834 multilayered element comprising three or more ad~acent layer~
116-120, Fig. 11. A quantity of whole blood or ser~m makes contact with, e.g., layer 116, ~fter having traver6ed zones 12g and 50g from one of the aperture6, e.g., aperture 30g.
5 Layer 116 i6 an ion-selective membrane containing an iono-phore and a solvent, 60 that the ion ~ of choice is car-ried or otherwise effectively penetrates to the underlying layers 117 and 118 where an electrical potential is generated proportional to the activity of that particular ion. Lsyer 10 117, in one embodi~ent, is a dried hydrophilic binder con-taining the salt ~ . Layer 118 in such instances is the ~ salt of an electrically conductive metal ~, and metal M forms layer 119. Because layer 119 i~ an elec-, trically conductive layer, a potential i6 measurable by an j 15 electrometer, not shown, via probes which contact layer 119.
Because the ISE's are paired, the other member of the pair i6 ¦ contacted with a reference liquid having a known activity of , the electrolyte in question. Such reference liquid is trans-~' ported simultaneously from the other aperture, e.g., aperture20 30g', through zones 12g and 50g. The reference liquid and i blood or blood serum flow together at portion 136 of zone t 12g, Fig. 10, to form a junction, permitting the electrical ll readings to be made. Any difference in the potentials s' measured at the paired electrodes is due to the two different¦! 25 ion activities of the two liquids. The difference i6 regi6-tered as a difference potential on the electrometer ~nd con-i verted into a measure of concentration of thé ionic analyte as is eonventional.
If the ISE pair is to measure Cl~, layers 116 and 3 117 are preferably replaced by sn interferant-barrier over-coat layer. Such a layer comprises, e.g., cellulose acetate containing a polyol.
It will be appreciated that each of the electrode pairs 114 is specific to the analysis of a different one of 35 the analytes. For the differential mode of mea6urement, each ISE of any pair is identical to the other of the pair. Thus, the two electrodes for one electrode pair 114I is con-structed and adapted to detect ~, the two electrode6 for pair 114II to detect Na0, the two electrode~ for pair ~1~9834 114III to detect Cl~, and the two electrodes for pair 114IV to detect HCO~. The chemistries of the layers of the electrodes are not part of this invention, and com-prise generally that described above for ion ~ with the appropriate selection of an ionophore for layer 116. For example, in the case of the ~ electrodes, layer 116 con-tains an ionophore such as valinomycin or one of the others listed in Research Disclosure, Vol. 161, Publication No.
16113, Sept. 1977, 2nd col. of p. 32, published by Industrial 10 Opportunities Limited, Homewell, Havant Hampshire PO91EF, United Kingdom. For the Na~ electrodes, the ionophore is preferably methyl monensin, and for HCO3~ the ionophore is preferably 4-octyl trifluoroacetophenone and the solvent is trioctyl propylammonium chloride. For the 15 ClQ electrodes, layers 116 and 117 are replaced as de-scribed earlier.

In use, a quantity of sample to be tested is depos-ited, preferably as a drop, in one of apertures 30g and 30g' 20 and a quantity of reference liquid in the other. The liquids spread by capillary action in a flow pattern that is par-tially shown by arrows 148 and 149, Fig. 13.
That is, the liquid introduced at the locus providedby aperture 30g, flows through zone 12g, and a portion then 25 flows into each of the apertures 70g and into zones 50g while the remainder continues to flow within zone 12g, arrow 150.
The liquid also flows into portion 136, Fig. 10, to contact the reference liquid deposited at 30g'. The reference liquid also contacts its ISE's positioned adjacent to the opposite 3 branch of the ion bridge.
To vent air trapped, at least portions of the edges 138 and 139, Fig. 10, of members 14b and 16b are left open to the atmosphere. No additional vent means, such as apertures, are necessary for zones 50g due to the short distance t, Fig.
35 11, traversed in zones 50g. However, such apertures are pre-ferred if the length of zones 50g is extended. Dimension t is preferably no larger than about 100 microns if no vent apertures are present.

~' .

~:119834 -16~
In the transport of the blood serum, such as in the use described in the embodiment of Figs. 10-13, it is pre-ferred that the dimensions of the device of the invention be chosen a~ ~ollows. For a grooved plastic ~urface 20g having 5 a groove depth dl of between about 3 and about 14 microns, Fig. 13, the effective spacing sl between the two surfaces can be varied between about 0.05 mm and about 0.5 mm for best results. Highly preferred values are between about 0.125 mm and about C.25 mm. Lesser values of 8l are useful, except 10 that when the separation distance sl approaches zero, spreading through the zone becomes extremely delayed.
If grooves are used at all, a preferred range for the width of the grooves is between about 5 microns and about 1 5 mm, it being noted that beyond about 5 mm, the rate and t 15 direction of spreading becomes insignificantly different from ~ the results achieved by a nominally smooth surface.
¦ A representative example within the aforedescribed ranges of dl sl, 1 and R for the above-described potenti-ometric analysis of blood serum is as follows:
i 20 Example sl =100 microns dl = 6.8 microns 1 1 = 2.0 mm ~ R - 0.2 mm ! 25 t = 75 microns Distance y between apertures 30g and 30g', Fig. 10, =10 mm Preferred materials for at least the opposing ~ur-faces of the members of either the first or second zone are 3 non-fibrous materials that are substantially impervious to blood serum. Examples of such materials include acetates such as cellulose triacetate, cellulose acetate propionate, and cellulose acetate butyrate; polystyrene; polyethylene;
polypropylene; ABS plastic; and polycarbonste. Such surface l 35 materials permit various chemical coatings to be applied, if desired, for example, surfactants.
It will be appreciated that a significant advantage of the construction of the ion bridge as described above is its generally open configuration in an enclosed environment ~i~9834 that nevertheless provides a controlled flow. Such a config-uration leaves ample room for the flow of whole blood, unli~e ion bridges which utilize porous ab~orbent means with void volumes less than about 50%. Furthermore, the materials de-~cribed in the preceding paragraph, by being free of fiber6,avoid the possibility of shorting out the lSE'6.
Because the total environment ifi generslly a closed one, evaporation from, and contsmin3tion of, zone 12g flre minimized. Dissolved gases tend to be retained in the liquid 10 transported, particularly when the lateral distance x, Fig.
2, between the access aperture and the ~econd transport zones, is at least 1 cm. Such prevention of ga~ 106s i~ par-ticularly important if a dis601ved gas is being tested, for example, HC0~ tested using ISE's 114 of Fig. 10.
The invention has been described in detail with par-~ ticular reference to preferred embodiments thereof, but it 'I will be understood that variations and modifications can be effected within the spirit and scope of the invention.

1. .

~! 25 i' Ii

Claims

What is claimed is:

1. In a liquid transport device comprising a) a first pair of opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid and to create a first zone of intended capillary liquid transport between said surfaces, and b) liquid access means permitting introduction of liquid into said first zone, whereby introduced liquid flows downstream from said access means by capillary attraction;
the improvement comprising at least a second pair of opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid and to provide a second zone of intended capillary liquid transport, said second pair of surfaces extending from only one of said first pair of surfaces, and diverting means in said one surface for directing a portion of the liquid away from said first zone into said second zone while the remainder of the liquid continues flow-ing in said first zone, said diverting means being i) located downstream from said access means at a predetermined location and ii) configured to insure complete wetting of said second pair of surfaces downstream from said one surface by the liquid moving therepast, and to provide a cross-sectional flow-through area greater than about 0.2 mm2.

2. A device as defined in claim 1, wherein said diverting means comprises an aperture in said one surface containing one or more flow portions, each of said portions either a) having a length and a width, measured in a plane transverse to the direction of liquid flow through said flow portion, such that the ratio of the length to the width is between about 2.5 and about 10.0, or b) having a cross-sectional flow-through area no greater than about 0.2 mm2;
whereby liquid will completely fin said aperture to maintain capillary flow therethrough while liquid flow con-tinues in said first zone.

3. A device as defined in claim 1, and further in-cluding a test element in said second zone.

4. A device as defined in claim 1, and further in-cluding a test element disposed adjacent said diverting means with said diverting means between said first zone and said element.

5. A device as defined in claim 3 or 4, wherein said test element is an ion-selective electrode.

6. A device as defined in claim 1, wherein the di-rection of flow through said diverting means extends gener-ally perpendicularly to the primary flow direction within said first zone.

7. A multidirectional capillary liquid transport device, comprising first and second zones of connected but separately extending capillary transport, each of said zones comprising at least two opposing surfaces spaced apart a dis-tance effective to induce capillary flow of introduced liquid in that zone;
access means to permit introduction of the liquid into said first zone, whereby liquid flows into said first zone downstream from said access means by capillary attrac-tion; and vent means in at least said first zone for venting trapped air from said first zone;
the surfaces of said second zone extending from only one surface of said first zone at an aperture in said one surface, said aperture being disposed downstream from said access means at a predetermined location and containing one or more flow portions each of which either a) has a length and a width measured in a plane transverse to the direction of liquid flow through said flow portion such that the ratio of the length to the width is between about 2.5 and about 10.0, or b) has a cross-sectional flow-through area no greater than about 0.2 mm2;
the total cross-sectional flow-through area of said aperture being greater than about 0.2 mm2, whereby flowing liquid encountering said aperture completely flows into said second zone to maintain capillary flow therethrough while liquid flow continues in said first zone.

8. A device as defined in claim 7, wherein the di-rection of flow through said aperture extends generally per-pendicularly to the primary flow direction within said first zone.

9. A device as defined in claim 7, and further in-cluding a test element in said second zone.

10. A device as defined in claim 9, wherein said test element is an ion-selective electrode.