Volume metering capillary gap device for applying a liquid sample onto a ...

VOLUME METERING CAPILLARY GAP DEVICE
FOR APPLYING A LIQUID SAMPLE ONTO A
REACTIVE SURFACE

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RELATED APPLICATION

This is a continuation-in-part of copending application Ser. No. 777,273, filed Sept. 18, 1985, now abandoned.

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FIELD OF THE INVENTION

The present invention relates to a device and method for distribution of a liquid sample in controlled and predetermined flow patterns and, more particularly, to a device and method that permits rapid and uniform 15 distribution of a defined volume of a liquid test specimen onto a reactive surface which enables visual or other sensing means to ascertain the presence of a sought after component in the liquid sample and/or the amount of said component. 20

DESCRIPTION OF THE PRIOR ART

Analytical elements have been known for many years. The chemical analysis of liquids such as water, foodstuffs, such as milk, as well as biological fluids such 25 as blood and urine are often desirable or necessary for the health and welfare of any population. Many different designs of test elements to facilitate analyses have been developed in the past. Some are suitable for liquid analysis which require the addition of a liquid reagent 30 for a substance under analysis termed an "analyte" which reagent upon contacting a liquid sample containing the analyte effects formation of a colored material or other detectable change in response to the presence of the analyte. Other systems depend on a dry system 35 such as pH papers and the like, where the paper or other highly absorbent carrier is impregnated with a material which is chemically reactive or responsive in contact with the liquid containing the analyte and generates a color or other type of change. Depending upon the 40 selection of responsive material, the change is usually qualitative or at best semi-quantitative. For diagnostic chemical analysis wherein the testing of biological fluids such as blood, plasma, urine and the like are utilized, it is preferable to produce highly quantitative results 45 rapidly and conveniently. Also, it is desirable to precisely control and monitor the amount of liquid specimen that is subjected to the test. This is important especially in tests which involve machine reading of test substrates where it is necessary that a calibrated amount 50 of the test specimen is exposed to the test substrate so that the proper reaction will take place and that any interference with optical detection or other detection of color changes is avoided.

A variety of devices and methods have been devel- 55 oped for transporting liquid in a controlled and predetermined flow pattern. Many of such items have been concerned with uncontrolled and undirected capillary flow of the liquid across surfaces. Some problems that have been encountered with uncontrolled flow include 60 formation of trapped air pockets and incomplete wetting of certain portions of the surface. Air pockets create problems when the test device is examined through a microscope or other automatic methods because the examination of the liquid and/or the wetted surfaces 65 results in different test data being collected. The examinations and automated systems are based on a presumption of the presence of the liquid in the scanning area

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and therefore the absence of the liquid in the relevant scanning area will throw off the value of the reading and will give an unreliable result. The problem of air pockets is a common occurrence particularly when dealing with configurations which have sharp corners and synthetic resin surfaces which are generally hydrophobic.

A variety of different types of liquid transport devices have been developed in the prior art including that shown in Columbus, U.S. Pat. No. 4,233,029, which describes a device containing a means for directing capillary flow along predetermined paths by use of grooves in the opposed surfaces of a capillary chamber.

Another configuration for the transport of a liquid test specimen is shown in Columbus, U.S. Pat. No. 4,254,083, which provides for an exterior drop receiving surface containing a particular opening configuration which is intended to facilitate the centering of the drop.

Buissiere et al., U.S. Pat. No. 3,690,836, describe a device consisting of a capillary space between two plastic sheets which are sealed in a continous perimeter and which enclose an uncompressed absorbent material which fills the capillary space. At least one opening at the top sheet provides for access to the reaction chamber.

A liquid transport device which provides for diversion of capillary flow into a second zone is shown in Columbus, U.S. Pat. No. 4,473,457. The device has two pathways for flow of the specimen and permits the introduction of two different specimens through two apertures. The two liquids then will flow towards and into a common area. The configuration of the structure of Columbus permits potentiometric determinations to be made. See also Columbus, U.S. Pat. No. 4,302,313, which shows a device suitable for potentionmetric analysis of liquid ions. Special grooved surfaces under the member 36 are said to control capillary flow.

Another device is shown by Columbus, U.S. Pat. No. 4,271,119, which has a downstream diverting aperture in a wall member of a first capillary zone which provides capillary flow into a second capillary zone extending from that wall member.

Columbus, U.S. Pat. No. 4,323,536, discloses a multianalyte test device. Liquid flow control means are included such that liquid is confined to a plurality of flow paths.

SUMMARY OF THE INVENTION

The present invention pertains to a means for volume metering of liquid samples onto a reactive surface in a capillary gap device of novel configuration. The device provides for a rapid and uniform distribution of a predetermined volume of a liquid test specimen onto a reactive surface for the determination of a particular component or components that may or may not be present in the liquid test specimen. The volume of sample applied to the surface is limited to that amount which resides within a sample capillary gap or sample reading chamber. Excess sample is wicked into an overflow capillary chamber by a proportioning channel which modifies the rate of flow thereby permitting the device to accommodate excess volume above the minimum required for the sample reading chamber without requiring any measuring, blotting, wipe-off or rinsing.

Major problems associated with dry reagent films and papers are solved by the present invention; namely, 3

application of a uniformly distributed sample onto a reactive surface and control of the sample volume.

The aforementioned advantages permit one to choose a sample volume appropriate to the chemistry and reactivity of the reactive material by varying the thickness 5 of the capillary gap and hence the total volume entrained by the sample reading chamber of the device.

Excess fluid beyond the capacity of the capillary overflow chamber may be absorbed by filter paper or other absorbent medium attached to the device adjacent 10 to or directly over a suitable opening of the overflow chamber.

Other features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the drawings. 15

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of one embodiment of the capillary gap device of the present invention;

FIG. 2 is a top view of the top layer of one embodi- 20 ment of the capillary gap device of the present invention showing the openings or ports formed therein; • FIG. 3 is a top view of the spacer layer of one embodiment of the capillary gap device of the present invention showing the chamber formed therein; 25

FIG. 4 is an end view of the capillary gap device taken along lines 4—4 in FIG. 1;

FIG. 5 is a perspective view of another embodiment of the present invention;

FIG. 6 is a top view of an alternative arrangement of 30 the present invention;

FIG. 7 is a top view of another embodiment of the invention;

FIG. 8 is an end view of the embodiment shown in FIG. 7 taken along lines 8—8; 35

FIG. 9 is a perspective view of another embodiment of the invention;

FIG. 10 is an exploded view of an alternative arrangement of the present invention;

FIG. 11 is a perspective view of the upper layer 40 shown in FIG. 10;

FIG. 12 is a schematic side view of another embodiment of the invention showing a particular configuration for a spacer layer;

FIG. 13 is a perspective .view of another embodiment 45 of the capillary gap device of the present invention;

FIG. 14 is a top view of the top layer of the embodiment of the invention shown in FIG. 13;

FIG. IS is a perspective view of another embodiment of the capillary gap device of the present invention; 50

FIG. 16 is a top view of the top layer of the embodiment of the invention shown in FIG. 15;

FIG. 17 is a graph of the reactivity per second and describes the effect of format design on the dose response film curve for a glucose sensitive film; and 55

FIG. 18 shows a comparison of test precision for an open and a capillary gap format device.

Major problems associated with dry reagent films and papers are solved by the device of the invention. It is difficult utilizing prior art materials to obtain an applica- 60 tion of an uniformly distributed sample over a finite surface area of a test surface. In many instances, the sample will not travel into the sample chamber under proper conditions, too much sample is in contact with the sample chamber or not enough of the liquid is in 65 contact therewith. The present invention permits close and carefully monitored control of the sample volume so that only a previously determined calibrated amount

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of liquid to be analyzed will be in contact with the test surface. Therefore, these advantages permit one to choose a sample volume that is appropriate to the particular test that is being carried out taking into consideration the nature of the fluid that is being tested and the nature of the reagent film. The present invention can be fabricated in various different dimensions and therefore the thickness of the capillary gap can be varied as desired. Hence, the capillary gap devices can be made in various sizes depending upon the total volume of the sample that is desired to be entrained of the sample. This will depend upon the particular means chosen for reading the results; i.e., either automatic or visual means. The device of the present invention provides a means for dealing with the problem of excess sample so that any excess liquid does not interfere with obtaining a proper reading. Thus, in accordance with the invention, excess fluid flows into an overflow chamber through an overflow proportioning channel and, if necessary, out an overflow port or opening. If desired, some sort of absorbing material can be either attached to the device or adjacent thereto so as to absorb the excess liquid.

It is important to note that the present invention is not simply a fluid transport or spreading device but instead is a volume metering device which is designed to accommodate a range of sample volumes from a minimum of about 5 to 10 micro liters up to about 100 to 200 micro liters without washing or wiping off the excess liquid.

It is therefore an important feature of the present invention to provide a fluid metering device in a capillary gap structure containing a sample chamber of a defined volume.

It is a further feature of the present invention to provide a capillary gap device which has a capillary lock for air release and prevention of backflow into the sample application port.

A further feature of the present invention is to provide for proportioned flow of the sample fluid into a capillary overflow chamber which accommodates the liquid volume beyond the minimum required to fill the sample chamber. The volume of the sample chamber can be varied to accommodate excess sample as well when this is compatible with the chemistry of the reagent film that is chosen.

A further feature of the present invention is to provide for complete removal of sample fluid from the sample application port by capillary action. Thus, no washing or wiping is required nor does any excess sample fluid remain exposed in the aperture. In operation in accordance with the invention, any residual sample which remains in the sample application port would be drawn into the overflow chamber and the sample application port is thereby evacuated. Any excess overflow beyond the capacity of the capillary overflow chamber can be taken care of by utilizing an absorbent pad as an optional feature of the invention.

A still further feature of the present invention is a capillary gap device wherein no exchange can occur between liquid in the sample chamber and liquid in the overflow chamber due to the creation of an air gap in the overflow proportioning channel. This can enchance the end point chemistries which are carried out in the sample chamber depending upon the particular nature of the reactive material.