TW201501694A - Analytical test strip with capillary sample-receiving chambers separated by a physical barrier island - Google Patents

Abstract

An analytical test strip for the determination of an analyte (such as glucose and/or hematocrit) in a bodily fluid sample (such as a whole blood sample) includes a first capillary sample-receiving chamber, a second capillary sample-receiving chamber, and a physical barrier island disposed between the first and second capillary sample-receiving chambers. Moreover, the physical island barrier is disposed such that bodily fluid sample flow between the first capillary sample-receiving chamber and the second capillary sample-receiving chamber is prevented during use of the analytical test strip.

Description

Analytical test strip with capillary sample receiving chamber separated by physical barrier islands

The present invention relates generally to medical devices, and more particularly to analytical test strips and related methods.

Determination of analytes in fluid samples (eg, detection and/or concentration determination) The characteristics of the sample (eg, blood volume ratio) are of particular interest in the medical field. For example, it may be desirable to measure the concentration of glucose, ketone bodies, cholesterol, lipoproteins, triglycerides, acetaminophen, and/or HbA1c in a sample of body fluids such as urine, blood, plasma, or interstitial fluid. Such assays can be implemented using analytical test strips based on, for example, visual, photometric or electrochemical techniques. The conventional electrochemical analysis test strips are described, for example, in U.S. Patent Nos. 5,708,247 and 6,284,125, the entireties of each of each of each

The present invention relates to an analytical test strip for determining an analyte in a one-piece liquid sample, the analytical test strip comprising: a first capillary sample receiving chamber; a second capillary sample receiving chamber; a physical barrier island between the first capillary sample receiving chamber and the second capillary receiving chamber, and wherein the physical barrier island The body fluid sample is prevented from flowing between the first capillary sample receiving chamber and the second capillary sample receiving chamber during use of the analytical test strip.

100‧‧‧Electrochemical analysis test strip

120‧‧‧Electrically insulating substrate layer

140‧‧‧ patterned conductor layer

140a‧‧‧electrode

160‧‧‧patterned insulation

180‧‧‧Electrode exposure window

200‧‧‧Enzyme reagent layer

220‧‧‧ patterned spacer layer

220a‧‧‧Physical Barrier Island

240‧‧‧Hydrophilic layer

260‧‧‧ top

262‧‧‧First capillary sample receiving chamber

264‧‧‧Second capillary sample receiving chamber

270a‧‧‧ sample opening

270b‧‧‧ sample opening

272a‧‧‧ sample opening

272b‧‧‧ sample opening

274‧‧‧First shared sample entry room

276‧‧‧Second shared sample entry room

600‧‧‧ method

610‧‧‧Steps

620‧‧‧Steps

630‧‧ steps

640‧‧‧Steps

650‧‧ steps

The drawings, which are incorporated in and constitute a part of this specification, illustrate the presently preferred embodiments of the present invention, and together with the <RTIgt; 1 is a simplified exploded view of an electrochemical analysis test strip according to an embodiment of the present invention; and FIG. 2 is a simplified top view of one of the layers of the electrochemical analysis test strip of FIG. 1; Simplified top view, which represents the substrate layer and spacer layer of the electrochemical analysis test strip of FIG. 1; FIG. 4 is a simplified side view of a portion of the electrochemical analysis test strip of FIG. 1, for the sake of clarity, the reagent layer is omitted, a patterned insulating layer and a patterned conductor layer; FIG. 5 is a simplified top view of the electrochemical analysis test strip of FIG. 1, showing different components thereof; and FIG. 6 is a flow chart for illustrating the present invention. An embodiment of the various stages of the method of determining an analyte in a sample of a monolith.

The following detailed description must be read with reference to the drawings in which the same elements in the different figures have the same number. The illustrations are not necessarily to scale, the illustrative embodiments are intended to be illustrative, and are not intended to limit the scope of the invention. The detailed description is to be construed as illustrative of illustrative embodiments This description enables those skilled in the art to make and use the invention, and The embodiments, changes, variations, substitutions and uses, including the current state of the art, are the best mode for carrying out the invention.

As used herein, the term "about" or "nearly" to any numerical value or range refers to a suitable dimensional tolerance that allows a component or collection of components to function in the intent described herein.

In general, an analytical test strip (eg, an electrochemical assay test strip) for determining an analyte (eg, glucose and/or blood volume ratio) in a body fluid sample (eg, whole blood) according to an embodiment of the invention includes A capillary sample receiving chamber, a second capillary sample receiving chamber, and a physical barrier island disposed between the first and second capillary sample receiving chambers. Additionally, the physical barrier island is configured to prevent a body fluid sample from flowing between the first capillary sample receiving chamber and the second capillary sample receiving chamber during use of the analytical test strip.

Analytical test strips in accordance with embodiments of the present invention have advantages in that, for example, the physical barrier islands maintain fluid integrity of the first and second capillary sample receiving chambers while being easy to manufacture. The fluid integrity advantageously prevents mixing of reagents and reaction byproducts between the first and second capillary sample receiving chambers to avoid causing incorrect analyte or body fluid sample characterization. In addition, since the physical barrier islands can be relatively small, the sample application openings of the first and second capillary sample receiving chambers can be juxtaposed to each other (for example, a distance of about 250 micrometers apart, which can be about 1 microliter. The blood sample is operatively bridged, such that a single application of the body fluid sample bridges the two sample application openings and fills the first and second capillary sample receiving chambers. Additionally, the physical barrier islands can be manufactured using conventional manufacturing techniques in a relatively simple and inexpensive manner.

1 is a simplified exploded view of an electrochemical analysis test strip 100 in accordance with an embodiment of the present invention. 2 is one of the layers of the electrochemical analysis test strip 100 The series simplifies the top view. 3 is a simplified top plan view of a substrate layer and a spacer layer (a portion of which is constructed as a solid barrier island) of the electrochemical analysis test strip 100. 4 is a simplified side view of a portion of an electrochemical analysis test strip 100 with the reagent layer, patterned insulating layer, and patterned conductor layer omitted for clarity. Figure 5 is a simplified top plan view of an electrochemical analysis test strip 100 showing its various components (including electrodes).

Referring to Figures 1 through 5, an electrochemical analysis test strip 100 for determining an analyte (e.g., glucose) in an integral liquid sample (e.g., a whole blood sample) includes an electrically insulating substrate layer 120, a patterned conductor layer 140. A patterned insulating layer 160 having an electrode exposure window 180 therein, an enzyme reagent layer 200, a patterned spacer layer 220 including a physical barrier island 220a, a hydrophilic layer 240, and a top layer 260.

Electrochemically analyzing the electrically insulating substrate layer 120 of the test strip 100, the patterned conductor layer 140 (which includes a plurality of electrodes 140a, particularly see FIG. 5), the patterned insulating layer 160, the enzyme reagent layer 200, and the patterned spacer layer 220 The configuration and alignment of (and its physical barrier islands 220a), hydrophilic layer 240, and top layer 260 results in defining a first capillary sample receiving chamber 262 and a second capillary sample receiving chamber 264 of the electrochemical analysis test strip 100.

The solid barrier islands 220a are disposed between the first capillary sample receiving chamber 262 and the second capillary sample receiving chamber 264, thereby preventing liquid from flowing between the two during use of the electrochemical analysis test strip 100.

It should be noted that in the embodiment illustrated in Figures 1 through 5, the physical barrier islands are disposed substantially parallel to the main flow direction of bodily fluids filled with the first and second capillary sample receiving chambers. Therefore, the physical barrier island does not prevent the body fluid from filling the first and second capillary sample receiving chambers, but prevents the body fluid that has entered any of the capillary sample receiving chambers from entering the other capillary sample receiving chamber.

In the perspective view of Fig. 4, the first and second capillary sample receiving chambers 262 and 264 have a height of about 100 μm, a width of from about 1.45 mm to 1.65 mm, and an oblique angle of about 2.55 mm. The sudden change in the vertical direction in which the stop joint is generated is an additional height of about 100 μm.

The patterned conductor layer 140 (including electrode 140a) of the electrochemical analysis test strip 100 can be formed from any suitable conductor material including, for example, gold, palladium, platinum, indium, titanium palladium alloys, and conductive carbon-based materials including carbon ink. Referring specifically to Figure 5, the electrode exposure window 180 of the patterned insulating layer 160 is exposed to three electrodes 140a (e.g., opposing/reference electrodes and first and second working electrodes) in the lower portion of the Figure, which are constructed for electrochemical use. The analyte (glucose) in the body fluid sample (whole blood) was measured. The electrode exposure window 180 also exposes two electrodes (in the upper portion of the figure) that are constructed for determining the whole blood volume ratio. The determination of the blood volume ratio using the electrodes of the analytical test strips is described in, for example, U.S. Patent Application Serial Nos. 61/581, 100, 61/581, 097, 61/581, 089, 61/530, 795, and 61/530, 808, the entire contents of each of which are incorporated herein by reference.

In use, a body fluid sample is applied to the electrochemical analysis test strip 100 and filled with the first and second capillary sample receiving chambers by capillary action, whereby the operative contact is disposed in the first and second capillary sample receiving The electrode in the chamber. With particular reference to Figure 3, the first capillary sample receiving chamber 262 has at least one sample application opening (i.e., two openings 270a and 270b), and the second capillary sample receiving chamber 264 has at least one sample application opening (i.e., two The samples are applied with openings 272a and 272b). Each of the first and second capillary sample receiving chambers is constructed such that the sample can be from the left hand side of the analytical test strip (using the sample application openings 270a and 272a) or the right hand side (using the sample application opening 270b) And 272b) are applied and filled with two capillary sample receiving chambers. In either case, the sample application opening of the first capillary sample receiving chamber and the second hair The sample application opening of the thin tube sample receiving chamber is juxtaposed so that a single body fluid sample can be simultaneously applied thereto.

In the embodiment of Figures 1 to 5, the width of the physical barrier island 220a is less than the width of the electrochemical analysis test strip (see, in particular, Figure 3, where "width" in this context refers to the horizontal direction of the view of Figure 3). In other words, although the physical barrier islands 220a are longitudinally disposed along the first and second capillary sample receiving chambers, the physical barrier islands do not extend to the side edges of the electrochemical analysis test strip.

The smaller width and arrangement of the physical barrier islands 220a are defined at the first sample application opening 270a of the first capillary sample receiving chamber 262 and the first sample application opening 272a of the second capillary sample receiving chamber 264. The first common sample entering chamber 274, and the second sample applying opening 270b of the first capillary sample receiving chamber 262 and the second sample applying opening 272b of the second capillary sample receiving chamber 264 The second shared sample enters chamber 276. For the sake of clarity, the areas of the first and second common sample entering chambers 274 and 276 in Figure 3 are shown in oblique lines.

The first common sample entry chamber 274 and the second common sample entry chamber 276 have the advantage that, for example, the applied body fluid sample can more easily overcome the surface tension to fill the single common sample into the chamber (and thus fill the chamber) The first and second capillary sample receiving chambers are compared to the surface tension of the two separate sample entering chambers. In addition, the width of each of the first and second common sample entering chambers (in this context, the vertical direction of FIG. 3) is greater than the width of each of the first or second sample applying openings, and is greater than two The sum of the widths of a sample application opening, or the sum of the widths of the two second sample application openings. Therefore, the user can more easily apply the body fluid sample to the relatively large width, as compared to the width of the sample application opening of the capillary sample receiving chamber.

The electrically insulating substrate layer 120 can be any suitable electrically insulating substrate layer known to those skilled in the art including, for example, nylon substrates, polycarbonate substrates, polyimide substrates, polyvinyl chloride Material, polyethylene substrate, polypropylene substrate, glycolated polyester (PETG) substrate or polyester substrate. The electrically insulating substrate layer can have any suitable dimensions including, for example, a width dimension of about 5 mm, a length dimension of about 27 mm, and a thickness dimension of about 0.35 mm.

The electrically insulating substrate layer 120 provides a structure that is easy to handle, and also serves as a substrate for applying (eg, printing or depositing) a subsequent layer (eg, a patterned conductor layer). It is noted that the patterned conductor layer used in the analytical test strip in accordance with embodiments of the present invention can take any suitable shape and be formed from any suitable material, including, for example, metallic materials and conductive carbon materials.

The patterned insulating layer 160 may be formed of, for example, screen-printable insulating ink. This type of screen-printable insulating ink is commercially available from Ercon (located at Wareham, Massachusetts U.S.A.) and sold under the name "Insulayer".

The patterned spacer layer 220 can be formed, for example, from a screen printable pressure sensitive adhesive sold by Apollo Adhesives, Tamworth, Staffordshire, or other suitable materials such as polyester and polypropylene. The thickness of the patterned spacer layer 220 can be, for example, 75 μm. In the embodiment of Figures 1-5, the patterned spacer layer 220 defines the outer walls of the first and second capillary sample receiving chambers 280.

The hydrophilic layer 240 can be, for example, a clear film having hydrophilic properties that facilitates wetting and filling of the electrochemical test strip 100 by a fluid sample (eg, a whole blood sample). The clear film is commercially available, for example, from 3M (Minneapolis, Minnesota U.S.A.) and Coveme (San Lazzaro di Savena, Italy). The hydrophilic layer 240 can be, for example, a polyester film coated with a surfactant that provides less than 10 degrees of hydrophilic contact. angle. The hydrophilic layer 240 can also be a polypropylene film coated with a surfactant or other surface treatment such as a MESA coating. The hydrophilic layer 240 may have a thickness of, for example, about 100 μm.

Where the choice of enzyme reagent depends on the analyte to be assayed, the enzyme reagent layer 200 can include any suitable enzyme reagent. For example, to determine glucose in a blood sample, the enzyme reagent layer 200 can include glucose oxidase or glucose dehydrogenase with other components necessary for functional operation. The enzyme reagent layer 200 may include, for example, glucose oxidase, sodium tricitrate, citric acid, polyvinyl alcohol, hydroxyethyl cellulose, potassium ferrocyanide, an antifoaming agent, colloidal cerium oxide, PVPVA, and water. Further details regarding the generality of the enzyme reagent layer and the electrochemical analysis test strip are described in U.S. Patent Nos. 6,241,862 and 6,733, 655 each incorporated herein by reference.

The top layer 260 can be formed from any suitable material, including, for example, polyester materials, polypropylene materials, and other plastic materials. The top layer 260 can have a thickness of, for example, about 50 [mu]m.

Manufacture can be made, for example, by sequentially forming patterned conductor layer 140, patterned insulating layer 160, enzymatic reagent layer 200, patterned spacer layer 220, hydrophilic layer 240, and top layer 260 on electrically insulating substrate layer 120. The test strip 100 is electrochemically analyzed. Any suitable technique known to those skilled in the art can be used to effect such sequential alignment formation, including, for example, screen printing, lithography, gravure printing, chemical vapor deposition, and tape lamination techniques.

Figure 6 is a flow chart illustrating stages of a method 600 of an embodiment of the present invention for determining an analyte (such as glucose) and/or a body fluid test in a sample of a unitary fluid (e.g., a whole blood sample). One of the characteristics (such as blood volume ratio). The method 600 includes (see step 610 of FIG. 6) applying an integral liquid sample to an analytical test strip such that the applied body fluid sample is filled with the first capillary sample of the analytical test strip. a chamber and a second capillary sample receiving chamber, and preventing the applied body fluid sample from being in the first capillary sample receiving chamber and the second capillary sample receiving chamber by a physical barrier island of the analytical test strip Flow between.

The method 600 also includes measuring a first reaction of the analytical test strip (eg, an electrochemical reaction from an electrode in the first capillary sample receiving chamber) and determining the body fluid sample based on the measured first electrochemical reaction One of the analytes (see steps 620 and 630 of Figure 6).

Steps 640 and 650 of method 600 also include measuring a second reaction of the analytical test strip (eg, an electrical reaction from an electrode in the second capillary sample receiving chamber) and determining the body fluid test based on the second reaction of the measurement One of the characteristics. The above measurement and measurement steps, if desired, may be performed using appropriate associated meters, and measurement steps 620 and 630 may be performed in any suitable order or in an overlapping manner.

Upon reading this disclosure, those skilled in the art will appreciate that the method 600 can be readily modified to incorporate any of the techniques, advantages and features of the analytical test strips in accordance with embodiments of the present invention and as described herein.

While the preferred embodiment of the present invention has been shown and described herein, it is understood that Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the invention. It is to be understood that various alternatives to the embodiments of the invention described herein may be used to practice the invention. The scope of the invention is defined by the scope of the invention, which is intended to cover the scope of the invention.

100‧‧‧Electrochemical analysis test strip

120‧‧‧Electrically insulating substrate layer

140‧‧‧ patterned conductor layer

160‧‧‧patterned insulation

180‧‧‧Electrode exposure window

200‧‧‧Enzyme reagent layer

220‧‧‧ patterned spacer layer

220a‧‧‧Physical Barrier Island

240‧‧‧Hydrophilic layer

260‧‧‧ top

Claims (20)

An analytical test strip for determining an analyte in a one-piece liquid sample, the analytical test strip comprising: a first capillary sample receiving chamber; a second capillary sample receiving chamber; and a first capillary test a physical barrier island between the sample receiving chamber and the second capillary receiving chamber, and wherein the physical barrier island is configured to prevent a body fluid sample from being in the first capillary sample receiving chamber during use of the analytical test strip The second capillary sample receives flow between the chambers. The analytical test strip of claim 1, wherein the first capillary sample receiving chamber has at least one sample application opening and the second sample receiving chamber has at least one sample application opening, and wherein the first capillary The sample application opening of the sample receiving chamber and the sample application opening of the second sample receiving chamber are juxtaposed such that a single body fluid sample can be simultaneously applied thereto. The analytical test strip of claim 1, wherein the first capillary sample receiving chamber has a first sample application opening and a second sample application opening, and wherein the second sample receiving chamber has a first A sample application opening and a second sample application opening. The analytical test strip of claim 3, wherein the physical barrier island extends longitudinally along the first capillary sample receiving chamber and the second capillary sample receiving chamber. For example, in the analysis test strip of claim 4, wherein the physical barrier island is configured such that: a first common sample entering chamber is defined in the first sample applying opening of the first capillary sample receiving chamber and the first sample applying opening of the second capillary sample receiving chamber, and a second sharing The sample entry chamber is defined at a second sample application opening of the first capillary sample receiving chamber and a second sample application opening of the second capillary sample receiving chamber. The analytical test strip of claim 5, wherein the width of the first common sample entering chamber is greater than the first sample applying opening of the first capillary sample receiving chamber and the second capillary receiving chamber a sum of widths of the first sample application openings, and wherein the width of the second common sample entry chamber is greater than the second sample application opening of the first capillary sample receiving chamber and the second capillary sample receiving chamber The sum of the widths of the second sample application openings. The analytical test strip of claim 1, further comprising: an electrically insulating substrate layer; a patterned conductor layer disposed on the electrically insulating substrate layer, the patterned conductor layer comprising a plurality of An electrode; a patterned insulating layer having a first electrode exposure window and a second electrode exposure window; an enzyme reagent layer disposed in the first electrode exposure window and the second electrode exposure window Above; and a patterned spacer layer, a hydrophilic layer; and a top layer, Wherein at least the electrically insulating substrate layer, the patterned insulating layer, the patterned spacer layer, the hydrophilic layer and the top layer define the first capillary sample receiving chamber and the second capillary sample receiving chamber, and wherein the physical barrier island A portion of the patterned spacer layer. For example, the analytical test strip of claim 1 is constructed, wherein the analytical test strip is constructed as an electrochemical analysis test strip. For example, in the analytical test strip of claim 1, wherein the body fluid sample is a whole blood sample. For example, in the analytical test strip of claim 1, wherein the analyte is glucose. The analytical test strip of claim 1, wherein the analyte is glucose, and the analytical test strip is configured to determine the analyte introduced into the body fluid sample of the first capillary sample receiving chamber and The blood volume ratio of the body fluid sample introduced into the second capillary sample receiving chamber. A method for determining an analyte in an integral liquid sample, the method comprising the steps of: applying a one-piece liquid sample to an analytical test strip such that the applied body fluid sample is filled with one of the analytical test strips a capillary sample receiving chamber and a second capillary sample receiving chamber, and preventing the applied body fluid sample in the first capillary sample receiving chamber and the second capillary sample receiving chamber by a physical barrier island Flowing; measuring at least a first reaction of the analytical test strip; and determining the analyte based on the first measured electrochemical reaction. The method of claim 12, the method further comprising: measuring a second reaction of the analytical test strip, the second reaction being dependent on a body fluid sample in the second capillary sample receiving chamber, and One of the characteristics of the body fluid sample is determined based on the second measurement reaction. The method of claim 12, wherein the body fluid sample is whole blood. The method of claim 12, wherein the analyte is glucose. The method of claim 12, wherein the applying step comprises applying a single body fluid sample to one of the first capillary sample receiving chamber sample application opening and the second sample receiving chamber sample application An opening, and wherein the sample application opening of the first capillary sample receiving chamber and the sample application opening of the second sample receiving chamber are juxtaposed such that the single body fluid sample can be simultaneously applied thereto. The method of claim 16, wherein the physical barrier island is applied from the sample application opening of the first capillary sample receiving chamber to the sample application opening of the second capillary sample receiving chamber, along the first A capillary sample receiving chamber and the second capillary sample receiving chamber extend longitudinally. The method of claim 17, wherein the physical barrier island is configured such that: a first common sample entry chamber is defined by the first sample application opening of the first capillary sample receiving chamber and a first sample application opening of the second capillary sample receiving chamber, and a second common sample entry chamber defined by the second sample application opening of the first capillary sample receiving chamber and the second A second sample application opening of the capillary sample receiving chamber is provided. The method of claim 18, wherein the width of the first common sample entry chamber is greater than the first sample application opening of the first capillary sample receiving chamber a sum of widths of the first sample application openings of the second capillary sample receiving chamber, and wherein the width of the second common sample entry chamber is greater than the second sample application of the first capillary sample receiving chamber The sum of the opening and the width of the second sample application opening of the second capillary sample receiving chamber. The method of claim 12, wherein the analytical test strip is constructed as an electrochemical test strip.