MXPA97006102A - Hollow troncoconic device for pru reagents - Google Patents

Abstract

The present invention relates to a device for use in an apparatus for measuring a concentration of an analyte in a sample of a biological fluid, characterized in that it comprises: (a) a hollow frustoconical body having open ends of different size, the open end smaller, having a lip extending inward, and (b) a porous membrane to accept the sample, fixed to raised portions of a surface of the lip, and substantially closing the smaller open end, the membrane comprising: (i) a first surface for accepting the sample and (ii) a reagent for reacting with the analyte in order to produce a color change on a second surface, opposite the first surface, which results in a change in the reflectance on the second surface, that can be measured and related to the concentration of the analyte in the sample

Description

HOLLOW TRQNCQONICO DEVICE FOR TEST REAGENTS BACKGROUND OF THE INVENTION 1. FIELD OF THE INVENTION This invention relates to a disposable measuring device for measuring the concentration of a nali-to in a biological fluid; very particularly, an apparatus for which the disposable device is a hollow ironcoconic device. 2. DESCRIPTION OF THE RELATED TECHNIQUE Medical diagnosis often involves measurements on biological fluids, such as blood, urine or saliva, that are obtained from a patient. Generally, it is important to avoid both the contamination of equipment and the. Personal with these fluids as the patient contination with fluids of others. Therefore, there is a need for diagnostic devices that minimize the risk of such contamination. Among the medical diagnostic devices that are most widely used today are the blood glucose monitor. Only in the United States are estimated 14 million people with diabetes. In order to avoid serious medical problems, such as loss of sight, blood circulation problem, kidney failure, etc., many of these people monitor their blood glucose on a regular basis and then continue the steps necessary to maintain your glucose concentration within an acceptable range. Blood contamination is a concern when measuring blood glucose. For example, when using the common types of whole-blood glucose meters (photometics), the determination of glucose is usually made from a blood sample that < _e applies to the test strip that is on the meter. To apply the blood sample obtained from a patient's finger, the patient's finger should be placed above and close to the test strip to inoculate the test strip with the blood sample. There is a risk that the patient's finger could make contact with a portion of the meter that is contaminated with blood from previous use by others, particularly when used in a hospital. This risk to the patient is minimized if The test strip is inoculated before being placed in the meter. This is called the "dosing out of the meter" approach. With this approach, the patient applies their blood sample to a reagent test strip as the first step in the measurement procedure. Then the strip is inserted into the meter. The patient's finger only makes contact with a new (clean) disposable strip, which can not be contaminated by the bleeding of another patient. The finger never contacts a contaminated portion of the meter. The focus of heavy metering of the meter has been used for some time, particularly with meters that operate fo or ethically, as well as in systems that measure hema-tocp. A disadvantage of dosing outside the meter is that the meter can not take a measurement at or below "zero time", which is the time at which the sample was applied to the strip. In a photometric meter, a reflectance reading of the inoculation of the strip allows the meter to correct-variations in the background color and placement of the strip. The meter can also determine the time zero in for'ma rna < -di straight and precise, which facilitates accurate measurements. Conversely, time zero can be difficult or impossible to determine if the strip is inoculated outside the meter. Although dosing out of the meter reduces the problem of contamination for the patient, the meter can still be contaminated with blood, therefore, there is a risk that other people may make contact with the contaminated meter, such as workers in a hospital and the repair technicians of the meters. In addition, if the patient is being assisted by health care personnel, such personnel may make contact with the patient's blood while removing the strip to dispose of it, after the test has been completed.

Meters that work electrochemically typically use "remote dosing", in which the test strip is placed on the meter before inoculation, but the point of application of the blood is far from the surfaces of the meter that can be contaminated. For example, the Gluco eter Elite "from Bayer Diagnostica and the Advantage" from Boehrmger Mannheirn incorporate electrodes with remote sample application. As with the heavy dosing of the meter, the removal of the strip can also pose a risk to meters that use remote dosing. Many systems have been described that are intended to reduce the risk of contamination for a patient and / or for other persons related to diagnostic tests. The patent of E.U.A. 4,952,373, issued on 28 August 1990 to Sugarman and others, describes a protection that is designed to prevent excess fluid in the diagnostic cartridges from being transferred to a monitor with which a cartridge is used. The protection is made of a thin film of plastic or metal and is fixed to a cartridge that is generally the size of a credit card. The patent of E.U.A. 5,100,620 issued March 31, 1992 to Brenne an, discloses an inverted funnel shaped body with a central capillary tube for transporting a liquid sample from a far sample application point to a test surface. The device can be used to transfer blood from a lancet to an area film. The patuto of E.U.fi. 3,991,617, issued on November 16, 1976 to Marteau d'Autry describes a device that is used with a pipette designed to be used with disposable tips. The device provided a push button mechanism to eject the tip from the end of the pipette. The common element of the above patents is that each of the described devices faces the risk of contamination of biological fluids and other potentially dangerous liquids.

BRIEF DESCRIPTION OF THE INVENTION In accordance with the present invention, a device for use in an apparatus for measuring a concentration of an analyte in a sample of a biological fluid comprises: (a) a co-shaped frustoconical body having open ends of different size and (b) ) a porous membrane to accept the sample, fixed to, and substantially closing, the smallest open end, the membrane comprising (i) a surface to accept the sample and di) a reagent to react with the analyte in order to produce, in a physically detectable parameter of the membrane, a change that can be measured and related to the concentration of the analyte in the sample. A method of this invention to measure a concentration of an analyte in a sample of a biological fluid comprises (a) providing a device comprising a hollow truncated body having open ends of different size, the small end of which is substantial. It is closed by a membrane having (i) a surface to accept the sample and (11) a reagent to react with the analyte in order to produce, in a physically detectable pair of the membrane, a change that can be measured and relate to the concentration of the analyte in the sample; (b) apply the sample to the surface of the membrane; (c) measure the change in the meter; and (d) determining the analyte concentration of the parameter change measurement. The device of the present invention can be advantageously used with a meter to measure a concentration of an analyte in a sample of biological fluid that is applied to the first surface of a porous membrane containing a reagent, which reacts with the analyte to produce a change in the reflectance of a second surface of the membrane, the membrane being fixed to and closing substantially from one end of a hollow frustoconical device. The meter collects "e (a) a body having a frustoconical distant section for coupling with the device, the section tapering inward to an end facing the second surface of the membrane, (b) an optical system in the body to direct a nano beam of light outside the far end and to accept 1 u; -reflected from the second surface of the membrane, (c) means for measuring reflected light in the body before and after applying the sample to the membrane, and (d) means for calculating the analyte concentration in the starting fluid. of the measured values of the reflected light. The device of the present invention allows a person to measure the concentration of analyte in a biological fluid, while minimizing the risk that the fluid or the user makes contact with the measuring device. In this way, the device reduces the likelihood of contamination of the device by the user and vice versa. The device is disposable and the term "device" and "disposable device" are used interchangeably throughout this specification and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of a device of this invention with a detached portion for better quality; Figure 2 is a cross-sectional view taken along the line 2-2 of Figure 1; Figure 3 is a perspective view of a meter and device of the invention before fixing them; Figure 4 is a perspective view of the meter and device in the process of obtaining a sample «le san re; Figure 5 is a partial cross-sectional view of the meter and device of Figure 4, taken along line 5-5 of Figure 4; Figure 6 is a side view of a partial cross section of a plurality of devices in a package; Figure 7 is a perspective view of a meter of this invention ejecting a device; Figure 8 is a longitudinal cross-sectional view, with certain elevation portions for clarity, of the meter of Figure 7 in a first position during use; Figure 9 is a side elevation view, partly in cross section, of the meter of Figure 7 in a second, ejection position; Figure 10 shows a perspective view of an alternative mode of a meter; Figure 11 is a perspective view of an alternative embodiment of a device of this invention; Figure J 2 is a fragmentary perspective view of the distal end of the device of Figure 11; Figure 13 is a cross-sectional view taken along line 13-13 of Figure 12; Figure 14 is a cross-sectional view taken along line 14-14 of Figure 12; Figure L5 is a cross-sectional view of a further embodiment of the distal end of a device of the invention; Figure 16 is a perspective view of the modality of a device and device before fixing them; Figure 17 is another modality "le un? Ne" l? «1o and device; Figure 18 is a perspective view of the remote end of one more mode of the meter and device; Figure 19 is a side view of the distal end of the meter * and device of Figure 18 shown in an assembled position.

DETAILED DESCRIPTION OF THE INVENTION The device of the present invention is generally adapted for use in an apparatus for measuring the concentration of analytes, such as alcohol, cholesterol, proteins, ketones, enzymes, femlalamine and glucose, in biological fluids such as blood, urine and saliva. In brief, the details for using the device in connection with the blood glucose meter are described; however, an expert in the medical diagnostic art could easily adapt the technology to measure other analytes in other biological fluids. Self-monitoring of blood glucose is usually done with meters that operate based on one of two principles. The first is the photometric type that is based on reagent strips that includes a composition that changes color - after applying the blood. The color change- is a measurement of the glucose concentration. The second type of blood glucose monitor is electrochemical and works with the understanding that blood applied to an electrochemical cell can produce an electrical signal - voltage, current or load, depending on the type of meter - that can be related to the concentration of glucose in the blood. The present invention allows convenient remote dosing for fo + or etric and electrochemical systems. In 1 L Briefly, the following description focuses on a photo-rich system. Similar devices can be used with an electrochemical system. With any type of system, the present device allows the meter to recall the entire reaction course, from the time the sample is applied until the glucose determination is made. The ability to measure the start time of the test makes it easier to determine the glucose concentration with precision. There are some advantages to using a photometric system instead of an electrochemical one to make a glucose determination. An advantage of a photometpco system is that measurements can be made at more than one wavelength of light, and corrections can be made for variations in blood hematocpto. The disposable device described here provides these advantages of the photo-rich system, while also allowing minimal contamination of the liquid. The disposable devices used in foamed measuring systems are generally made in the form of a thin rectangular strip. The shape derives from the original test strip configuration called "immersive and readable". One end serves as a handle, while the chemical reaction with the blood sample is carried out in the other ext emo. These rectangular disposable devices form the male portion of the boundary with the medium Jor. That is, the strip is retained by characteristics of the meter that enclose the device "lesechable. This method of retention favors the contamination of the meter with fluid sample. To avoid contamination problems, the present disposable device takes the form of a hollow frustoconical body, which provides the female portion of the colmdance with the meter. That is, the disposable device encloses a portion of the meter and serves as a cover to prevent contamination of the meduor with the fluid sample. Figure 1 illustrates in a partial section an embodiment of this invention in which the disposable device LO is a hollow cone-shaped frustum body. The membrane 12 is fixed to the smaller end 14. An optional lip 16 provides a surface to which the membrane 12 is fixed with an adhesive 18. Optional indentations 20 are spaced around the surface of the cone to provide a retention mechanism together with a slot in a meter. Figure 2 is a cross section of the disposable body of Figure 1 taken along line 2-2. As shown in Figure 2, the membrane is fixed to the exterior of the disposable device. Alternatively, as shown in Figure 11, the membrane can be attached to the interior of the disposable device. Figure 3 is an exploded perspective view of a photometric meter and a disposable device of the type shown in Figure 1. The meter 30 # has an elongated configuration with a distal section 32 which is substantially in a cylindrically symmetrical frustoconical body. , along whose perimeter there is optionally a slot 34. Note that the disposable device is housed over the remote section of the cushion so that there is a precisely defined space G between the distal end 36 of the meter 30 and the bottom surface of the membrane 12. The precise position contributes to the precision and reliability of the measurement. In the cut, a light source 38 and a detector 40 can be seen, which provides illumination to the disposable device and to detect the reflected light of the disposable device, respectively. As described above, the measurement of reflected light from the disposable device determines the concentration of glucose in the sample applied to the membrane. Although only one source and detector is shown in Figure 3, multiple sources can be used, which optionally have different output spectra and / or multiple detectors. Figure 4 is a perspective view of the manner in which a device and meter of Figure 3 can be used to obtain a sample S obtained from a finger, which is a great advantage for users who have difficulty in seeing. Figure 5 is a cross section of a portion of the distal section 32 of the meter 30 and disposable device 10, illustrating the way in which the mdentations 20 and the slot 34 positively locate the meter 30 den of the disposable device 10, leaving a space G. Note that space G ensures that the blood that penetrates through the membrane does not contaminate the meter. The dimension of space, although not critical, is preferably at least approximately .5 inin. An advantage of the device of the invention, when used with a meter of the type shown in Figure 3, it is that the devices can be in a stack, conveniently housed in a container 42, as shown in Figure 6. Afterwards, a device can be simply secured inserting the remote section 32 of the meter 30 into the container 42 and engaging the slot 34 and the indentations 20. After a test has been completed, a used disposable device can be ejected into a waste container U, as shown in FIG. figure 7, as long as there is an optional ejection mechanism per pressure button. Push-button ejection mechanisms of the type that are known and used to be used are suitable for this invention (see, for example, U.S. Patent 3,991,617). A mechanism of this type is illustrated in Figures 8 and 9, which show a push-button mechanism mounted on a meter of the type shown in Figure 3. The elements of the mechanism include an arrow 44, which attaches to the ejector. 46 and pressure button 48. Press button 48 operates through arrow 44 to cause ejector 4b to latch onto disposable device 10 of remote section 32 of meter 30. Spring 50 operates to return the ejector 46 and pressure button 48 to its retracted position. Ejection by pressure button, which allows the disposable device to be removed without direct contact, helps to avoid contamination. The "expendable" devices to be used-with pressure push-button ejection mechanisms of the type shown in FIGS. 8 and 9 preferably have a flange 19. FIG. 10 illustrates a modality "of a meter" of this invention. , which melts a screen 50 to illustrate the analyte concentration measured by the meter. The screen may be a light emitting diode (LED) screen, a liquid crystal display (LCD) or a similar screen well known in the art. Although the above description and the figures contemplate a disposable device having a circular cross section, that geometry is not essential and, in fact may not be preferred. A primary consideration in the selection of geometry in a photornétpco system is the optical design. Generally, reflectometry determines at least a minimum angular separation (typically 45 °) between a detector and specularly reflected light. This in turn requires at least a minimum apex angle of the conical disposable device. However, it is an advantage for a user to see your <"je« or for dosing, and a large vertex angle interferes with the view. Therefore, a disposable device «jue has a cross section * Ib The rectangular body may be preferred, such as the hollow trunk body, ie a rectangular pyramid 110 shown in FIG. 11. In that case, the angular separation between the detector and the specularly reflected light determines only the minimum feasible value of L, the longitudinal dimension of the largest open end. However, the disposable device may be smaller and may interfere slowly in the user seeing his own finger. In addition, membranes can be manufactured from battens or sheets at lower cost and with less waste of material. However, a circular cross section is advantageous when an arrangement of several sources and / or detectors is used on the optical system. Since contamination is possible if excess sample of the disposable device is allowed to drip, it is convenient to adapt large samples without dripping the samples. Several designs can serve to retain excess sample. One is shown in Figures 12, 13 and 14. Figure 12 illustrates the disposable device of Figure 11 with detents 124 on the surface of the small end of the "jeeechable" device. As shown in FIGS. 13 and 14, the patterns allow capillary flow to fill the resulting space between the membrane and the upper internal surface of the device. An alternative way to form said spaces is to adhere the membrane to the disposable device with thick adhesive, leaving spaces to adapt the excess sample. Another way to absorb the excess of sample is to fix an absorbent pad 126 on the front surface of the membrane, as shown in Figure 15. Figure 16 is an exploded perspective view of a meter and disposable device. of the type shown in Figure 11. The distal section 132 of the edger 130 has an optional slot 134, which is similar to the slot 34, for retaining the disposable device. The elongated neck 130 facilitates the collection of disposable devices and elongated containers 42 shown in Figure 6. The screen 150 illustrates the concentration of analyte measured. Figure 17 illustrates an alternative embodiment of a meter adapted for use with the disposable device of Figure 11. Figure 18 illustrates the distal portion of yet another embodiment of the disposable device 210 and the meter 230. The distal section 232 engages the disposable device 210. Note that slots 234 are an alternative to slot 34 (or 134) for capturing indentations, such as 220, on the disposable device. Figure 19 shows a side view of the modality shown in Figure 18. In the above < In this invention, a blood sample is collected on the surface of the membrane that faces outwards. The glucose in the sample interacts with a membrane reagent to produce a change in color, which changes the reflectance of the membrane surface that faces inward. The light source in the meter illuminates the surface of the membrane that faces towards and measures the intensity of light reflected from that surface. Using the appropriate calculations, the change in reflectance determines the concentration of glucose in the sample. A variety of combinations of membriana and reagent compositions are known for photometric determinations of blood glucose concentration. A preferred membrane / reagent composition is a polyarynide matrix that incorporates an oxidase enzyme, a peroxidase and a dye or pair of dyes. The enzyme oxidase is preferably glucose oxidase. The peroxidase is preferably horseradish peroxidase. A preferred pair of dyes is 3-? Net and L-2-benzot? Azole mona-hydrazone hydrochloride with 3,3-d? Methalamo? Nobenzoic acid hydrochloride. Details of the membrane / reactive combination and variations of the isma appear in the U.S. patent. 5,304,468, issued April 19, 1994, to Phillips et al., Incorporated herein by reference. Another preferred membrane / reagent composition is a polysulfone to isotropic membrane (available from Merntec America Corp., Timonium, MD) which incorporates glucose oxidase, horseradish peroxidase and the pair of dyes C3-met? L-2-benzothiazolinone-hLdrazonal N-sulfonyl benzens? Monosodium fonate combined with 8-an? L? No-l acid -naphthalenesulfommonium ammonium. Details of the combination of rne brane / reacti or and variations thereof appear in the patent application of E.U.A. No. 08 / 302,575, filed September 8, 1994, incorporated herein by reference. Those skilled in the art will understand that the foregoing descriptions of embodiments of this invention illustrate the practice of the present invention but are in no way limiting. Variations of the details presented herein can be made without departing from the scope and spirit of the present invention.

Claims (11)

NOVELTY OF THE INVENTION CLAIMS

1. - A device for use in an apparition to measure a concentration of an analyte in a sample of a biological fluid, comprising: (a) a hollow frustoconical body having open ends of different size and (b) a porous membrane to accept the sample, fixed to, and close to, the open end of the membrane, the membrane comprising: (i) a surface to accept the sample and (n) a reagent for react with the analyte in order to produce, in a physically detectable parameter of the membrane, a change that can be measured and related to the concentration of the analyte in the sample.

2. The device according to claim 1, further characterized by the fact that the frustoconical body has a rectangular cross-section.

3. The device according to claim 1, further characterized in that the frustoconical body has a circular cross section.

4. The device according to claim 1, further characterized in that the reagent reacts with the analyte to produce a change in color and the membrane parameter is a reflectance of a second surface, opposite to the first surface. 71

5. - The device according to claim 4, further characterized in that the membrane comprises poiiarnide.

6. The device according to claim 4, further characterized in that the membrane comprises polysulfone.

7. The device according to claim 1, further characterized in that the truncated body has a plurality of femurial circumferential mdentations.

8. The device according to claim 1, further characterized in that the smaller open end has a lip that extends inwardly and the membrane is fixed to a "lip" surface.

9. The device according to claim 8, characterized in that "the membrane is adhered to the lip in a plurality of points, are separated by regions where it is not adhered.

10. The device according to claim 9, further characterized in that the points at which the membrane is adhered to the lip comprise elevated portions of the surface of the lip.

11. The device according to claim 1, further characterized in that it comprises an absorbent pad on the first surface of the membrane. 00 L2. ~ The device in accordance with claim 1, further characterized in that the large open end has a rim flange extending towards the end.