MXPA97006103A - Measurement of analytic concentration through the use of a hu troncoconic device - Google Patents

Abstract

The present invention relates to a method for measuring the concentration of an analyte in a biological fluid sample involving a hollow disposable device in frustoconical form, the smaller end of the frustoconical device having a porous membrane, to which the sample is applied; preferably, a reagent in the membrane reacts with the analyte to produce a color change, the device is mounted on a meter, which measures the color change and calculates the concentration of the analyte in the sample from the change; devices are released from the meter without touching them, to protect against contamination

Description

MEASUREMENT OF THE CONCENTRATION OF RNRLITOS THROUGH THE USE OF A HUECO TRONCQCNIC DEVICE BACKGROUND OF THE INVENTION 1. FIELD OF THE INVENTION This invention < -It refers to a positive measure of discard or par-a concentration of a \ nalit. on a biological fluid; very important, an apparatus for which the dLsposL ivo dcseeplable os í n positive tconcoco con i coueque ,, - DESCRIPTION OF THE RELATED TECHNIQUE The doctor or physician often applies measurements in biological fluids, such as blood, urine, etc. saliva, which is obtained from a lens. It is important to avoid both the contamination of equipment and personnel with these fluids, as well as the patient's contamination with fluids from others. Therefore, there is a need for diagnostic devices that minimize the risk of such contamination. In the medical diagnostic devices that are widely used today is the blood glucose monitor. In the United States alone, 14 pullons of people with diabetes are estimated. In order to avoid serious medical problems, such as loss of vision, blood circulation problems, kidney failure, etc., many of these people monitor their blood glucose on a regular basis and then follow the steps necessary to maintain your glucose concentration within a certain scale. The contamination of the blood is of concern when measuring glucose in the r-an re. For example, when < • The most common types of whole-blood glucose meters (photome-rich), glucose determination is usually made from a blood sample that is applied to the test strip that is about the meter To apply the sample of blood obtained from a patient's finger, b the patient's finger should be placed above and near the patient's finger.

• Test test to inoculate the test sample with the blood sample. There is a risk that the patient's finger may make contact with a portion of the medication that is connate with blood from previous use by others, particularly when used in a hospital. This risk to the patient is reduced. To the minimum if the test strip is inoculated before being placed in the meter, this is called the "dosing out of the meter" approach. With this entogue, the patient applies his 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 blood of another patient. The finger never makes contact with a contaminated portion of the meter. The approach to dosing out of the meter has been used for a certain period of time, par ticularly with meters that operate f-otomet icly, as L as in L sterns that are used to hen or to. One disadvantage of dosing out of the meter is that the meter can not take an original measurement below the "zero time", which is the time the sample was applied to the strip., In a photometric meter, A reading by reflectance before 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 time zero more directly and accurately, which facilitates accurate measurements. By con- trast, time zero can be difficult or impossible to determine if the strip is inoculated outside the medium. Although the 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 the workers a hospital and the repair technicians of the meters. Adornas, if the patient is being helped by health care personnelThis personnel can make contact with the blood of the patient while removing the strip to dispose of it, after the test has been compiled, the meters that work electrically typically use "remote dosing", in the 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 meters "lueorneter Elite" of Bayer Diagnostics and the The Boehrmger Mannheim fldvantagef incorporates electrodes with remote sample application, as with the heavy dosing of the meter, the removal of the strip can also involve a risk for meters that use two rernot a. many systems that are intended to reduce the risk of contamination for a patient and / or for other persons related to diagnostic tests, US Patent No. 4,952,373, issued on April 28. Gosto 1990 to Sugarman and others, describes a protection (jue is designed to prevent excess liquid in the diagnostic cartridges is transferred to a monitor with which cartridge is used. The protection is made of a thin film of plastic or metal and is fixed to a cartridge (generally the size of a credit card.) US Patent 5,100,620 issued March 31, 1992 to Brenne an, describes a body In the form of an inverted funnel with a central capillary tube for transporting a sample of liquid from a remote application point to a test surface, the device can be transferred from a lancet to a reagent film. The US patent 3,991,817, issued in Iñ de November of J976 to Marteau d'Autry describes a device that is used with a pipette designed to be used with disposable tips. The device provides a pressure button mechanism to eject the tip of the pipette from 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 powerful liquids.

BRIEF DESCRIPTION OF THE INVENTION In accordance with the present invention, a device for use in an apparition for measuring a concentration of an analyte in a sample of a biological fluid comprises: (a) a coarse-coded body having open ends of size different and (b) a porous membrane to accept the sample, fixed to, and substantially closing, the small end, the membrane comprising (i) a surface to accept the sample and (LI) a reagent to react- 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. One method of this invention to measure a concentration of an analyte in a sample of a biological fluid comprises (a) providing a device that comprises a hollow trunk body having open ends of different size, the end of which is in. s small is substantially 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 ( You can measure and relate the concentration of the analyte in the sample, (b) apply the sample to the surface of the membrane, (c) measure the change in the parameter, and (d) determine the concentration. ANALYZING THE MEDIUM OF THE PARAMETER CHANGE 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 membrane. by The reactor 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 substantially closing one end of a hollow frustoconical device. The meter comprises (a) a body having a different section in frusto-conical shape for coupling with the device, the section is tapering inward to an end facing the second surface of the membrane, (b) an optical system in the body to dp a beam of light out from the far end and to accept reflected light from the second surface of the membrane, (c) means to measure the reflected light in the body before and after applying the sample to the membrane, and (d) means for calculating the analyte concentration in the fluid from the measured values of the reflec ted light. The device of the present invention allows a person to measure the concentration of analyte in a biological fluid, while minimizing the risk of the fluid or the user making contact with the measuring apparatus. In this way, the device reduces the likelihood of contusion of the device by the user and vice versa. The device is disposable and the term "device" and "disposable device" are used indiscriminately 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 improvement; 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 arrangement in the process of obtaining a sample of 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 5 is a sectional side view t ransver < -the partial 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 parts in elevation even-greater 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; Fig. 10 is a perspective view of a fashion alternative lity of a meter; Figure 11 shows a perspective view of an alternative embodiment of a device of this invention; Figure 12 is a fragmentary perspective view of the distal end of the device of Figure 11; Figure 13 is a cross-sectional view taken at the same time as line 11-13 of Figure 12"Figure 14 is a cross-sectional view taken along line 14-14 of the figure Figure 2 is a cross-sectional view of a further embodiment of the distal end of a device of the invention; Figure 1 (5) is a perspective view of the mode of a meter and device before being fixed; Fig. 17 is another embodiment of a positive dia meter, Fig. 18 is a perspective view of the distant ext of a further mode of the meter and device, Fig. 19 is a side view of the distal end of the meter and device; Figure 18 is 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 analysts, such as alcohol, estero 1, proteins, ketones, enzymes, ilalanine and glucose, in biological fluids such as blood, urine and saliva. In brief, the details are described for using the device in connection with automated blood glucose monitoring; However, an expert in the medical diagnostic technique could easily adapt the technology to measure other analytes in other biological fluids. Autologous blood glucose is usually done with meters that operate based on one of two principles. EJ first is the type fotometpco that is based n strips of reagent that includes a composition that changes color after applying the blood. The color change is a measurement of 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 with the concentration of glucose in the blood. The present invention allows convenient remote dosing for photochemical and electrochemical systems. Briefly, the following description focuses on a rich photonet system. Similar devices can be used with a eJect rochemic system. With any type of system, the present device allows the meter to monitor 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 concentration of glucose with precision. There are some advantages to using a photoelectric system instead of an olecymic and oxytoic to make a glucose determination. An advantage of a photometric system is that measurements can be made at more than one wavelength of light, and corrections can be made with variations in blood hernatocyte. The disposable device described here provides these advantages of the photomechanical system, while also allowing minimal contamination of the meter. The disposable devices used in standard measuring systems are generally made in the form of a thin rectangular strip. The shape derives from the configuration of the original test strip called "immersion and readable". One end serves as a handle, while the chemical reaction with the blood sample is carried out in the other row. These rectangular disposable devices form the male fiorcion of the colmdancia with the meter. That is, the strip is retained by characteristics of the meter that enclose the disposable device. This method of retention favors the contamination of the meter with fluid sample. In order to avoid the problems of contamination, the present disposable device adopts the shape of a hollow frustoconical body, which provides the female portion of the contact with the meter. That is, the disposable device encloses a portion of the meter and serves as a cover to prevent contamination of the meter with the fluid sample df1. FIG. 1 illustrates in a partial section an embodiment of this invention in which DISCARD 10 is a hollow cone-shaped eleven-cone 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. n, along 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 outside of the disposable device. AlternativelyAs shown in Figure 11, the membrane can be fixed to the interior of the disposable device. Figure 3 is an exploded perspective view of a photointernet meter and a disposable device of the type shown in Figure 1. The meter 30 has an elongated configuration with a distal section 2 which is substantially a rigid body. t-symmetrical indp carnent, along whose perimeter there is optionally a slot 34. Note that the disposable device is housed over the remote section of the meter such that there is a precisely defined space G between the distal end 36 of the meter. meter-30 and The lower surface of the membrane 12, The precise position contributes to precision and reliability of the measurement. In the cut-off, an IR uX source and a detector 40 can be seen, which provides illumination to the scrap device and for detecting the reflected light of the 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 in Fig. 3 only one source and detector is present, multiple sources can be used, which optional They have different output spectra and / or multiple detectors Figure 4 is a perspective view of the form 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 of seeing Figure 5 is a cross-section of a pair of the remote section 32 of the meter 30 and disposable device 10, illustrating the way in which the indentations 20 and the slot 34 positively locates the dispenser 30 inside the disposable device 10, leaving a space G. Note that the space G ensures that the blood (thru) penetrates through the membrane does not contaminate the meter. The space, although not critical, is preferably at least about 5 million years. An advantage of the device of the invention, when used with a meter of the type shown in FIG. 3, is that the devices may be in a stack, conveniently housed in a container 42, as shown in FIG. 6. a device can be secured simply by 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 container of waste U, as shown in Figure 7, as long as there is an optional ejection mechanism per push button, push button ejection mechanisms of the type are widely known and used are suitable for this invention ( See, for example, US Pat. No. 3,991,617.) Such a mechanism is shown in FIGS. 8 and 9, which show a pressure button mechanism mounted on a meter of the type shown. FIG. 3. The mechanism elements include an arrow 44, which connects the ejector 46 and the pressure button 48 ,. The pressure button 4 H operates through the arrow 44 to cause the ejector '46 to disengage the disposable device 10 from the remote section 32 of the meter 30. The spring 50 functions to return the ejector 46 and the pressure button 48. to its retracted position. The ejection by pressure button, which allows the disposable device to be removed without direct contact, helps to avoid contamination. Disposable devices to be used with pressure push-button ejection mechanisms of the type shown in Figs. 8 and 9 preferably have a flange 19. JO Figure Llust to a mode of a meter of this invention, which includes a screen 50 to illustrate- the anaiite concentration measured by the meter. The screen may be a light emitting diode (IED) 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 it may not be preferred,). One consideration for the selection of geometry in a photomepco system is the optical design. Generally, the reflecting plate 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 his finger for dosing, and a large vertex angle interferes with the view. Therefore, a disposable device having a rectangular cross section may be preferred, such as the hollow oncoconic body of a rectangular pyramid 110 shown in FIG. 11. In that case, the angular separation between the detector and the Specifically reflected light determines only the minimum feasible value of L, the longitudinal dimension of the larger open end.However, the disposable device may be smaller and less interfere with the user seeing his or her own finger.Moreover, membranes may be fabricated from slats 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 in the optical system, since contamination is possible if It is advisable to adapt excess samples of the disposable positive sample, it is convenient to adapt large samples without dripping the samples. have the excess sample. One is shown in Figures 12, 13 and 14. Figure 12 illustrates the disposable device of Figure 11 with indentations 124 on the surface of the small end of the disposable device. As shown in FIGS. 13 and 14, the indentations allow capillary flow to fill the remaining space between the membrane and the upper internal surface of the device. An alternative way of forming said spaces is to adhere the membrane to the disposable device with thick adhesive, leaving spaces to adapt the excess of sample. Another way to absorb the excess sample is to fix an absorbent pad 126 on the front surface of the membrane, as shown in Figure L5. Figure 16 is a perspective view, '-TI! -. Explosion of a meter and a disposable device of the type shown in FIG. 11. The distal section 132 of the means 130 has an optional slot 134, which is similar to the slot 34, it is desirable to retain the disposable device. The lengthened neck 130 facilitates the attachment of disposable devices of the elongated containers 42 shown in Fig. Fi. Screen L50 illustrates the concentration of measured analyte. FIGURE 17 illustrates an alternative modality of a meter adapted for use with the disposable device of FIG. 11. FIG. 18 illustrates the distal portion of yet another mode of disposable device 2J0 and meter 230. The distal section of FIG. 232 is accommodated with the disposable device 210. Note that the slots 234 are an alternative to the slot 34 (or 134) for capturing indentations, such as 220, on the disposable device. Figure 19 is a side view of the embodiment of Figure 18. In the method of this method, a blood sample is collected on the surface of the outward facing membrane. The glucose in the sample interacts with a reagent of the membrane to produce a color change, which changes the reflectance of the membrane surface that faces inward. The light source in the editor illuminates the surface of the membrane that looks inward 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 membrane combinations and reagent compositions are known to have photonic concentrations of blood glucose concentration. A . Preferred membrane / reactive composition is a polyarynide matrix that incorporates an oxidase enzyme, a peroxidase and a dye or pair of dyes. The enzyme one or idase is preferably glucose oxidase. The peroxidase is preferably horseradish peroxidase. A preferred dye pair is 3-? Net hydrochloride 11-2-benzothiazoimone hydrazone plus 3,3-d? Rnet? Aiam? Nobenzoic acid. Details of the membrane / reagent combination and variations thereof appear in the patent of E.U.A. 5,304,468, issued April 19, 1994, to Phillips et al., Incorporated herein by reference. Another preferred membrane / reagent composition is an amsotropic polysulfone membrane (available from Merntec America Corp., Timomurn, MD) that incorporates glucose oxidase, rube peroxidase and the dye pair r3-? Net? I-2-benzothiazole mona -hi drazonal N-sulfonyl benzensul ronato onosodium combined with 8-an acid? ll no-l-na f alensul phonic-ammonium. Details of the combination of membrane / reactor and variations thereof appear in the patent application of E.U.A. series No. 08 / 302,575, filed on September 08, 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 (5)

NOVELTY OF THE INVENTION CLAIMS

1. - A method for measuring a concentration of an analyte in a sample of a biological fluid comprising (a) providing a device comprising a hollow frustoconical device having open ends of different size, the smaller outer surface of which is closed substially by a membrane having (?) a first surface to accept the sample and (ii) a reagent to react with the anajite to produce, in a physically detectable parameter of the membrane, a measurable change which relates to the concentration of the analyte in the sample; (b) apply the sample to the first surface; (c) measure the change in the parameter; and (d) determining the concentrator of the analyte from the measurement of the change in torque.

2. The method according to claim 1, further characterized in that the device is provided at one end and an elongated network, which supports the device and measures the parameter change.

3. The method according to claim 2, further characterized in that the elongated device has a frusto-conical distance section to be coupled with the device for making the measurement.

4. The method according to claim 3, further characterized in that the device in the former meter comprises assembling a removable blernente a peripheral slot in the distant section of the meter with i ndentaciones in ui. perimeter of the device, without the user making direct contact with the device.

5. The method according to claim 1, further characterized in that the reagent reacts with the analyte to produce a color change, and the pair of the membrane whose change is measured is a Lectanci of a second surface, opposite to the first surface. h.- The method according to the rei indication 5, further characterized because the sample is whole blood and the analyte is blood blood glucose. 7. The method according to claim 1, further characterized in that it comprises the step of removing the device from the meter, without making direct contact with the device.