- INTEGRATED SYSTEM FOR ANALYSIS OF BIOLOGICAL FLUID CONSTITUENTSBACKGROUND OF THE INVENTIONFIELD OF THE INVENTIONThe invention relates to the monitoring of a medical condition by means of the collection, detection and interpretation of bioloq) coa fl uids.
DESCRIPTION OF THE RELATED TECHNIQUEThere were biological variables with collected? R? Ed? An or a variety of dossiers, which include. veni puncture, saliva, sweat and urine, to name a few * * do the most common. After the collection, we had to process the sample or the rat in another way, in order to carry out a chemical test. In some cases we can directly analyze the sample using modern technology. stick submerged or by means of instruments1 abora compi icated "Complicated" There are often errors in the processing or ma ulation of the sample, which makes it necessary to add additional samples, with time delays and reduced patient care.
The problems associated with obtaining a sufficient sample quantity, necessary to test by the commonly used methodologies, increase even more when the sample source is a small animal or a child. The advent of domestic testing devices for conditions such as diabetes and pregnancy, has highlighted the importance of the collection of the results and the media- lity of the results, as well as the intimacy of the test. - ~ The current technology is in a state of development in which: 1) a sample can be collected by the LO method from a method that causes discomfort or pain; and 2) the collected sample is then tested separately for the desired component, if the quantity and / or the quality of the sample is correct .. From the above it is clearly seen that it would be a significant advance in the technique that could be provided a*** The integrated list to obtain both the collection and the test of the sample, in the form of a simple device used. Some of the aspects required by said system are: 1-trial tests, the elimination of undesirable and additional steps, of the procedures (which reduces the error and the inconveniences) and, in the case of repetitive tests, the elimination of the inconvenience and discomfort of the First of all, the monitoring of blood constituents is particularly important in the context of diabetes, a metabolic disorder that affects millions of people.The levels of sugar (gLucose) in the blood are directly indicative of Diabetic condition The blood glucose test has been carried out for many years in an invasive manner, taking a sample of blood and determining excessively the glucose level, usually by means of a blood glucose test. a quinua reaction that is followed by a comparative test ~ colóri et rica. A recent breakthrough in the non-invasive test is described and claimed in US Patent No. 5,13 < 3,023 from Stanley and co-inventors. The teachings of the patent seek to monitor glucose in the blood, which is penetrated through a mucous or epithelial membrane. S mentions in the patent vain exemplary tests in which gLucose is collected in a sample collector and *** byte is tested with conventional techniques.
SUMMARY OF THE INVENTIONConsequently, it is an objective of the invention to provide an integrated system for the analysis of biological fluid constituents, which solves the disadvantages mentioned above, of the dispositions of this general type, hitherto known, and which claim the collection and test of The sample < > n the form of a simple, easy-to-use meta-system. It is another object of the invention to improve the accuracy of the test results compared to the prior art, and to eliminate the need for repetitive testing and the inconvenience and discomfort of performing the tests. With the ob et LVOS above and other objectives in mind, according to the invention, there is provided an integrated system for analyzing the constituents of a biological fluid, comprising means for collecting in a non-invasive manner an analyte of fluid from a patient's body, and indicating means that respond to the. analyte of the body fluid to indicate a condition of the analyte of the body fluid; elective interpretation means that receive the indicating means or electronically interpret the means indicators with respect to the condition of the fluid analysis of the body. In a preferred embodiment, the body flux is a fluid of the excreted body transdermally. In accordance with a further aspect of the invention, the med LOS gatherers are in the form of a multilayer Laminate structure, which includes a layer of chemical reagent, coated with a test reaction and a color developer specifically provided for a given test; an activation gel layer, arranged underneath the chemical reactive layer, a layer of collecting gel, "arranged under the layer of ge! of activation, and a layer of membrane of interface with the skin, arranged under the layer of collection gel, to place it on the skin of the patient. According to another aspect of the invention, the activating gel layer is a hygroscopic biopoi i epco gel with a biochemical intermediate incorporated therein, to react with the analyte of the body fluid collected and which produces a specific by-product in the reaction. n, even if "" is detected in the chemical reagent layer. Preferably, the biochemical medium is an enzyme. In accordance with yet another aspect of the invention, the collection gel layer includes a hygroscopic biopolic gel with an increased i - osmotic flux incorporated in it, and selected specifically for the fluid analyte of the body which is going to be- analyzed. In accordance with a further aspect of the invention, the indicator means are in the form of a color wheel; the color wheel being divided into a plurality of color segments, each of which communicates with the reliable chemical reagent layer exhibiting a color-given, in response to a given amount of fluid from the body fluid, processed through the layers, In addition to another additional aspect of the invention, the electronic means of interpretation include a light source for illuminating the indicating means detected therein; a photosensor that perceives an intensity of reflection from the indicator means, and means to interpret the measured reflection intensity and give information regarding a result of the interpretation. Taking into account the aforementioned objects, also according to a further aspect of the invention, an apparatus of collection and indication for analysis of the constituents is of a biological biology, comprising collecting means for collecting " Non-invasive way a fluid analyte of a patient's body, in the form of a laminated structure of several layers, which includes a layer of chemical icactLVO, a layer of activation gel, placed under the layer of chemical reagent, a collection gel layer, is used under the activation gel layer, and a layer of interface membrane with the skin, arranged underneath the collection gel layer, to place it on the skin of a patient; media- * - nd? chemicals that respond to the analyte of the body fluid to indicate a condition of the body fluid analyte. ?) and preference is given to the uniqueness of the flow < the body., r: n other words, the system of the invention includes three main operating components. The first is the test pair that works with the collection and analysis component; The second is the Mechanic / Reader holder that allows a health care professional to review the data in a quick and meaningful way; and (iii) the third component, the electronic component of interpretation, this last component of the system is configured to read the "par-che" component in the case of visual or visual, or if a numerical value is required. The new method is to combine the test chemistries known to the technicians in the field of healing with the medium of fluid collection, in a way that is more accurate, and to give the report in that format. that causes a sufficient amount of body fluid to be absorbed into the body of the skin for the chemical test to proceed and then be able to read and record the results in a short time. This invention is an integral component of the invention, which allows the SLS to function as a non-invasive skin test for clinical analysts, which is shown and described. It is the jet / lector and the "'electronic nterprotodor. All this works as a new and novel system to evaluate chemical analysts from biological fluids obtained in a non-invasive manner. Other aspects that are < The golden characteristics of the present invention are set forth in the appended claims. The invention incorporated in an integrated system for the analysis of the constituents of a biological fluid is well illustrated and described here, although it is not intended to limit it to the details shown, since various modifications and structural paths can be made therein. without departing from the spirit of the invention, and within the scope and scale of equivalence of the renouncements. However, the construction of the invention, together with its additional objectives and advantages, will be better understood from the following description. 'ipcion of the specific modality, when read together with the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGSThe figure is a diagrammatic view, on the lower floor, of a picker wheel, a color wheel according to the invention. Figure Ib is a sectional view of the device, taken following the J-line T-I of the figure. Figure 2a is a top plan view of a type of strip mode, of the collector / test patch. Figure 2I: > is a v / ista in section, taken following the line TT-TI of figure 2a. The figure is an enlarged view of a detail of figure lb, showing the mixed construction, constituted by several layers. Figures 4a and 4b are perspective views of two"Checkers" of exemplary subject / reader, will use them with - * the system »Fig. 5a is a top view - of an electronic reader according to the invention. Figure 5b is a perspective view of the reader of Figure 5a. Figures 5c and 5d are views similar to those of Figures 5a and 5b, respectively, of another embodiment of the reader. Figure fi is a circuit diagram for the electonic reader of the system, "The fi lm 7 is a diagramatic view of the OptLco reader system, in common with the third phase with a computer device. 8 is a flowchart illustrating a main operating program of the optical reader, Figure 9 is a diagram of an ainp circuit 1 L fi odor recorder, opt i rn L ect. Fig. 10 € • < a diagram of a light source - "" * • v) "tuned and an optimized photosensor circuit; and Figure Ll is a diagram of an optimized LED driver.
DESCRIPTION OF THE PREFERRED MODALITIESNow making reference to the figures of the book in detail and, first of all, particularly to the Figures 1 and 2 of the ius, we see an ecolabel / proof patch of a mixed construction consisting of several layers. The patch includes an occluder support 4 on the dorsal side of the device. The support 4 works like the osten, and at the same time as the upper-outer protective layer to which a 5 r-color is attached. A center of the color wheel is perforated to allow the insertion of the active collection components 2 or of the test / collection components 2, so that they are centered within the color wheel 1. The function of the color wheel 1 is to provide the visualization of the reaction10 test, based on the differential rich coloprnet chemistry employed, will rely on a given analyte. Consequently, we can refer to the color wheel as an indicator means. The active collection components 2 can be called the collecting means. Applied on the perimeter of the support,Long and arginal with respect to the color wheel, there is a layer of adhesive, which allows the device to be placed on the skin and remain in contact with the skin during the required period of time. AND\? a preferred embodiment, the central region on top of the collection components 2, is covered with a transparent layer. The layer 16 is formed of a non-porous material, such as, for example, acetate. With reference to FIG. 3, the test and collection reaction area 2 consists of several layers 7--1D, which form a central part of the system. Each layer has a specific function. layer 10 is a layer of chemical reagent thatIt is coated with the specific test reagents and the specific color developer required for any given test. Layer 9 is a layer of activating gei, which is constituted by a selected hygroscopic biopolymeric gel, in which a biochemical intermediate is incorporated, such as an enzyme that will react with the collected sample to produce a very specific byproduct that is removed. to be detected by the test layer reagent. The layer 8 is a collection gel layer and includes the selected hygroscopic iopol imep co gel, which incorporates an increased osmotic flux for the anaesthenent. The osmotic flux enhancers or enhancers are well known to those skilled in the art. They include: distilled water, ionized water, ethanol, your dimethyl ether and other similar compounds. The layer 7 is a velocity contouring membrane and the membrane of interface with the skin. The purpose of layer 7 is to provide a flow- With ta te and interstitial fluid or ot fluid to the collection gei R, under the influence of the osmotic flow-enhancer. The individual area segments 5 and the color wheel 1 are color definition segments in the form of cake strokes, which are used to evaluate the results of the test on the basis of the color developed in the test / collection area 2. The one of FIGS. 2a and 2b constitutes an additional embodiment of the i-echo patch of the invention.
In place of the round confi ruration, the device is provided in the form of a con fi guration of traditional "windows", and the colors are exhibited around the perimeter of the concavity square 2 of test / collection. The shape is suitable for certain parts of the body or for use in some animal species other than man.This design incorporates the adhesive in the area of the color display and leaves the area 3 free of contact adhesive. The panel will simplify the removal and manipulation of the display. Referring now to Figure 4, a holder / reader device is in the form of a book that incorporates a clear area for visualization of the results. and the placement of the test / collector- of aThe way that only the segment or sector of results is visible. In other words, the person taking the tests places the color wheel or the indicator portion of the parkIt has been placed inside the receptacles 6 of the canvas in the same way, so the avalanche practitioner, who is responsible for the final interpretation of the test, can quickly remove the sheets. The holder's construction / reader is such that a usual daily number of tests can be displayed on a given page.The holder also 5 allows the user to be reminded to perform The tests at a given time or sequence of the holders and a space for written comments or other pertinent information related to the test performed With reference now to figures 5a and 5b, a reading device can be programmed electronic and interpretation to give specific diagnostic information, based on the results of a reading of the test / collector device.The "patches" or "vendites" can be read directly by the device as an auxiliary- The visually impaired or even to eliminate the "operator" error. Additional information can be stored with respect to the sequential target readings with a subsequent summary display or for interface transmission to an 11-year-old computer. The round patch is placed in a compartment 13, where it is read when the lid is closed. It is provided with a slot 14 for the insertion of the sold strip, again it relies on reading the color information and displaying and / or storing it.'result. A connector 15 is provided to form an interface with the device by means of an inodem and / or a reliable host computer to transmit the stored data to a remote diagnosis location, in the consul's tone of a physician, by example. The cont ol buttons 12 are used to change the mode, to start and stop and to calibrate the device, when required. An exhuditor 11, has the form of an exhibition to L fanu epca by LED or an LCD(liquid crystal display) that gives all the necessary instructions to the operator, and also the results, in accordance with the instructions of the program. With reference to figure F, in which the individual components of the reading device are in- tected. For example, the patch l (for example, the color wheel) is exposed to a light source, for example an infrared light emitting diode or LED (for example, Omron EE ~ CJY124). A photosensor collects the reflected optical wavelength (for example, EE-SY124 ié Omron). A light source exciter is provided for the purpose of establishing a constant current source pair to the LED, in order to obtain a stable light output for the measurement. A photosensor amplifier converts the output signal of the photosensor to a voltage serial on a scale that is appropriate for the next conversion from analog to dLgital (A / D) A converter-le A / I), connected current below, convert the voltage signal that is proportional to the intensity of ln-f lecfancia to a digital r-eignal for further processing(for example, ADC 0804 from National Semiconductor) the digital information is transmitted to a microcomputer of a single wafer or capsule (for example, of the Tntei R051 sene). The microcomputer includes a read-only memory segment (ROM), a segment of random access memory (RAM), input and output terminals (I / O ports), an internal time-controller and a processor unit to center L (CPU). The microcomputing provides all the necessary processing for the serial, the control of the procedure, the interpretation of the keypad, display, and functions of clock control and time control. The LCD segment displays information for the operator in the form of text and graphics (Epson EA-D16015). A 1/0 method (input / output) is the necessary circuit for T / 0 operations andFinally, a keypad allows the operator to produce certain information. Figure 7 illustrates the circuit of Figure 6, as when in communication with a host computer, preferably a personal computer (PC). With reference to Figure 0, the start of the program can be triggered by a start button or it can be started automatically by closing the lid 13 or by inserting the par-che into slot 14. After an initial routine Lzation , the program moves to the main enú. If the device has not been calibrated for a certain period of time, or if it is the first measurement in a test series, the program will vune to a calibration routine. After calibration, the program asks if the measurement is going to use a single measurement operation or if the sample is being continuously serviced.
EXAMPLESIn a first generation of tests, an ecologous patch or glucose tester was tested in a first example.
Invader The active area of a peroxide test piece was coated (EM Science, Axis Div. E. Merck Co.) with a fi lmeric gel which contained 50 units of peroxidase reagent (Sigrna Chemical Co.) and 150 axis units the enzyme glucose-ox ejasa (Sigma Chemical Co.). The coated test strip was then allowed to dry. Subsequently, the test arc was coated with an enrichment or flow enhancer, comprising a gelled ethyl alcohol / water mixture. The test coated area was then placed on the test patch and covered with a support membrane. The test patch was then placed on the exposed skin, behind the ear of a human patient. After 45 minutes the patient's patch was removed and indicated the level of glucose transferred. In a second example the preparation was yes my lar to that of the first example, except < ? ue < -e mix the incrementing gel or favor the flow and the reaction gel, in"Equal proportions, and then applied to the underlying test area, before use.After 30 minutes, it was possible to clearly see the results.In each of the examples, the axis indicators the patches were also subjected to an electronic measurement. The indication of the glucose axis level is displayed, the electronic system and / or exact numerical readings of the patient's glucose levels, and in a second generation, the patient and device axis, the glucose meter was configured so that had the color wheel printed on its dorsal side (the top face)., The destination area 2 is covered in a simple way with a clear, non-porous plastic film (for example, axis 5 acetate) IB. It is visible during the test, and it was possible to have the final reading before removing the patch.The presence of axis could be avoided by substantial measurement errors with this structure, since the errors caused when removing the patch could be avoided. alter temporary between10 mechanical confi guration axis layers. Also the hair and the fat in some cases could be attached to the surface when the patch is removed. It is also quite important that direct electronic reading was tested, in situ, by means of a probe15 fiber optics and other devices. To this purpose, the electronic device was directly connected to the par-che and < -e obtained the lecture without the need of the elective law. In terms of the chemical composition of the system, 0glucose-oxydase remains the same, except that the EM Science test liras were treated by the manufacturer with a sensitivity of at least 1 ppm or more. I incorporate the strip directly. I also have a coi poo in the pa t tiras de rueba > The claias, supplied by Eastman KodaL Co., will endeavor to provide the possibility of observation "through" the superior fiarte of 10.so that a reading is obtained before the par-che. The test strips of E. Koclak replaced the strips of L. "M. Science in the target area for the analyte to be stolen.With respect to the gel-axis layers, a vai-layer system was added. in the second generation of tests, which gave a shorter time < je elimination of transudate and, in such a way, a faster test.At that point, a test ten (10) minutes proved to be practical. , because of the reliable results of these tests, that even shorter times could be obtained in the context of the invention.It is essential to note, in this sense, that a reliable indi - cation is convenient in the term of 15 minutes. This is due to the fact that prolonged periods of testing make it impossible to obtain a rapid reaction and in a timely manner in urgent situations.The first layer was placed directly on the layer') chemical reagent and consisted of a CMC gel e * n a water solution of between f] .. 5 and 10% w / v. The preferred percentage was from 0.75 to 1.0%, and the solution was hypotonic with respect to the fluid i nt erst iciai. The second layer was placed on the first layer and consisted of a Carbopol gel axis mixture containing ethyl alcohol, ethyl ether and water, in a ratio of 25.25: 50. The gel was between a mixture of 0.5-25% weight / volume. Optionally, encapsulated solvents were added to the gel layer in order to increase the osmotic flow of the transudate. The microencapsulated material may contain solvents, such as ethyl chloride, freon, di methyl sulfoxide (DMSO), 11con oils, etc. They all have boiling points at low temperature. Appropriate nycroencapsution procedures and other similar pertinent information can be obtained, for example, from the < patent pending in axis No. Sene '07 / 865,309, 07 / 952,049, 07 / 927,837, 08 / 139,316 and 08 / 141,19; which are incorporated here as reference. It is known that previous solvents increase diffusion from the skin. However, it is also known that they evaporate immediately upon exposure to air. In the case of the patch according to the invention, the capsules were broken by the application of the filter and the rapid evaporation of the solvent increased the rate of diffusion (Jesde Ja skin, to a degreeIt is possible to increase the amount of transudate and decrease the amount necessary for the collection and analysis of the components. The optimized electronic subcoding circuits of the electronic device are illustrated in the figures. 9-11, the values for the discrete component and the model numbers are par-a integrated circuits.