WO2023061471A1 - Dispositif d'analyse de glucose dans les larmes et son procédé de production - Google Patents

Dispositif d'analyse de glucose dans les larmes et son procédé de production Download PDF

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WO2023061471A1
WO2023061471A1 PCT/CN2022/125319 CN2022125319W WO2023061471A1 WO 2023061471 A1 WO2023061471 A1 WO 2023061471A1 CN 2022125319 W CN2022125319 W CN 2022125319W WO 2023061471 A1 WO2023061471 A1 WO 2023061471A1
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tear
detection
sugar
glucose
reagent
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PCT/CN2022/125319
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Chinese (zh)
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贺坚慧
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上海微银生物技术有限公司
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/535—Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose

Definitions

  • the invention relates to the technical field of glucose detection, in particular to a tear sugar detection device and a production process thereof.
  • Diabetic retinopathy also known as diabetic retinopathy
  • diabetic retinopathy is the most important complication of diabetes. It has the characteristics of high incidence and blindness. However, diabetic retinopathy has no obvious symptoms in the early stage. It has reached the advanced stage, thus missing the best time for drug and surgical treatment, so early detection and early treatment are the best ways to prevent diabetes.
  • a related study compared the diabetic retinopathy group with the non-diabetic retinopathy group, and found that the tear sugar content of the diabetic retinopathy group was higher than that of the non-diabetic retinopathy group. content, and the difference was statistically significant.
  • the above clinical data show that the tear sugar content has a high correlation with the risk of diabetes mellitus disease in diabetic patients, so it is possible to prevent diabetes mellitus disease by regularly testing the tear sugar content.
  • the tear sugar was tested using a self-made polyethylene gelatin sponge lacrimal device, which needs to be placed in the subfornix of the conjunctiva for a long time to absorb a large volume of tears, or a capillary glass tube is used to collect tears from the outer canthus tear film of the tested eye.
  • these sampling methods are only suitable for scientific research, and are not suitable for non-professionals to measure tear sugar regularly and repeatedly; and although the existing tear sugar detection technology solves the problem of non-invasive micro-quantitative tear collection, it is difficult to complete the detection of tear glucose. The steps are cumbersome.
  • the reagent packaging for a single-person test requires a special cuvette to place an integrated device consisting of tear fluid sampling strips and miniature reagent bottles, it has the problems of many detection steps and high cost of consumables. It is convenient for storage and transportation, and it is not suitable for non-professionals.
  • the object of the present invention is to provide a tear sugar detection device and its production process.
  • the device can quickly detect tear glucose, is suitable for non-professionals to measure tear sugar regularly, and can be used for the prevention of diabetic retinopathy.
  • the present invention provides a tear sugar detection device, which includes a tear sugar detection strip and a support assembly, and the tear sugar detection strip includes two identical detection strip units connected side by side along the first direction ,
  • the test strip unit includes a tear sampling area arranged along the second direction, a hydrophobic isolation zone and a handle, the hydrophobic isolation zone is located between the tear sampling area and the handle, and the two test strip units
  • the holding part is connected and separated between the tear fluid sampling area and the hydrophobic isolation zone;
  • the tear fluid sampling area is used to collect tear fluid, and the collected tear fluid reacts with the glucose detection reagent to measure tear sugar, the hydrophobic isolation belt is used to prevent tear fluid from further spreading, and the gripping part is used to adhere to the support component to fix the tear sugar.
  • the tear sugar test strip ;
  • the first direction is perpendicular to the second direction.
  • the tear sampling area includes an outer canthus tear film contact area of the tested eye, a pH buffer zone and a detection reagent belt arranged along the second direction, and the outer canthus tear film contact area of the tested eye is close to the detection zone.
  • the pH buffer zone is located between the outer canthus tear film contact area of the subject eye and the detection reagent zone, and there is a gap between the pH buffer zone and the detection reagent zone;
  • the pH buffer strip is coated with a pH buffer reagent
  • the detection reagent strip is coated with a glucose detection reagent
  • the glucose detection reagent includes a chromogen reagent and an enzyme reagent
  • the detection reagent strip includes a first detection strip and a second detection strip adjacently arranged along the second direction, and the first detection strip smears With the chromogen reagent, the second detection zone is coated with the enzyme reagent.
  • the edge of the tear sampling area is arc-shaped; between the tear sampling area and the hydrophobic isolation zone, each unit is provided on both sides of the tear sugar detection strip along the first direction.
  • the hydrophobic isolation zone is coated with a waterproofing agent, and the hydrophobic isolation zone includes a plurality of hydrophobic isolation strips arranged side by side along the second direction;
  • the waterproofing agent is composed of one or more of polyethylene wax, palm wax emulsion, paraffin wax emulsion, Tianshi wax emulsion, water-soluble wax, wax emulsion, hydrogen-containing silicone oil, nano-silicon, soluble hot-sol and acrylic resin
  • the mixture of water and water is made in a ratio of 1:1-1:100.
  • the chromogen reagent is selected from 2,4,6-tribromo-3-hydroxybenzoic acid, N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline sodium salt, N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methoxyaniline sodium salt, N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3 -Methylaniline sodium salt, N-ethyl-N-(3-sulfopropyl)-3-methoxyaniline sodium salt, 3,5-dichloro-2-hydroxybenzenesulfonate sodium, N-2-ethyl (3-methylphenyl)aminoethylacetamide, N-ethyl-N-ethanesulfonate sodium m-toluidine, 2,4-dichlorophenol and 3,3',5,5'-tetramethyl One or more of benzidines;
  • the enzyme reagents include glucose oxidase, peroxidase and 4-aminoantipyridine;
  • the pH buffer reagent is prepared by mixing and dissolving one or more of strong base and weak salt compounds including sodium carbonate, sodium citrate and sodium acetate in water, and the concentration is 1-30g/L.
  • the support assembly includes two support bars whose surfaces are parallel and correspondingly arranged, one end of the two support bars is connected, and the other end is separated to form a groove for accommodating the handle.
  • the tear sugar detection device is used to qualitatively measure tear sugar in both eyes according to the qualitative tear sugar is a significant pathogenic influencing factor of diabetic retinopathy, and is used to quantitatively measure tear sugar according to the parallel relationship between tear sugar and blood sugar, which is used for blood sugar monitoring .
  • the tear sugar detection device is used for qualitative measurement of tear sugar, and the color development result can be used for the risk stratification of diabetic patients with diabetes.
  • the tear sugar detection result By comparing the tear sugar detection result with the color of the glucose standard, it can be obtained Corresponding numerical range and lacrimal sugar positive or negative results, and based on the clinical assessment results, the critical value applied to the risk stratification of diabetes mellitus disease in diabetic patients is obtained, so as to stratify the risk of diabetes mellitus disease in diabetic patients, if Diabetic patients with 2+ in one eye, >0.30mmol/L and above, or 1+ in both eyes, >0.15mmol/L and above are all judged to be positive for the risk of diabetic reticulopathy in this test, and the risk of related diabetic reticulopathy is significantly increased.
  • the present invention also provides a production process for a tear sugar detection device, which is used to manufacture the tear sugar detection device as described above, comprising the following steps:
  • S1 Manufacture a first module and a second module, the length of the first module along the first direction is greater than or equal to the width of N tear sugar detection strips, and the length of the second module along the first direction The length is greater than or equal to the width of N support components, and the first module includes a groove for accommodating the second module, where N ⁇ 2;
  • S2 apply the pH buffer agent, the glucose detection reagent and the water repellent on the first module along the first direction, and run through the first module to form a first overall zone, a second overall band and the third total band, the first total band, the second total band and the third total band correspond to the pH buffer band, the detection reagent band and the The hydrophobic isolation zone;
  • the present invention provides a tear sugar detection device, which integrates sampling and detection.
  • the device detects tear sugar, it only needs to place the detection strip at the tear film of the outer canthus of the eye to be tested. Minutes later, after the sampling area is full of tears, the test results can be obtained by colorimetry, so that patients can obtain tear sugar test results through non-invasive collection methods, which can be used for the management of chronic diseases of diabetes without strong professional knowledge.
  • the device adopts the method of separately coating the chromogen and enzyme reagent in the pH buffer zone and the glucose detection reaction zone, instead of overlapping or coating together, which can ensure that the chromogen and enzyme reagent The activity is not greatly lost during the entire coating and drying process, and there is no need to use consumables such as cuvettes, which has a high cost performance; further, the detection device combines two tear glucose test strips into one combination, Only the grip part is connected by riding sutures. At the same time, by adding support to the grip part, the hardness of the rear end of the grip part is strengthened, which reduces the damage rate of the test strip during the packaging and test unsealing process. When the suture is torn, the test of left and right tear sugar can be started; finally, the device can not only qualitatively measure tear sugar for the prevention of diabetic retinopathy, but also quantitatively measure tear sugar by using the parallel relationship between tear sugar and blood sugar.
  • the present invention also provides the production process of the above-mentioned device.
  • the production process adopts the production process of coating and marking first and then die-cutting, and the coating and marking of a single line can meet the requirements of mass production.
  • FIG. 1 is a schematic diagram of a single tear sugar detection strip unit of a tear sugar detection strip of a tear sugar detection device provided by an embodiment of the present invention
  • Fig. 2 is a schematic diagram of the tear sugar detection strip of the tear sugar detection device provided by an embodiment of the present invention
  • Fig. 3 is a schematic diagram of a support assembly of a tear sugar detection device provided by an embodiment of the present invention.
  • Fig. 4 is a schematic diagram of a tear sugar detection device provided by an embodiment of the present invention.
  • Fig. 5 is a schematic diagram of the production process of the tear sugar detection device provided by an embodiment of the present invention.
  • Fig. 6 is a schematic diagram of the production process of the tear sugar detection device provided by an embodiment of the present invention.
  • Fig. 7 is a schematic diagram of the comparison of the detection results of the tear sugar detection device provided by an embodiment of the present invention.
  • Fig. 8 is a schematic diagram of a standard curve of the gray value of the detection results of the tear sugar detection device provided by an embodiment of the present invention.
  • a-the first test strip unit b-the second test strip unit, 1-tear fluid sampling area, 2-hydrophobic isolation zone, 3-holding part, 4-support component, 10-the outer canthus tear film contact area of the tested eye, 11-pH buffer zone, 12-first detection zone, 13-second detection zone, 21-first hydrophobic isolation zone, 100-first module, 200-second module.
  • first and second are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features. Thus, a feature defined as “first” and “second” may explicitly or implicitly include one or more of these features.
  • “plurality” means at least two, such as two, three, etc., unless otherwise specifically defined.
  • FIGs 1 to 4 are schematic diagrams of a tear sugar detection device provided by an embodiment of the present invention.
  • the tear sugar detection device provided in this embodiment includes a tear sugar detection strip and a support assembly 4.
  • the tear sugar detection The strip includes two identical tear sugar detection strip units connected side by side: the first detection strip unit a and the second detection strip unit b, and the detection strip unit is divided into a tear sampling area 1, a hydrophobic isolation strip 2 and a grip part 3 , the hydrophobic isolation strip 2 is located between the tear sampling area 1 and the holding part 3, the first detection strip unit a and the second detection strip unit b are connected at the holding part 3, in the
  • the tear sampling area 1 is separated from the hydrophobic isolation zone 2; the tear sampling area 1 is used to collect tears and react with glucose detection reagents to measure tear sugar concentration, and the hydrophobic isolation zone 2 is used to prevent further diffusion of tears, so
  • the holding part 3 is used for bonding with the supporting component 4 to fix the tear sugar test strip.
  • the tear sampling area 1 includes a test eye outer canthus tear film contact area 10, a pH buffer zone 11 and a detection reagent strip.
  • the test eye outer canthus tear film contact area 10 is close to one end of the test strip unit, and the pH The buffer strip is located between the outer canthus tear film contact area 10 of the subject eye and the detection reagent strip.
  • the inventors have found through research that when testing tear sugar, it is necessary to detect both the left and right eyes to be more accurate.
  • the tester can tear the tear sugar detection strip along the central axis, and use the first The detection strip unit a and the second detection strip unit b detect the left and right eyes respectively.
  • the tear sampling area 1 is full of tears.
  • the detection result can be obtained by colorimetry, and because the support assembly 4 has a certain rigidity, it is very suitable for use by non-professionals.
  • the optimal width of the hydrophobic isolation zone 2 is generally 3-12mm.
  • mm can be composed of several 1-3 mm wide linear strips arranged in parallel next to each other, wherein one side (right side in Fig.
  • the first hydrophobic isolation zone 21 constitutes the hydrophobic isolation zone 2 and
  • the boundary line of the tear sampling area 1 the first hydrophobic isolation zone 21 is composed of a straight line strip next to the tear sampling area 1, and is next to the first water sampling area 1 in the direction away from the tear sampling area 1
  • the hydrophobic isolation zone 21 can be coated with several hydrophobic linear strips arranged next to each other in parallel.
  • a cutout is respectively provided on both sides of the first hydrophobic isolation zone 21 in the length direction (the up-and-down direction in FIG.
  • An incision is also provided on both sides in the length direction, and the incision outline of the first hydrophobic isolation zone 21 and the incision outline of the detection reagent strip are spliced into a smooth arc.
  • Both the first hydrophobic isolation zone 21 and the detection reagent zone of the two detection strip units connected in parallel have cutouts.
  • the four cutouts respectively located on the two test strip units are symmetrical about the symmetry line of the two test strip units, and the edge of the tear sampling area is generally made into a circular arc, so that it is in line with the outer canthus tear of the tested eye.
  • the contact area of the membrane is the smallest to avoid eye irritation, and the basic tears are collected.
  • the existence of small incisions is to avoid corners from poking around the eyelids of the tester.
  • the arc shape and small incisions are set to improve the comfort of the tester when taking tears. Spend.
  • the detection reagent strip In order to improve detection accuracy, the detection reagent strip generally adopts the glucose oxidase coupling Trinder reaction of the formula of two reagents (enzyme reagent and chromogen reagent), and the detection reagent strip is divided into the first detection strip 12 and the second detection strip.
  • Detection zone 13 the first detection zone 12 is made by smearing a chromogen reagent, and the second detection zone 13 is made by smearing an enzyme reagent.
  • the second detection zone 13 is made by applying a chromogen reagent.
  • a pH buffer zone 11 is provided between the outer canthus tear film contact zone 10 of the subject's eye and the detection reagent zone, and the pH buffer agent is applied.
  • chromogen reagents and pH buffers used to maintain and provide an ideal biochemical reaction environment for detecting tear sugar
  • the inventors found that the pH buffer zone 11 and the detection
  • the reagent strips are not overlapped or coated together, and there is a certain gap between them, which can ensure that the activity of the chromogen and the enzyme reagent can be fully applied during the entire coating and drying process. No major losses in the process.
  • the glucose detection reagent, the water repellent and the pH buffering agent are streaked and coated on the tear fluid sampling area 1 and then dried to form the detection reagent strip (the first detection strip 12 and the second strip) Two detection zone 13), the hydrophobic isolation zone 2 and the pH buffer zone 11.
  • the application concentration of the glucose detection reagent, the waterproofing agent and the pH buffering agent is generally 1-30 g/L.
  • the chromogen reagent generally includes 2,4,6-tribromo-3-hydroxybenzoic acid, N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline sodium salt, N -Ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methoxyaniline sodium salt, N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methyl Aniline sodium salt, N-ethyl-N-(3-sulfopropyl)-3-methoxyaniline sodium salt, 3,5-dichloro-2-hydroxybenzenesulfonate sodium, N-2-ethyl (3 -methylphenyl)aminoethylacetamide, N-ethyl-N-ethanesulfonic acid sodium m-toluidine, 2,4-dichlorophenol and 3,3',5,5'-tetramethylbenzidine One or more of them; the enzyme reagent generally includes
  • the support assembly 4 generally includes two support bars with parallel surfaces, one end of the support bar is connected, and the other end is separated to form a groove for accommodating the handle 3.
  • the support strip is generally made of hard paper with a certain rigidity, and the tear detection strip is made of qualitative filter paper.
  • the rear end of the holding part 3 has a sticking area for the tear sugar detection strip, the optimum length is 5-30 mm, and the holding part 3 can be inserted into the groove of the support assembly 4, and is connected with the wall of the groove Adhere to each other; the outer canthus tear film contact zone 10 of the subject eye, the pH buffer zone 1, the first detection zone 12 and the second detection zone 13, and the hydrophobic isolation zone 2 are all symmetrical along the central axis.
  • the present invention is a tear fluid glucose detection device integrating sampling and detection.
  • There are two modes for interpretation of the results of the device one is qualitative or semi-quantitative interpretation mode, and the detection result is compared with the glucose standard concentration color block. , so as to qualitatively draw the concentration range of tear sugar.
  • the other is the quantitative interpretation mode, which uses instruments and equipment to detect the color depth of the glucose detection reagent strip in the sampling area after color development, and compares the obtained gray value with the standard glucose curve stored in the instrument to obtain the tear sugar concentration.
  • a diabetic has 2+ in one eye, >0.30mmol/L and above, or 1+ in both eyes, >0.15mmol/L and above, it is judged to be positive for the risk of diabetes mellitus disease in this test.
  • Tear sugar is colorless, light yellow, and 1+ in one eye, ⁇ 0.15mmol/L, all of which are judged to be negative for the risk of diabetes in this test.
  • the number of diabetic patients enrolled in this test is 155 cases (the course of disease, fasting blood sugar and glycosylated hemoglobin value of diabetic patients are counted at the same time), of which 51 cases are diagnosed as diabetic patients, and 104 cases are non-diabetic diabetic patients.
  • the result statistics are as follows:
  • the proportion of tear sugar high value 4+ positive in the early and late stages of diabetic reticulosis is the highest, the early stage of diabetic reticulum disease accounts for 33.3%, and the late stage accounts for 30.0%, which is also the highest in the total proportion regardless of stage;
  • Double tear glucose (qualitative) positive rate is the highest in the early (90.5%) and late (73.3%) patients of diabetic reticulosis, and it is also the highest in the total proportion regardless of stage;
  • Tear fluid glucose (qualitative) monocular or binocular positive is not proportional to the stage of diabetic retinopathy, and the proportion of monocular and binocular positive is relatively scattered.
  • Diabetes reticulosis was significantly correlated with diabetes duration ⁇ 10 years and tear glucose (qualitative);
  • Diabetic retinopathy was correlated with glycosylated hemoglobin ⁇ 8.0% and fasting blood glucose ⁇ 8.0mmol/L but not significant.
  • diabetic retinopathy Several factors related to diabetic retinopathy were analyzed: duration of diabetes ⁇ 10 years, glycosylated hemoglobin ⁇ 8.0%, fasting blood glucose ⁇ 8.0mmol/L and tear glucose (qualitative). Taking diabetic retinopathy as the dependent variable, logistic regression analysis was performed on these four factors, and the results are as follows:
  • the P value of the course of disease ⁇ 10 years is 0.003, and the P value of tear glucose (qualitative) is 0.003, both of which are less than 0.005. Therefore, the duration of diabetes ⁇ 10 years and tear glucose (qualitative) are important pathogenic factors of DR;
  • glycosylated hemoglobin ⁇ 8.0% and fasting blood glucose ⁇ 8.0mmol/L are both greater than 0.05, which are not important pathogenic factors of diabetic retinopathy.
  • Tear fluid glucose (qualitative) is related to fasting blood glucose ⁇ 8.0mmol/L;
  • the fasting blood glucose ⁇ 8.0mmol/L related to tear glucose (qualitative) was used as the dependent variable of tear glucose (qualitative), which is the pathogenic factor of diabetic reticulosis.
  • Logistic regression analysis was carried out, and the results are as follows:
  • tear glucose (qualitative) is an independent risk factor for DRD
  • chi-square test and logistic regression analysis showed that tear glucose (qualitative) was correlated with fasting blood glucose ⁇ 8.0mmol/L but not significant, and not related to the course of diabetes Therefore, tear glucose (qualitative) is an independent factor affecting the pathogenesis of diabetic retinopathy that has a certain degree of correlation with hyperglycemia.
  • Qualitative or semi-quantitative interpretation mode is the most common method convenient for non-professionals to use. This method first performs quantitative value transfer and uses four glucose concentration standards (S1 0.153mmol/L, S2 0.306mmol/L, S3 0.613mmol /L and S4 1.226mmol/L) in the sampling area of each 3 ⁇ l pointing tear glucose detection device, the color after the color reaction is made into a standard color block and printed on the instruction manual to complete the value transfer. The higher the concentration, the more color color block. deep.
  • glucose concentration standards S1 0.153mmol/L, S2 0.306mmol/L, S3 0.613mmol /L and S4 1.226mmol/L
  • the collected micro-tear fluid is reacted with a high-sensitivity glucose oxidase reagent to develop color, and the test result is compared with the color of the standard color block on the instruction manual to obtain the qualitative result and concentration range of tear glucose.
  • the test result is read through the micro-reflected light to read the gray value, and according to the standard curve of glucose value stored in the instrument, as shown in Figure 8, the conversion is carried out
  • the content of tear glucose can be obtained.
  • the tear sugar value may be delayed by 30 minutes
  • the tear sugar and capillary blood sugar are detected at the same time for diabetics.
  • the change of tear glucose concentration and capillary blood sugar are parallel. Relationship, can be used for blood sugar detection.
  • Another advantage of the present invention is that it provides a production process for the above-mentioned tear sugar detection device.
  • the production process adopts the form of module combination and cutting, and is suitable for mass production of the above-mentioned tear sugar detection device. Referring to Fig. 5 and Fig. 6, the steps of this production process are as follows:
  • S2 apply the pH buffer agent, the glucose detection reagent and the water repellent on the second module 200 along the first direction, and run through the second module 200 to form a first overall zone, a second The second total zone and the third total zone, the arrangement of the first total zone, the second total zone and the third total zone along the first direction is consistent with the pH buffer zone and the pH buffer zone of the tear detection strip.
  • the arrangement of the detection reagent strip and the hydrophobic isolation strip along the length direction of its elongated shape is the same;
  • S3 Place the end of the second module 200 away from the first total belt, the second total belt and the third total belt in the groove of the first module 100, and make it contact with the wall of the groove Paste to form the total module;
  • step S2 and step S3 of the method is not unique, it can be coating first and then combining, or combining first and then coating.
  • the production process is to first make the tear glucose detection device into two modules: the first module 100 and the second module 200.
  • the width of the tear glucose detection device can be set to 10 mm.
  • the length of the module needs to be greater than the sum of the widths of 30 tear glucose detection devices, so the length of the first module 100 and the second module 200 should be greater than 300 mm, and the first module 100 can be 40 mm in height and 100 grams in height Heavy cotton fiber single-sided self-adhesive paper, the height of one side after folding in half is 20 mm, and the inner surface is one side of self-adhesive, which can be pasted together with the holding part of the second module 200, and the length of qualitative filter paper and the above-mentioned
  • the length of the first module 100 is the same as the height of 50 mm as the second module 200, and the first module 100 is overlapped with the long side of the second module 200 and the fold line of the inner surface of the first module 100.
  • the present invention is waterproof
  • the selection of the agent and the optimum working concentration depend on three factors.
  • the first is the actual waterproof effect, which means that the tears can be completely blocked on the filter paper and cross the hydrophobic isolation zone 2 after being applied;
  • the second is that the effective period of the waterproof effect is longer than The validity period of the pH buffer and the glucose detection reagent is long;
  • the third is that it does not inhibit the work of the pH buffer and the glucose detection reagent.
  • a polyethylene wax waterproofing agent can be mixed with water at a ratio of 1:30 and coated with a width of 1 mm, and then dried at 60° C. for 2 hours.
  • the coating of the first hydrophobic isolation belt 21 can , that is, the area away from the tear sampling area 1, three different numbers of hydrophobic lines can be coated next to the first hydrophobic isolation zone 21, and then dried at 60°C for 2 hours; the coating of the hydrophobic isolation zone 2 is completed.
  • a solution with a working concentration of 10g/L is used to coat the pH buffer zone 11 with a straight line of 1mm width, and then dry at 60°C after scribing and coating; finally, the detection reagent strip can be coated with 2.4.6-tribromo- 3-Hydroxybenzoic acid is used as the chromogen, and the final working concentration of the chromogen is 15g/L, and the 2mm-width parallel to the first hydrophobic isolation zone 21 is coated at 1mm behind the pH buffer zone 11.
  • the first detection zone 12 is vacuum-dried at a temperature below 20°C for 3 hours after the scribing is completed, and then the first detection zone 12 and the first hydrophobic isolation zone 21 are coated with a 2mm-wide gap between the first detection zone 12 and the first hydrophobic isolation zone 21.
  • the outer canthus tear film contact area 10 in front of the pH buffer zone 11 cuts the tear glucose detection device template coated with the chemical reagent into a single tear glucose detection device finished product with a knife mold in the shape of the tear glucose detection device.
  • the advantage of the present invention is that it provides a tear sugar detection device, which integrates sampling and detection.
  • the device detects tear sugar, it only needs to clamp the detection strip between the upper and lower eyelids, and after a few minutes, the sampling area After the tears are filled, the test results can be obtained by colorimetry, so that patients can obtain tear sugar test results through non-invasive collection methods, which can be used for chronic disease management of diabetes, without strong professional knowledge, and patients can complete it independently in the community and at home;
  • the device adopts the method of separately coating the chromogen and the enzyme reagent in the pH buffer zone and the glucose detection reaction zone, instead of overlapping or coating together, which can ensure the activity of the chromogen and enzyme reagent throughout the coating.
  • the present invention also provides a kind of production process of this device, this production process adopts the production process of first coating scribing and then die-cutting, and coating scribing is carried out by modularization instead of single strip line, which can meet the requirements of mass production.

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Abstract

Un dispositif d'analyse de glucose dans les larmes comprend une bandelette réactive au glucose dans les larmes et un ensemble de support (4), la bandelette réactive au glucose dans les larmes comprenant deux unités de bandelette réactive (a, b) identiques reliées en parallèle dans une première direction ; les unités de bandelette réactive (a, b) comprenant chacune une zone d'échantillonnage de larme (1), une zone d'isolement hydrophobe (2), et une partie de maintien (3) ; la zone d'isolement hydrophobe (2) se situant entre la zone d'échantillonnage de larme (1) et la partie de maintien (3) ; les deux unités de bandelette réactive (a, b) étant reliées au niveau de la partie de maintien (3), et étant séparées entre la zone d'échantillonnage de larme (1) et la zone d'isolement hydrophobe (2) ; la zone d'échantillonnage de larme (1) étant configurée pour échantillonner des larmes et les faire réagir avec un réactif d'analyse de glucose pour analyser le glucose dans les larmes, la zone d'isolement hydrophobe (2) étant configurée pour empêcher la dispersion des larmes, et la partie de maintien (3) étant configurée pour être liée à l'ensemble de support (4) de façon à améliorer la rigidité de la bandelette réactive au glucose dans les larmes ; et la première direction étant une direction de largeur de la bandelette allongée réactive au sucre dans les larmes. Le dispositif d'analyse de glucose dans les larmes peut rapidement analyser le glucose dans les larmes, est approprié pour que des non-professionnels analysent régulièrement le glucose dans les larmes, peut mesurer qualitativement le glucose dans les larmes pour la prévention de la rétinopathie diabétique, et peut également mesurer quantitativement le glucose dans les larmes au moyen de la relation parallèle entre le glucose dans les larmes et la glycémie.
PCT/CN2022/125319 2021-10-15 2022-10-14 Dispositif d'analyse de glucose dans les larmes et son procédé de production WO2023061471A1 (fr)

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CN114113065B (zh) * 2021-12-27 2024-05-24 东北师范大学 一种柔性无创眼贴式可穿戴传感器及其应用

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