TR202004203A2 - A MEASUREMENT SYSTEM FOR TEAR CHEMICALS IN TEARS FOR DIAGNOSIS OF DISEASES. - Google Patents

Abstract

The measurement system (1), which is the subject of the invention, contains a sensor biosensor set (6) that changes color according to the amount of tear chemicals in the tear, including dopamine, glucose, ascorbate, lactate and proteins. When the measurement process is completed, the sensing biosensor set (6) is analyzed visually, so that the level of various chemicals such as dopamine in the tears can be determined.

Description

DESCRIPTION A MEASUREMENT SYSTEM FOR TEAR CHEMICALS IN TEARS FOR THE DIAGNOSIS OF DISEASES Technical Field This invention relates to a measurement system that enables the detection of the levels of chemicals in tears for diseases detectable through tears. Prior Art While an increase in dopamine levels in the Striatum region of our brain causes the onset of schizophrenia, a decrease in dopamine levels can lead to neurological degeneration in the brain and Parkinson's disease due to increased iron levels. Additionally, deterioration in dopamine level balance is detected in people who are addicted to drugs and in cases of HIV virus infection due to this addiction3. The level of dopamine secretion in the brain, which is one of the most important markers for checking the condition of people with suspected or diagnosed neurological diseases, especially Parkinson's disease, can unfortunately be very difficult to detect. Scientific research has proven that the dopamine level in tears is directly related to changes in the brain4. Systemic diseases (diseases that affect the entire body) are diagnosed by patient-reported symptoms, symptoms observed during examination, or by chemical analysis of blood and/or urine samples obtained from a medical history file. Patient samples typically contain ions, antibodies, hormone levels, and levels specific to various diseases. It is sent to a diagnostic laboratory to determine the levels of a wide range of markers, including biomarkers. 29280.14 DESCRIPTION A MEASUREMENT SYSTEM FOR TEAR CHEMICALS IN TEARS FOR THE DIAGNOSIS OF DISEASES Technical Field This invention relates to a measurement system that enables the detection of the levels of chemicals in tears for diseases detectable through tears. Prior Art While an increase in dopamine levels in the Striatum region of our brain causes the onset of schizophrenia, a decrease in dopamine levels can lead to neurological degeneration in the brain and Parkinson's disease due to increased iron levels. Additionally, deterioration in dopamine level balance is detected in people who are addicted to drugs and in cases of HIV virus infection due to this addiction3. The level of dopamine secretion in the brain, which is one of the most important markers for checking the condition of people with suspected or diagnosed neurological diseases, especially Parkinson's disease, can unfortunately be very difficult to detect. Scientific research has proven that the dopamine level in tears is directly related to changes in the brain4. Systemic diseases (diseases that affect the entire body) are diagnosed by patient-reported symptoms, symptoms observed during examination, or by chemical analysis of blood and/or urine samples obtained from a medical history file. Patient samples typically contain ions, antibodies, hormone levels, and levels specific to various diseases. It is sent to a diagnostic laboratory to determine the levels of a wide range of markers, including biomarkers. 29280.14 After a period of time ranging from minutes to days, depending on the test, the laboratory report is sent back to the doctor and the results are communicated to the patient. In order to facilitate these analysis methods, home test kits were developed in the 1950s. These test kits react to biomarkers of diseases through color change. Color changing strips used by the patient, a non-specialist relative, or a specialist are graded using a color guide. The color comparison result determines the concentration range of the analyzed biomarker. Blood and blood plasma or serum, which are very important among body chemicals, are not always sufficient for the examination of diseases. Because the concentration change of chemicals in the blood is too small to be detected in some cases, which causes difficulties in measurements and/or incorrect diagnoses. For example, the dopamine concentration in the blood of a healthy individual is around 475X10'9 mM. On the other hand, the concentration of dopamine in tears can be around 37'0<10'3 mM. In other words, the molarity of dopamine in tears is approximately 780,000 times greater than its concentration in blood. The concentrations of some other chemicals in tears are sufficient for measurement. Therefore, tears provide a more suitable basis for use in the diagnosis of many diseases. Likewise, while the molarity of lactate is between 2 and 5 mM in tears, it is 0.36 mM in blood plasma. While the molarity of ascorbatin is between 0.22 and 1.31 mM in tears, it is found between 0.04-0.06 mM in blood plasma (it is approximately 15 times more concentrated in tears). patent: GB784548 6 Contact Lens Sensors in Ocular Diagnostics Nicholas M. et.al. DOl: 10.1002/adhm. 29280.14 After a period of time ranging from minutes to days, depending on the test, the laboratory report is sent back to the doctor and the results are communicated to the patient. In order to facilitate these analysis methods, home test kits were developed in the 1950s. These test kits react to biomarkers of diseases through color change. Color changing strips used by the patient, a non-specialist relative, or a specialist are graded using a color guide. The color comparison result determines the concentration range of the analyzed biomarker. Blood and blood plasma or serum, which are very important among body chemicals, are not always sufficient for the examination of diseases. Because the concentration change of chemicals in the blood is too small to be detected in some cases, which causes difficulties in measurements and/or incorrect diagnoses. For example, the dopamine concentration in the blood of a healthy individual is around 475X10'9 mM. On the other hand, the concentration of dopamine in tears can be around 37'0<10'3 mM. In other words, the molarity of dopamine in tears is approximately 780,000 times greater than its concentration in blood. The concentrations of some other chemicals in tears are sufficient for measurement. Therefore, tears provide a more suitable basis for use in the diagnosis of many diseases. Likewise, while the molarity of lactate is between 2 and 5 mM in tears, it is 0.36 mM in blood plasma. While the molarity of ascorbatin is between 0.22 and 1.31 mM in tears, it is found between 0.04-0.06 mM in blood plasma (it is approximately 15 times more concentrated in tears). patent: GB784548 6 Contact Lens Sensors in Ocular Diagnostics Nicholas M. et.al. DOl: 10.1002/adhm. 29280.14 Analyte in Tears and Blood Molarity Molarity Related Disease Lactate 2 _ 5 0.36-0.75 Liver diseases and cancer Dopamine 0.3 7 475 <10'9 Parkinson, Glaucoma Table 1. Molarity comparison of analytes in tears and blood In another scientific study7, using an ELISA kit, Higher levels of dopamine were found in tear fluid than in plasma: Dopamine Concentration pg/ml (mean ± Standard error) Plasma (blood plasma) 97.2 ± 11.80 Tears (Schirmer Strip) 279 ± 14.8 Tears (capillary tube) 470.4 ± 37.64 Table 2. Tears and Comparison of dopamine concentration in blood. Colorimetry and fluorescence determination of dopamine, which is the subject of the invention, is carried out with the Cu-MnxOy/C-dots/TMB composite system. This sensor reacts to tear fluid containing dopamine molecules. The color of the sensor material coated on carbon nano-particles and copper-manganese oxide based TMB, in the free state 29280.14 Analyte in Blood in Tears Molarity Molarity Related Disease Lactate 2 _ 5 0.36-0.75 Liver diseases and cancer Dopamine 0.3 7 475 <10'9 Parkinson, Glaucoma Table 1. Molarity comparison of analytes found in tears and blood Another scientific study7, using an ELISA kit, found higher levels of dopamine in tear fluid than in plasma: Dopamine Concentration pg/ml (mean ± Standard error) Plasma (blood plasma) 97.2 ± 11.80 Tears (Schirmer Strip) 279 ± 14.8 Tear (capillary tube) 470.4 ± 37.64 Table 2. Comparison of dopamine concentration in tears and blood. Colorimetry and fluorescence determination of dopamine, which is the subject of the invention, is carried out with the Cu-MnxOy/C-dots/TMB composite system. This sensor reacts to tear fluid containing dopamine molecules. The color of the sensor material coated on TMB based on carbon nano-particles and copper-manganese oxide is 29280.14 dark blue in the free state and becomes transparent by being affected by the dopamine found in tears. This color change is associated with dopamine concentration. In the known state of the technique, some of the methods used to detect diseases in individuals - especially for Parkinson's disease - and their disadvantages can be expressed as follows: 1. When the cells that produce dopamine in the brain lose 60% to 801%, sufficient amounts of dopamine cannot be produced and motor symptoms of Parkinson's disease appear. In this regard, Parkinson's disease is determined clinically by looking at motor symptoms, lifestyle factors and medical history data. In this method, since the diagnosis of Parkinson's is made based on clinical data, laboratory measurements are needed to support this, because there is a high possibility of confusion with Parkinson's disease-like diseases or diseases that mimic Parkinson's disease. 2. Since there is no reliable way to directly measure dopamine levels in the brain, some indirect ways are used to determine this level imbalance. Doctors can measure the density of dopamine transporters, which are directly associated with the nerve cells that use dopamine. This test involves injecting a radioactive material that binds to dopamine transporters, which doctors can measure using a camera. In this method, dopamine level cannot be shown directly since indirect dopamine measurement is made. On the other hand, the use of radioactive materials used in this method is generally not preferred due to their harmful effects. 3. As another method, diffusion-weighted magnetic resonance imaging (DA-MRI) findings of the Substantia Nigra in Parkinson's disease 9 Clinical Features of Parkinson's Disease, Neurology Symposium Series for Non-Neurologists No: 42, Nuclear Medicine. 43(l):el-e7, JAN 2018 29280.14 is dark blue and becomes transparent by being affected by the dopamine found in tears. This color change is associated with dopamine concentration. In the known state of the technique, some methods used to detect diseases in individuals - especially for Parkinson's disease - and their disadvantages can be expressed as follows: 1. When 60% to 801% of dopamine-producing cells in the brain are lost, sufficient amounts of dopamine cannot be produced and motor symptoms of Parkinson's disease appear. In this regard, Parkinson's disease is determined clinically by looking at motor symptoms, lifestyle factors and medical history data. In this method, since the diagnosis of Parkinson's is made based on clinical data, laboratory measurements are needed to support this, because there is a high possibility of confusion with Parkinson's disease-like diseases or diseases that mimic Parkinson's disease. 2. Since there is no reliable way to directly measure dopamine levels in the brain, some indirect ways are used to determine this level imbalance. Doctors can measure the density of dopamine transporters, which are directly associated with the nerve cells that use dopamine. This test involves injecting a radioactive material that binds to dopamine transporters, which doctors can measure using a camera. In this method, dopamine level cannot be shown directly since indirect dopamine measurement is made. On the other hand, the use of radioactive materials used in this method is generally not preferred due to their harmful effects. 3. As another method, diffusion-weighted magnetic resonance imaging (DA-MRI) findings of the Substantia Nigra in Parkinson's disease 9 Clinical Features of Parkinson's Disease, Neurology Symposium Series for Non-Neurologists No: 42, Nuclear Medicine. 43(l):el-e7, JAN 2018 can also be viewed at 29280.14. With the diffusion MRI technique, images resulting from the molecular movements of water in the tissue are obtained. Since this method is an expensive and limited imaging method, it cannot be applied to all patients or people with suspicious conditions. Additionally, it may take hours to obtain laboratory results of dopamine analysis using MRI and similar methods. But monitoring the treatment process may not always require very high-precision measurements. Especially in point-of-care tests, rapid measurement and results are more important than sensitivity. 4. ELISA kit, which makes quantitative determination of dopamine in urine and blood plasma through color change, is available on the market. These kits are for research purposes only and should not be used in clinical, therapeutic or diagnostic procedures. Dopamine is extracted using a cis-diol-specific affinity gel and acylated to N-acyl-dopamine, which is then enzymatically converted to N-acyl-3-methoxytyramine. Dopamine binds to the solid phase of the microtiter plate. Sample and solid phase bound Acylated dopamine derived from dopamine competes for a fixed number of antiserum binding sites. When the system is in equilibrium, free antigen and free antigen-antiserum complexes are washed away. Antibody bound to solid phase dopamine is detected by anti-rabbit IgG / peroxidase. Substrate TMB / peroxidase reaction is monitored at 450 nm. The amount of antibodies bound to solid-phase dopamine is inversely proportional to the dopamine concentration of the sample. The ELISA kit is considered an expensive measurement method (at its current price and requires technical knowledge to use. ELISA kits available on the market are calibrated for urine and plasma and tear It is not suitable for testing. Additionally, it takes hours for the test results to appear. It can also be viewed on 22(2):75-9 29280.14. With the diffusion MRI technique, images resulting from the molecular movements of water in the tissue are obtained. Since this method is an expensive and limited imaging method, it cannot be applied to all patients or people with suspicious conditions. Additionally, it may take hours to obtain laboratory results of dopamine analysis using MRI and similar methods. But monitoring the treatment process may not always require very high-precision measurements. Especially in point-of-care tests, rapid measurement and results are more important than precision. 4. ELISA kit, which makes quantitative determination of dopamine in urine and blood plasma through color change, is available on the market. These kits are for research purposes only and should not be used in clinical, therapeutic or diagnostic procedures. Dopamine is extracted using a cis-diol-specific affinity gel and acylated to N-acyl-dopamine, which is then enzymatically converted to N-acyl-3-methoxytyramine. Dopamine binds to the solid phase of the microtiter plate. Sample and solid phase bound Acylated dopamine derived from dopamine competes for a fixed number of antiserum binding sites. When the system is in equilibrium, free antigen and free antigen-antiserum complexes are washed away. Antibody bound to solid phase dopamine is detected by anti-rabbit IgG / peroxidase. Substrate TMB / peroxidase reaction is monitored at 450 nm.The amount of antibody bound to solid phase dopamine is inversely proportional to the dopamine concentration of the sample. The ELISA kit is considered an expensive measurement method (at its current price and requires technical knowledge to use. ELISA kits available on the market are calibrated for urine and plasma and are not suitable for tears. In addition, it takes hours for test results to appear. 22(2):75-9 29280.14 Patent applications within the state of the art are as follows: The document describes apparatus, systems and methods using contact lenses having one or more sensors that detect an analyte in the tear fluid and one or more cavities that collect the tear fluid. This lens detects an analyte in the collected tear fluid. It contains at least one sensor configured to detect the presence of tears. The claims of this patent include collecting the tear sample into a micro-scale chamber and then analyzing it by the sensor with a microprocessor. The signals detected by the sensor are transmitted to a device connected to the internet through electronic circuits and antennas. In the Chinese patent application document numbered CN107860805, an electrochemical dopamine aptamer sensor based on aptamer-gold nanoparticle / reduced graphene oxide-Nile inavi nanocomposite is mentioned. dopamine detection biosensor is mentioned. It contains a field effect transistor (FET) that forms the source of an electrode and detects electric current. The functional layer contains a reactant that reacts selectively with dopamine. A contact lens with a hydrogel coating on its surface is mentioned. Within the scope of this application, a method has been developed using aptamer molecules in colorimetric analysis. No method or methodology that produces numerical output is presented to observe the color change and transfer analysis information. In the European patent application document numbered EP3131454, a functional contact lens and its associated systems and methods are mentioned. The contact lens of the invention is used to detect the changes resulting from the detection of at least one target analyte by electronic and electrochemical methods and to transmit the detected signal externally through an antenna integrated into the lens structure. 29280.14 Patent applications in the state of the art are as follows: In the document, apparatus, systems and methods using contact lenses having one or more sensors that detect an analyte in tear fluid and one or more cavities collecting tear fluid are mentioned. This lens contains at least one sensor configured to detect the presence of an analyte in the collected tear fluid. The claims of this patent include collecting the tear sample into a microscale chamber and then analyzing it by the sensor equipped with a microprocessor. The signals detected by the sensor are transferred to a device connected to the internet via electronic circuits and antennas. In the Chinese patent application document numbered CN107860805, an electrochemical dopamine aptamer sensor based on aptamer-gold nanoparticle / reduced graphene oxide-Nile inavi nanocomposite is mentioned. dopamine detection biosensor is mentioned. It contains a field effect transistor (FET) that forms the source of an electrode and detects electric current. The functional layer contains a reactant that reacts selectively with dopamine. A contact lens with a hydrogel coating on its surface is mentioned. Within the scope of this application, a method has been developed using aptamer molecules in colorimetric analysis. No method or methodology that produces numerical output is presented to observe the color change and transfer analysis information. In the European patent application document numbered EP3131454, a functional contact lens and its associated systems and methods are mentioned. The contact lens of the invention is used to detect the changes resulting from the detection of at least one target analyte by electronic and electrochemical methods and to transmit the detected signal externally through an antenna integrated into the lens structure. It is used to transmit 29280.14 to the device. Wireless driven contact lens with glucose sensor for colorimetric detection and data transmission is mentioned. The contact lens contains an electrochemical sensor that allows the measurement of the glucose level in the person's tear fluid. This contact lens provides power via RF antenna or photovoltaic Device and can also transfer data via electrochemical sensor. It does not perform colorimetric detection and data transfer. Their working methods are mentioned. The device of the invention is placed on the eyelid flesh (lacrimal punctum or conjunctival sac) of the person and detects the chemical composition of the tears with one or more sensor materials sensitive to one or more components. Each sensor material transmits the person's medical status via electromagnetic signals. It does not recommend any coding method for disease diagnosis. devices are mentioned. The analysis method used in these devices is colorimetric, but in the detection method, the color change is detected from the wavelength change. In the Turkish patent application document numbered TR 2015/l 7446, the tear glucose level sensing contact lens design is mentioned. The invention is for the use of diabetic patients and is related to the development of material that will detect the glucose level in tears with the biosensor on it. No method or methodology that produces numerical output is presented to observe the color change and transfer analysis information. In the European patent application document numbered EP3148435, a system for displaying information regarding the health of individuals is mentioned. It is used to transmit 29280.14. Wireless driven contact lens with glucose sensor for colorimetric detection and data transmission is mentioned. The contact lens contains an electrochemical sensor that allows the measurement of the glucose level in the person's tear fluid. This contact lens provides power via RF antenna or photovoltaic Device and can also transfer data via electrochemical sensor. It does not perform colorimetric detection and data transfer. Their working methods are mentioned. The device of the invention is placed on the eyelid flesh (lacrimal punctum or conjunctival sac) of the person and detects the chemical composition of the tears with one or more sensor materials sensitive to one or more components. Each sensor material transmits the person's medical status via electromagnetic signals. It does not recommend any coding method for disease diagnosis. devices are mentioned. The analysis method used in these devices is colorimetric, but in the detection method, the color change is detected from the wavelength change. In the Turkish patent application document numbered TR 2015/l 7446, the tear glucose level sensing contact lens design is mentioned. The invention is for the use of diabetic patients and is related to the development of material that will detect the glucose level in tears with the biosensor on it. No method or methodology that produces numerical output is presented to observe the color change and transfer analysis information. In the European patent application document numbered EP3148435, a system for displaying information regarding the health of individuals is mentioned. In the European patent application document No. 29280.14 EP2846182, an ophthalmic lens that can provide interconnection with an external device is mentioned. A disposable lens applied for diagnosis to an electronic operating device is mentioned. In the patent document EP2569667, an inetot for the preparation of an ophthalmic lens containing a QR code is mentioned. The invention described in this context offers a printing method for printing and transferring QR codes and similar codes onto the lens, and does not mention its use in the form of any detection or sensor. In the European patent application document numbered EP3159693, the detection device method and program are mentioned and it is an electronic device consisting of pressure, temperature and motion sensors. system has been presented. The mouth water (saliva) sample, which is one of the body fluids, contacts the test cell and causes a color change. This color change is analyzed with a digital photograph and the results are sent to the user in the form of a QR code. Commercially available urine analysis strips are used to determine many parameters such as pH value of urine, protein, glucose and pregnancy hormone (hCG) through color change. A few drops of urine sample are transferred onto the colored cells on the test strips and the color change is waited for a certain period of time. The results are obtained by directly comparing the color blocks written on the box. Color blocks represent pseudovalues, actual values will vary close to pseudovalues". There are some problems and risks that limit the use of these strips: There is a high probability of error in color reading by eye. In the European patent application document No. 29280.14 EP2846182, an ophthalmic lens that can provide interconnection with an external device is mentioned. . a disposable lens applied to an electronic operating device for diagnosis is mentioned. In the patent document EP2569667, an inetot is mentioned for the preparation of an ophthalmic lens containing a QR code. The invention described in this context is a printing method for printing and transferring QR codes and similar codes onto the lens. and does not mention its use in the form of any detection or sensor. In the European patent application document numbered EP3159693, the detection device method and program are mentioned, and it is an electronic device consisting of pressure, temperature and motion sensors. The system is presented. A sample of mouth water (saliva), which is a body fluid. , contacts the test cell, causing a color change. This color change is analyzed with a digital photograph and the results are sent to the user in the form of a QR code. Commercially available urine analysis strips are used to determine many parameters such as pH value of urine, protein, glucose and pregnancy hormone (hCG) through color change. A few drops of urine sample are transferred onto the colored cells on the test strips and the color change is waited for a certain period of time. The results are obtained by directly comparing the color blocks written on the box. Color blocks represent pseudo values, their actual values will vary close to the pseudo values". There are some problems and risks that limit the use of these strips: There is a high probability of error in color reading by eye. 29280.14 - Since the references are printed on a sheet of paper on the box, unrealistic reference colors can be presented. - Wide values Since the range is given, it is difficult to determine the exact number. - Since it is not possible to look at more than one cell color at the same time, the reading time may pass and the color scale may change. - The difficulty of keeping track of the results and the possibility of confusion are high. - Difficulty in recording the results and reporting difficulties and possibilities of errors (manually) - There are difficulties in taking notes). - Strips and cells cut in large sizes cause high material consumption. - Test cells cut in large sizes require more urine samples. - In the user manual, it is stated that the strips should be kept in a small glass (200 ml) of urine sample. It is stated that this amount is required and this amount is too much for other body fluids other than urine. In order to prevent some of these problems, there are studies that determine the results of urine analysis by image processing using a mobile phone application. For example, Vivoois analyzes a few drops of the urine sample after it touches the strip kit and determines numerical values for the user. The image processing method helps for more accurate color analysis, but in this study the problem of sample collection and the risk of confounding the results were not eliminated. Brief Description of the Invention The aim of the invention is to realize a measurement system that is easy to use, has high reliability, low cost, can be recorded and does not require technical training, to determine the level of various tear chemicals such as dopamine. 29280.14 - Since the references are printed on a piece of paper on the box, unrealistic reference colors may be presented. - Since a wide range of values is given, it is difficult to determine an exact figure. - Since it is not possible to look at more than one cell color at the same time, the reading time may pass and the color scale may change. - It is difficult to follow up the results and the possibility of confusion is high. - There are difficulties in recording and reporting the results and the possibility of errors (trouble taking notes manually). - Strips and cells cut in large sizes cause high material consumption. - Test cells cut to large sizes require more urine samples. - The user manual of the strips states that they should be kept in a small glass (200 ml) of urine sample, and this amount is too much for body fluids other than urine. In order to prevent some of these problems, there are studies that determine the results of urine analysis by image processing using a mobile phone application. For example, Vivoois analyzes a few drops of the urine sample after it touches the strip kit and determines numerical values for the user. The image processing method helps for more accurate color analysis, but in this study the problem of sample collection and the risk of confounding the results were not eliminated. Brief Description of the Invention The aim of the invention is to realize a measurement system that is easy to use, has high reliability, low cost, can be recorded and does not require technical training, to determine the level of various tear chemicals such as dopamine. 29280.14 Detailed Description of the Invention The contact sensor structure realized to achieve the purpose of this invention is shown in the attached figures; Among these figures: This is the view of the measurement system of the invention if it has a strip-shaped substrate. It is a demonstration of the working principle of the measuring system subject to the invention if it has a strip-shaped substrate. It is the view of the measurement system that is the subject of the invention if it has a substrate in the form of a strip placed under the eyelid. It is the demonstration of the working principle of the measurement system that is the subject of the invention if it has a substrate in the form of a strip placed under the eyelid. This is the appearance of the measurement system subject to the invention if it has a substrate in the form of a contact lens. It is a demonstration of the working principle of the measurement system subject to the invention if it has a substrate in the form of a contact lens. The parts in the figures are numbered and their equivalents are given below: 1. Measuring system 2. Substrate 21. Absorbent 22. Non-absorbent part 23. Holding area 3. Code area 31. Code 32. Reference colors 4. Sensor area. The part to be placed under the eyelid 6. Sensor biosensor set 29280.14 Detailed Description of the Invention The contact sensor structure realized to achieve the purpose of this invention is shown in the attached figures; Among these figures: This is the view of the measurement system of the invention if it has a strip-shaped substrate. It is a demonstration of the working principle of the measuring system subject to the invention if it has a strip-shaped substrate. It is the view of the measurement system that is the subject of the invention if it has a substrate in the form of a strip placed under the eyelid. It is the demonstration of the working principle of the measurement system that is the subject of the invention if it has a substrate in the form of a strip placed under the eyelid. This is the appearance of the measurement system subject to the invention if it has a substrate in the form of a contact lens. It is a demonstration of the working principle of the measurement system subject to the invention if it has a substrate in the form of a contact lens. The parts in the figures are numbered and their equivalents are given below: 1. Measuring system 2. Substrate 21. Absorbent 22. Non-absorbent part 23. Holding area 3. Code area 31. Code 32. Reference colors 4. Sensor area. Part to be placed under the eyelid 6. Sensor biosensor set 29280.14 The measurement system (1) of the invention is used to determine the level of tear chemicals including dopamine, glucose, ascorbate, lactate and proteins, and - at least one absorbent suitable for collecting tears at least one substrate (2) containing part (21) and at least one non-absorbent part (22), - number of sensors, sensor type, purpose of use and method of use of the sensor, located in the non-absorbent part (22) of the substrate (2), At least one code field (3) containing at least one code (31) containing information about one, more or all of the production date and LOT number information, - at least one field for each analyte that is located on the substrate (2) and is desired to be detected. It contains at least one sensor area (4) containing at least one sensor biosensor set (6) that is suitable for interacting with the said analyte and whose color changes as a result of this interaction. In an embodiment of the invention, the substrate (2) may be in the form of a strip on which a tear sample taken from the patient's eye can be dropped. If a strip of this structure is used, a local anesthetic eye drop USP solution (Proparacaine Hydrochloride Ophthalmic Solution (15%)16), which will not prevent eye irritation, is dropped into the patient's eye in order to obtain a baseline tear sample, and a sample of the resulting tears is taken through a micropipette. It is dropped onto the absorbent part (21) on the surface of the substrate (2) in strip form. In another embodiment of the invention, the substrate (2) can be in the form of a strip that collects tears directly from the eye by placing it under the eyelid. In another embodiment of the invention, the substrate (2) ), can be in the form of a contact lens that is positioned like an ordinary contact lens placed directly on the pupil and enables the collection of tears directly from the eye. It is used to determine the level of tear chemicals, - at least one substrate (2) containing at least one absorbent part (21) and at least one non-absorbent part (22) suitable for collecting tears, - in the non-absorbent region of the substrate (2). At least one code field (3) located in (22) containing at least one code (31) containing information about one, more or all of the sensor number, sensor type, sensor's intended use and usage method, production date and LOT number information, - at least one sensor located on the substrate (2) containing at least one sensor biosensor set (6), at least one for each analyte to be detected, that is suitable for interacting with the said analyte and whose color changes as a result of this interaction. It contains the field (4). In an embodiment of the invention, the substrate (2) may be in the form of a strip on which a tear sample taken from the patient's eye can be dropped. If a strip of this structure is used, a local anesthetic eye drop USP solution (Proparacaine Hydrochloride Ophthalmic Solution (15%)16), which will not prevent eye irritation, is dropped into the patient's eye in order to obtain a baseline tear sample, and a sample of the resulting tears is taken through a micropipette. It is dropped onto the absorbent part (21) on the surface of the substrate (2) in strip form. In another embodiment of the invention, the substrate (2) can be in the form of a strip that collects tears directly from the eye by placing it under the eyelid. In another embodiment of the invention, the substrate (2) ), can be in the form of a contact lens that is positioned like an ordinary contact lens placed directly on the pupil and allows tear removal directly from the eye. The middle region (21 and 23) of this lens 29280.14 has high light transmittance (90% and above) and the tear sample is It provides the patient's view within the expected time for collection. In addition, support will be taken from the middle area (23) as a holding point to place the contact lens on the eye surface. In an embodiment of the invention, the surface of the substrate (2) in strip form has at least one holding area (23) that allows the user to easily hold the substrate (2), excluding the absorbent part (21) and the non-absorbent part (22). In an embodiment of the invention, if the substrate (2) is in the form of a strip placed on the eyelid, there is a part (5) to be placed under the eyelid, which is suitable for placing it under the eyelid in order to directly contact the tear. In an embodiment of the invention, the measurement system (1) in question includes at least one reference color (32) to compare with the color of the sensor biosensor set (6). For the tear chemical, it corresponds to its color at a certain concentration. In an embodiment of the invention, the substrate (2) can be produced from any material such as paper, cellulose, acrylic, plastic or PMMA (polymethyl methacrylate). In an embodiment of the invention, the information contained in the code field (31) can be iQR, QR code, datamatrix etc. It can be coded by any method available in the art or that can be developed in the future. In an embodiment of the invention, the sensor biosensor set (6) interacts with tear chemicals, including dopamine, glucose, ascorbate, lactate and proteins, and at the end of this interaction, the color of the sensor biosensor set (6) becomes 29280.14. The middle area (21 and 23) has high light transmittance (90% and above) and provides the patient's vision in the expected time to collect the tear sample. In addition, support will be taken from the middle area (23) as a holding point to place the contact lens on the eye surface. In an embodiment of the invention, the surface of the substrate (2) in strip form has at least one holding area (23) that allows the user to easily hold the substrate (2), excluding the absorbent part (21) and the non-absorbent part (22). In an embodiment of the invention, if the substrate (2) is in the form of a strip placed on the eyelid, there is a part (5) to be placed under the eyelid, which is suitable for placing it under the eyelid in order to directly contact the tear. In an embodiment of the invention, the measurement system (1) in question includes at least one reference color (32) to compare with the color of the sensor biosensor set (6). For the tear chemical, it corresponds to its color at a certain concentration. In an embodiment of the invention, the substrate (2) can be produced from any material such as paper, cellulose, acrylic, plastic or PMMA (polymethyl methacrylate). In an embodiment of the invention, the information contained in the code field (31) can be iQR, QR code, datamatrix etc. It can be coded by any method available in the art or that can be developed in the future. In an embodiment of the invention, the sensor biosensor set (6) interacts with tear chemicals, including dopamine, glucose, ascorbate, lactate and proteins, and at the end of this interaction, the color of the sensor biosensor set (6) becomes 29280.14. It is changing. Thus, the presence and/or concentration of the chemicals in question can be detected. Examples of the said sensor biosensor set (6) include, but are not limited to, Cu-Mn-O micro-crystals and carbon nano-particles to measure dopamine level and boric acid to measure glucose level. Different detecting biosensors (6) may also contain different concentrations of the same analyte. In an embodiment of the invention, the sensor biosensor set (6) is used for printing, dip-coating, spin-coating, spray-coating, electric fiber coating (electrospinning), inkjet printing, microjet. It can be produced by microjet printing and nanojet printing methods, but it is not limited to these. In one embodiment of the invention, the sensor area (4) contains more than one sensor biosensor set (6) arranged to form a pattern. This Pattern can be a matrix, circle, ellipse, triangle, etc. It can be created in any shape, smooth or irregular. Likewise, reference colors (32) are formed by a matrix, circle, ellipse, triangle, etc. of size mXn. It can be created in any shape, smooth or irregular. The measurement system (1) of the invention includes at least one strip substrate (2) with at least one absorbent part (21) and at least one non-absorbent part (22) suitable for collecting tears, and having at least one holding area (23). . Preferably in the non-absorbent region (22) of the strip substrate (2), there is at least one device containing information about one, several or all of the number of sensors, sensor type, purpose and method of use of the sensor, production date and LOT number of the strip substrate (2). There is at least one code field (3) containing code (31). On the strip substrate (2), at least one sensor area (4) containing at least one sensor biosensor set (6), at least one for each analyte to be detected, that is suitable for interacting with the said analyte and whose color changes with this interaction. ) is located. The tear band varies from 29280.14. Thus, the presence and/or concentration of the chemicals in question can be detected. Examples of the said sensor biosensor set (6) include, but are not limited to, Cu-Mn-O micro-crystals and carbon nano-particles to measure dopamine level and boric acid to measure glucose level. Different detecting biosensors (6) may also contain different concentrations of the same analyte. In an embodiment of the invention, the sensor biosensor set (6) is used for printing, dip-coating, spin-coating, spray-coating, electric fiber coating (electrospinning), inkjet printing, microjet. It can be produced by microjet printing and nanojet printing methods, but it is not limited to these. In one embodiment of the invention, the sensor area (4) contains more than one sensor biosensor set (6) arranged to form a pattern. This Pattern can be a matrix, circle, ellipse, triangle, etc. It can be created in any shape, smooth or irregular. Likewise, reference colors (32) are formed by a matrix, circle, ellipse, triangle, etc. of size mXn. It can be created in any shape, smooth or irregular. The measurement system (1) of the invention includes at least one strip substrate (2) with at least one absorbent part (21) and at least one non-absorbent part (22) suitable for collecting tears, and having at least one holding area (23). . Preferably in the non-absorbent region (22) of the strip substrate (2), there is at least one device containing information about one, several or all of the number of sensors, sensor type, purpose and method of use of the sensor, production date and LOT number of the strip substrate (2). There is at least one code field (3) containing code (31). On the strip substrate (2), at least one sensor area (4) containing at least one sensor biosensor set (6), at least one for each analyte to be detected, that is suitable for interacting with the said analyte and whose color changes with this interaction. ) is located. The part (5) to be placed under the eyelid is placed directly under the eyelid so that the tears can be absorbed by the ribbon 29280.14 substrate (2). The measurement process is carried out by contacting the measurement system (1) of the invention with the tear for a predetermined period of time. At the end of the measurement process, the image of the code field (3) and the sensor field (4) is recorded by a camera, etc. It is captured by an image sensor. This sensing device can be a camera-enabled mobile phone or portable computer. This image is then processed and analyzed by the device that captured the image or a central server. Processing of the said image; calibrating the image in question, obtaining the color information of the sensor biosensor set (6), normalizing the said color information in line with the calibration data, comparing the said normalized and/or non-normalized color information with the data in the said device and/or central server and as a result of this comparison. It may include one, several or all of the processes of interpreting the obtained information according to the table or tables located on the said device and/or the central server. Processing of the image can be carried out by any image processing algorithm that is known in the state of the art or that can be developed in the future. In an application of the invention that can be used together with other applications, the information and/or comments obtained as a result of processing the images are added to the user's profile kept on the said device and/or central server. Thus, the user can easily see the results of the measurements he has made in the past and the comments made in line with these results. In an embodiment of the invention that can be used together with other applications, an optical element such as a filter or a lens can be attached in front of the image sensor. The optical element in question can be used to change various properties such as color, focus and/or polarization of the light to be transmitted, but is not limited to these. The part (5) to be placed under the eyelid is placed directly under the eyelid so that 29280.14 can be absorbed by the substrate (2). The measurement process is carried out by contacting the measurement system (1) of the invention with the tear for a predetermined period of time. At the end of the measurement process, the image of the code field (3) and the sensor field (4) is recorded by a camera, etc. It is captured by an image sensor. This sensing device can be a camera-enabled mobile phone or portable computer. This image is then processed and analyzed by the device that captured the image or a central server. Processing of the said image; calibrating the image in question, obtaining the color information of the sensor biosensor set (6), normalizing the said color information in line with the calibration data, comparing the said normalized and/or non-normalized color information with the data in the said device and/or central server and as a result of this comparison. It may include one, several or all of the processes of interpreting the obtained information according to the table or tables located on the said device and/or the central server. Processing of the image can be carried out by any image processing algorithm that is known in the state of the art or that can be developed in the future. In an application of the invention that can be used together with other applications, the information and/or comments obtained as a result of processing the images are added to the user's profile kept on the said device and/or central server. Thus, the user can easily see the results of the measurements he has made in the past and the comments made in line with these results. In an embodiment of the invention that can be used together with other applications, an optical element such as a filter or a lens can be attached in front of the image sensor. The optical element in question can be used to change various properties such as color, focus and/or polarization of the light to be transmitted, but is not limited to these. 29280.14 If the substrate (2) considered within the scope of the invention is in the form of a strip on which a sample of the tear taken from the patient's eye can be dropped, it can be applied as follows (Figure 2): l- In order to obtain basal tears, eye drops that will not prevent eye irritation are used and applied for approximately 60 minutes. seconds. 2- Then, a sample of the basal tear fluid is taken from a subject close to the patient's eyelids, with the help of a micropipette (Micro Capillary Tubes (MCT)) or cellulose sponge and polyester rod. 3- A few drops of the tear sample are dropped onto the sensor area (4) located on the absorbent body (21) of the measurement system (1) that is the subject of the invention. 4- An image is taken from the code area (3). - The captured image is sent to the developed software on the remote server (cloud) over the internet and image analysis is performed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file. If the substrate (2) considered within the scope of the invention is in the form of a strip placed under the eyelid. For example, it can be applied as follows (Figure 2.1. In order to obtain basal tears, eye drops that will not prevent eye irritation are used and kept for approximately 60 seconds. 2.2. Then, the part (5) of the measurement system (1) that is the subject of the invention to be placed under the eyelid is placed under the eyelid and held for approximately 60 seconds. 2.3. At the end of this period, the measurement system (1) of the invention is removed from under the eyelid. 2.4. The image is taken from the code area (3). 29280.14 The substrate (2) considered within the scope of the invention is a sample on which a tear sample taken from the patient's eye can be dropped. If it is in the form of a strip, it can be applied as follows (Figure 2): l- In order to obtain basal tears, eye drops that will not prevent eye irritation are used and kept for approximately 60 seconds. 2- Then, a micropipette (Micro Capillary Tubes (MCT)) is applied from a subject close to the patient's eyelids. )) or with the help of a cellulose sponge and polyester stick, a sample of the basal tear fluid is taken. 3- A few drops of the tear sample are dropped onto the sensor area (4) located on the absorbent body (21) of the measurement system (1) that is the subject of the invention. 4- An image is taken from the code area (3). - The captured image is sent to the developed software on the remote server (cloud) over the internet and image analysis is performed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file. If the substrate (2) considered within the scope of the invention is in the form of a strip placed under the eyelid. For example, it can be applied as follows (Figure 2.1. In order to obtain basal tears, eye drops that will not prevent eye irritation are used and kept for approximately 60 seconds. 2.2. Then, the part (5) of the measurement system (1) that is the subject of the invention to be placed under the eyelid is placed under the eyelid and held for approximately 60 seconds. 2.3. At the end of this period, the measurement system (1) of the invention is removed from under the eyelid. 2.4. The image is taken from the code area (3). 29280.14 The captured image is sent to the developed software on the remote server (cloud) over the internet and image analysis is performed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file. The substrate (2) considered within the scope of the invention is placed directly on the pupil. It can be applied in the form of a contact lens, which is positioned like an ordinary contact lens and allows the tear to be removed directly from the eye, for example as follows (Figure 6): In order to obtain basal tears, eye drops that will not prevent eye irritation are used and kept for approximately 60 seconds. Then, the measurement system (1) of the invention, which has a substrate (2) in the form of a contact lens, is placed on the patient's pupil like a lens and kept for approximately 60-300 seconds. While in the user's eye or after removal, an image is taken from the code area (3). The captured image is sent to the developed software on the remote server (cloud) over the internet and the image is analyzed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file. 29280.14 The received image is sent to the developed software on the remote server (cloud) over the internet and image analysis is performed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file. The substrate (2) considered within the scope of the invention can be applied in the form of a contact lens that is positioned like an ordinary contact lens placed directly on the pupil and allows tear to be removed directly from the eye, for example as follows ( Figure 6): To obtain basal tears, eye drops that will not prevent eye irritation are used and kept for approximately 60 seconds. Then, the measurement system (1) of the invention, which has a substrate (2) in the form of a contact lens, is placed on the patient's pupil like a lens and kept for approximately 60-300 seconds. While in the user's eye or after removal, an image is taken from the code area (3). The captured image is sent to the developed software on the remote server (cloud) over the internet and the image is analyzed. Thus, the color and contrast or wavelength differences detected in the image are compared with analytical tables and the amount of tear chemical is determined. This amount is sent to the application and the user is informed and the reports are added to the patient's file.

Claims (1)

1.CLAIMS. To determine the level of tear chemicals, - at least one substrate (2) containing at least one absorbent part (21) and at least one non-absorbent part (22) suitable for receiving tears, - in the non-absorbent region (22) of the substrate (2). ) at least one code field (3) containing at least one code (3 `1) containing information about one, more or all of the sensor number, sensor type, sensor's intended use and usage method, production date and LOT number information, - at least one sensor located on the substrate (2) and containing at least one sensor biosensor set (6), at least one for each analyte to be detected, that is suitable for interacting with the said analyte and whose color changes as a result of this interaction. A measurement system (1) characterized by area (4). . A measurement system (1) as in Claim 1, characterized by a substrate (2) in the form of a strip onto which a tear sample taken from the patient's eye can be dropped. . A measurement system (1) as in Istein 1, characterized by a substrate (2) in the form of a strip that is placed under the eyelid and collects tears directly from the eye. . A measurement system (1) as in Claim 1, characterized by the substrate (2) in the form of a contact lens, which is positioned like an ordinary contact lens placed directly on the pupil and enables the collection of tears directly from the eye. . A measurement system (1) as in claim 2 or ?, which includes at least one holding area (23) that allows the user to easily hold the substrate (2). 29280.14 A measurement system (1) as in claim 1, which includes a part (5) to be placed under the eyelid, which is suitable for placing it under the eyelid in order to directly contact the tear, in case it is in the form of a strip placed on the eyelid. A measurement system (1) as in Claim 1, containing at least one reference color (32) to compare with the color of the sensor biosensor set (6). A measuring system (1) as in Istein 1, which contains a strip substrate (2) made of any material such as paper, cellulose, acrylic, plastic, PMMA (polymethyl methacrylate). A measurement system (1) as in Claim 1, containing a sensor biosensor set (6) suitable for interacting with tear chemicals including dopamine, glucose, ascorbate, lactate and proteins. A measurement system (1) as in Claim 17, characterized by a sensor field (4) containing more than one sensor biosensor set (6) arranged to form a pattern. A measurement system (1) as in Claim 10, characterized by any pattern that is not m. A measurement system (1) as in Claim 10, containing reference colors (32) in any way that are not m. By contacting a measurement system (l) as in any of the above claims with the tear for a predetermined time, the image of the 29280.14 code area (3) and the sensor area (4) is displayed by a camera, etc. A measurement method characterized by the steps of capturing the image by means of an image sensor, processing and analyzing the captured image by the device that captures the image or by a central server. The image processing step; calibrating the image in question, obtaining the color information of the sensor biosensor set (6), normalizing the said color information in line with the calibration data, comparing the said normalized and/or non-normalized color information with the data in the said device and/or central server and as a result of this comparison. A measurement method as in claim 13, characterized in that it includes one, several or all of the processes of interpreting the obtained information according to the table or tables located in the said device and/or the central server. A measurement method as in claim 13, which includes the step of adding the obtained information and/or comments to the user's profile kept on the said device and/or central server. The sensor biosensor set (6) can be used in printing, dip-coating, spin-coating, spray-coating, electric fiber coating (electrospinning), inkjet printing, microjet printing, The production method of a measuring system (l) as in any one of claims 1 to 12, characterized in that it is produced according to any of the nanojet (nanojet printing) methods. 29280.14 TR TR