Medical measurement system that can measure gluten in blood

Abstract

The invention is a medical measurement system for measuring gluten levels in the blood. The system consists of an electronic circuit that reads the test values and a strip sensor based on gluten-sensitive nanoflower electroactive material that can be integrated into the electronic circuit and provides ease of individual use with practical and low-cost measurements. This measurement system enables people with conditions such as celiac disease and gluten intolerance to monitor gluten daily.

Description

[0001] MEDICAL MEASUREMENT SYSTEM THAT CAN MEASURE GLUTEN IN BLOOD

[0002] Technical Field Related to the Invention

[0003] The invention relates to a medical measurement system combined with a nanoflowerbased gluten selective sensor for the regular and practical determination of gluten from blood. This medical measurement system improves the quality of life of patients with gluten-related disorders such as celiac disease and facilitates food control.

[0004] State of the Art

[0005] Gluten is a combination of two proteins, gliadin and glutenin, responsible for the elastic texture of the dough. When flour is mixed with water, gluten forms a network that traps carbon dioxide produced by yeast, allowing the dough to rise during the fermentation process. This gives bread and other bakery products their characteristic texture and structure. Gluten is most commonly found in cereals such as wheat, barley and rye. Typical foods that contain gluten include bread, pasta, cereals and bakery products. In addition, gluten can often be present as a thickening or stabilising agent in less obvious sources such as soups, sauces and processed foods. It is important for people with gluten sensitivity to read food labels carefully and be aware of hidden sources of gluten in their diet. Although gluten is harmless for the majority of people, some people may experience adverse reactions. The best known condition associated with gluten sensitivity is celiac disease, an autoimmune disorder. Non-celiac gluten sensitivity is another condition in which individuals experience gastrointestinal symptoms similar to those in celiac disease but without an autoimmune response.

[0006] Celiac disease is an autoimmune disease triggered by gluten intake. When people with celiac disease consume gluten, the immune system attacks the lining of the small intestine, causing inflammation and damage. This can lead to malabsorption of nutrients, leading to various symptoms such as diarrhoea, weight loss, fatigue and, in severe cases, long-term complications. Non-celiac gluten sensitivity is a condition in which individuals experience gastrointestinal symptoms such as bloating, abdominal pain and diarrhoea after consuming gluten. Unlike celiac disease, it does not lead to an autoimmune response or damage to the small intestine. The precise mechanisms behind non-celiac gluten sensitivity are not fully understood, making diagnosis difficult.

[0007] To prevent gluten-related disorders, people need to follow a regular gluten-free diet. This includes avoiding wheat, barley and rye and reading food labels carefully to identify hidden sources of gluten. Choosing naturally gluten-free foods such as fruits, vegetables, lean proteins, and gluten-free cereals can ensure a balanced diet. Public awareness and gluten detection play a vital role in preventing gluten exposure, as individuals need to be informed about safe food choices, cooking practices and crosscontamination risks. Various methods are used in the field of gluten detection. Enzyme- Linked Immunosorbent Assay (ELISA) is a common technique that uses antibodies to detect gluten proteins. Polymerase chain reaction (PCR) is a molecular biology method that identifies gluten DNA, while mass spectrometry measures proteins based on their mass and charge. Rapid gluten detection kits provide rapid results by offering on-site testing using immunochromatographic analyses. Near Infrared Spectroscopy (NIRS) measures light absorption for rapid gluten content detection. Liquid Chromatography- Mass Spectrometry (LC-MS) combines liquid chromatography with mass spectrometry to accurately identify and quantify gluten peptides.

[0008] Medical sensors are another technology that is considered to be used to measure the level of gluten in the human body. A medical sensor is a complex device designed to measure or detect specific physiological or biological information from the human body or other living organisms. These sensors play an important role in healthcare by providing real-time data vital for diagnosing, monitoring and treating various medical conditions. Used in a wide range of applications and medical environments, from home healthcare to hospitals, medical sensors exhibit essential characteristics such as sensitivity, accuracy, biocompatibility, wireless connectivity, portability and durability. These sensors are designed for precision and accuracy, enabling healthcare professionals to rely on the data for accurate diagnosis and decision-making. Portability is another vital feature of medical sensors, designed to be particularly lightweight and unobtrusive, allowing people to continue their daily activities while using them. Highly sensitive devices and methods such as PCR, NIRS, and LC-MS used in the state of the art are useful for gluten determination. However, since these devices and methods require high-cost equipment, time and trained operators, these applications that currently measure gluten value from blood do not provide enough practical use in the patient's daily life.

[0009] Antibody-based ELISA and immunochromatographic rapid test kits in the present art are practical analytical methods for gluten determination. However, the main problem with gluten determination with these methods is the inability to determine the gluten content in heat-treated food samples, which causes conformational changes in antigen masking or modifying antibody recognition sites [1 -3], Therefore, these methods fail to meet the sensitivity and accuracy criteria, which are critical features of medical sensors.

[0010] Due to the limitations and inadequacies of the solutions in the current technique, the impracticality of the analytical devices and methods used due to the complex and costly steps involved, and the inadequacy of the practical methods to provide reliable results, a development in the field of medical measurement systems to be used for gluten determination has become necessary.

[0011] Brief Description and Objectives of the Invention

[0012] The medical measurement device subject to the invention is a medical measurement system that can be used by people with celiac disease or other gluten sensitivity, which measures the gluten level in the blood practically. The medical measurement system in question includes a strip sensor formed by combining nanoflower-based composite reference sensor and polymeric liquid membrane sensors, and an electronic circuit in which this strip sensor can be integrated. The nanoflowers used in the measurement system are Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin nanoflower structures that form gluten-sensitive electroactive materials to be used in the structure of the sensors.

[0013] Considering that the reference sensor (electrode) formed on the strip produces a constant potential, the potential changes occurring in the system will occur depending on the gluten concentration in the sample to be dripped on the gluten selective potentiometric biosensor in strip form, and accordingly, both the amount of gluten in standard solutions and the amount of gluten in real samples will be quantitatively determined.

[0014] One object of the invention is to facilitate the diagnosis of gluten-based disorders. For this purpose, the device, which consists of uncomplicated and small-sized parts, facilitates practical and individual diagnosis. Furthermore, the low cost of each analysis provides an advantage in regular use.

[0015] The invention aims to increase the nutritional safety of the person. In addition to the ease of use of the medical measurement system in question, the sensitive and accurate results obtained from the tests serve this purpose.

[0016] With the use of this medical measurement system, public awareness of celiac disease and gluten intolerance can be strengthened and the understanding of such health problems can be improved. It improves the quality of life of people living with gluten disorders by eliminating the loss of time and reliance on costly devices to monitor daily gluten levels. In addition, it contributes to the rapid and reliable determination of gluten content of packaged products in the food industry and contributes to the gluten labelling of foods.

[0017] Description of Figures

[0018] Figure 1. Strip sensor components

[0019] Reference Numbers

[0020] 1 . Polymeric strip surface

[0021] 2. Conductor rods

[0022] 3. Insulation

[0023] 4. Gluten selective sensor

[0024] 5. Gluten selective strip sensor Detailed Description of the Invention

[0025] The invention relates to a portable, easy-to-use, low-cost medical measurement system for measuring the gluten level in blood, which provides precise and highly accurate results. The measuring device in question comprises a gluten selective strip sensor (5) and an electronic system into which it is integrated.

[0026] The mentioned gluten selective strip sensor (5) consists of a solid reference sensor and a biosensor in the form of a polymeric liquid membrane or composite prepared with a nanoparticle-based gluten-sensitive electroactive material.

[0027] The nanoflower-based gluten-sensitive electroactive material to be used in the structure of gluten selective sensors (4) enables the detection of gluten in the sample solution and is gliadin-inorganic hybrid nanoflowers containing Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin.

[0028] The first of the gluten selective sensors (4) preferred in the invention contains different ratios of nanoflower-based electroactive material, polyvinyl chloride (PVC), ortho- nitrophenyl octylether (o-NPOE), dibutyl phthalate (DBP), dioctyl sebacate (DOS), dioctyl phthalate (DOP), sodium tetraphenylborate (NaTPB) and potassium tetrakis chlorophenyl borate (KTCIPB).

[0029] The second of the gluten selective sensors (4) preferred in the invention comprises different ratios of the sensor components of electroactive material, graphite, multiwalled carbon nanotube (MWCNT) and paraffin oil.

[0030] The reference sensor is a silver / silver chloride electrode.

[0031] The method of solid reference sensor material preparation includes the following steps: i. Dissolution of 950 mg polyvinylalcohol (PVA) in 20 mL deionised water at 60 °C using a magnetic heater / stirrer ii. adding 50 mg potassium chloride (KCI) and stirring for 1 hour, iii. then allowing the mixture to cool, iv. 50 mg graphite, 35 mg epoxy and 15 mg hardener will be homogenised by mixing with 1 mL tetrahydrofuran (THF), adding 1.0 mL of the cooled PVA-KCI mixture to this mixture and mixing and removing the solvent components of this mixture.

[0032] The method of manufacturing said gluten selective strip sensor (5) and combining it with a solid reference electrode comprises the following steps: i. Pressing 2 mm wide copper conductor rods (2) onto a polymeric strip surface (1 ) printed from a 3D printer with an aspect ratio of 2 cm / 4 cm and attaching them with the help of a suitable polymeric adhesive ii. applying insulation (3) over the polymeric strip surface (1 ), leaving 0.5 cm of the lower ends of the conductor rods (2) exposed, iii. electrochemical coating of the exposed end of the conductor rod (2), which will serve as a solid reference sensor, with silver by immersing it in 0.1 M AgNO3 solution through which nitrogen gas is passed to prevent the dissolved oxygen from forming oxide, iv. After the silver plating process is completed, the polymeric strip surface (1 ) is immersed in 0.1 M HCI solution through which nitrogen gas is passed to prevent the dissolved oxygen from forming oxide, and the silver surface is converted into silver chloride by the electrochemical plating process, v. pressing the solid reference sensor material and attaching it to the silver chloride-coated surface, vi. insulation (3) of the edges of the gluten selective sensor (4) with a suitable polymeric adhesive, vii. Forming a rough conductive solid-state contact surface by mixing 50 mg graphite, 35 mg epoxy and 15 mg hardener with 1 mL tetrahydrofuran (THF) on the lower 0.5 cm section of the conductor rod (2), which will serve as the main body of the gluten selective sensor (4) on the polymeric strip surface (1 ), viii. attachment on this surface of the sensor form containing the components of the gluten selective sensor (4) in a composite or polymeric liquid structure decided as a result of potentiometric performance data, ix. obtaining the sensor response from the sensor's active surface by applying insulation (3) with a suitable polymeric adhesive to the open parts of the sensor at the junction points of the copper conductor rod (2) and the solid contact. The electronic circuit consists of a microcontroller module, a D / A module and a power management module. The microcontroller module controls an external digital-to- analogue converter; the amplifier circuit provides a constant and stable output between the working electrode (gluten selective strip sensor (5)) and the reference electrode and automatically regulates the potential shift during the electrochemical interaction. The medical measurement system shows the meaningful reading of the data obtained from the sensor by the patient.

[0033] REFERENCES

[0034] 1- Osorio, C. E., Mejias, J. H. ve Rustgi, S. 2019. "Gluten detection methods and their critical role in assuring safe diets for celiac patients", Nutrients, 11 (12), 2920.

[0035] 2- Loria Gutierrez, A., Blanco Barrantes, J. ve Ramirez Elizondo, G. 2021. "Validation of an enzyme-linked inmunosorbent assay (ELISA) kit for the quantification of gliadins in medicines and cosmetics", International Journal of Modern Pharmaceutical Research, 5(2), 17-21.

[0036] 3- Matic, J. J., Mandic, A. I., Beljkas, B. M., Milovanovic, I. L. ve Jovanov, P. T. 2008. "Analytical validation of an enzime-linked immunosorbent assay for the determination of gluten", Food Processing, Quality and Safety, 35(4), 183-188.

Claims

CLAIMS1. A medical measurement system to be used to measure gluten levels in the blood characterised by the following: a. A gluten selective sensor (4) in a polymeric liquid membrane structure containing polyvinyl chloride (PVC), ortho-nitrophenyl octylether (o-NPOE), dibutyl phthalate (DBP), dioctyl sebacate (DOS), dioctyl phthalate (DOP), sodium tetraphenyl borate (NaTPB), potassium tetrakis chlorophenyl borate (KTCIPB) and nanoflower-based electroactive material containing Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin; or a solid gluten selective sensor (4) in composite structure containing graphite, multi-walled carbon nanotube (MWCNT), paraffin oil and nanoflower based electroactive material containing Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin; or a gluten selective strip sensor (5) containing a silver / silver chloride electrode reference sensor. b. An electronic circuit consisting of a microcontroller module, D / A module and power management module2. A medical measurement system for measuring gluten level according to claim 1 , characterised in that the gluten selective sensor (4) is a gluten selective biosensor in a polymeric liquid membrane structure containing polyvinyl chloride (PVC), ortho-nitrophenyl octylether (o-NPOE), dibutyl phthalate (DBP), dioctylsebacate (DOS), dioctyl phthalate (DOP), sodium tetraphenyl borate (NaTPB), potassium tetrakis chlorophenyl borate (KTCIPB) and nanoflower-based electroactive material containing Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin.

3. A medical measurement system for measuring gluten level according to claim 1 , characterised in that the gluten selective sensor (4) in the system is a solid reference sensor in a composite structure comprising graphite, multi-walled carbon nanotube (MWCNT), paraffin oil and nanoflower-based electroactive material containing Cu3(PO4)2@gliadin and Zn3(PO4)2@gliadin.

4. A method for the preparation of solid reference sensor material characterised by the following steps:i. Dissolution of 950 mg polyvinylalcohol (PVA) in 20 mL deionised water at 60 °C using a magnetic heater / stirrer ii. adding 50 mg potassium chloride (KCI) and stirring for 1 hour, iii. then allowing the mixture to cool, iv. 50 mg graphite, 35 mg epoxy and 15 mg hardener will be homogenised by mixing with 1 mL tetrahydrofuran (THF), adding 1.0 mL of the cooled PVA- KCI mixture to this mixture and mixing and removing the solvent components of this mixture.

5. A method of manufacturing a gluten selective strip sensor (5) and combining it with a solid reference electrode, characterised in that the method comprises the following steps: i. Pressing 2 mm wide copper conductor rods (2) onto a polymeric strip surface (1 ) printed from a 3D printer with an aspect ratio of 2 cm / 4 cm and attaching them with the help of a suitable polymeric adhesive ii. applying insulation (3) over the polymeric strip surface (1 ), leaving 0.5 cm of the lower ends of the conductor rods (2) exposed, iii. electrochemical coating of the exposed end of the conductor rod (2), which will serve as a solid reference sensor, with silver by immersing it in 0.1 M AgNO3 solution through which nitrogen gas is passed to prevent the dissolved oxygen from forming oxide, iv. After the silver plating process is completed, the polymeric strip surface (1 ) is immersed in 0.1 M HCI solution through which nitrogen gas is passed to prevent the dissolved oxygen from forming oxide, and the silver surface is converted into silver chloride by the electrochemical plating process, v. pressing the solid reference sensor material and attaching it to the silver chloride-coated surface, vi. insulation (3) of the edges of the gluten selective sensor (4) with a suitable polymeric adhesive,vii. Forming a rough conductive solid-state contact surface by mixing 50 mg graphite, 35 mg epoxy and 15 mg hardener with 1 mL tetrahydrofuran (THF) on the lower 0.5 cm section of the conductor rod (2), which will serve as the main body of the gluten selective sensor (4) on the polymeric strip surface (1 ), viii. attachment on this surface of the sensor form containing the components of the gluten selective sensor (4) in a composite or polymeric liquid structure decided as a result of potentiometric performance data, ix. obtaining the sensor response from the sensor's active surface by applying insulation (3) with a suitable polymeric adhesive to the open parts of the sensor at the junction points of the copper conductor rod (2) and the solid contact.

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