Blood sugar reagent strips are key consumables used to detect blood sugar concentrations. Their production process involves multiple precision links. The following is a detailed introduction from aspects such as core steps and technical points:
1. Preparation of raw materials
1. key raw material
1)Enzymes: Glucose oxidase (GOD), glucose dehydrogenase (GDH), etc., used to catalyze the glucose reaction to produce detectable signals.
2)Coenzyme/electronic mediators: such as ferricyanide, ferrocene derivatives, etc., help transfer electrons and amplify reaction signals.
3)Buffer system: phosphate, Tris-HCl, etc. to maintain the pH stability of the reaction environment.
4)Solid phase carrier: usually nitrocellulose membrane, polyester membrane, etc., used to immobilize reagents and form reaction channels.
2. auxiliary materials
Insulating layers, conductive layers (such as carbon paste, silver paste), protective films, etc., are used to build the physical structure of the reagent strip.
2. Chip/substrate preparation
1. basis-selecting
Polyester (PET) or plastic sheets are commonly used as the substrate and require good flatness and chemical stability. Each company can choose different thicknesses of PET based on its own design.
2. conductive layer printing
1)Carbon paste and silver paste are printed on the substrate respectively through screen printing technology to form electrodes (working electrode, reference electrode, counter electrode).
2)Silver paste is used to improve electrical conductivity, and carbon paste is used to carry enzymes and reaction reagents.
3. drying and solidifying
The printed substrate needs to be dried at a constant temperature (such as 60 - 80 ℃) for several hours to ensure that the conductive layer adheres firmly.
3. Reagent coating and curing
1. Mixing of enzymes and reagents
Dissolve glucose oxidase/dehydrogenase, coenzyme, buffer, etc. in buffer solution in proportion to form a uniform reagent slurry.
2. precision coating
1)Use microfluidic coating equipment or inkjet printing technology to accurately coat the reagent slurry on designated areas of the electrode surface.
2)The coating accuracy needs to be controlled at the micron level to ensure the uniformity of the reagent in the reaction area.
3)To talk about a small point here, the mixture of enzymes and reagents has some viscosity. Choosing a good equipment is very particular. In addition to 2), the accuracy of reagent volume is also very important.
3. curing treatment
1)After coating, it needs to be dried and cured at low temperature (such as 4 ℃) or in a vacuum environment to avoid enzyme deactivation. This process is not unique, and each company can explore the process based on actual conditions.
2)Some processes require lyophilization to extend the shelf life of the reagent strips. This process is not unique, and each company can explore the process based on actual conditions.
4. Structural assembly
1. lamination process
1)Attach an insulating layer (to prevent short circuiting of the electrode) and a protective film (to cover the reaction area) on the substrate in turn.
2)Each layer is fixed by hot pressing or adhesive to form a complete reagent strip structure.
2. cutting and forming
A precision cutting machine is used to cut a large-area substrate into individual reagent strips, the size usually being a few millimeters wide and a few centimeters long.
5. Quality inspection and calibration
1. performance test
1)Sensitivity test: Use glucose standard solutions with different concentrations to test the response value of the reagent strip to ensure that the detection range (such as 1.1 - 33.3mmol/L) meets the requirements.
2)Repeatability test: Repeat the test on samples at the same concentration, and the error must be controlled within ± 15%(refer to ISO 15197 standard).
3)Anti-interference test: Detect the interference of vitamin C, uric acid and other substances on the results to ensure accuracy.
2. Calibration and calibration
Each batch of reagent strips needs to be calibrated with a calibration solution (a solution with a known glucose concentration) to generate a calibration curve that is used to convert the electrical signal into a blood sugar concentration value.
6. Packaging and sterilization
1. sealed package
1)Individual reagent strips are packed into aluminum foil bags with desiccant to prevent moisture from failing.
2)Put multiple reagent strips into plastic boxes and match them with moisture-proof packaging.
2. sterilization processing
Some processes require ethylene oxide sterilization or ultraviolet disinfection to ensure a sterile environment, especially medical grade reagent strips.
VII. Finished product inspection and warehousing
1. sampling test
Samples are taken according to batches, and the sensitivity, accuracy, shelf life and other tests are repeated. After passing the test, they are labeled and put into storage.
2. Expiration date labeling
The validity period of reagent strips is usually 1 - 2 years and must be used within a specified time (such as 3 months) after opening.
8. Technical difficulties and key control points
1. Maintenance of enzyme activity: The temperature and humidity of the production environment need to be strictly controlled to avoid detection errors caused by enzyme inactivation.
2. Microfluidic accuracy: Small deviations during the coating and assembly process will affect blood sample absorption and reaction efficiency, relying on high-precision equipment.
3. Anti-interference ability: Reduce the influence of endogenous substances (such as uric acid) and exogenous substances (such as drugs) through formulation optimization (such as adding anti-interference agents).
4. Mass production consistency issues: By controlling the environment and introducing automated instruments, improving the accuracy of instruments and equipment facilities, reducing human operations, and producing products with consistent quality and efficient output.
9. Application scenarios and development trends
1. Main applications: Self-blood sugar monitoring of diabetic patients, hospital clinical testing, scientific research experiments, etc.
2. Technology upgrade: Currently moving towards more minimally invasive (such as non-invasive testing), high sensitivity (expanded testing range) and integration (wireless connection to blood glucose meters).
Through the above processes one to seven, the blood sugar reagent strip can convert the glucose concentration in the blood into an electrical signal or optical signal to achieve rapid detection. The process details of different manufacturers may differ, but the core principles and quality control standards are basically the same.
