For active medical device products, the effectiveness of the production cleaning process can directly affect the reliability of the final product. If the intermediate products are cleaned, the cleaning methods and requirements shall be clearly defined, and the cleaning effect shall be verified. The author found that when the environmental requirements were not strictly controlled in the production process or the cleaning products were not strictly followed by the operating instructions, there would be a deterioration in the performance of the products due to the introduction of pollutants. For example, chemical impurities can lead to product corrosion, dust particles can form a conductive path and cause product leakage or short circuit. Once the pollutant is introduced into the medical device product, the risk of damage will appear after the product is put into use, which will affect the treatment effect of the patient and even endanger the patient's life and health. In this paper, the pollutants introduced in the production of active medical devices are analyzed, and the selection of cleaning solvents and cleaning methods are discussed. If passive medical devices involve cleaning agents and welding processes discussed below, manufacturers can also make reference. In order to evaluate the effectiveness of the cleaning process of active medical device products, it is necessary to understand the inherent characteristics of the pollutants introduced in the production process and the cleaning solvents and cleaning methods used to effectively remove or reduce the pollutants.
Types and sources of pollutants
1.1 Type of contamination The contaminants introduced during the production of active medical devices can be classified into two types: polar and non-polar. polar contaminants are present in the form of ions in an aqueous solution, and can be removed by water, an aqueous solvent, alcohol or acetone, such as an activator in the flux and a salt on the trace. The polar contaminants are essentially inorganic compounds. Non-polar contaminants are not dissolved in water unless a detergent or a soaping agent is added to the water, such as resin, grease, and oil. Non-polar contaminants are typically subjected to a cleaning process using a chloride solvent or a fluoride solvent. 1.2 Sources of common contaminants In a humid environment, ionic contaminants may cause a metal-to-metal displacement plasma reaction between the insulator or the conductor to cause a failure of the product or damage to the product. This phenomenon, if it occurs on a cardiac pacemaker product, may therefore implement a large-range product recall. Therefore, the implantable active medical device is used under high humidity conditions to ensure the eradication of ionic contaminants. The active medical device contaminants are mainly derived from welding, bare hands contact, plating, spraying, and the like. 1. 2.1 Flux The welding process is a common production process of active medical devices, and is a special process. In the manufacture of active medical devices, the flux is one of the most common pollutants in the circuit. The main function of the flux is to reduce the surface tension of the solder and improve the welding performance. At the same time, the surface defects of the oxides, the sulfides and the metal surfaces of the solder and the surface of the solder to be welded are removed, so that the necessary cleanliness of the metal surface is achieved, and good adhesion is provided for the welding. There are a wide variety of flux, commonly used fluxes include pure resin, activated resin, and water-soluble flux. In the industry, it is generally accepted that the pure resin flux will not damage the integrated circuit board as long as it is properly cleaned. Once the resin residue is not effectively removed, the resin residue will adsorb the ionic impurities, and the resin will form a layer of hard-to-detect insulating film, so that the surface of the weld appears to be in good condition but is in fact a false welding or a virtual welding. In the industry, the activated resin is used as the flux, and the main reason is that it is easier to remove the oxide than the pure resin. The stronger the active resin activator, the stronger the welding position and less the welding defect. It is noted that if the residue is not effectively removed after the welding, it will form a corrosion or short circuit at the product welding. The water-soluble flux uses a wetting agent instead of the resin to reduce the surface tension of the solder and improve the welding performance. However, it is more corrosive than the resin-based flux, and all the residues must be completely eliminated after the welding. Most of the production enterprises mainly use the resin-based flux, mainly because the water-soluble flux will remain a large amount of ionic contaminants after the welding. 1. 2. 2 Manual In the process of the production of medical device products, if the bare hands are operated, a hand is left on the surface of the product. The trace is the main source of salt, grease and oil stain on the surface of the product. In the wet environment, the salt is dissolved into free-moving high sodium ions and chloride ions, resulting in electrical displacement, leakage or reduced electrical insulation properties of the metal. The trace salt is a water-soluble substance soluble in water, alcohol, acetone, fluoride or chlorine compound solution, and the fluoride or chlorine compound solution can effectively remove grease and oil stain. The medical device production enterprise should adopt a cleaning process capable of simultaneously removing polar and non-polar contaminants, and the production operation process shall be as close as possible to prevent the hand track from affecting the performance of the product. Other common impurities are dust, residue and insoluble particles. Of course, the medical device products may also be contaminated during use. In order to select an effective cleaning process, the medical device manufacturer should be fully aware of the type of contamination that may be introduced during the production process. This can facilitate the enterprise's in-depth understanding of the problems that may occur during the manufacturing process and take the necessary measures to ensure the production of reliable products.
2.1 the basic requirement of cleaning agent selection is to select and use suitable cleaning solvent as one of the important indexes in the process of evaluating cleaning process. Firstly, the compatibility between clean solvent and cleaned substance should be considered, and the cleaning solvent used for cleaning electronic parts and integrated circuit board should have the characteristics of non-conductivity, non-corrosiveness and not reducing the quality of cleaned matter. Second, the chemical purity of detergent and the cleanliness of containers should be considered, including the storage of raw materials and containers for cleaning operation. If the cleaning solvent is incompatible with the cleaned parts, it will reduce the performance of the product and even cause damage to the product. For example, electrolytic capacitors are easily damaged by halogen solvents. Once the halide cleaner becomes liquid or gaseous and diffuses into the capacitor, it will corrode a few months later and cause the product to fail. To prevent this from happening, alcohol should be used as a cleaner for capacitors instead of halides. Cleaning electronic parts and integrated circuit boards are available with polar cleaners, non-polar cleaners, or mixtures of two different types of cleaners. Non-polar cleaners can dissolve oil, grease and some resins, polar cleaners dissolve polar residues such as hand salt, activators in resin fluxes. To clean both polar and nonpolar pollutants, chlorides and fluorine cleaners can be added with methanol, isopropanol, acetone, deionized water or other suitable liquid solvents. 2.2 commonly used detergents for the production of medical devices include alcohol, methanol, isopropanol, chlorides, fluoride solvents and deionized water, the main cleaning uses of which are shown in Table 1.
Methanol and isopropanol are considered as natural solvents for solid resin flux. Studies have shown that alcohol is probably the best cleaning agent for ion pollutants at present, while methanol and alcohol are easier to remove ion residues than isopropanol. Chlorides detergents have higher boiling point and higher cleaning power than fluoride detergents, so chloride cleaners are often used for low temperature cleaning. Fluoride detergents have low boiling point and average cleaning ability. They can be used as steam detergents or cryogenic detergents. Trichloromethane and trichloroethylene are commonly used chloride cleaners, which are mainly used to remove resin flux residues. Trichloromethane produced by Dow Corning is one of the common varieties. Fluoride detergents (such as trichlorofluoroethane) are widely used in the medical device industry, mainly because they clean grease and oil, but their cleaning ability to resin flux is general. Freon produced by DuPont is one of the common varieties. Using Freon cleaner to clean the product alone may not be able to effectively remove the polar contaminants, such as trace salt, flux activator, often need alcohol or deionized water for re-cleaning. It is important to note that Freon cleaners react with silicone rubber, polystyrene, acrylic plastics, zinc, aluminum, etc. When choosing Freon as cleaning agent, the manufacturer should consider whether it has chemical effect with cleaned product. Water cannot dissolve the resin flux, but it can dissolve the water-soluble flux. Deionized water is usually used to remove residual ionic pollutants from water-soluble flux. Deionized water and alcohol are generally used as cleaning media for the final process to avoid the presence of chlorides and fluoride cleaner residues.
Common cleaning methods for medical device products include manual cleaning, automatic cleaning and combination of the two methods. Manual cleaning method is mainly manual cleaning tools, according to the scheduled requirements of cleaning products. Commonly used cleaning tools can be sprayed with cleaning agent and washing water spray gun, brush, nylon cleaning block and so on. The automatic cleaning method is the way that the automatic special equipment completes the whole cleaning process automatically according to a certain procedure, the common way is ultrasonic cleaning. Because there are some individual differences among different people in manual cleaning, which leads to some uncontrollability of cleaning process, it is recommended to use automatic cleaning method when conditions permit. Ultrasonic cleaning is widely used in medical equipment industry, combined with proper cleaning agent can improve the cleaning effect of pollutants. The high frequency oscillation signal from the ultrasonic generator is transmitted to the medium (cleaning solvent) by converting the transducer into the high frequency mechanical oscillation. The ultrasonic wave in the cleaning liquid dredge the forward radiation of the dense phase. Tens of thousands of tiny bubbles with a diameter of 50 ~ 500 μ m are produced by the flow of liquid, and the tiny bubbles in the liquid vibrate under the action of sound field. These bubbles are formed and grown in the negative pressure region of ultrasonic longitudinal propagation, while in the barotropic region, when the sound pressure reaches a certain value, the bubble increases rapidly and then closes suddenly. And when the bubble closes, it produces a shock wave, and it produces thousands of atmospheric pressures around it, destroying insoluble pollutants and dispersing them in the cleaning fluid, and when the group particles are wrapped in oil and adhere to the surface of the cleaning piece, the oil is emulsified. Solid particles and separation from the cleaning parts to achieve the purpose of purification. In this process known as "cavitation", bubble closure can form several degrees of high temperature and more than 1000 pressure instantaneous high pressure. Before using ultrasonic cleaning, the manufacturer should evaluate the influence of ultrasonic vibration frequency on the performance of cleaned parts and cleaning agents. At the same time, the cleaning tank should be verified whether the ultrasonic does not touch the area or the ultrasonic cleaning of the product is not uniform phenomenon. Some studies have shown that the optimum frequency of ultrasonic cleaning for cavitation is (20 ~ 25) KHz, and the optimum temperature is (55 ~ 60) C.).
Cleaning is a complex process. Therefore, enterprises should do clean verification and form clean process operation documents. The operation document should specify the maximum load per cleaning and the cleaning times of the solvent to prevent the contaminants from being reattached to the cleaned substance; if the contaminants are found to be re-attached to the washed substance, the clean solvent may be used for re-cleaning; The maximum and minimum cleaning times should be determined, and the location of the cleaning material should be considered to meet the maximum cleaning area; the cleaning agent variety and cleaning concentration should be determined; and the cleaning time and cleaning temperature (if any) should be determined. The position operator shall be trained and familiar with the cleaning operation process, strictly follow the operation documents and make clean records, and maintain the cleaning equipment on a regular basis.