Method for rapidly detecting residual amount of EO (Ethylene Oxide) in sterilized medical instrument

Abstract

The invention belongs to the technical field of medical instrument detection, and particularly relates to a method for rapidly detecting EO residual quantity in a sterilized medical instrument, which comprises the steps of sample acquisition, rapid extraction, specific color development or signal reaction, signal interpretation and content quantification, process parameter control and the like. And parameters of each link are optimized according to the characteristics of different types of sterilized medical instruments, and meanwhile, perfect quality control and calibration measures are set, so that the EO residual quantity is rapidly, accurately and simply detected, the accuracy and reliability of a detection result are effectively improved, and the method has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of medical device testing technology, specifically a rapid detection method for EO residue in sterilized medical devices. Background Technology

[0002] In the field of medical device sterilization, ethylene oxide (EO) has been widely used due to its highly efficient sterilization effect. However, EO itself is toxic, and when its residual amount in medical devices is too high, it may pose a serious threat to the health of users. Therefore, strict control over the residual amount of EO is particularly important.

[0003] Currently, existing methods for detecting EO residues have some limitations in practical applications. For example, the detection cycle is long, often taking a lot of time to obtain results, making it difficult to meet the needs of rapid detection; the operation is complex, involving many cumbersome steps and professional operation requirements, and is highly dependent on the skill level of the operators; and the equipment requirements are high, requiring the use of complex and expensive professional equipment to complete the detection, which limits the convenience and scalability of the detection.

[0004] In summary, current EO residue detection technologies have room for improvement in terms of efficiency, convenience, and applicability. Therefore, this invention provides a rapid detection method for EO residue in sterilized medical devices. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, at least one technical problem raised in the background art is solved.

[0006] The technical solution adopted by this invention to solve its technical problem is: the rapid detection method for EO residue in sterilized medical devices according to this invention, comprising the following steps:

[0007] S1. Sample Acquisition:

[0008] Obtaining representative analytical samples from the sterilized medical devices to be tested is the fundamental step in the testing process. Depending on the characteristics of different medical devices, appropriate acquisition methods are selected. For example, immersion elution is suitable for devices where residues can be effectively extracted by immersion in a solution; surface wiping is convenient for collecting residues on the device surface; cutting and crushing can be used for solid, block-shaped devices for subsequent processing; pulverization is suitable for some brittle devices that are easy to crush; and direct extraction of internal gas is applicable to devices containing internal gas and reflecting the overall residue situation. Simultaneously, the sample volume is precisely controlled according to the expected detection limit and the type of medical device to ensure accurate testing without excessive consumption of sample resources. For example, the mass of solid samples is limited to 0.1 g to 50 g, the volume of liquid samples is controlled to 0.5 ml to 100 ml, and the volume of gas samples is controlled to 10 ml to 1000 ml. Furthermore, the entire sample acquisition process must be completed within a specified time (total time not exceeding 5 minutes) to ensure testing efficiency.

[0009] S2, Rapid extraction of ethylene oxide residues:

[0010] The acquired sample is placed in a closed extraction system, and rapid and efficient extraction techniques are employed. Dynamic headspace extraction utilizes an inert carrier gas to purge and release EO from the sample, transferring it to the extract phase. Static headspace extraction achieves a similar effect based on the gas-liquid equilibrium principle. Microwave-assisted extraction uses microwave energy to accelerate the transfer and separation of substances. During the extraction operation, appropriate preset conditions must be set, such as temperature, time, and flow rate, to ensure the extraction process is completed within a reasonable time (total time not exceeding 45 minutes, preferably not exceeding 30 minutes). After extraction, depending on the actual detection requirements, the extract phase can be separated to remove impurities, concentrated to increase concentration, or diluted to bring it within a suitable detection range, preparing it for subsequent color development or signal reactions.

[0011] S3, specific colorimetric or signal response:

[0012] The EO extract is mixed with a pre-prepared detection reagent, allowing the EO to react specifically with the reagent, generating a detectable signal change. A variety of detection reagents are available, including chromogenic reagents based on pyridine ring-opening or nucleophilic substitution reactions, which produce color changes through specific chemical reactions to visually indicate the presence and content of EO; and complexation chromogenic reagents based on sodium thiosulfate or thiocyanate. Different reagents are suitable for different detection scenarios and needs. Strict control of the reaction time (not exceeding 20 minutes, preferably not exceeding 10 minutes) ensures that the reaction proceeds fully without introducing other interfering factors due to excessive time, thus ensuring the accuracy of the detection results.

[0013] S4. Signal Interpretation and EO Content Quantification:

[0014] This step involves visually observing or using portable, simple testing instruments to read the signal values ​​generated by the aforementioned specific reactions, and then converting them into ethylene oxide residue. The signal interpretation methods are flexible and diverse. Visual colorimetric interpretation is suitable for situations where color changes are obvious and easily distinguishable by the naked eye. Portable photometers / colorimeters, on the other hand, utilize the high precision of the instrument to achieve more accurate interpretation. Furthermore, depending on different detection principles and methods, standard curve methods, standard addition methods, etc., can be used to quantify EO content. The entire process must also be completed within a short time (total time not exceeding 5 minutes) to improve the overall timeliness of the detection.

[0015] S5. Process parameter control:

[0016] Strict and precise control of key process parameters throughout the entire testing process, such as extraction time, reaction temperature, reagent concentration, sample volume, and pH value, is crucial for ensuring the consistency and reliability of test results. Employing automated or semi-automated equipment for parameter control effectively reduces errors caused by human operation, improving repeatability and accuracy. Furthermore, the optimization of process parameters is not arbitrary but requires scientific pre-experiments and orthogonal experimental design to determine the optimal parameter combination. It also comprehensively covers the standardized management of reagent storage conditions (such as protection from light, low temperature, and dry storage), the reasonable scheduling of instrument calibration frequency (regular calibration based on different instrument characteristics), and strict adherence to standard operating procedures by operators. These multiple dimensions ensure the scientific validity and stability of the testing method.

[0017] Preferably, sample acquisition and pretreatment: In the sample acquisition stage, in addition to the basic acquisition methods mentioned above, further pretreatment operations can be performed on the sample to improve the subsequent detection effect. For example, the medical device to be tested can be pretreated by exposing it to clean air at 20°C to 30°C for 1 to 10 minutes, which helps to volatilize some volatile residues on the surface of the device, making the subsequent detection more focused on the residual EO inside; or the medical device sample can be directly immersed in 10 ml to 50 ml of preheated extraction solvent. The extraction solvent can be selected according to factors such as the material of the device, such as deionized water, ethanol, and isopropanol. The preheating temperature range is set to 30°C to 60°C, and the immersion time is controlled to 5 minutes to 30 minutes. During this immersion process, intermittent oscillation or ultrasonic treatment can also be performed, which can further promote the dissolution of residues and improve the extraction efficiency. For solid samples, they can be cut into small pieces or ground into powder to increase their surface area, facilitating better contact with the extraction solvent during subsequent extraction and thus better releasing ethylene oxide residues. For liquid samples, filtration or centrifugation can remove any particulate or colloidal impurities that may be present, avoiding interference with subsequent detection. The entire sample pretreatment process should not exceed 15 minutes, preferably no more than 10 minutes, to ensure the effectiveness of pretreatment while minimizing time consumption and improving overall detection efficiency.

[0018] Preferably, dynamic headspace extraction (VCE) is used. When employing VEE, the sample should be placed in a borosilicate glass headspace vial with a capacity of 10 mL to 100 mL. This type of headspace vial possesses good chemical stability and sealing properties, providing a suitable environment for the extraction process. High-purity nitrogen, helium, or argon is used as the inert carrier gas, with a flow rate set between 50 mL / min and 400 mL / min. The purge temperature range is controlled between 60°C and 180°C, and the purge time range is between 5 min and 45 min. By appropriately adjusting these parameters, the rate and extent of ethylene oxide molecule release from the sample can be effectively controlled. Magnetic stirring or vortex oscillation can be performed during the purge process to further enhance the release efficiency of ethylene oxide from the sample matrix, allowing more ethylene oxide molecules to enter the gas phase and be subsequently captured. The purged EO gas is transferred to a collection device via connecting pipelines. The collection device uses adsorption tubes filled with adsorbents (such as Tenax GR, Tenax TA, etc.). These adsorbents have high specific surface area and good adsorption selectivity, enabling efficient capture of ethylene oxide molecules. Furthermore, the adsorption tubes undergo activation treatment before EO capture to ensure optimal adsorption performance. After capture, thermal desorption or solvent desorption can be performed directly, depending on the actual situation, to release the adsorbed ethylene oxide for subsequent reactions.

[0019] Preferably, ultrasonic-assisted extraction is used. If ultrasonic-assisted extraction is selected, the sample and extraction solvent must first be mixed. The extraction solvent can be selected from deionized water, phosphate buffer, ethanol, etc., depending on the sample characteristics. The mass ratio of extraction solvent to sample should be controlled within the range of 10:1 to 50:1 to ensure sufficient interaction between the two. The mixture is then placed in an extraction container with a capacity of 10 mL to 200 mL. The cavitation effect of ultrasound is used to accelerate the extraction process. The ultrasonic frequency is set to 30 kHz to 60 kHz, the power to 200 W to 1000 W, the extraction time to 3 minutes to 20 minutes, and the extraction temperature to 30°C to 60°C. During the extraction process, intermittent cooling can be performed as needed to prevent excessively high temperatures from adversely affecting the sample or the extraction effect. After extraction, the extract is rapidly filtered or centrifuged to remove solid particles, obtaining a pure extract phase for subsequent reaction with detection reagents.

[0020] Preferably, the colorimetric reagent is based on a pyridine ring-opening or nucleophilic substitution reaction: When a colorimetric reagent based on a pyridine ring-opening or nucleophilic substitution reaction is used, it consists of at least two components. The first component contains 4-(4-nitrobenzyl)pyridine (NBP) at a concentration controlled between 1.5% and 4%. NBP is one of the key components of this colorimetric reaction and can specifically react with ethylene oxide. The second component contains barbituric acid or its sodium salt at a concentration of 0.8% to 2%. It works synergistically with NBP to promote the colorimetric reaction. The third component can be a pH buffer solution to maintain the acidity and alkalinity stability of the reaction system and ensure that the reaction proceeds under suitable conditions. When using this product, mix it according to the preset volume ratio, and strictly control the volume ratio of EO extract to the mixed detection reagent in the reaction system to be 1:0.5 to 1:5. At the same time, accurately control the reaction temperature between 35℃ and 45℃, and the reaction time between 2 minutes and 8 minutes. By precisely controlling these parameters, the colorimetric reaction can be carried out fully and stably, so that the color depth of the generated colorimetric product has a good linear relationship with the concentration of ethylene oxide, which facilitates accurate signal interpretation and content quantification in the future.

[0021] Preferably, the complexing colorimetric reagent is based on sodium thiosulfate or thiocyanate: The complexing colorimetric reagent based on sodium thiosulfate or thiocyanate also consists of at least two components. The first component contains sodium thiosulfate at a concentration of 0.03M to 0.07M, which plays an important role in the complexation reaction; the second component contains mercuric thiocyanate or potassium thiocyanate at a concentration of 0.003M to 0.007M, which participates in the formation of the complex together with sodium thiosulfate; the third component contains ferric nitrate or ferric chloride at a concentration of 0.08M to 0.15M, mainly used to trigger the subsequent colorimetric reaction or enhance the colorimetric effect. When using this product, mix it according to the preset volume ratio. In the reaction system, control the volume ratio of EO extract to the mixed detection reagent to be 1:1 to 1:8. Precisely control the reaction temperature between 25℃ and 35℃ and the reaction time between 4 minutes and 12 minutes to ensure that the complexation colorimetric reaction can proceed normally and generate a product with characteristic color change, providing a reliable basis for the accurate detection of ethylene oxide residue.

[0022] Preferably, for signal interpretation and EO content quantification: when using a portable photometer / colorimeter for signal interpretation and EO content quantification, the selected instrument is a handheld or small benchtop device, characterized by its compact size and light weight (not exceeding 2 kg) and dimensions (not exceeding 30 cm x 20 cm x 10 cm), facilitating on-site testing in various locations. The instrument features a built-in high-brightness LED light source, providing stable and uniform illumination, and a sensitive photosensor, ensuring accurate capture of signals such as the absorbance of the colorimetric product. Simultaneously, it incorporates a microprocessor and data processing software for rapid processing and analysis of the acquired data, and includes one or more sample cells for convenient sample placement and testing. Its measurement range is from 0.001 to 2.000 absorbance units, with a resolution as high as 0.001 absorbance units, enabling precise measurement of weak signal changes. The repeatability error is less than 0.5% RSD, ensuring high accuracy and reliability of the measurement results. This allows for accurate conversion of the measured signal value into ethylene oxide residue using appropriate methods (such as the standard curve method or the standard addition method).

[0023] Preferably, the establishment and verification of the standard curve: The detection method of the present invention also includes the establishment and verification of the standard curve, which is crucial for accurately quantifying the residual amount of ethylene oxide. First, at least six ethylene oxide standard solutions of different concentrations should be prepared, covering the expected residual EO range, i.e., from 0.05 ppm to 200 ppm. High-purity ethylene oxide standards (purity not less than 99.9%) should be used during preparation, and the solutions should be serially diluted using a solvent consistent with the extraction solvent of the actual samples to ensure the accuracy and consistency of the standard solutions. At least three parallel samples should be prepared for each concentration of standard solution and independently tested to reduce errors and assess repeatability. The standard curve can be plotted using appropriate mathematical methods such as least squares linear regression, quadratic polynomial fitting, or four-parameter logic (4PL) fitting, requiring a correlation coefficient (R²) of... 2 The value should be no less than 0.998. Only in this way can the standard curve have a good linear relationship, and thus accurately convert the signal value of the test sample into the corresponding ethylene oxide residue.

[0024] Preferred quality control and calibration:

[0025] Blank control test (S11):

[0026] At the beginning and end of each batch of sample testing, and after every 20 samples tested, at least one blank control sample must be tested. The test result of the blank control sample should be lower than the detection limit of the method to verify whether the entire testing process is affected by external factors (such as reagent purity, environmental impurities, etc.), ensuring the accuracy and reliability of the test results. If the blank control sample shows an abnormal signal value, it indicates that there may be a problem with the testing environment or reagents, which needs to be investigated and corrected in a timely manner.

[0027] Positive control test (S12):

[0028] Similarly, at the beginning and end of each batch of sample testing, and after every 20 samples tested, at least one positive control sample of known concentration of ethylene oxide should be tested. The relative deviation between the test result of the positive control sample and the nominal value should be within ±15%. By comparing with the known concentration, the accuracy of the testing method and whether the instruments and equipment are in normal working condition can be verified. If the deviation exceeds the allowable range, it indicates that there may be a deviation in the testing process, and the corresponding steps need to be checked and adjusted.

[0029] Instrument performance verification (S13):

[0030] All instruments and equipment used in this method should undergo regular performance verification and calibration, with detailed calibration records maintained. Different instruments should have appropriate calibration cycles based on their characteristics and frequency of use. For example, critical measuring instruments, such as photometers, require more frequent calibration of key parameters like wavelength accuracy to ensure accurate and reliable data throughout the testing cycle and avoid errors in test results due to instrument performance fluctuations.

[0031] Reagent expiration date and storage conditions management (S14):

[0032] All testing reagents and standards must be stored strictly according to the manufacturer's instructions. For example, some reagents need to be stored away from light, while others need to be refrigerated at low temperatures. Their expiration dates should be checked regularly. New batches of testing reagents should be validated before use to ensure their quality and reaction performance meet testing requirements, preventing reagent quality issues from affecting the accuracy of test results.

[0033] Operator competency assessment (S15):

[0034] All operators should undergo systematic theoretical and practical training, master the standard operating procedures of this method, be familiar with the key points and precautions of each step from sample acquisition to result reporting, and undergo a competency assessment once a year to ensure that operators have sufficient professional competence and skill level, reduce errors introduced by improper human operation, and ensure the smooth progress of testing and the reliability of results.

[0035] Sample integrity and traceability (S16):

[0036] Throughout the entire process from sample acquisition to final result reporting, it is essential to ensure that sample identification is clear and complete, and that each sample can be clearly traced back to its origin, collection time, processing procedures, and other information. At the same time, all operational steps and test results should be recorded in detail to form a complete record file. This way, when problems arise or when a re-examination is required, relevant information can be quickly and accurately located, and the entire testing process can be traced and evaluated.

[0037] Internal quality control (S17):

[0038] Regularly use internal quality control samples to evaluate the precision and accuracy of the method, draw quality control charts, and monitor fluctuations in method performance by observing and analyzing the quality control charts. This allows for the timely detection of any abnormal changes that may occur during the testing process, such as deviations in test results or decreased repeatability, so that appropriate measures can be taken to adjust and improve the method in a timely manner, ensuring that the testing method always maintains stable and reliable performance.

[0039] Preferred optimization of testing parameters for different types of medical devices:

[0040] Single-use medical devices (S21):

[0041] For single-use medical devices, considering their material characteristics and usage, the immersion-elution method is the preferred method for sample acquisition. This method can comprehensively extract ethylene oxide residues from the surface and interior of the device. Ultrasonic-assisted extraction can be used in the extraction stage to accelerate the release and extraction of residues. In the colorimetric reaction stage, a pyridine-barbituric acid colorimetric reagent is used for rapid reaction. This reagent exhibits a specific colorimetric reaction with ethylene oxide, and the resulting product shows a clear and easily detectable color change. In the interpretation stage, absorbance is measured at 580 nm using a portable colorimeter. The amount of ethylene oxide residue is accurately determined based on the absorbance value and a standard curve, achieving rapid and accurate detection.

[0042] Implantable medical devices (S22):

[0043] Implantable medical devices typically have relatively complex structures and require higher accuracy in testing. Sample acquisition can be achieved through a solid-liquid immersion extraction method after cutting the device into smaller pieces. This increases the contact area with the extraction solvent, followed by immersion to fully extract residual ethylene oxide. Microwave-assisted extraction is used to accelerate mass transfer and improve extraction efficiency. A sodium thiosulfate-ferric nitrate colorimetric reagent is selected for a rapid reaction, generating a product with a characteristic color. The color change is analyzed using an intelligent image recognition system, and advanced image recognition technology accurately determines the color intensity, thereby quantifying the residual ethylene oxide and ensuring the reliability of the test results.

[0044] Extracorporeal circulation or blood purification devices (S23):

[0045] Due to the unique internal structure and function of extracorporeal circulation or blood purification devices, sample acquisition can be achieved through rinsing with cleaning solution or direct extraction of internal gases to obtain samples representative of the overall residual status of the device. Dynamic headspace extraction can be used for extraction, leveraging its advantages to efficiently extract ethylene oxide. The detection reagent is a pH-indicator-based reaction system, where color changes caused by pH variations indicate the presence and content of ethylene oxide. Interpretation is performed using a portable pH meter or a visual colorimetric card, selecting the appropriate interpretation method based on the specific circumstances to intuitively obtain test results and meet the testing requirements of these devices.

[0046] Reusable medical devices (S24):

[0047] The surface residue situation of reusable medical devices is quite complex. Sample acquisition can be achieved by surface wiping, which is a simple way to collect ethylene oxide residues from the device surface. Extraction can be performed using solid-phase microextraction, which has the advantages of good selectivity and simple operation. After extraction, the extract is analyzed and reacted with specific enzymes or biosensor systems. The signal is read by an electrochemical sensor. With the high sensitivity and accuracy of electrochemical detection, the amount of ethylene oxide residue can be accurately determined, ensuring the safety of these devices during reuse.

[0048] The beneficial effects of this invention are as follows:

[0049] 1. The rapid detection method for EO residue in sterilized medical devices described in this invention significantly reduces the time consumed in each step by optimizing technical means in multiple stages such as sample acquisition, extraction, colorimetric reaction, and signal interpretation. For example, in the sample acquisition stage, the acquisition method and sample quantity are precisely controlled to ensure that representative samples are acquired in a short time (no more than 5 minutes); the extraction process adopts efficient extraction technology and strictly limits the extraction time (total not exceeding 45 minutes, preferably not exceeding 30 minutes); the colorimetric reaction and signal interpretation are also set with reasonable time ranges (not exceeding 20 minutes and 5 minutes respectively). The whole process realizes a rapid workflow from sample collection to obtaining detection results. Compared with traditional detection methods, it can complete the detection of ethylene oxide residue in a shorter time, effectively meeting the urgent need for rapid detection in practical applications and helping to improve the efficiency of medical device production, distribution, and use.

[0050] 2. The rapid detection method for EO residue in sterilized medical devices described in this invention integrates and optimizes the entire detection process, avoiding the cumbersome and complex operational steps of traditional detection methods. For example, it clarifies multiple sample acquisition methods for different types of medical devices, allowing operators to select only the appropriate method based on the device type; the extraction stage provides clear and concise operating parameters and conditions for different extraction techniques, reducing operational difficulty; the colorimetric reaction and signal interpretation stages also provide simple and easy-to-use operating procedures and judgment methods. Furthermore, the close connection and clear logic between each stage make the entire detection process easier to understand and execute, reducing human error caused by operational complexity. Even technicians with general training can perform the detection work proficiently, broadening the applicability of the detection method.

[0051] 3. The rapid detection method for EO residues in sterilized medical devices described in this invention involves strict control and meticulous optimization of process parameters at each key stage. This includes precise setting of extraction time, reaction temperature, reagent concentration, sample volume, and pH value. Optimal parameter combinations are determined through scientific pre-experiments and orthogonal experimental design, ensuring that each step is conducted under optimal conditions. This minimizes sources of error and allows the detection results to more accurately reflect the actual ethylene oxide residue in the medical device. Furthermore, comprehensive quality control and calibration measures are established, covering blank control testing, positive control testing, instrument performance verification, reagent expiration and storage condition management, operator competence assessment, and internal quality control. These measures enable real-time monitoring of potential problems during the testing process, timely detection and correction of deviations, and guaranteeing the accuracy and reliability of every test result. Attached Figure Description

[0052] The invention will now be further described with reference to the accompanying drawings.

[0053] Figure 1 This is a schematic diagram of the method flow of the present invention. Detailed Implementation

[0054] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0055] like Figure 1 As shown in the embodiments of the present invention, the rapid detection method for EO residue in sterilized medical devices is described in detail below with reference to specific implementation examples:

[0056] Case 1: Taking disposable plastic syringes as an example (corresponding to disposable medical devices)

[0057] Sample acquisition (S1):

[0058] A certain number of disposable plastic syringes were selected as the sterile medical devices to be tested. Due to their plastic material and relatively simple structure, the immersion-elution method was used for sample acquisition. The syringes were cut into suitable small segments (approximately 1-2 cm in length) to increase the contact area with the extraction solvent. Approximately 5 grams (ranging from 0.1 g to 50 g) of the sample segment were weighed and placed in a clean, stoppered glass container. 20 ml (ranging from 10 ml to 50 ml) of ethanol preheated to 40°C (ranging from 30°C to 60°C) was added to the container as the extraction solvent. The immersion time was set to 15 minutes (ranging from 5 minutes to 30 minutes), with gentle shaking every 5 minutes to promote the dissolution of residues. The entire sample acquisition process was conducted at room temperature (approximately 25°C) and took approximately 3 minutes (not exceeding 5 minutes), which met the requirements.

[0059] Rapid extraction of ethylene oxide residues (S2):

[0060] Ultrasonic-assisted extraction was used. The soaked sample and extraction solvent mixture were transferred to a 50 mL (range 10 mL to 200 mL) plastic extraction container. The ultrasonic frequency was set to 40 kHz (range 30 kHz to 60 kHz), the power to 500 W (range 200 W to 1000 W), the extraction temperature to 40 °C (range 30 °C to 60 °C), and the extraction time to 10 minutes (range 3 minutes to 20 minutes). During the extraction process, intermittent cooling was performed using a cold water bath to prevent excessive temperature from affecting the extraction effect. After extraction, the mixture was filtered through rapid filter paper to remove solid particles such as syringe fragments, obtaining a clear extract phase. This process took approximately 2 minutes, and the total extraction time was approximately 12 minutes (not exceeding 30 minutes).

[0061] Specific colorimetric or signal response (S3):

[0062] A chromogenic reagent based on the ring-opening reaction of pyridine was selected. The first component, 4-(4-nitrobenzyl)pyridine (NBP), had a concentration of 2% (within the range of 1.5% to 4%), the second component, barbituric acid, had a concentration of 1% (within the range of 0.8% to 2%), and the third component was a phosphate buffer solution with a pH of 7. The three components were mixed at a volume ratio of 1:1:1 (according to a preset volume ratio) to prepare the detection reagent. Then, the extract phase and the mixed detection reagent were mixed thoroughly at a volume ratio of 1:2 (within the range of 1:0.5 to 1:5). The mixture was placed in a constant-temperature water bath, and the reaction temperature was set to 40℃ (within the range of 35℃ to 45℃), with a reaction time of 5 minutes (within the range of 2 minutes to 8 minutes). During this time, a vortex mixer was used to oscillate at a speed of 800 rpm to ensure sufficient contact between the reactants and to allow the ethylene oxide and chromogenic reagent to fully undergo the chromogenic reaction.

[0063] Signal interpretation and EO content quantification (S4):

[0064] Signal interpretation was performed using a portable colorimeter (meeting the instrument characteristics described in claim 7). The colorimeter wavelength was set to 580 nm. A cuvette containing the solution after the colorimetric reaction was placed in the colorimeter sample cell, and the absorbance value was read. This colorimeter has a built-in high-brightness LED light source and a high-sensitivity photosensitive sensor. Its measurement range, resolution, and repeatability error all meet the requirements, enabling accurate measurement of absorbance changes in the colorimetric product. Then, based on a pre-plotted standard curve (by preparing at least six ethylene oxide standard solutions of different concentrations ranging from 0.05 ppm to 200 ppm, and performing linear regression fitting using the least squares method, with a correlation coefficient R0), the signal was analyzed. 2 (Plotted with a value not less than 0.998), the measured absorbance value is substituted into the standard curve equation to calculate the residual amount of ethylene oxide. The entire signal interpretation and content quantification process is simple to operate and takes about 3 minutes (not exceeding 5 minutes).

[0065] Process parameter control (S5) and quality control:

[0066] Process parameter control:

[0067] Throughout the entire testing process, all key process parameters are strictly controlled. For example, parameters such as extraction time, reaction temperature, and reagent concentration are precisely executed using pre-set parameters from automated ultrasonic extraction equipment and constant temperature water baths to minimize human error. The extraction solvent, ethanol, is stored in a cool, dark place, and its expiration date is checked regularly to ensure reagent quality. Colorimeters and other instruments are calibrated quarterly according to regulations to ensure stable and reliable performance, including key indicators such as wavelength accuracy. All operators have undergone systematic professional training, are familiar with each operating step and its corresponding parameter requirements, and strictly adhere to standard operating procedures when performing testing tasks.

[0068] Quality control:

[0069] Blank control test (S11): Before the start of this test batch, after the end of the test batch, and after every 20 syringe samples, a blank control sample was tested (using the same extraction solvent, colorimetric reagent, etc., and performing the same operation procedure, but without syringe samples). The test results were all below the detection limit of this method, indicating that the entire test process was not interfered with by external impurities or other factors, and the test environment and reagents were in normal condition.

[0070] Positive control test (S12): Similarly, a positive control sample with a known concentration of ethylene oxide was tested at the corresponding node. In this case, a positive control sample with a concentration of 10 ppm was selected. The relative deviation between the test results and the nominal value was within ±15%, which verified that the test method and the instrument equipment could accurately detect the content of ethylene oxide and were in normal working condition.

[0071] Instrument performance verification (S13): For the ultrasonic extraction equipment, constant temperature water bath, portable colorimeter and other instruments used, record the calibration time, calibration parameters and calibration results in detail, and perform performance verification and calibration according to the established cycle to ensure that the instruments can always provide accurate and reliable data.

[0072] Reagent expiration date and storage conditions management (S14): When purchasing and storing various test reagents such as ethanol and colorimetric reagents, their production date, expiration date and other information should be clearly marked. They should be stored in accordance with the storage conditions required by the manufacturer (such as ethanol should be stored away from light and at room temperature, and colorimetric reagents should be refrigerated at low temperature). Before use, the expiration date should be checked again and the appearance of the reagents should be observed to ensure that they are normal. New batches of reagents should be tested in a preliminary experiment to verify that their performance meets the requirements before they are officially put into use.

[0073] Operator competency assessment (S15): All operators involved in this test hold relevant professional qualification certificates and participate in annual training sessions organized by the organization to update theoretical knowledge and conduct practical operation assessments for this test method. They are proficient in the entire process from sample acquisition to result reporting, ensuring the accuracy and reliability of the test work.

[0074] Sample integrity and traceability (S16): Starting from the collection of syringe samples, each sample is uniquely identified and its source, collection time, operator and other information are recorded. In subsequent processing, testing and other stages, the time, parameters, reagents and instruments used in each step are recorded in detail to form a complete test record archive, which is convenient for traceability and review of the test process at any time.

[0075] Internal quality control (S17): The internal quality control samples are tested regularly (e.g., once a month). The fluctuation of the method performance is monitored by plotting a quality control chart. During this test, the quality control chart shows that all data points are within the controllable range and no abnormal fluctuations occur, indicating that the precision and accuracy of the test method remain stable and can reliably detect ethylene oxide residues.

[0076] Case 2: Taking implantable cardiac stents as an example (corresponding implantable medical devices)

[0077] Sample acquisition (S1):

[0078] Several sterilized implantable cardiac stents were selected as samples for testing. Given their delicate structure and predominantly metallic alloy composition, a solid-liquid immersion extraction method was used to obtain the samples. First, the cardiac stents were carefully cut into small pieces (approximately 2-3 mm on each side) using a specialized small cutting tool. Approximately 0.5 grams (ranging from 0.1 to 50 grams) of the chopped sample were weighed and placed in a clean glass extraction bottle. 15 ml (ranging from 10 to 50 ml) of preheated phosphate buffer solution at 50°C (ranging from 30 to 60°C) was added as the extraction solvent. The immersion time was set to 20 minutes (ranging from 5 to 30 minutes), with gentle stirring every 8 minutes to ensure sufficient contact between the sample and the extraction solvent, facilitating the dissolution of residual ethylene oxide. The entire sample acquisition process was conducted in a clean environment at a constant temperature of 22°C and took approximately 5 minutes (not exceeding 5 minutes).

[0079] Rapid extraction of ethylene oxide residues (S2):

[0080] Microwave-assisted extraction (MAE) was employed. A glass extraction flask containing the sample and extraction solvent was placed in a microwave extractor. The microwave power was set to 600 watts (within a suitable power range), the extraction temperature to 55°C (within the range of 30°C to 60°C), and the extraction time to 12 minutes (within a reasonable extraction time range). The microwave extractor was then started. After extraction, the flask was allowed to cool to room temperature. Any remaining small metal particles or other impurities were removed by centrifugation (5000 rpm for 5 minutes) to obtain a clear extract phase. This process took approximately 18 minutes in total (not exceeding 30 minutes).

[0081] Specific colorimetric or signal response (S3):

[0082] A sodium thiosulfate-ferric nitrate complexation colorimetric reagent was selected, wherein the concentration of the first component, sodium thiosulfate, was 0.05M (within the range of 0.03M to 0.07M), and the concentration of the second component, ferric nitrate, was 0.12M (within the range of 0.08M to 0.15M). The two components were mixed at a volume ratio of 1:2 (according to a preset volume ratio) to prepare the detection reagent. The extract phase and the mixed detection reagent were mixed thoroughly at a volume ratio of 1:3 (within the range of 1:1 to 1:8), and placed in a constant temperature incubator. The reaction temperature was set at 30℃ (between 25℃ and 35℃), and the reaction time was 8 minutes (between 4 minutes and 12 minutes). During the reaction, the reactants were gently shaken to ensure sufficient contact, promoting the complexation colorimetric reaction between ethylene oxide and the detection reagent to generate a product with a specific color change.

[0083] Signal interpretation and EO content quantification (S4):

[0084] A smart image recognition system is used for signal interpretation. The reacted solution is placed in a standard cuvette with a white background and then placed in the image acquisition area. The smart image recognition system captures color images of the solution using a high-resolution camera, processes the images using a built-in color analysis algorithm, analyzes color changes, and then quantifies the residual amount of ethylene oxide based on a pre-established model of the correspondence between color and ethylene oxide concentration (established through numerous standard sample experiments). This system has high-precision color recognition capabilities, accurately distinguishing subtle color differences. The entire signal interpretation and content quantification process takes approximately 4 minutes (no more than 5 minutes).

[0085] Process parameter control (S5) and quality control:

[0086] Process parameter control:

[0087] Throughout the entire testing process, parameters such as power, temperature, and time for microwave-assisted extraction are strictly controlled through precise settings on the microwave extraction instrument to ensure a stable and efficient extraction process. The reaction temperature is precisely maintained using a constant temperature incubator, and reagent concentrations are adjusted according to precise mixing ratios, all utilizing automated or semi-automated equipment to minimize errors caused by human factors. Simultaneously, the storage conditions of reagents such as phosphate buffer and colorimetric reagents are strictly managed, requiring low-temperature storage and regular checks of expiration dates. Instruments such as the microwave extraction instrument and intelligent image recognition system are regularly calibrated and maintained, with detailed calibration parameters and results recorded to ensure optimal instrument performance. Operators undergo systematic training specifically for detecting ethylene oxide residues in implantable medical devices, are proficient in the key operational points and precautions of each step, and strictly adhere to standard operating procedures when performing testing.

[0088] Quality control:

[0089] Blank control test (S11): Blank control samples (using the same extraction solvent, colorimetric reagent, etc., and the same operating procedure, but without cardiac stent samples) were tested at the beginning and end of the testing of this batch of cardiac stent samples and after every 20 samples. The test results were all far below the detection limit of this method, indicating that the testing process was not affected by external factors and that the environment and reagents met the requirements.

[0090] Positive control test (S12): Test a positive control sample of ethylene oxide at a known concentration (e.g., set to 8 ppm) at the corresponding node. If the relative deviation between the test result and the nominal value is within ±15%, it proves that the test method and instrument equipment can accurately detect the ethylene oxide content and are in normal working condition.

[0091] Instrument performance verification (S13): Record in detail the calibration status of instruments and equipment such as microwave extractors and intelligent image recognition systems, including calibration time, calibration institution, calibration parameters and verification results after calibration. Perform performance verification and calibration according to the prescribed cycle to ensure the accuracy and reliability of the instruments. For example, the microwave power output accuracy of the microwave extractor is verified once a year, and the color recognition accuracy of the intelligent image recognition system is calibrated every six months.

[0092] Reagent expiration date and storage conditions management (S14): When purchasing various reagents, the expiration date, storage conditions and other information should be clearly marked. They should be stored in strict accordance with the requirements. For example, phosphate buffer should be refrigerated at 4°C and colorimetric reagents should be stored in a light-proof and low-temperature environment. Before use, the reagent status and expiration date should be carefully checked. New batches of reagents should be tested for performance to ensure that they meet the testing requirements before they can be used.

[0093] Operator competency assessment (S15): All operators involved in the testing have participated in professional training courses covering theoretical knowledge related to implantable medical device testing, detailed operating procedures of this testing method, and practical operation skills training. A competency assessment is conducted annually, covering aspects such as operating procedures, result accuracy, and handling of abnormal situations. This ensures that operators possess solid professional skills and good operational levels, guaranteeing the high-quality completion of the testing work.

[0094] Sample integrity and traceability (S16): Starting from the collection of cardiac stent samples, each sample is identified in detail, and its source (such as manufacturer, batch number, etc.), collection time, collection personnel and other basic information are recorded. In subsequent processing, testing and other stages, each step of the operation is also recorded in detail, including the instruments and equipment used, reagents, operating parameters, time and other information, forming a complete and traceable test record file, which facilitates the review and evaluation of the entire testing process when needed.

[0095] Internal quality control (S17): Test samples regularly (e.g., quarterly) using internal quality control samples, and plot quality control charts to monitor fluctuations in the performance of the testing method. By observing and analyzing the quality control charts, any abnormalities that may occur during the testing process can be detected in a timely manner. In this testing process, the quality control charts showed that all indicators were stable, indicating that the precision and accuracy of the testing method were good and that it could reliably detect the residual amount of ethylene oxide in cardiac stents.

[0096] Case 3: Taking an extracorporeal circulation hemodialysis machine as an example (corresponding to extracorporeal circulation or blood purification devices)

[0097] Sample acquisition (S1):

[0098] Several sterilized extracorporeal circulation hemodialysis machines were selected as the test subjects. Considering their internal structure and functional characteristics, samples were obtained by rinsing with a cleaning solution. The hemodialysis machines were connected to a specially configured cleaning solution circulation device, and an appropriate amount (about 100 ml) of physiological saline was used as the cleaning solution. The solution was circulated inside the dialyzer at a certain flow rate (about 50 ml / min) for 10 minutes (within a reasonable time range). The cleaning solution after rinsing was collected as the sample. This process aims to thoroughly flush out and collect the residual ethylene oxide inside the dialyzer. The entire sample acquisition process took about 12 minutes (not exceeding 5 minutes; considering the connection and rinsing steps in actual operation, the time limit was appropriately relaxed, but it is still within an acceptable range).

[0099] Rapid extraction of ethylene oxide residues (S2):

[0100] Dynamic headspace extraction (DSE) was used to transfer the collected washing solution sample to a 50 mL (10 mL to 100 mL) borosilicate glass headspace vial. After sealing the headspace vial, an inert carrier gas system (high-purity nitrogen) was connected. The carrier gas flow rate was set to 200 mL / min (50 mL / min to 400 mL / min), the purge temperature to 120 °C (60 °C to 180 °C), and the purge time to 30 min (5 min to 45 min). During the purge process, magnetic stirring was performed at 300 rpm to enhance the release efficiency of ethylene oxide. The purged ethylene oxide gas is transferred through a connecting pipeline to a collection device filled with TenaxGR adsorbent (which has been activated as required before use) for capture. After collection, thermal desorption is used to desorb the adsorbed ethylene oxide at 250°C (within a suitable thermal desorption temperature range) for 8 minutes (within the corresponding desorption time range) and release it into the system used for subsequent reaction. The entire extraction process takes about 38 minutes (not exceeding 45 minutes).

[0101] Specific colorimetric or signal response (S3):

[0102] A pH indicator-based reaction system was selected as the detection reagent. A detection reagent solution containing a suitable pH indicator (such as bromothymol blue) was prepared according to a specific formula. The desorbed ethylene oxide and the detection reagent were mixed thoroughly at a certain volume ratio (e.g., 1:4, within a reasonable volume ratio range). The mixture was placed at room temperature, and the color change of the solution over time was observed. Since the reaction between ethylene oxide and the detection reagent causes a change in the pH value of the solution, which in turn leads to a change in the color of the pH indicator, this indicates the presence and approximate content of ethylene oxide. The reaction time was set to 15 minutes (within an appropriate reaction time range), during which the mixture could be shaken appropriately to ensure sufficient contact between the reactants.

[0103] Signal interpretation and EO content quantification (S4):

[0104] For signal interpretation, a portable pH meter can be used. The pH meter's electrodes are inserted into the solution after the reaction, and the pH value is read. Then, based on a pre-established table of pH values ​​and ethylene oxide concentrations (drawn through numerous standard sample experiments), the residual ethylene oxide content can be roughly quantified. Alternatively, a visual colorimetric chart can be used for direct color comparison. The color of the solution after the reaction is compared with the corresponding color range on the standard colorimetric chart to quickly determine the approximate range of residual ethylene oxide. The entire signal interpretation and content quantification process is simple to operate and takes approximately 4 minutes (no more than 5 minutes).

[0105] Process parameter control (S5) and quality control:

[0106] Process parameter control:

[0107] Throughout the entire testing process, all parameters of dynamic headspace extraction are strictly controlled, such as headspace vial capacity, carrier gas flow rate, purge temperature, time, and the selection and activation of the adsorbent. Automated carrier gas supply and temperature control equipment ensure precise parameter execution and minimize errors. For reagent preparation, precise formulations and proportions are followed to guarantee the accuracy of the reaction system. Portable pH meters and other instruments are regularly calibrated and maintained to ensure accurate and reliable pH measurements. For example, pH meter electrode calibration is performed monthly as required. Strict management of reagent storage conditions is maintained, such as storing pH indicator solutions away from light and regularly checking expiration dates. Operators undergo systematic training in testing extracorporeal circulation devices, are familiar with the operational procedures of each step of this testing method, and strictly adhere to standard operating procedures to ensure the accuracy of test results.

[0108] Quality control:

[0109] Blank control test (S11): At the beginning and end of each batch of hemodialysis machine sample testing, and after every 20 samples tested, blank control samples (using the same cleaning solution, test reagents, etc., and performing the same operating procedures, but without hemodialysis machine samples) were tested. The test results were all below the detection limit of this method, indicating that the testing process was not affected by external factors and that the environment and reagents met the requirements.

[0110] Positive control test (S12): At the corresponding node, a positive control sample of ethylene oxide with a known concentration (e.g., set to 5 ppm) was tested. The relative deviation between the test result and the nominal value was within ±15%, which verified that the test method and instrument equipment can accurately detect the content of ethylene oxide and are in normal working condition.

[0111] Instrument performance verification (S13): Record in detail the calibration status of various instruments and equipment used (such as dynamic headspace extraction devices, portable pH meters, etc.), including calibration time, calibration institution, calibration parameters, and verification results after calibration. Perform performance verification and calibration according to the prescribed cycle to ensure stable and reliable instrument performance. For example, the carrier gas flow control accuracy of the dynamic headspace extraction device is verified every six months, and the pH measurement accuracy of the portable pH meter is calibrated every quarter.

[0112] Reagent expiration date and storage conditions management (S14): When purchasing various reagents such as cleaning solutions and pH indicator solutions, the expiration date and storage conditions should be clearly marked. They should be stored in strict accordance with the requirements, such as storing cleaning solutions at room temperature and storing pH indicator solutions away from light. Before use, the reagent status and expiration date should be carefully checked. New batches of reagents should be tested for performance to ensure that they meet the testing requirements before they can be used.

[0113] Operator competency assessment (S15):

[0114] All personnel involved in the ethylene oxide residue testing of extracorporeal circulation hemodialysis machines received professional and comprehensive training. The training covered everything from relevant theoretical knowledge, such as the properties of ethylene oxide, the detection principle, and the impact of different instrument characteristics on the detection, to the details of each operational step involved in this detection method, including the correct use of the cleaning solution circulation device during sample acquisition, the setting of various parameters for dynamic headspace extraction, key points for reagent preparation, and the use of pH meters and colorimetric cards in signal interpretation. Furthermore, a competency assessment is conducted annually, assessing not only the standardization and accuracy of practical operations but also the ability to identify and handle abnormal situations. This systematic training and assessment mechanism ensures that operators consistently possess solid professional skills, strictly adhere to standard operating procedures to complete the testing work, and guarantee the reliability of the test results.

[0115] Sample integrity and traceability (S16):

[0116] From the initial sample collection from the hemodialysis machine, each sample is meticulously and uniquely identified, clearly indicating its origin information, such as the manufacturer's name, specific batch number, and production date. Basic details like the collection time and the name of the operator responsible for collection are also recorded. In subsequent stages, including sample acquisition via washing solution, dynamic headspace extraction, colorimetric reaction, and signal interpretation, detailed records are kept of the specific model of the instruments used, reagent names and dosages, operational parameters (such as temperature, flow rate, and time), and specific time points. This information is integrated to form a complete and traceable testing record archive. Whether for routine result review or in special circumstances requiring a retrospective analysis of the entire testing process, key information can be quickly and accurately located, enabling a comprehensive evaluation and analysis of the testing process.

[0117] Internal quality control (S17):

[0118] Regular testing (e.g., every two months) is conducted using internal quality control samples. Data from multiple tests is compiled and analyzed to create quality control charts, providing a visual indicator of performance fluctuations in the testing method. In this testing of hemodialysis machines, the quality control charts showed that all data points remained within reasonable and stable ranges, without significant deviations or abnormal fluctuations. This indicates that the current testing method maintains good precision and accuracy, reliably and consistently detecting ethylene oxide residues in extracorporeal circulation hemodialysis machines, providing strong technical support for quality control of such medical devices.

[0119] As can be seen from the above specific implementation examples of different types of sterilized medical devices, the rapid detection method for ethylene oxide residue in sterilized medical devices of the present invention can flexibly apply optimized technical means in each step according to the characteristics of different devices. While ensuring the accuracy and reliability of the detection results, it can effectively achieve the purpose of rapid detection, and provide strong technical support for the quality monitoring and safe use of medical devices.

[0120] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for rapid detection of the residual amount of EO in sterilized medical devices, characterized by, Comprising the following steps: S1, sample acquisition: acquire a representative analysis sample from the sterilized medical device to be detected, the sample acquisition method includes soaking elution, surface wiping, cutting and shearing, crushing or directly extracting internal gas, etc., the sample amount is accurately controlled according to the expected detection limit and the type of medical device, the mass of solid sample is 0.1-50g, the volume of liquid sample is 0.5-100ml, and the volume of gas sample is 10-1000ml, and the total time consumption is not more than 5 minutes; S2, rapid extraction of ethylene oxide residues: place the sample in a closed extraction system, and use fast and efficient extraction techniques such as dynamic headspace extraction, static headspace extraction, microwave-assisted extraction, etc. to transfer the EO residues to the extraction phase under the preset conditions. The total time consumption of the extraction process is not more than 45 minutes, preferably not more than 30 minutes. After the extraction is completed, the extraction phase can be separated, concentrated or diluted as needed; S3, specific color development or signal reaction: mix the EO extract with the pre-prepared detection reagent, so that the EO reacts specifically with the detection reagent, the detection reagent includes color developing reagent based on pyridine ring opening or nucleophilic substitution reaction, complex color developing reagent based on sodium thiosulfate or thiocyanate, etc. The reaction time is not more than 20 minutes, preferably not more than 10 minutes; S4, signal interpretation and EO content quantification: observe with the naked eye or use a portable simple detection instrument to read the signal value generated by the reaction, and convert the signal value into the residual amount of ethylene oxide. The signal interpretation method includes naked eye colorimetric interpretation, portable photometer / colorimeter detection, etc. The EO content quantification can use standard curve method, standard addition method, etc. The total time consumption is not more than 5 minutes; S5, process parameter control: strictly control the key process parameters such as extraction time, reaction temperature, reagent concentration, sample amount, pH value, etc. The control method can use automatic or semi-automatic equipment. The optimization of process parameters should be carried out through pre-experiment and orthogonal experiment design. It also includes the storage conditions of reagents, the calibration frequency of instruments, the execution of standard operating procedures of operators, etc.

2. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 1, wherein, The sample acquisition and pretreatment are as follows: expose the medical device to be detected to clean air at 20-30℃ for 1-10 minutes, or directly immerse the medical device sample in 10-50ml of preheated extraction solvent, the extraction solvent includes deionized water, ethanol, isopropanol, etc., the preheating temperature is 30-60℃, the soaking time is 5-30 minutes, and intermittent shaking or ultrasonic treatment can be carried out during the process. For solid samples, they can be cut into small pieces or ground into powder. For liquid samples, they can be filtered or centrifuged. The total time consumption of sample pretreatment is not more than 15 minutes, preferably not more than 10 minutes.

3. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 2, wherein, The rapid extraction of ethylene oxide residues adopts dynamic headspace extraction, and the specific parameters are as follows: the sample is placed in a borosilicate glass headspace bottle with a capacity of 10-100 ml, the inert carrier gas is selected from high-purity nitrogen, helium or argon, the carrier gas flow rate is 50-400 ml / min, the purging temperature is 60-180℃, the purging time is 5-45 min, magnetic stirring or vortex oscillation can be performed during the purging process, the purged EO gas is transmitted to the trapping device through the connecting pipeline, the trapping device is an adsorption tube filled with adsorbent, the adsorbent is selected from Tenax GR, Tenax TA and the like, the adsorption tube needs to be activated before trapping EO, and thermal desorption or solvent desorption can be directly performed after trapping.

4. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 2, wherein, The rapid extraction of ethylene oxide residues adopts ultrasonic-assisted extraction, and the specific parameters are as follows: the sample is mixed with an extraction solvent selected from deionized water, phosphate buffer, ethanol and the like, the mass ratio of the extraction solvent to the sample is 10:1 to 50:1, the mixture is placed in an extraction container with a capacity of 10-200 ml, the ultrasonic frequency is 30-60 kHz, the power is 200-1000 W, the extraction time is 3-20 min, the extraction temperature is 30-60℃, the extraction can be performed by ultrasonic bath or ultrasonic probe, and intermittent cooling can be performed during the extraction process. After the extraction is completed, the extraction liquid is filtered or centrifuged to remove solid particles.

5. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 4, wherein, The detection reagent is a color developing reagent based on pyridine ring opening or nucleophilic substitution reaction, which is composed of at least two components, the first component contains 4-(4-nitrobenzyl)pyridine (NBP) with a concentration of 1.5%-4%, the second component contains barbituric acid or its sodium salt with a concentration of 0.8%-2%, and the third component can be a pH buffer solution. When used, the components are mixed according to the preset volume ratio, the volume ratio of the EO extract to the mixed detection reagent in the reaction system is 1:0.5-1:5, the reaction temperature is accurately controlled at 35-45℃, and the reaction time is accurately controlled at 2-8 min.

6. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 4, wherein, The detection reagent is a complex color developing reagent based on sodium thiosulfate or thiocyanate, which is composed of at least two components, the first component contains sodium thiosulfate with a concentration of 0.03-0.07 M, the second component contains mercury thiocyanate or potassium thiocyanate with a concentration of 0.003-0.007 M, and the third component contains ferric nitrate or ferric chloride with a concentration of 0.08-0.15 M. When used, the components are mixed according to the preset volume ratio, the volume ratio of the EO extract to the mixed detection reagent in the reaction system is 1:1-1:8, the reaction temperature is accurately controlled at 25-35℃, and the reaction time is accurately controlled at 4-12 min.

7. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 6, wherein, The signal interpretation and EO content quantification use portable photometer / colorimeter detection. The instrument is a handheld or small desktop device, weighing no more than 2 kg, with a size of no more than 30 cm x 20 cm x 10 cm, built-in high-brightness LED light source and photosensitive sensor, with one or more sample cells, built-in microprocessor and data processing software, measuring range of 0.001 to 2.000 absorbance units, resolution of 0.001 absorbance units, and repeatability error of less than 0.5% RSD.

8. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 7, wherein, The rapid detection method further comprises a standard curve establishment and verification step, at least 6 different concentrations of ethylene oxide standard solution are prepared, the concentration range covers the expected EO residual range from 0.05 ppm to 200 ppm, the preparation of standard solution should use high purity ethylene oxide standard, at least 3 parallel samples of each concentration of standard solution should be prepared and independently detected, the standard curve can be drawn by least square method for linear regression, quadratic polynomial fitting or four parameter logic (4PL) fitting, the correlation coefficient (R 2 ) should not be less than 0.

998.

9. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 8, wherein, The rapid detection method further comprises the following quality control and calibration steps: S11, blank control detection: at the beginning and end of each batch of sample detection, and after every 20 samples are detected, at least one blank control sample is detected, and the detection result should be lower than the detection limit of the method; S12, positive control detection: at the beginning and end of each batch of sample detection, and after every 20 samples are detected, at least one known concentration of ethylene oxide positive control sample is detected, and the relative deviation between the detection result and the nominal value should be within ± 15%; S13, instrument performance verification: all instruments used for detection of the method should be periodically verified and calibrated, and there should be detailed calibration records; S14, reagent shelf life and storage condition management: all detection reagents and standards should be strictly stored according to the manufacturer's instructions, and their shelf life should be checked regularly. New batch of detection reagents should be verified before use; S15, operator ability assessment: all operators should be systematically trained in theory and practice, master the standard operating procedures of the method, and be assessed for ability once a year; S16, sample integrity and traceability: from sample acquisition to final result report, the sample identification should be clear and complete, all operation steps and detection results should be recorded in detail, and complete traceability should be provided; S17, internal quality control: internal quality control samples are used to evaluate the precision and accuracy of the method periodically, and quality control charts are drawn to monitor the fluctuation of the method performance.

10. The method for rapid detection of residual amount of EO in sterilized medical devices according to claim 8, wherein, The rapid detection method is suitable for detecting the residual amount of ethylene oxide in at least one of the following sterilized medical devices, and the detection parameters are optimized according to the characteristics of the medical devices: S21, disposable medical devices: sample acquisition can preferentially use soaking elution method, extraction can use ultrasonic assisted extraction, pyridine-barbituric acid color reagent is selected for rapid reaction, and interpretation is measured by portable colorimeter at 580 nm; S22, implantable medical devices: sample acquisition can use solid-liquid soaking extraction after cutting, microwave assisted extraction can be used for extraction, sodium thiosulfate-ferric nitrate color reagent is selected for rapid reaction, and interpretation is analyzed by intelligent image recognition system for color change; S23, extracorporeal circulation or blood purification devices: sample acquisition can use flushing with cleaning fluid or direct extraction of internal gas, dynamic headspace extraction can be used for extraction, pH indicator-based reaction system is selected for detection reagent, and interpretation is performed by portable pH meter or visual colorimetric card; S24, repeat use of medical devices: sample acquisition can employ surface swabbing, extraction can employ solid phase microextraction, and after resolution, reaction with specific enzymes or biosensing systems, and reading of signals by electrochemical sensors.

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