Low-carriage contamination discrete full-automatic biochemical analyzer

Abstract

The application discloses a low-carrying-pollution separated full-automatic biochemical analyzer and relates to the medical examination field. In the biochemical analyzer detection, a plurality of different reagents are often needed, and the same distribution needle is used to continuously change and suck and distribute different reagents; and the distribution needle also needs to suck and distribute different samples. The inside of the distribution needle is narrow, the allowed cleaning time of the instrument during operation is extremely short, and therefore, the residual reagents and samples in the distribution needle are often difficult to clean, and the residual components in the distribution needle cause carrying pollution to the subsequent sucked and distributed reagents and samples; in addition, the contact type stirring device of the instrument is continuously contacted with the mixture of different samples and reagents during detection, and the device cannot be completely cleaned, which is one of the reasons causing the carrying pollution. The carrying pollution is one of important reasons influencing the detection result quality of the biochemical analyzer. The application automatically performs the carrying pollution detection and evaluation between the reagents and the samples and automatically adopts intelligent solving measures to the carrying pollution, so that the carrying pollution of the instrument is reduced.

Description

Technical Field

[0001] This invention relates to the field of medical testing and detection technology, specifically to a discrete fully automated biochemical analyzer with low carryover contamination. Background Technology

[0002] In modern medical testing, fully automated biochemical analyzers provide crucial diagnostic indicators for understanding the causes and progression of patient diseases by rapidly analyzing liquid samples such as serum, plasma, cerebrospinal fluid, and urine. Current fully automated biochemical analyzers primarily employ a discrete structure and operating mode, characterized by high speed, a wider range of detection methods, and lower reagent and sample consumption. However, with advancements in medical technology and rising diagnostic standards, the number of biochemical reagents required is gradually increasing. Medical institutions, regardless of size, face challenges such as a large number of samples to be tested, a wide variety of reagents, the need to complete testing and generate reports in the shortest possible time, and the requirement to ensure high-quality results. Because the instruments have only a limited number of dispensing needles to draw and dispense different reagents and samples, and only a few seconds are allowed for cleaning after each needle transfer, and even with contact stirring devices, the cleaning time after stirring is extremely short, contamination often occurs because the dispensing needles and contact stirring devices retain residues of previously handled reagents and samples, leading to inaccurate test results. This contamination is a prominent technical challenge in the operation of fully automated biochemical analyzers.

[0003] Fully automated biochemical analyzers typically have a limited number of dispensing needles dedicated to dispensing dozens of different reagents. These reagents vary greatly in pH, viscosity, and composition; some reagent components may even react with others or inhibit each other. Furthermore, the amount of reagent drawn in biochemical testing is often 10-100 times the amount of sample, making reagent contamination a more significant and primary source of contamination. Regarding sample contamination, some instruments are equipped with only one or two dedicated dispensing needles for dispensing large quantities of diverse samples, while others use dispensing needles for both reagent and sample dispensing. When the concentration difference between samples is too large, the residue from a previously high-concentration sample can significantly deviate from the results of subsequent samples with normal or lower concentrations, thus requiring control. Moreover, reagent and sample contamination often coexist in formal testing, and mixed reagent and sample contamination also exists. Only by effectively eliminating these contaminants can the quality of biochemical test results be ensured.

[0004] The term "excessively high concentration" in this context refers to a situation where any one of the test components in the sample is present at an excessively high level. However, in routine testing, not all components in a sample will be present at high levels; often, only some components or a single component may be present at an excessively high level. The "excessively high concentration" here refers to a situation where the concentration of a specific component in the sample is excessively high, also known as the concentration of a specific component exceeding a threshold. When the concentration of any component in a sample exceeds the threshold, it can affect the instrument's testing results for other samples using the same reagent, leading to falsely high results. Therefore, when any component in a sample reaches or exceeds the threshold concentration for that component, the sample with the concentration exceeding the threshold for that reagent should be tested according to the rules designed in this invention. Subsequent samples undergoing testing for that specific reagent should be protected from contamination by measures such as automatic retesting, and the retested result should be used as the actual reported result.

[0005] In addition, the stirring device of the fully automated biochemical analyzer equipped with a contact stirring device is also often one of the causes of contamination. In the scheme designed in this invention, the detection, evaluation and corrective measures for contamination also include the evaluation and treatment of the influencing factors of the contact stirring device. When the instrument detection and evaluation shows that there is contamination, the solution is to change the order of reagent items and / or increase the cleaning measures between reagent items.

[0006] Existing fully automated biochemical analyzers primarily attempt to eliminate contamination by improving the polishing and cleaning of the inner and outer surfaces of the dispensing needles, thereby reducing residues on the surfaces of components that come into contact with reagents and samples. During operation, they rely heavily on operator experience, optimizing reagent sequencing based on differences in reagent acidity / alkalinity and known contamination patterns. However, these analyzers often only have a pre-set sequencing order. During operation, additions or removals of reagents, or the introduction of new reagents, disrupt the original sequence, rendering it ineffective. Furthermore, validating the sequencing for effective contamination control relies entirely on operator experience, or involves cumbersome manual verification, making it difficult to establish a systematic, comprehensive, and effective contamination control mechanism in response to changing testing needs. The inability to effectively, systematically, and stably eliminate contamination in biochemical analyzers remains a prominent and common problem in current biochemical testing applications. Furthermore, existing biochemical analyzers employ measures such as increasing the frequency of cleaning the dispensing needle and stirring device, including adding extra cleaning agents, to reduce carryover contamination in fully automated biochemical analyzers. However, equipping them with excessive cleaning agents inevitably occupies instrument space and may even consume reagent loading space. Excessive cleaning significantly reduces instrument operating speed and wastes considerable water and cleaning agents. Moreover, verifying the appropriateness and effectiveness of the selected cleaning conditions is extremely cumbersome and difficult. Therefore, existing biochemical analyzers lack a systematic and comprehensive ability to control carryover contamination. Because the design of various existing fully automated biochemical analyzers has not fully and comprehensively considered the complexity of carryover contamination during biochemical analysis, and lacks a systematic and comprehensive effective method to eliminate carryover contamination between reagents, between samples, and between reagents and samples, while some technical measures in the design and application of existing biochemical analyzers have a certain control effect on carryover contamination, they are far from completely and effectively solving the problem of carryover contamination in actual use of fully automated biochemical analyzers. This often leads to distorted or erroneous test results.

[0007] To address the aforementioned challenges, this invention presents an automated detection, verification, and correction method for carryover contamination between different reagents in biochemical analyzer testing. This method comprehensively analyzes the causes of carryover contamination in fully automated biochemical analyzer testing and takes comprehensive, systematic, and effective measures to address it. Therefore, it can comprehensively, systematically, stably, and effectively reduce and control various carryover contaminations in fully automated biochemical analyzers, thereby effectively improving the quality of instrument test results.

[0008] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and should not be construed as an admission or implication in any way that such information constitutes prior art known to those skilled in the art. The fully automated biochemical analyzer involved in this invention specifically refers to a discrete fully automated biochemical analyzer. Summary of the Invention

[0009] Purpose of the Invention: The technical problem to be solved by this invention is to address the shortcomings of existing biochemical analyzer technology, especially the shortcomings of mainstream discrete biochemical analyzers. This invention provides a low-carryover-contamination discrete fully automated biochemical analyzer that can effectively reduce carryover contamination detected by the analyzer. This solution, without changing the structure of the existing fully automated biochemical analyzer, increasing the number of dispensing needles, or increasing the use of cleaning agents, automatically detects, evaluates, and optimizes the carryover contamination factors involved in instrument operation. It establishes a stable system to reduce and control various carryover contaminations that may be encountered during instrument operation, thereby achieving the effect of reducing instrument carryover contamination and improving the quality of fully automated biochemical analyzer test results.

[0010] To address the aforementioned technical problems, this invention discloses a low-contamination discrete fully automated biochemical analyzer, comprising a reaction plate, various test cups disposed on the reaction plate, and dispensing needles for transferring reagents and samples required for testing into each test cup; the instrument performs tests on different items for each sample separately in one test cup, and when performing tests on different reagent items, each reagent item uses one or more reagents, characterized in that...

[0011] The instrument is configured to: automatically detect and verify, before performing formal testing, whether the unverified reagent contamination between all adjacent different reagent items in the proposed reagent item arrangement meets the contamination standard requirements; automatically take corrective measures for reagent item arrangements that do not meet the contamination standard requirements, the corrective measures being enhanced cleaning conditions and / or adjusting the reagent item arrangement; after correction, the instrument automatically detects and verifies again whether the reagent contamination between corresponding different reagent items in the corrected reagent item arrangement meets the contamination standard requirements, and when a reagent item arrangement that does not meet the contamination standard requirements is detected again, it is automatically corrected again, and then automatically verified again, until the reagent contamination between all adjacent different reagent items in all reagent item arrangements to be used by the instrument meets the contamination standard requirements; then, the instrument automatically saves the reagent item arrangements that have been verified to be qualified in terms of reagent contamination; in the formal testing stage, the instrument automatically uses the verified qualified reagent item arrangements that meet all testing requirements to perform the testing.

[0012] Furthermore, the instrument is also configured as follows:

[0013] During the formal testing phase, the instrument prioritizes the reagent items that have been verified and qualified and can meet the requirements for performing all reagent items on all samples at the current time. If there are multiple reagent item arrangements, they are selected according to the following priority order: first, the arrangement that meets the reagent contamination standard and does not require enhanced cleaning conditions is selected; if not, the arrangement that meets the reagent contamination standard but requires enhanced cleaning conditions is selected.

[0014] If only a portion of the reagents in the required reagent sequence for instrument testing have not been verified to be contaminated, the instrument will only perform reagent contamination verification and necessary corrections on that unverified portion of the reagent sequence.

[0015] The instrument automatically saves the order of each verified reagent item, so that the instrument can save more than one verified reagent item order. In all subsequent tests, dilution retests or direct retests, the instrument will automatically call the corresponding verified reagent item order to perform the test according to the reagent items required for the actual test.

[0016] For adjacent reagent items whose arrangement is determined to be non-compliant with the contamination standard after testing and verification, and which still do not meet the contamination standard after one enhanced cleaning, the instrument can automatically set the arrangement of these reagent items as a repulsive reagent item arrangement order. When arranging the subsequent reagent item arrangement order, the instrument will automatically avoid using the repulsive reagent item arrangement order; or the repulsive reagent item arrangement order can be set manually. After the repulsive reagent item arrangement order is set, the instrument will always automatically avoid using the repulsive reagent item arrangement order during the execution of the pre-designed reagent item sorting and testing operation. The confirmation of the repulsive reagent item arrangement order is related to the different reagent detection principles of the same reagent, as well as the formulation and process of reagents produced by different companies.

[0017] Specifically, the instrument verifies and corrects the order of reagent items as follows:

[0018] In the aforementioned testing and validation, each reagent item is tested at least twice using the same sample to obtain at least two test results. The difference between the at least two test results for the same reagent item using the same sample is compared to evaluate whether the reagent item's contamination from preceding reagent items meets the required contamination standards. If any reagent item arrangement is found to be inconsistent with contamination requirements, the arrangement is automatically corrected by changing the reagent item order and / or by enhanced cleaning. The corrected reagent item arrangement is then retested, and only the corrected arrangement is used. In the validation testing, the same sample is used for each reagent item; the sample can be any one of quality control material, serum, air, or water.

[0019] The contamination standard for the reagent depends on the repeatability requirements of the reagent item and is evaluated using absolute or relative differences.

[0020] In one embodiment, before performing formal testing, the instrument prioritizes grouping samples with identical required test reagents into one or more groups, and then groups other samples with partially identical required test reagents into one or more groups. When testing the grouped samples, within each group, the instrument adopts a batch testing mode centered on the test reagent: first, one reagent test is performed to test all samples in the group that require that test reagent, and then another reagent test is used to test all samples in the group that require that test reagent, and so on, until all reagent tests in the group are completed; then, the same process is performed on the next group of samples until all reagent tests in all sample groups are completed; samples that cannot be grouped are tested separately; and throughout the entire testing process, the order in which all reagent tests are performed follows the order in which the instrument has validated and approved the reagent tests.

[0021] In one embodiment, the instrument also has the function of automatically identifying and correcting contamination between samples under the same reagent item; and the function of automatically identifying and correcting contamination between samples detected by any reagent item, the function including:

[0022] For each reagent item, a contamination threshold is determined for the sample carrying capacity of the reagent item. This threshold is the concentration value at which the sample concentration during the test of the reagent item is so high that it causes unacceptable deviation in the test results of other samples when the same reagent item is subsequently tested. Samples that reach or exceed this concentration value are called over-threshold samples of the reagent item.

[0023] During the formal testing process, the instrument automatically monitors whether all samples exceed the threshold for each reagent item. When testing any reagent item for any sample, it automatically determines whether there was a sample that had just been tested for that reagent item and exceeded the threshold, regardless of whether the sample that exceeded the threshold was tested for a different reagent item or the same reagent item. Furthermore, regardless of the actual reagent item tested on the previous sample, if the sample tested in the next adjacent test exceeded the threshold for the subsequent reagent item, the instrument automatically retests the sample for that reagent item and uses the retest result as the final test result for that sample for that item, thereby avoiding testing errors caused by sample contamination.

[0024] In one embodiment, the instrument also has the function of identifying and correcting contamination carried by samples from different reagent items, specifically selecting any one of the following two schemes, or using both of the following schemes simultaneously:

[0025] Option 1: Following the confirmed order of reagent items, a sample exceeding the threshold for one reagent item is placed at the end of the list of reagent items immediately preceding it for testing. The subsequent reagent items are then tested more than once using the same sample, which can be any of the following: a normal value sample, a low value sample, or water for that reagent item. If the relative deviation of multiple test results for the same reagent item and the same sample exceeds a preset allowable deviation range, the instrument automatically increases the cleaning intensity when switching between the two reagents and re-verifies the process. If the improved cleaning conditions are confirmed to eliminate carryover contamination (i.e., the relative deviation of multiple test results for the same reagent item and the same sample does not exceed the allowable deviation range), the improved cleaning process conditions automatically replace the previous cleaning process conditions for instrument use.

[0026] Option 2: When the instrument detects a sample exceeding the threshold for any specific reagent item, the instrument automatically tracks that sample. Regardless of whether the sample is included in the same or different reagent item tests, if the sample is immediately followed by the first sample test of that specific reagent item in any test, the instrument automatically retests the first sample of that specific reagent item and uses the retest result as the official report result. However, if the two samples were tested using different reagents, and enhanced cleaning measures have been taken between the two reagent item tests, then automatic retesting is selected, and the retest result is used as the official test result. Alternatively, if the enhanced cleaning measures taken ensure that the carryover contamination between the two tests has been eliminated after the previous tests at different times, then retesting is not initiated for subsequent samples of that specific reagent item, and the original test result is used directly.

[0027] In one embodiment, the reaction disk is provided with two concentric and parallel detection cup rings, one inner and one outer. Multiple detection cups are evenly and equidistantly installed on these two detection cup rings. Each detection cup ring is equipped with two dedicated reagent dispensing needles and one dedicated sample needle. When the instrument performs testing, some items of each sample are placed in one detection cup ring on the reaction disk, while the remaining items are placed in the other detection cup ring. During testing, the instrument only needs to verify whether the reagent contamination under the reagent item arrangement for each ring on the reaction disk is controllable before proceeding; it does not need to completely check whether the arrangement of all reagent items required for testing by the instrument meets the controllable contamination requirements. The reagent item arrangement and cleaning conditions stored in the instrument are suitable for testing the inner and outer ring detection cups, and when the instrument performs testing, the arrangement of all reagent items required for testing in both the inner and outer ring detection cups meets the contamination control standards.

[0028] In one embodiment, the fully automated biochemical analyzer is equipped with a dedicated dispensing needle device for independently aspirating and dispensing samples; and a dedicated dispensing needle device for independently aspirating and dispensing reagents. When performing tests on the same reagent items, the dispensing needle dedicated to aspirating and dispensing reagents repeatedly aspirates and dispenses the same reagents from the same source as needed for the test. During this period, when the dispensing needle only aspirates and dispenses the same reagents, it can directly aspirate and dispense the same reagents without cleaning, or it can be cleaned before aspirating and dispensing the same reagents.

[0029] In one embodiment, the fully automated biochemical analyzer is equipped with only one or two dispensing needles, and at least one dispensing needle must be used to simultaneously aspirate and dispense reagents and samples at once. That is, when performing a test, at least one dispensing needle configured by the instrument aspirates the first reagent according to regulations, and then directly aspirates and dispenses the sample before dispensing the first reagent. The aspirated reagent and sample are then added to a test cup. The dispensing needle is then cleaned internally and externally before performing the next reagent and sample aspiration and dispensing, or performing another reagent dispensing separately. According to the design of this invention, the instrument can detect contamination carried by different reagent items in different order according to the actual operating mode of the instrument. If the detected contamination exceeds the allowable standard, optimization and improvement are automatically performed, and the actual sample is tested normally using the reagent item detection order and cleaning conditions that have been verified to meet the contamination standard.

[0030] The instrument also automatically reduces contamination by grouping samples and prioritizing the use of the same reagents for testing.

[0031] In one embodiment, the instrument is selected from fully automated blood coagulation analyzers, fully automated immunoassay analyzers, fully automated urine analyzers, fully automated fecal analyzers, fully automated food / beverage analyzers, fully automated semen analyzers, fully automated allergen analyzers, fully automated sample processors, fully automated gene detectors, fully automated pesticide residue analyzers, or fully automated water quality analyzers.

[0032] Beneficial effects:

[0033] 1. The automated and intelligent fully automated biochemical analyzer carry-over contamination control mode designed in this paper is a specially automated, comprehensive and systematic carry-over contamination testing and evaluation system and automatic correction system designed for the actual detection process of the instrument. It can establish a detection process that can meet the requirements of multiple reagent items in one or more tests of the instrument without much human intervention. It can effectively control the carry-over contamination when the instrument performs multiple tests with different reagent item arrangements, and completely solves the problem of reagent carry-over contamination of discrete biochemical analyzers that has not been effectively solved for a long time.

[0034] 2. The method designed in this invention can effectively eliminate contamination carried over from different reagents, different samples, and overlapping mixing of different reagents and different samples;

[0035] 3. This design adopts a method of grouping different samples for detection, which can greatly reduce the frequency of changing the reagent dispensing needle to dispense different reagents during instrument operation, further reducing the carry-over contamination between different reagents. It can also reduce the drawback of previous biochemical analyzers where the dispensing needle repeatedly dispensed different reagents and repeatedly carried different contaminants into the reagent bottle after dispensing different reagents. This better protects the unused reagents in the reagent bottle from or reduces the degree of contamination.

[0036] 4. The operating mode of this design is suitable for various existing discrete fully automated biochemical analyzers with different structures and design features;

[0037] 5. This design scheme mainly adopts the method of actively eliminating carried-on pollution, which greatly reduces the need for passive treatment after carried-on pollution occurs;

[0038] 6. This design not only proactively prevents reagent contamination but also automatically identifies and corrects erroneous test results caused by sample contamination. Therefore, it significantly improves the quality of instrument test results, greatly reduces reliance on operator skills and experience, and effectively reduces the operator's workload and difficulty.

[0039] 7. The instrument designed using this method stores multiple validated optimized procedures. During testing, the instrument automatically adopts a validated procedure that effectively controls contamination, ensuring that the instrument always operates under controlled contamination conditions. Instruments using this design can readily handle contamination under different testing reagents and requirements, demonstrating strong practicality.

[0040] 8. After optimizing the workflow of the discrete fully automated biochemical analyzer, this invention not only reduces the contamination carried by the instrument, but also reduces some unnecessary cleaning, thus reducing the consumption of water and cleaning agents during instrument operation and lowering the operating cost of the instrument.

[0041] In summary, this discrete fully automated biochemical analyzer with low carryover contamination effectively reduces and eliminates instrument carryover contamination and improves the quality of instrument test results through the optimization and modification of the detection process. This design provides multifaceted improvements to the detection quality and performance of the fully automated biochemical analyzer. Attached Figure Description

[0042] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention in the above and / or other aspects will become clearer.

[0043] Figure 1 This is a top view of the fully automated biochemical analyzer provided in the first embodiment of the present invention.

[0044] Figure 2 This is a top view of a fully automated biochemical analyzer provided in the second embodiment of the present invention.

[0045] Figure 3 This is a top view of a fully automated biochemical analyzer provided in the third embodiment of the present invention.

[0046] The accompanying labeling is as follows:

[0047] 1. Reaction plate; 2. Sample loading device; 7. Optical detection unit; 8. Multi-stage cleaning device for test cups; 11. Test cup position; 311. First reagent loading device; 312. Second reagent loading device; 411. First dispensing arm; 412. Second dispensing arm; 413. Third dispensing arm; 421. Fourth dispensing arm; 431. Fifth dispensing arm; 432. Sixth dispensing arm; 511. First cleaning device; 512. Second cleaning device; 513. Third cleaning device; 521. Fourth cleaning device; 531. Fifth cleaning device; 532. Sixth cleaning device; 611. First stirring device; 612. Second stirring device; 621. Third stirring device; 631. Contact stirring device. Detailed Implementation

[0048] The instrument designed in this invention is capable of automatically detecting carryover contamination between different unverified reagent items in the testing process to be performed. It automatically evaluates whether the carryover contamination between different reagent item testing sequences meets the carryover contamination standard requirements and has the function of taking corrective measures for carryover contamination where the testing sequence between different reagent items does not meet the carryover contamination standard requirements. This design ensures that the entire testing process required by the instrument, including the arrangement of all different reagent items used in the testing process, meets the carryover contamination standard. All reagent item testing sequences used by the instrument during testing are implemented according to the scheme designed in this invention, even when dilution and retesting or direct retesting are required in actual testing, the reagent item arrangement sequence specified in this invention must still be followed.

[0049] Furthermore, the instrument designed in this invention also has the function of automatically detecting and verifying whether the carryover contamination between different reagents and different samples is controllable during formal testing. This function is executed automatically. The method is also designed to proactively correct for risk points of carryover contamination detected, and automatically verify the effectiveness of the corrective measures after correction. This design also includes the function of proactively identifying and correcting factors that lead to carryover contamination, thereby comprehensively, effectively, and stably ensuring that various types of carryover contamination in the fully automated biochemical analyzer are effectively controlled. These functions will be described in detail below.

[0050] The present invention provides a low-carry-contamination discrete fully automated biochemical analyzer, comprising a reaction plate, each test cup disposed on the reaction plate, and a dispensing needle for transferring reagents and samples required for testing to each test cup; the instrument performs tests on each sample for different items in one test cup, and when the instrument performs tests on different reagent items, each reagent item uses one or more specific reagents.

[0051] Based on the above, the instrument is configured to: automatically detect and verify whether the reagent contamination between adjacent reagent items in all proposed reagent item arrangements meets the contamination standard requirements before formal testing; automatically take corrective measures for reagent item arrangements that do not meet the contamination standard requirements, including enhancing cleaning conditions or adjusting the reagent item arrangement between reagent items that do not meet the contamination standard requirements; or a combination of both to reduce the contamination between reagent items; after implementing corrective measures, the instrument automatically detects and verifies again whether the reagent contamination between corresponding reagent items in the corrected reagent item arrangement meets the contamination standard requirements, and automatically corrects again when a reagent item arrangement that does not meet the contamination standard requirements is detected again, and automatically verifies again after correction, until the reagent contamination between all adjacent reagent items in all required reagent item arrangements meets the contamination standard requirements; then, automatically save the verified reagent item arrangement that meets the contamination standard requirements; during the formal testing phase, the instrument automatically uses the verified reagent item arrangement that meets all testing requirements to perform the test.

[0052] Specifically, in the above verification tests, each reagent item is tested at least twice. The reagents used in the verification tests are the same reagents currently used by the instrument. The samples used in the verification tests are the same type of sample, which can be any one of quality control, serum, air, or water. Alternatively, when the same item is tested twice or more, the same sample is used for all tests. During the verification tests, the dosage of each reagent and sample, as well as the cleaning conditions of each reagent dispensing needle and contact stirring device when changing reagents, are also the conditions that will be used when the instrument performs formal tests.

[0053] After verification and testing, the instrument automatically compares multiple test results obtained from each reagent item. When the difference between the first test result and subsequent test results for more than one reagent item is less than a threshold, it indicates that under the current reagent item arrangement and cleaning conditions, the preceding reagent has no contamination effect on the following reagent; however, this does not mean that the two reagents will be free of contamination if their order is reversed. When the first test result for more than one reagent item is higher than the values ​​of subsequent test results, and the difference is greater than or equal to a set threshold (e.g., 0.5%), it is determined that the preceding reagent for the two adjacent reagent items has a significant contamination effect on the test results of the following reagent. The instrument can establish more than one contamination level based on the degree of difference in test results and take different corresponding measures according to the severity of the contamination, including strengthening cleaning, adjusting the order of reagent item testing, or using both simultaneously.

[0054] The instrument also features a function to set the order of reagents with significant contamination as a exclusionary order. This means that the contamination between adjacent reagents in this order cannot be eliminated by a single cleaning cycle. For reagents identified as exclusionary, the instrument will automatically avoid including them in the reagent testing sequence plan. This function simplifies contamination caused by poor reagent sequencing, reduces repeated instrument validation and optimization, and improves instrument efficiency. The exclusionary reagent sequence can be fixed in the instrument software or set by the operator based on practical experience. The exclusionary reagent sequence refers to a specific arrangement between adjacent reagents, but it does not mean that all forward and reverse arrangements of these two reagents will result in exclusionary sequences. It generally refers to one possible arrangement direction. However, if verification shows that both forward and reverse arrangements between these two reagents result in strong contamination, then regardless of whether they are arranged forward or reverse, they will be excluded. The instrument will only use an exclusionary reagent sequence when it is absolutely unavoidable, but it must be used only after thorough cleaning to ensure that the contamination of this reagent sequence meets the contamination standards during actual testing.

[0055] The instrument can also be verified through testing, and the operator or instrument designer can fix the exclusion order of specific items. For example, it can automatically set specific items to not be arranged next to each other; or specifically, when two specific reagent items meet, only one reagent item is allowed to be tested first and the other reagent item is allowed to be tested later; or when the two specific items are arranged next to each other for testing, additional cleaning must be set before the test can be performed.

[0056] Furthermore, in biochemical testing, reagents for the same item may have more than one different detection principle, and the actual reagent components of the same name may differ. In addition, reagents with the same name and detection principle may also have differences in composition and process between reagents produced by different companies. Therefore, the order of these exclusionary reagent items should be determined after confirmation based on the differences in reagent principle and method and the different manufacturers.

[0057] As a specific embodiment of the present invention, the instrument establishes four levels of contamination based on the degree of difference in the detection results, namely, Level A contamination, Level B contamination, Level C contamination, and Level D contamination.

[0058] If the absolute value of the difference between the first test result and the subsequent test result of any reagent item in this verification test is greater than or equal to 0.5% and less than 1.5%, it is determined that the previous reagent item has Class A reagent carry-over contamination to the subsequent reagent item. For Class A reagent carry-over contamination, the instrument will automatically strengthen the cleaning conditions when switching between reagents, such as adding a water cleaning.

[0059] If the absolute value of the difference between the first test result and the subsequent test result of any reagent item in the verification test is greater than or equal to 1.5% and less than 3%, it is determined that the previous reagent item has Class B reagent carry-over contamination to the subsequent reagent item. For Class B reagent carry-over contamination, the instrument automatically performs an additional cleaning with cleaning agent on the reagent dispensing needle and a cleaning with cleaning agent on the contact stirring needle (if the instrument uses a contact stirring device). After that, the reagent dispensing needle and the stirring needle are cleaned with water once more.

[0060] If the absolute value of the difference between the first and second test results of any reagent item in the verification test is greater than or equal to 3% and less than 4.5%, it is determined that the former reagent item has Class C reagent carry-over contamination to the latter reagent item. For Class C reagent carry-over contamination, the instrument will automatically strengthen the cleaning conditions when switching between reagents, such as using acidic or alkaline cleaning agents, followed by an additional water cleaning.

[0061] If the absolute value of the difference between the first and second test results of any reagent item in the verification test is greater than or equal to 4.5%, it is determined that the former reagent item has a Class D reagent carryover contamination to the latter reagent item. For Class D reagent carryover contamination, the instrument will automatically adjust the arrangement order of the reagent items and strengthen cleaning to ensure the elimination of carryover contamination.

[0062] In summary, the reagent arrangement and cleaning process, determined through testing and verification, ensure that contamination carried by the reagent arrangement is effectively controlled.

[0063] In this embodiment, the instrument is also configured to:

[0064] Before performing formal testing, the system automatically checks whether all reagent items to be performed are arranged in the order of reagent items that are stored in the instrument and comply with the carry-on contamination control.

[0065] During the formal testing phase, the instrument prioritizes the reagent items that have been verified and qualified and can meet the requirements for performing all reagent items on all samples at the current time. If there are multiple reagent item arrangements, they are selected according to the following priority order: first, the arrangement that meets the reagent contamination standard and does not require enhanced cleaning conditions is selected; if not, the arrangement that meets the reagent contamination standard but requires enhanced cleaning conditions is selected.

[0066] If the arrangement of all adjacent reagent items in the reagent item sequence required for instrument detection has not been verified for reagent contamination, the instrument will automatically start the detection and verification of reagent contamination between all adjacent reagent items in the unverified reagent item sequence and perform necessary corrections.

[0067] If only a portion of the reagents in the required reagents sequence for testing have not been verified to be contaminated, then only the unverified portion of the reagents in the sequence will be verified for contamination and the necessary corrections will be performed.

[0068] The instrument automatically saves the order of each verified reagent item, so that the instrument can save more than one verified reagent item order. In all subsequent tests, dilution retests or direct retests, all reagent items required for the actual test will be automatically called up in the corresponding verified reagent item order to perform the test.

[0069] Because the cleaning capabilities and contamination levels vary after replacing components such as pumps, needles, and tubing, and because reagents of the same name from different brands may differ in composition, concentration, and formulation, the contamination levels can also vary. Therefore, this instrument is also configured to automatically re-execute the aforementioned detection verification, correction, and storage functions after reagent brand, batch number, cleaning agent, or key instrument component repair or replacement. The key instrument components include the dispensing needle, contact stirring device, or cleaning pump. The instrument automatically saves updated and improved reagent item order and the improved cleaning procedures for different reagent replacements, automatically executing tests according to the prescribed reagent item order and cleaning procedures in subsequent tests. Alternatively, the instrument can be set to periodically perform contamination detection assessment and automatic optimization of the reagent item order.

[0070] Furthermore, the instrument also features a group-based testing method for samples. Before formal testing, the instrument prioritizes grouping samples with identical required reagents into one or more sample groups. It then groups samples with partially identical required reagents into one or more groups. When testing grouped samples, within each group, the instrument employs a batch testing mode centered on specific reagents: first, one reagent is tested on all samples in the group requiring that reagent; then, another reagent is used to test all samples in the group requiring that reagent, and so on, until all reagents in the group are completed. The same process is then repeated for the next group of samples until all reagents in all sample groups are completed. Samples that cannot be grouped are tested separately. Throughout the entire testing process, the order in which all reagents are executed follows the instrument-verified reagent order.

[0071] This fully automated biochemical analyzer uses a sample grouping method, allowing for the centralized testing of the same reagent items from different samples. During this process, the corresponding reagent dispensing needles can continuously draw and dispense the same reagent. These dispensing needles can be repeatedly drawn and dispensed without cleaning, significantly reducing cross-contamination between different reagents and mitigating the risk of reagent contamination caused by frequent reagent changes in existing fully automated biochemical analyzers. Furthermore, when performing tests on the same reagent items, the dispensing needles can directly draw and dispense the same reagent from the same reagent bottle repeatedly without cleaning, further reducing the frequency of contact between dispensing needles and different reagents, thus further reducing reagent contamination. It also helps reduce contamination of the reagent bottles caused by different reagents and cleaning water introduced when the dispensing needle repeatedly draws and dispenses different reagents into different bottles.

[0072] For biochemical analyzers equipped with contact stirring devices, the frequency of reagent replacement is greatly reduced when the instrument continuously tests the same reagent items, which also helps to reduce carryover contamination during the testing process.

[0073] However, in certain special circumstances, such as when the number of samples is too small, or when separate calibration or quality control testing is required, the instrument can directly perform testing on ungrouped samples, but the order of the reagent items for testing will continue to follow the validated order of reagent items.

[0074] The instrument designed in this invention also has the function of controlling and reducing sample contamination. Its specific implementation methods include the following measures.

[0075] Based on sample grouping and testing, the instrument is also designed with the function of automatically identifying and correcting cross-contamination between samples of the same reagent item. To achieve this function, the instrument first determines the cross-contamination threshold between samples for each reagent item through pre-validation. The specific pre-validation method is as follows: samples with high and low concentrations of the same component are cross-tested, and samples of the same concentration are tested twice or more each time. When the test result of the high-concentration sample of the same component causes a deviation to the test result of the corresponding low-concentration sample of the same component to a certain extent (e.g., ≥0.1%), it is determined that the high-concentration sample of the component of that reagent item will cause cross-contamination to the test results of the normal concentration or low-concentration sample of the same reagent item in subsequent tests. This high concentration is set as the sample concentration threshold for that reagent item. Samples that reach or exceed this threshold are considered over-threshold samples for that reagent item. During the formal testing process, the instrument automatically monitors whether all samples are over-threshold samples for each reagent item, or whether each component of each sample reaches or exceeds the threshold level.

[0076] Furthermore, the instrument also has an automatic monitoring and identification function to determine whether the test of any item on any sample is affected by sample contamination. The instrument automatically determines whether a sample exceeding the threshold for that item has just been tested before the test. If the determination result is yes, the instrument automatically retests the sample that may be affected by contamination and uses the retest result as the final test result for that sample on that item, thereby avoiding test errors caused by sample contamination.

[0077] Under the premise of using a validated reagent arrangement order, i.e., effectively controlling cross-contamination between reagents, the instrument also controls cross-sample contamination caused by different component concentrations in different samples. The function of identifying and correcting cross-sample contamination between different reagents can be implemented by selecting either of the following two schemes, or using both schemes simultaneously:

[0078] Option 1: Following the confirmed reagent item order, the sample exceeding the threshold for the next reagent item is placed at the end of the reagent item order before the reagent item for testing. Immediately following, the same sample for the next reagent item is tested more than once. This sample can be any of the following: a normal value sample, a low value sample, or water for that reagent item. When the relative deviation of multiple test results for the same reagent item and the same sample exceeds a preset allowable deviation range, the instrument automatically increases the cleaning intensity when switching between the two reagents and verifies again that the improved cleaning conditions can eliminate carryover contamination. That is, if the relative deviation of multiple test results for the same reagent item and the same sample does not exceed the preset allowable deviation range, the improved cleaning process conditions automatically replace the previous cleaning process conditions for the instrument to retain.

[0079] Option 2: When the instrument detects a sample exceeding the threshold for any specific reagent item, the instrument automatically tracks the sample exceeding the threshold. Regardless of whether the sample is included in the same or different reagent item tests, if the sample is immediately followed by the first sample of the aforementioned specific reagent item after any item test, the instrument automatically retests the first sample of that specific reagent item and uses the retest result as the official report result. However, if the two samples were tested using different reagents and enhanced cleaning measures were taken between the two reagent item tests, the instrument will choose to automatically retest and use the retest result as the official test result, or it will not initiate a retest for subsequent specific reagent item samples and will directly use the original test result.

[0080] When performing automatic dilution and testing on samples with excessively high test results, if the diluted sample has recovered to below the threshold range, it is no longer considered a sample exceeding the threshold, and therefore there is no need to retest subsequent samples.

[0081] In addition, the instrument can also perform sample concentration difference detection according to the validated reagent item arrangement. When the test result of a certain item for a sample is significantly higher than the set threshold, the instrument automatically records and analyzes the test results of subsequent reagent items for that sample. It can also perform more than one test using the same reagent and the same sample. If the following situation occurs: when a reagent item obtains a sample test result that is too high or too low, the test result of another reagent item also shows a corresponding deviation exceeding the standard, the instrument determines that there is carryover contamination between these two adjacent reagent items. To address this carryover contamination, the instrument can employ one of the following two corrective measures or a combination of both: adjusting the arrangement order of the two adjacent reagent items; or / and cleaning the dispensing needle and contact stirring device when replacing reagents between the two adjacent reagent items.

[0082] The instrument automatically verifies whether changing the order can effectively eliminate the impact of the carried contamination. If the order is not changed, in subsequent actual testing, whenever the test result of the previous reagent item is too high or too low, which may lead to the test result of the subsequent reagent item being too high or too low, the instrument automatically retests the sample immediately following the subsequent reagent item, uses the retest result to give the report, or makes a specific annotation on the test result used, instead of using the previous test result as the report result.

[0083] There is currently no unified standard for the carry-over contamination requirements of different reagent items. This instrument design provides modifiable setting standards, allowing users to set carry-over contamination control standards according to their actual needs. The instrument will then make judgments and handle the contamination automatically based on the standards set by the users.

[0084] The instrument is also configured to automatically review whether all reagent items to be performed are in a sufficient order to complete the test before the formal test is performed, provided that the existing reagent items are in a manner that meets the carry-over control requirements. If the existing reagent items are in a manner that has been verified to meet the carry-over standards, the necessary reagent items should be added and verified to meet the carry-over standards. During the formal testing phase, the instrument prioritizes the use of the validated reagent item sequence, ensuring that this sequence meets all reagent requirements for all samples. If all adjacent reagent item sequences in the required testing sequence have not undergone reagent contamination verification, the instrument automatically initiates reagent contamination detection and verification for all adjacent reagent items in the unvalidated sequence and performs necessary corrections. If only some reagent item sequences in the required testing sequence have not undergone reagent contamination verification, only those unvalidated sequences undergo reagent contamination verification and necessary corrections. The instrument automatically saves all validated reagent item sequences, ensuring that it retains more than one validated reagent item sequence. During subsequent testing, the instrument automatically uses validated reagent item sequences as needed.

[0085] The instrument also possesses the ability to determine and automatically correct for contamination carried over to samples tested for the same reagent. When the instrument performs continuous testing on samples of different known concentrations using the same reagent, if the sample concentration reaches a certain level, causing an unacceptable deviation in the test results for subsequent samples with known concentrations at normal or lower levels, it is determined that the sample reaching a certain concentration causes contamination in subsequent sample testing. When it is determined that samples with a concentration of a certain level or higher than that concentration standard will cause contamination in subsequent sample results for that reagent, the samples reaching or exceeding the certain concentration standard are considered to be samples exceeding the threshold for that reagent. When the instrument detects samples exceeding the threshold during actual testing for that reagent, it automatically retests subsequent samples for that reagent. The instrument establishes sample thresholds for different reagents in this manner as an evaluation and treatment method for controlling sample contamination.

[0086] Before the fully automated biochemical analyzer using this method is officially put into use, or after changes in major conditions such as instrument and reagents, it should first automatically verify the sample contamination control process when using the same reagents for testing. It should also automatically test and complete the sequential arrangement of more than one of the commonly used reagent items (including arrangements of partially identical and partially different reagents, arrangements of completely different reagents, etc.) and cleaning process before it can be put into use. Furthermore, when the user needs to change the reagent types, the instrument has the function of automatically optimizing and verifying the sorting of the newly added reagent types.

[0087] The instrument and detection method designed in this paper also have the ability to group samples with the same reagent items to be tested. Within a sample group, each reagent item is tested for the sample group one by one before the next reagent is replaced. This method will greatly reduce the frequency of changing the dispensing needle to draw different reagents, thus effectively reducing the frequency of reagent carryover. It is also conducive to observing and correcting carryover contamination between samples, making carryover contamination control easier and more effective.

[0088] In some embodiments, the reaction disk is provided with two concentric and parallel detection cup rings, one inner and one outer, on which multiple detection cups are evenly and equidistantly installed; each detection cup ring is equipped with two dedicated reagent dispensing needles and one dedicated sample dispensing needle; when the instrument performs the test, some items of each sample are placed in one of the detection cup rings on the reaction disk for testing, while the other items of each sample are placed in the other detection cup ring for testing; when the instrument performs the test, it only needs to verify whether the reagent contamination under the order of reagent items to be tested in each ring on the reaction disk is controllable and meets the contamination standard requirements before the work can be performed; it is not necessary to check whether the order of reagent items to be tested by the current instrument meets the controllable contamination requirement; the reagent item order stored in the instrument and the cleaning conditions under this order are applicable to the testing of the detection cups in the inner and outer rings of the instrument.

[0089] In some embodiments, the discrete fully automated biochemical analyzer has multiple dispensing needles, wherein at least one of the dispensing needles is dedicated to dispensing reagents and at least another dispensing needle is dedicated to dispensing samples.

[0090] In one particular embodiment, the discrete fully automated biochemical analyzer is equipped with at least the dispensing needle corresponding to the specific reagent sequence.

[0091] In another specific embodiment, the discrete fully automated biochemical analyzer is equipped with only one dispensing needle, which sequentially performs dispensing operations for different reagents in the specific reagent sequence and dispensing operations for different samples in a time-division multiplexing manner.

[0092] The established testing sequence and carry-over contamination control measures are not suitable for instruments with different structures and components. Each instrument should establish its own carry-over contamination control procedure based on this method. Instruments of the same model and structure can refer to this procedure, but it must be verified before use.

[0093] The method of this application will be described in detail below with reference to the following embodiments. The test cup in the following embodiments represents the test container of this application. The discrete fully automated biochemical analyzer of this application can be a fully automated blood coagulation analyzer, a fully automated immunoassay analyzer, a fully automated urine analyzer, a fully automated stool analyzer, a fully automated food / beverage analyzer, a fully automated semen analyzer, a fully automated allergen analyzer, a fully automated pesticide analyzer, or a fully automated water quality analyzer.

[0094] Example 1

[0095] Carryover contamination in fully automated biochemical analyzers is a significant factor affecting test results. Discrete biochemical analyzers are currently the mainstream type of fully automated biochemical analyzer. During biochemical testing, these instruments involve repeated contact between different reagents and samples through shared dispensing needles, contact stirring devices, and test cups, all of which can lead to carryover contamination. The dispensing needle, in particular, is a major challenge due to its characteristics: large reagent volume required for each test, large contact area with different reagents, significant differences in reagent properties, narrow internal space making thorough cleaning difficult, and limited cleaning time allowed by the high speed of the instrument. Carryover contamination from reagent residue in the dispensing needle is the primary challenge for biochemical analyzers. While some instruments use non-contact stirring devices, carryover contamination in these instruments primarily originates from residue in the dispensing needle.

[0096] See Figure 1The fully automated biochemical analyzer provided in this embodiment includes a reaction disk 1, a sample loading device 2, a first reagent loading device 311, a second reagent loading device 312, a first dispensing arm 411, a second dispensing arm 412, a third dispensing arm 413, a first cleaning device 511, a second cleaning device 512, a third cleaning device 513, a first stirring device 611, a second stirring device 612, an optical detection unit 7, and a multi-stage cleaning device for detection cups 8. A ring of detection cup positions 11 is arranged around the periphery of the reaction disk 1. The sample loading device 2 is used to load sample containers. The first reagent loading device 311 is used to load first reagent bottles. The second reagent loading device 312 is used to load second reagent bottles. The first dispensing arm 411, the second dispensing arm 412, and the third dispensing arm 413 each carry a dispensing needle. The first dispensing arm 411 is positioned between the reaction disk 1 and the first reagent loading device 311, and quantitatively transfers the first reagent through its dispensing needle. The second dispensing arm 412 is positioned between the reaction disk 1 and the sample loading device 2, and quantitatively transfers the sample through its dispensing needle. The third dispensing arm 413 is positioned between the reaction plate 1 and the second reagent loading device 312, and quantitatively delivers the second reagent via its dispensing needle. A first cleaning device 511 cleans the dispensing needle carried by the first dispensing arm 411. A second cleaning device 512 cleans the dispensing needle carried by the second dispensing arm 412. A third cleaning device 513 cleans the dispensing needle carried by the third dispensing arm 413. Both the first stirring device 611 and the second stirring device 612 are used to stir and mix the liquid in the test cup. A multi-stage test cup cleaning device 8 and an optical detection unit 7 are respectively positioned along the movement trajectory of the test cup. The multi-stage test cup cleaning device 8 cleans the test cup. The optical detection unit 7 performs optical measurements on the liquid in the test cup. See also... Figure 1 Along the rotation direction of the reaction disk, the first distribution arm 411, the optical detection unit 7, the second distribution arm 412, the first stirring device 611, the third distribution arm 413, the second stirring device 612, and the multi-stage cleaning device for the detection cup 8 are arranged sequentially at intervals.

[0097] The core improvement of this embodiment lies in the instrument's configuration to automatically perform the detection, evaluation, correction, and verification functions for cross-contamination between reagents, while also possessing the ability to identify and correct cross-contamination between samples. This significantly improves the instrument's level of cross-contamination control, more effectively ensuring the quality of instrument test results. Furthermore, these functions are completed fully automatically and intelligently with high efficiency, requiring no additional workload, difficulty, or time consumption for the operator, thus greatly enhancing the instrument's ease of use.

[0098] In actual use of biochemical analyzers, there are dozens of common biochemical testing reagents. These reagents differ in composition, pH, and color, and some even inhibit each other or act as substrates for each other. Furthermore, there are differences in the detection principles of the same reagent, and even differences in the brands and compositions of the same reagents with the same detection principle. The reagent dispensing needle often needs to repeatedly draw up different reagents, and because the dispensing needle often draws up a large amount of reagent and has a narrow internal space, the limited cleaning time during testing often results in incomplete cleaning, leading to residues and cross-contamination between reagents. In addition, the concentrations of various components in the samples to be tested in biochemical tests can vary, sometimes drastically. Therefore, the sample dispensing needle also faces the same risk of residues and cross-contamination. Moreover, the instrument often uses contact stirring needles during testing, which are constantly in contact with different reagents and samples. If these devices are not effectively cleaned, they also contribute to cross-contamination. In addition, the condition of instrument components, such as changes in the surface properties of the inner and outer surfaces of the dispensing needle and the contact stirring device after long-term use, pump aging and pressure drop, aging and replacement of instrument pipelines, valves, pumps, and dispensing needle components, as well as ambient temperature, instrument water supply temperature, and water quality differences, can all lead to variations in instrument contamination levels. Therefore, conducting contamination assessments when relevant influencing factors change, or periodically evaluating instrument contamination, can serve as a basis for effective control of contamination. Previously, instrument contamination assessments required operators to perform them themselves. Due to the cumbersome operation, operators often could only verify contamination between a limited number of reagent items that were clearly identified or suspected based on daily test results, or they would directly attempt to eliminate contamination in suspected heavily contaminated items through enhanced cleaning and other measures without verification. However, such approaches cannot address the diverse changes in the order of reagent items required for biochemical testing. The simply set reagent item order often lacks systematic verification and cannot completely eliminate contamination in biochemical analyzers.

[0099] Therefore, this embodiment adopts a new approach and method to manage and control reagent contamination of the instrument and designs a dedicated process.

[0100] I. Automated Detection and Validation of Contamination in Reagent Rooms

[0101] Before performing formal testing, the instrument automatically detects and verifies the contamination carried by all adjacent different reagent items in the proposed reagent item arrangement.

[0102] Specifically, the proposed reagent item arrangement order is derived from a reagent testing sequence set based on rules comprehensively considering factors such as differences in reagent acidity / alkalinity, reagent color, and the degree of cross-contamination between reagents in actual work. This sequence can be derived from the instrument manufacturer's factory settings or from a user-optimized testing sequence based on actual testing results from reagent suppliers. Furthermore, the instrument automatically arranges the reagent items in a repulsive order according to the set requirements for the order of repulsive reagent items. The instrument can also set the interval number of repulsive reagent items based on operator experience or pre-set / selectable settings, and this setting is modifiable.

[0103] Specifically, in the validation test for reagent contamination of the above-mentioned reagent items, each reagent item is performed at least twice. The reagents used in this validation test are the reagents currently used by the instrument, and the samples used in this validation test are the same type of sample. The sample can be any one of quality control, serum, air, or water, or the same sample can be used for two or more tests of the same item. During this validation test, the amount of each reagent and sample used, as well as the cleaning conditions of each reagent dispensing needle and contact stirring device when changing reagents, are also the conditions that will be adopted when the instrument performs formal tests.

[0104] II. Automatic Corrective Measures

[0105] After verification and testing, the instrument automatically compares multiple test results obtained from each reagent item. When the difference between the first test result obtained from more than one test for each reagent item and subsequent test results is less than a threshold or meets the allowable deviation range, it indicates that under the current reagent item arrangement and the current cleaning conditions, the preceding reagent item has no reagent-carrying contamination effect on the immediately following reagent item. However, this does not mean that there will be no contamination between two reagent items after the order of the two reagents is reversed. Therefore, the arrangement order not only specifies the connection between reagent items but also the connection order between reagent items. However, when the first test result obtained from more than one test for any reagent item is higher than the values ​​of subsequent test results, and the difference is greater than or equal to the set threshold (e.g., 0.5%, or the deviation exceeds the required allowable range), it is determined that the preceding reagent of the two adjacent reagent items has a significant reagent-carrying contamination effect on the test result of the subsequent reagent. The instrument can establish more than one reagent-carrying contamination level based on the degree of difference in test results and take different corresponding measures according to the severity of reagent-carrying contamination, including strengthening cleaning, adjusting the order of item execution, or implementing both measures simultaneously to control reagent-carrying contamination.

[0106] In this embodiment, the instrument establishes four levels of contamination based on the degree of difference in the detection results: Level A contamination, Level B contamination, Level C contamination, and Level D contamination.

[0107] If the absolute value of the difference between the first test result and the subsequent test result of any reagent item in this verification test is greater than or equal to 0.5% and less than 1.5%, it is determined that the previous reagent item has Class A reagent carry-over contamination to the subsequent reagent item. For Class A reagent carry-over contamination, the instrument will automatically strengthen the cleaning conditions when switching between reagents, such as adding a water cleaning.

[0108] If the absolute value of the difference between the first test result and the subsequent test result of any reagent item in the verification test is greater than or equal to 1.5% and less than 3%, it is determined that the previous reagent item has Class B reagent carry-over contamination to the subsequent reagent item. For Class B reagent carry-over contamination, the instrument automatically performs an additional cleaning with cleaning agent on the reagent dispensing needle and a cleaning with cleaning agent on the contact stirring needle (if the instrument uses a contact stirring device). After that, the reagent dispensing needle and the stirring needle are cleaned with water once more.

[0109] If the absolute value of the difference between the first and second test results of any reagent item in the verification test is greater than or equal to 3% and less than 4.5%, it is determined that the former reagent item has Class C reagent carry-over contamination to the latter reagent item. For Class C reagent carry-over contamination, the instrument will automatically strengthen the cleaning conditions when switching between reagents, such as using acidic or alkaline cleaning agents, followed by an additional water cleaning.

[0110] If the absolute value of the difference between the first and second test results of any reagent item in the verification test is greater than or equal to 4.5%, it is determined that the former reagent item has a Class D reagent carryover contamination to the latter reagent item. For Class D reagent carryover contamination, the instrument will automatically adjust the arrangement order of the reagent items and strengthen cleaning to ensure the elimination of carryover contamination.

[0111] In summary, the reagent arrangement and cleaning process determined through testing and verification ensure that reagent contamination is effectively controlled under the established reagent arrangement conditions.

[0112] III. Re-verification and Saving

[0113] After correction, the instrument automatically re-detects and verifies whether the contamination carried by reagents between different reagents in the corrected reagent item arrangement meets the contamination carry-over standard requirements. If the contamination carry-over standard requirements are not met, correction is performed again until the contamination carried by reagents between all adjacent different reagents in all required reagent item arrangements meets the contamination carry-over standard requirements. Then, the instrument automatically saves the reagent item arrangement that has been verified to be qualified in terms of contamination carry-over. In the formal testing phase, the instrument can automatically use the verified qualified reagent item arrangement that meets all testing requirements to perform the test.

[0114] When the number of reagents required for testing by the instrument increases or decreases, the order of reagents to be used will change. When the required order of testing needs to be changed, the instrument can automatically activate the above-mentioned automatic assessment and correction function for contamination, and set the order of newly added reagents as needed to meet all the actual testing needs of the instrument.

[0115] When the instrument is currently required to perform reagent tests, it should prioritize using existing and validated reagent sequences and testing procedures. When using an existing approved reagent sequence and procedure, it must be retested and verified to meet contamination standards before use. Alternatively, in special circumstances, a temporary option may be allowed to not validate a small number of newly created reagent sequences, but enhanced cleaning measures must be taken between these newly added sequences to reduce contamination. However, this temporary measure is only permitted for a limited number of uses.

[0116] To improve efficiency, the instrument provided in this embodiment is further configured such that when only some adjacent items in the reagent item sequence to be performed by the instrument have not been verified for contamination, the instrument only performs detection, verification, and necessary correction on the unverified portion; if all adjacent item pairs have not been verified, then the entire reagent item sequence is verified. Both verification and correction are performed automatically, achieving high efficiency and ease.

[0117] Because the cleaning capabilities and contamination levels vary after replacing components such as pumps, needles, and tubing, and because reagents of the same name from different brands may differ in composition, concentration, and formulation, the contamination levels may also vary. Therefore, the instrument provided in this embodiment is also configured to automatically re-execute the detection verification, correction, and storage functions after reagent brand, batch number, cleaning agent, or key instrument component repair or replacement. The key instrument components are the dispensing needle, contact stirring device, or cleaning pump. The instrument automatically saves the updated and improved reagent item arrangement order and the improved cleaning procedure for different reagent replacements, and automatically performs the tests according to the prescribed reagent item arrangement order and cleaning procedure in subsequent tests.

[0118] The specific verification process is as follows: The instrument performs automatic testing according to the currently set reagent item order, using existing reagents, cleaning conditions, and selecting any identical test sample. First, it performs one or more tests on the preceding reagent item in the reagent item order, following the standard testing procedure for that item (the time for each step, such as reagent addition, stirring, sample volume, and reaction detection, is exactly the same as the actual test). For example, following the standard procedure, the dispensing needle draws one portion of the first reagent into a test cup, and then, following the normal testing procedure, one sample and one portion of the second reagent (if the item requires a second reagent) are added to the test cup, and the process is completed. The entire process of mixing and testing is completed. After aspirating the reagent for the previous reagent item, the instrument performs cleaning according to the pre-set dispensing needle in the "cleaning method required for aspirating other reagents after aspirating this reagent" setting. Subsequently, each subsequent reagent item is tested twice or more, and the samples used for each identical test are exactly the same. The samples can be any of serum, quality control materials, water, or air. The instrument also performs the same testing and verification for other reagent items to be tested in the same way. The test is fully automated. The order of reagent items that do not meet the requirements for reagent contamination is corrected, and the verification is repeated until the contamination standard requirements are met.

[0119] Alternatively, a single test can be used to assess the carryover contamination between any two reagents, most of the selected reagents, or all of the reagents required for testing, and to improve the arrangement of reagents that fail the test until the order of all required reagents meets the carryover contamination requirements.

[0120] After the test, the instrument automatically evaluates the test results according to the following rules: If, under the same reagent and sample conditions, the difference between the first test result of the second reagent and the second test result is greater than the set standard, such as 1-10%, or the difference is greater than a certain absolute value, such as 0.3 mg / L; or if, under the same conditions, the difference between the net absorbance value of the first test result of the second reagent and the net absorbance value obtained by subtracting the blank from the subsequent one or more test results is greater than or equal to the absolute value of the set threshold, or exceeds the preset percentage limit, then it is determined that the execution order of the two items has unacceptable carryover contamination under the existing cleaning conditions and should be improved.

[0121] Furthermore, the validation process includes assessing contamination carried by reagents arranged from the first to the last, as well as evaluating the contamination carried between the last reagent and the first reagent in the list.

[0122] When it is determined that there is a risk of contamination between the two items, the instrument automatically takes corrective measures. The corrective measures are selected from any one or a combination of two or more of the following: increasing the number of cleaning times or the amount of cleaning agent, increasing the type of cleaning agent, increasing the number of water rinsings after cleaning with cleaning agent, or directly increasing the number of water rinsings, or using half or full amount of subsequent reagents for rinsing, etc.

[0123] Furthermore, the instrument can automatically optimize the reagent sorting process. This automatic optimization involves adjusting the testing order of adjacent reagents with severe contamination to connect them with other reagents; or combining the change in reagent sorting order with enhanced cleaning. In short, the instrument must ensure that the reagent sorting order used in formal testing meets the contamination standards. Alternatively, based on historical experience, the instrument can automatically adjust the connection order between different reagents to reduce contamination and improve testing reliability. The instrument can also set the sorting order of reagents with severe contamination as a repulsive reagent sorting order, automatically avoiding its use. Regardless of the specific measures taken, it is ultimately essential to ensure that all set reagent sorting orders meet the contamination standards during testing.

[0124] Specifically, the evaluation criteria are that the net absorbance difference should be ≤0.001 OD, or the absorbance value difference should be ≤0.1%; or the difference between the test results before and after the same reagent item should be ≤ the absolute value or percentage value of the set result. However, the acceptable contamination for different reagent items can be different standards.

[0125] If, after the above-mentioned contamination detection and evaluation, all the contamination evaluation results of the reagent detection sequence set by the instrument are qualified, the instrument will automatically prompt / display that the current contamination index of the instrument is qualified, and the instrument can be put into operation.

[0126] However, if the above test verification shows that there is contamination between some of the reagent items, the instrument will automatically take one or more corrective measures for the contaminated items, including adding one or more corrective measures. Specific measures include: increasing the amount of cleaning agent, increasing the type of cleaning agent, increasing the number of times to rinse with water after cleaning with cleaning agent, or directly increasing the number of water rinsing, using half or full amount of subsequent reagent required for testing for rinsing, or adjusting the arrangement of adjacent reagents as a corrective measure.

[0127] During the formal testing phase, multiple workflows suitable for different reagent items are often required. When the instrument performs testing, if there are different samples or sample groups with different reagent items, the instrument automatically arranges the reagent items according to their order, activating a validated and optimized reagent sorting workflow and processing scheme. This allows for flexible responses to changes in reagent item combinations, ensuring that the biochemical analyzer results are not affected by carryover contamination. In other words, even when performing the same batch of tests, the instrument can easily and effectively control carryover contamination when performing different item sequences. For example, triglyceride reagents generally have extremely high carryover contamination for bile acids. Therefore, in general reagent sorting, one or more other items are inserted between triglycerides and bile acids, or the bile acid reagent is placed before the triglyceride item; similar high carryover contamination exists between other items as well. However, when the project arrangement makes it unavoidable to place triglycerides before bile acids, the instrument automatically applies an acidic or alkaline cleaning agent after the dispensing needle draws in the triglyceride reagent, followed by a water cleaning. If the instrument's stirring device is a contact type, the dispensing needle can also draw in or add an additional amount of cleaning agent to the test cup. After the test cup rotates to the stirring device, the stirring device is also thoroughly cleaned using cleaning agents. This effectively eliminates the impact of residual triglyceride reagent on bile acid reagent detection when the dispensing needle subsequently draws in bile acid reagent and the stirring device comes into contact with the bile acid reagent. The cleaning process can involve first cleaning the dispensing needle once or more in the cleaning tank, then drawing in the cleaning agent, or separately drawing in the cleaning agent and water, adding each to a test cup for enhanced cleaning of the dispensing needle and the stirring device.

[0128] Under the condition that the instrument adopts a validated reagent arrangement order, that is, under the premise of effectively controlling reagent contamination, the instrument also has the function of identifying and correcting sample contamination between different reagent items. The following scheme is specifically selected:

[0129] When the instrument detects a sample where the concentration of a component detected by any specific reagent item reaches or exceeds the threshold, the instrument automatically tracks the sample exceeding the threshold. Regardless of whether the sample is included in the same or different reagent item tests, if the first sample of that specific reagent item is immediately performed after the sample is tested, the instrument automatically retests the first sample of that specific reagent item and uses the retest result as the official report result. However, if the two samples were tested using different reagents and enhanced cleaning measures were taken between the two reagent item tests, the instrument will choose to automatically retest and use the retest result as the official test result, or it will not initiate a retest for the subsequent specific reagent item samples and will directly use the original test result.

[0130] The instrument also has the function of automatically diluting and retesting samples with excessively high test results. Specifically, during sample testing according to the validated reagent test sequence, when the test result of a sample is significantly higher than the set threshold, the instrument automatically records and analyzes the test results of that sample and subsequent reagent tests. If the following situation occurs: when a reagent test obtains a sample test result that is too high or too low, and the test result of another reagent test is also correspondingly high or low, and the change in the test result is indeed related to the difference in the concentration of the corresponding component in the previous sample, then the instrument determines that there is mixed contamination between the two adjacent reagent tests. To address this contamination, the instrument can employ one or a combination of the following two corrective measures: adjust the order of the two adjacent reagent items, or simultaneously automatically verify whether changing the order can effectively eliminate the contamination effect; if the order is not changed, during subsequent testing, whenever the test result of the preceding reagent item is too high or too low, which may lead to the test result of the following reagent item being too high or too low, the instrument will automatically retest the next sample immediately following the following reagent item, report the retest result, and make a specific annotation on the retest result, instead of using the previous test result as the report result.

[0131] In this embodiment, before performing formal testing, the instrument automatically evaluates and corrects the impact of carryover contamination on each reagent item to be tested for different concentrations of samples, confirming that it meets the carryover contamination control standards. Specifically, when performing different sample tests for the same test item, the test immediately following an abnormal sample exceeding the threshold is automatically retested. The purpose is to reduce the carryover contamination interference of abnormally high-value samples on subsequent results and improve the consistency between subsequent test results and the true values.

[0132] The instrument also has the function of automatically diluting and retesting samples with excessively high test results. Furthermore, when the instrument automatically dilutes samples with excessively high test results (exceeding the threshold) for retesting, if the actual concentration of the diluted sample has returned to below the threshold range, it is no longer considered an excessively high-threshold sample, and therefore there is no need to retest subsequent samples.

[0133] Specifically, the instrument can also perform sample concentration difference detection during a validated reagent item arrangement. When the test result of a certain item for a sample is significantly higher than a set threshold, the instrument automatically records and analyzes the test results of that sample and subsequent reagent items. Alternatively, it can perform more than one test using the same reagent and the same sample. If the following occurs: when a reagent item obtains a sample test result that is too high or too low, and the subsequent test result of another reagent item also shows a corresponding difference exceeding the standard, the instrument determines that there is carryover contamination between these two adjacent reagent items. To address this carryover contamination, the instrument can employ one of the following two corrective measures, or a combination of both: adjusting the arrangement order of the two adjacent reagent items; or / and cleaning the dispensing needle and contact stirring device when replacing reagents between the two adjacent reagent items.

[0134] Furthermore, retesting can be performed on a sample following an abnormally high value, avoiding the abnormally high value condition, and the test result of the retested sample is used as the true test result. It can also include retesting after diluting abnormally high-threshold samples; when retesting diluted samples exceeding the threshold, if the measured concentration of the diluted sample (this value is not the sample concentration obtained by back-calculating the dilution ratio) does not reach or exceeds the threshold of the project, then the test of the sample following the dilution and retesting does not need to be retested.

[0135] Specifically, the over-threshold sample refers to a sample in the same reagent item whose concentration of the detection result reaches or exceeds the preset threshold of that item; the threshold of the sample item can be adjusted and set based on verification experience, and may be related to the reagent composition, method, and process.

[0136] When the required reagents for instrument operation change, resulting in a change in the reagent testing order, the instrument must perform the following before re-performing the test: automatically evaluate and correct the impact of contamination carried over to each newly added reagent for different concentration samples; verify and correct the contamination carried over between different reagents in the changed order; and then verify the impact of the high-concentration sample from the previous reagent test on the results of the subsequent reagent test under the determined reagent testing order. If there is an impact, the instrument will automatically set a high-limit threshold for the results of the previous high-concentration sample test. If the previous reagent test results in a high value that reaches the threshold in the actual test, the instrument will automatically discard the results of the subsequent reagent test and automatically retest the reagent and the sample, using the retest results.

[0137] When any of the following conditions change: the brand of reagents used by the instrument, the principle of the method, or the reagent setting conditions (such as dosage), the instrument needs to test, verify, and optimize the original reagent item arrangement to ensure that, under the improved conditions, the order of reagent items used by the instrument to perform the test meets the requirements of the reagent contamination standard.

[0138] Example 2

[0139] The difference between this embodiment and Embodiment 1 is that, in this embodiment, the instrument is further configured such that: the instrument not only optimizes the sorting of reagent items to effectively control reagent contamination during the testing process, but also divides the samples to be tested into one or more groups according to the same reagent items; then, it further divides the samples with partially the same reagent items into at least one group; the number of samples in each group is greater than or equal to 2; samples with too few samples or different reagent items from other samples can be tested separately.

[0140] The instrument automatically retrieves the available reagents according to the required testing order, regardless of whether the samples are grouped or not. When testing grouped samples, the instrument executes the first reagent test for all samples within a group, and only after all samples in that group have been tested is the second reagent test performed, and so on, until all samples in all groups have been tested. This allows the instrument to perform tests on the same reagents consecutively. During the testing of the same reagent, a dedicated reagent dispensing needle continuously draws and dispenses the same reagent. Under these conditions, the dispensing needle can repeatedly draw and dispense the same reagent from the same reagent bottle without cleaning, depending on the number of tests required. Because the same reagent is continuously added to each reaction vessel during this period, cross-contamination between reagents is significantly reduced. Furthermore, the reduced frequency of the dispensing needle drawing other reagents, cleaning, and re-entering the reagent bottle significantly reduces contamination within the reagent bottle, thus extending the reagent's shelf life.

[0141] The instrument can perform tests on ungrouped samples one by one in the order specified by the instrument, either before or after this step.

[0142] Among them, the same reagent item refers to reagent items that use the same specific reagent type, sample reagent addition sequence, addition amount and addition logic;

[0143] According to the corresponding reagent item sequence, each sample in the same group is processed sequentially for each reagent item; and different samples in the same group are processed according to the corresponding group execution sequence for each reagent item, and the detection process is controlled for carryover contamination according to the carryover contamination control procedure, including automatic retesting of the test results of the affected sample when a sample exceeds the threshold.

[0144] Example 3

[0145] The difference between the method in this embodiment and that in embodiment 1 is that the instrument in this embodiment is executed on a fully automated biochemical analyzer with only one dispensing arm and one stirring device. The dispensing arm carries a dispensing needle, which sequentially performs the dispensing operations of different reagents in the specific reagent sequence and the dispensing operations of different samples in a separate and grouped manner.

[0146] Figure 2 A top view of the low-carryover-contamination fully automated biochemical analyzer of this embodiment is shown. See also Figure 2 In this embodiment, the only distribution arm is the fourth distribution arm 421, and the only stirring device is the third stirring device 621. Figure 2 A fourth cleaning device 521 for cleaning the dispensing needles carried by the fourth dispensing arm 421 is also shown.

[0147] See Figure 2 In this embodiment, all reagents share the same reagent loading device, namely the first reagent loading device 311. The sample loading device 2 and the reagent loading device are integrated or independent of each other, but both are set within the same spatial range. The dispensing needle carried by the fourth dispensing arm 421 can draw samples from the sample loading device 2 or reagents from the first reagent loading device 311.

[0148] The fully automated biochemical analyzer provided in this embodiment is configured as follows: a carry-on contamination control process for the instrument is established with reference to Embodiment 1 or Embodiment 2; samples are divided into at least one group according to a certain number of samples with the same reagent items to be performed, and the number of samples in each group is greater than or equal to 2; then, the carry-on contamination control process described above and the set sample groups are followed one by one to perform the detection of each sample; or the samples are not grouped and are directly performed in order according to the sample loading order or other rules.

[0149] Example 4

[0150] The difference between this embodiment and Embodiment 1 is that, as Figure 3 The instrument in this embodiment is a fully automated biochemical analyzer with only a fifth dispensing arm 431, a sixth dispensing arm 432, and a contact stirring device 631. Each dispensing arm carries a dispensing needle; one dispensing needle is used for both aspirating and dispensing reagents and samples, while the other dispensing needle is dedicated to dispensing reagents. The fifth dispensing arm 431 is equipped with a fifth cleaning device 531, and the sixth dispensing arm 432 is equipped with a sixth cleaning device 532.

[0151] The fully automated biochemical analyzer provided in this embodiment is configured to: automatically set the contamination control standards for sample detection using the same reagents as illustrated in Embodiment 1; group samples with the same reagent items into one or more groups according to the current reagent item requirements of the current group; and perform detection according to sample grouping. The instrument's dispensing needle performs detection by batch dispensing reagents and samples, ensuring that the total time for each reagent item is not less than 600 seconds, and ensuring that the maximum time difference between the same reagent addition time point, sample addition time point, corresponding stirring time point, and detection time point between each detection cup for the same reagent item is less than 10 seconds. In this embodiment, priority is given to ensuring that the already added reagents and samples complete the detection according to this principle, while the addition time of the first reagent entering the detection is optimized and compromised. During the test, one dispensing needle first draws a quantitative amount of the first reagent, then cleans it on the surface of the corresponding cleaning pool, and then draws a certain amount of sample at the sample position. The drawn first reagent and sample are then added together into a test cup, thus completing the aspiration and dispensing of the first reagent and sample. When the test requires the addition of a second reagent, the other dispensing needle draws a quantitative amount of the second reagent and dispenses it into the test cup, thus completing the test of each sample and each reagent item one by one.

[0152] Example 5

[0153] The difference between this embodiment and Embodiment 1 is that the detection cups arranged concentrically around the perimeter of the reaction plate 1 are arranged in two or more rings, with the detection cups evenly spaced in each ring; the stirring device is configured to stir two or more layers of detection cups, rather than just one ring; the instrument is equipped with one or more dispensing needles for each ring of detection cups; the instrument is equipped with one or more dedicated dispensing needles for each ring of detection cups; and the instrument is also equipped with one or more stirring devices for each ring of detection cups. Different detection cup rings of the instrument perform different reagent items. Therefore, in this embodiment, the instrument evaluates and sets corrective measures for the reagent items to be performed on different rings of detection cups, the sample contamination for each item, and the mixed contamination of each reagent and sample. During formal testing, each reagent, sample dispensing needle, and detection cup performs the set reagent items. In this embodiment, before sample testing, the instrument divides samples into one or more groups according to the same reagent items; in addition, samples with some items are also grouped; the samples are tested according to the groups. During testing, some items of each sample are placed in the inner ring of the test cups on the reaction plate; while the remaining items are placed in the test cups on the outer ring of the reaction plate. In this case, the instrument only needs to verify that the order of the required test items in the inner and outer test cups on the reaction plate is within acceptable limits for reagent contamination before proceeding; it is not necessary to check the entire sequence of reagents to ensure that contamination is within control. The instrument's stored test item order and cleaning conditions are applicable to all tests conducted on both the inner and outer test cup rings.

[0154] Using the low-carry-contamination liquid dispensing method of this application, the analytical workflow of the fully automated biochemical analyzer in this embodiment is similar to that in Embodiment 1.

[0155] Example 6

[0156] Based on any of the above embodiments, the measures for enhanced cleaning of the reagent dispensing needle and sample needle are selected from any one or a combination of two or more of the following:

[0157] Measure 1: For cleaning methods that originally only used water, a cleaning solution should be selected first for cleaning, followed by rinsing with water, and the number of cleaning with the cleaning solution and the number of rinsing with water should be more than one.

[0158] Measure 2: If a cleaning solution has already been used, another cleaning solution can be added before water rinsing.

[0159] 3) On the basis of the original cleaning or on the basis of additional cleaning, use the subsequent reagents used in the current reagent project to perform half or full rinsing.

[0160] Measure 3: After rinsing with water, directly draw and dispense the subsequent reagents used for the current reagent item without adding a sample and perform one test procedure, or use water as a sample and perform one test procedure.

[0161] And measure four: the cleaning agent and the rinse solution of the reagents for subsequent testing are distributed into the testing cup as described in the testing process, in order to perform enhanced cleaning of the contact stirring device of the fully automated biochemical analyzer.

[0162] Example 7

[0163] The instrument in this embodiment also has the functions of automatically identifying and correcting contamination carried by samples under the same reagent item and identifying and correcting contamination carried by samples under different reagent items.

[0164] The automatic identification and correction function for contamination carried by samples under the same reagent item includes:

[0165] For each reagent item, a contamination threshold is determined between samples. This threshold is the concentration value at which the sample concentration of that reagent item is so high that it causes unacceptable deviation in the test results of other samples that subsequently undergo the same test. Samples that reach this threshold are considered to be over-threshold samples for that reagent item.

[0166] During the formal testing process, the instrument automatically monitors whether all samples are above the threshold for each reagent item. When testing any item for any sample, it automatically determines whether a sample above the threshold for that item has just been tested before. If the determination result is yes, the instrument automatically retests the sample that may be affected by contamination and uses the retest result as the final test result for that sample for that item, thereby avoiding testing errors caused by sample contamination.

[0167] Specifically, the function of identifying and correcting contamination carried by samples from different reagent items can be selected from either of the following two schemes, or both of the following schemes can be used simultaneously:

[0168] Option 1: Following the confirmed reagent item order, the sample exceeding the threshold for the next reagent item is placed at the end of the reagent item order before the reagent item for testing. Immediately following, the same sample for the next reagent item is tested more than once. This sample can be any of the following: a normal value sample, a low value sample, or water for that reagent item. When the relative deviation of multiple test results for the same reagent item and the same sample exceeds a preset allowable deviation range, the instrument automatically increases the cleaning intensity when switching between the two reagents and verifies again that the improved cleaning conditions can eliminate carryover contamination. That is, if the relative deviation of multiple test results for the same reagent item and the same sample does not exceed the preset allowable deviation range, the improved cleaning process conditions automatically replace the previous cleaning process conditions for the instrument to retain.

[0169] Option 2: When the instrument detects a sample exceeding the threshold for any specific reagent item, the instrument automatically tracks the sample exceeding the threshold. Regardless of whether the sample is included in the same or different reagent item tests, if the sample is immediately followed by the first sample of the aforementioned specific reagent item after any item test, the instrument automatically retests the first sample of that specific reagent item and uses the retest result as the official report result. However, if the two samples were tested using different reagents and enhanced cleaning measures were taken between the two reagent item tests, the instrument will choose to automatically retest and use the retest result as the official test result, or it will not initiate a retest for subsequent specific reagent item samples and will directly use the original test result.

[0170] Example 8

[0171] Based on any of the above embodiments, the measures to enhance the cleaning of the contact stirring device are selected from any one or a combination of the following:

[0172] Measure 1: After dispensing the reagents, the reagent dispensing needle immediately draws one or more portions of a cleaning agent and adds them to a test cup. When the test cup reaches the position of the stirring device, the stirring device penetrates into the test cup to perform stirring, so that the part of the stirring device in contact with the liquid in the test cup is further cleaned.

[0173] Measure 2: Add one or more different cleaning agents to different test cups. When the test cups reach the position of the stirring device, the stirring device goes deep into the test cups to perform stirring, so that the part of the stirring device in contact with the liquid in the test cups is further cleaned. Then, if the stirring device is running normally until it is cleaned by water in the cleaning tank, it is then added to another test cup with a different cleaning agent for stirring and cleaning. After that, it is cleaned by water in the cleaning tank again before stirring is performed on the new test sample.

[0174] In this embodiment, the sample loading device is disc-shaped. When the instrument needs to repeatedly pick up samples, the sample loading disc rotates back and forth to transfer the sample to the sample dispensing needle to achieve repeated sample picking up.

[0175] Example 9

[0176] The difference between this embodiment and other embodiments is that the sample loading device used in this embodiment is a track-type sample loading device. When the instrument needs to repeatedly test each group of samples, the sample loading device moves back and forth on the track to meet the instrument's sample absorption needs.

[0177] Example 10

[0178] The low-contamination discrete fully automated biochemical analyzer designed in this embodiment also has the function of automatically re-executing the detection verification, correction, and storage functions according to the operator's requirements after the reagent brand, batch number, cleaning agent, or key instrument component is changed, or after repair and replacement. The key instrument components are dispensing needles, contact stirring devices, or cleaning pumps. The instrument automatically saves the updated and improved reagent item arrangement order and the improved cleaning procedure for different reagent replacements. In subsequent tests, it automatically performs the tests according to the prescribed reagent item arrangement order and cleaning procedure.

[0179] Alternatively, an automatic revalidation time can be set for the instrument. When the time expires, the instrument will automatically perform the test and verification according to the existing test reagent items in the correct order. If the test and verification fails to meet the contamination standard, the test and verification will be performed automatically to correct the contamination standard. The instrument will also automatically save the updated and improved test reagent items in the correct order and the cleaning procedure when changing different reagents. In subsequent tests, the instrument will automatically perform the tests according to the prescribed test reagent items in the correct order and the cleaning procedure.

[0180] Example 11

[0181] The low-carryover-contamination discrete fully automated biochemical analyzer designed in this embodiment can also define the arrangement order of reagents that would cause significant carryover as a "rejection reagent arrangement order." This rejected reagent arrangement order is automatically avoided in the instrument's automatic reagent arrangement sequence for testing. Specifically, if reagents are arranged AB, reagent A will cause significant carryover to reagent B. Therefore, the instrument automatically determines the reagent arrangement order "AB" as a rejected reagent arrangement order and automatically avoids the "AB" arrangement when arranging reagent testing sequences. However, if the BA arrangement meets the carryover requirements, the instrument can automatically select the BA arrangement in the arranged reagent testing sequence; or, provided the arranged reagent arrangement order meets the carryover standards, the instrument can select the ACDB arrangement or ADCB arrangement. The instrument's priority principle for the arrangement order is that the planned reagent testing sequence does not contain reagents with significant carryover.

[0182] When the instrument automatically determines which reagents should be excluded from the reagent testing sequence during reagent item arrangement, it eliminates the need for repeated verification and optimization of unreasonable reagent item arrangements, significantly improving instrument efficiency and ease of operation. The order of excluded reagent items can be fixed in the instrument software or set by the operator based on practical experience. The instrument automatically avoids setting and using any test order set to exclude reagent items. However, because reagents with the same name may have different detection principles (e.g., blood glucose testing can be done using the glucose oxidase method or the hexokinase method), and the same reagent item may have different reagent components, the degree of exclusion may vary. Furthermore, even reagents with the same detection principle may have different formulations from different manufacturers, resulting in varying degrees of contamination in actual use. Therefore, reagents with the same name but different principles and from different brands may not have the same degree of contamination, and the contamination between different reagent items should ultimately be confirmed through actual testing.

[0183] In addition, when necessary, the instrument also has the function of automatically setting the interval detection number for the arrangement of rejection reagent items. That is, when there is a confirmed rejection reagent item among the reagent items detected by the instrument, the instrument not only isolates the rejection reagent item, but also sets the minimum interval detection number between the rejection reagent items to ensure that the carryover effect of the rejection reagent item is reduced to a level that fully meets the requirements; or the instrument can also effectively reduce carryover contamination by automatically setting reagent items that are not affected by carryover contamination between rejection reagent items; or the instrument can use the above reagent item detection arrangement method in combination with enhanced cleaning method to eliminate carryover contamination;

[0184] In summary, the instrument can be implemented using one or more of the above-mentioned design methods to ensure that the contamination carried by each test result meets the standard requirements when the instrument performs normal testing.

[0185] Example 12

[0186] The instrument provided by this invention is also applicable to fully automated blood coagulation analyzers, fully automated immunoassay analyzers, fully automated urine analyzers, fully automated fecal analyzers, fully automated food / beverage analyzers, fully automated semen analyzers, fully automated allergen analyzers, fully automated pesticide analyzers, or fully automated water quality analyzers, etc.

[0187] This invention provides a concept and method for a discrete fully automated biochemical analyzer with low carryover contamination. Many methods and approaches exist for implementing this technical solution; the above description is merely a preferred embodiment of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of this invention, and these improvements and modifications should also be considered within the scope of protection of this invention. All components not explicitly stated in this embodiment can be implemented using existing technologies.

Claims

1. A low-contamination discrete fully automated biochemical analyzer, comprising a reaction plate, test cups disposed on the reaction plate, and dispensing needles for transferring reagents and samples required for testing into each test cup; the instrument performs tests on different items for each sample separately in one test cup, and when performing tests on different reagent items, each reagent item uses one or more reagents, characterized in that, The instrument is configured to: automatically detect and verify, before performing formal testing, whether the unverified reagent contamination between all adjacent different reagent items in the proposed reagent item arrangement meets the contamination standard requirements; automatically take corrective measures for reagent item arrangements that do not meet the contamination standard requirements, the corrective measures being enhanced cleaning conditions and / or adjusting the reagent item arrangement; after correction, the instrument automatically detects and verifies again whether the reagent contamination between corresponding different reagent items in the corrected reagent item arrangement meets the contamination standard requirements, and when a reagent item arrangement that does not meet the contamination standard requirements is detected again, it is automatically corrected again, and then automatically verified again, until the reagent contamination between all adjacent different reagent items in all reagent item arrangements to be used by the instrument meets the contamination standard requirements; then, the instrument automatically saves the reagent item arrangements that have been verified to be qualified in terms of reagent contamination; in the formal testing stage, the instrument automatically uses the verified qualified reagent item arrangements that meet all testing requirements to perform the testing.

2. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 1, characterized in that, The instrument is also configured to: During the formal testing phase, the instrument prioritizes the reagent items that have been verified and qualified and can meet the requirements for performing all reagent items on all samples at the current time. If there are multiple reagent item arrangements, they are selected according to the following priority order: first, the arrangement that meets the reagent contamination standard and does not require enhanced cleaning conditions is selected; if not, the arrangement that meets the reagent contamination standard but requires enhanced cleaning conditions is selected. If only a portion of the reagents in the required reagent sequence for instrument testing have not been verified to be contaminated, the instrument will only perform reagent contamination verification and necessary corrections on that unverified portion of the reagent sequence. The instrument automatically saves the order of each verified reagent item, so that the instrument can save more than one verified reagent item order. In all subsequent tests, dilution retests or direct retests, the instrument will automatically call the corresponding verified reagent item order to perform the test according to the reagent items required for the actual test. For adjacent reagent items whose arrangement relationship is determined by testing and verification to be non-compliant with the contamination standard requirements and still does not meet the contamination standard requirements after one enhanced cleaning condition, the instrument has the ability to automatically set the arrangement relationship of the reagent items to the order of exclusion reagent items. When arranging the order of reagent items to be used subsequently, the instrument automatically avoids using the order of the excluded reagent items; or the order of the excluded reagent items is set manually; after the order of the excluded reagent items is set, the instrument always automatically avoids using the order of the excluded reagent items during the execution of the pre-designed reagent item sorting and detection operation; the confirmation of the order of the excluded reagent items is related to the different reagent detection principles of the same reagent, as well as the formulation process of reagents produced by different companies.

3. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 1, characterized in that, The specific method by which this instrument verifies and corrects the order of reagent items is as follows: In the aforementioned testing and validation, each reagent item is tested at least twice using the same sample to obtain at least two test results. The difference between the at least two test results for the same reagent item using the same sample is compared to evaluate whether the reagent item's contamination from preceding reagent items meets the required contamination standards. If any reagent item arrangement is found to be inconsistent with contamination requirements, the arrangement is automatically corrected by changing the reagent item order and / or by enhanced cleaning. The corrected reagent item arrangement is then retested, and only the corrected arrangement is used. In the validation testing, the same sample is used for each reagent item; the sample can be any one of quality control material, serum, air, or water. The contamination standard for the reagent depends on the repeatability requirements of the reagent item and is evaluated using absolute or relative differences.

4. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 1, characterized in that, Before performing formal testing, the instrument prioritizes grouping samples with identical required test reagents into one or more groups. Then, it groups other samples with partially identical required test reagents into one or more groups. When testing grouped samples, within each group, the instrument adopts a batch testing mode centered on the test reagent: first, one reagent test is performed on all samples in the group requiring that test; after completion, another reagent test is used on all samples in the group requiring that test, and so on, until all reagent tests in the group are completed. Then, the same process is repeated for the next group of samples until all reagent tests for all sample groups are completed. Samples that cannot be grouped are tested separately. Throughout the entire testing process, the order of all reagent tests performed follows the order of reagent tests validated by the instrument.

5. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 4, characterized in that, The instrument also has the function of automatically identifying and correcting contamination carried between samples under the same reagent item; And an automatic identification and correction function for cross-sample contamination for any reagent test, including: For each reagent item, a contamination threshold is determined for the sample carrying capacity of the reagent item. This threshold is the concentration value at which the sample concentration during the test of the reagent item is so high that it causes unacceptable deviation in the test results of other samples when the same reagent item is subsequently tested. Samples that reach or exceed this concentration value are called over-threshold samples of the reagent item. During the formal testing process, the instrument automatically monitors whether all samples exceed the threshold for each reagent item. When testing any reagent item for any sample, it automatically determines whether there was a sample that had just been tested for that reagent item and exceeded the threshold, regardless of whether the sample that exceeded the threshold was tested for a different reagent item or the same reagent item. Furthermore, regardless of the actual reagent item tested on the previous sample, if the sample tested in the next adjacent test exceeded the threshold for the subsequent reagent item, the instrument automatically retests the sample for that reagent item and uses the retest result as the final test result for that sample for that item, thereby avoiding testing errors caused by sample contamination.

6. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 4 or 5, characterized in that, The instrument also has the function of identifying and correcting contamination carried by samples between different reagent items. Specifically, you can choose any one of the following two schemes, or use both of the following schemes simultaneously: Option 1: Following the confirmed order of reagent items, a sample exceeding the threshold for one reagent item is placed at the end of the list of reagent items immediately preceding it for testing. The subsequent reagent items are then tested more than once using the same sample, which can be any of the following: a normal value sample, a low value sample, or water for that reagent item. If the relative deviation of multiple test results for the same reagent item and the same sample exceeds a preset allowable deviation range, the instrument automatically increases the cleaning intensity when switching between the two reagents and re-verifies the process. If the improved cleaning conditions are confirmed to eliminate carryover contamination (i.e., the relative deviation of multiple test results for the same reagent item and the same sample does not exceed the allowable deviation range), the improved cleaning process conditions automatically replace the previous cleaning process conditions for instrument use. Option 2: When the instrument detects a sample exceeding the threshold for any specific reagent item, the instrument automatically tracks that sample. Regardless of whether the sample is included in the same or different reagent item tests, if the sample is immediately followed by the first sample test of that specific reagent item in any test, the instrument automatically retests the first sample of that specific reagent item and uses the retest result as the official report result. However, if the two samples were tested using different reagents, and enhanced cleaning measures have been taken between the two reagent item tests, then automatic retesting is selected, and the retest result is used as the official test result. Alternatively, if the enhanced cleaning measures taken ensure that the carryover contamination between the two tests has been eliminated after the previous tests at different times, then retesting is not initiated for subsequent samples of that specific reagent item, and the original test result is used directly.

7. The low-carryover-contamination discrete fully automated biochemical analyzer according to any one of claims 1 to 6, characterized in that, The reaction disk is equipped with two concentric and parallel detection cup rings, one inner and one outer. Multiple detection cups are evenly and equidistantly mounted on these rings. Each detection cup ring is equipped with two dedicated reagent dispensing needles and one dedicated sample needle. During testing, the instrument performs some tests on one detection cup ring of each sample, while performing tests on the other. The instrument only needs to verify whether the reagent contamination is controllable under the required reagent sequence for each ring on the reaction disk before commencing operation; it does not require checking the entire reagent sequence for all required tests to ensure controllable contamination. The existing reagent sequence and cleaning conditions are suitable for testing the inner and outer ring detection cups, and the sequence of all required reagent tests for both the inner and outer ring detection cups meets the contamination control standards.

8. The low-carryover-contamination discrete fully automated biochemical analyzer according to any one of claims 1 to 7, characterized in that, The fully automated biochemical analyzer is equipped with a dedicated dispensing needle for independently aspirating and dispensing samples, and a dedicated dispensing needle for independently aspirating and dispensing reagents. When performing tests on the same reagent, the dispensing needle can repeatedly aspirate and dispense the same reagent as needed. During this period, when the dispensing needle is only aspirating and dispensing the same reagent, it can directly aspirate and dispense the same reagent without cleaning, or it can be cleaned before aspirating and dispensing the same reagent.

9. The discrete fully automated biochemical analyzer with low carryover contamination according to any one of claims 1 to 7, characterized in that, The fully automated biochemical analyzer is equipped with only one or two dispensing needles, and at least one dispensing needle must be used to simultaneously aspirate and dispense reagents and samples at one time. That is, when performing a test, at least one dispensing needle configured by the instrument aspirates the first reagent first, and then directly aspirates and dispenses the sample before dispensing the first reagent. The aspirated reagent and sample are then added together into a test cup. The dispensing needle is then cleaned internally and externally before the next reagent and sample aspiration and dispensing is performed, or a separate reagent dispensing is performed. The instrument with this structure is also designed according to the present invention and, according to the actual operating mode of the instrument, detects the contamination carried by different reagent items in different order. When the detected contamination exceeds the allowable standard, it automatically performs optimization and improvement, and uses the reagent item detection order and cleaning conditions that have been verified to meet the contamination carried standard to perform normal testing of the actual sample. The instrument also automatically reduces contamination by grouping samples and prioritizing the use of the same reagents for testing.

10. The low-carryover-contamination discrete fully automated biochemical analyzer according to claim 1, characterized in that, The instrument is selected from fully automated blood coagulation analyzers, fully automated immunoassay analyzers, fully automated urine analyzers, fully automated fecal analyzers, fully automated food / beverage analyzers, fully automated semen analyzers, fully automated allergen analyzers, fully automated sample processors, fully automated gene detectors, fully automated pesticide residue analyzers, or fully automated water quality analyzers.

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