(1) According to the structure of the reaction device, automatic biochemical analyzers are mainly divided into two categories: flow systems and discrete systems.
1. Flow pattern means that the chemical reaction of the sample to be tested with the same test item mixed with reagents is completed in the same pipeline flow process. This is the first generation of automatic biochemical analyzer.
2. Discrete means that the chemical reaction of each sample to be tested after mixing with reagent is completed in its own reaction cup. There are several kinds of branches.
(1) Typical discrete automatic biochemical analyzer. This instrument is the most widely used.
(2) Centrifugal automatic biochemical analyzer, in which each sample to be tested is mixed with reagent in its own reaction tank under the action of centrifugal force to complete chemical reaction and determination. Because the mixing, reaction and detection are almost completed at the same time, the analysis efficiency is high.
3. The bag-type automatic biochemical analyzer replaces the reaction cup and colorimetric cup with reagent bag, and each sample to be tested reacts and determines in its own reagent bag.
4. The solid-phase reagent self-defined biochemical analyzer (also called automatic analyzer for dry chemical formula) is to fix the reagent on a carrier such as film or filter paper, and drop each sample to be tested on the corresponding test strip for reaction and determination. Its advantages are quick operation and easy carrying.
(2) Basic structure of typical discrete automatic biochemical analyzer
1. sample system
Samples include calibrators, quality controls and patient samples. The system usually consists of sample loading, conveying and distribution devices.
Common sample loading and conveying equipment are:
(1) Sample tray, that is, the turntable for placing samples has one or more circles inside and outside, which is placed alone or nested with reagent turntable or reaction turntable, and rotates with the sample distribution arm during operation. Some use replaceable sample trays, which are divided into working areas and standby areas, in which a plurality of arc-shaped sample sectors are placed as transfer tables, and instruments are automatically placed and replaced during determination, all of which have certain requirements on the height, diameter and depth of sample cups or test tubes placed on the sample trays, some need special sample cups, and some can directly use blood collection test tubes. The number of sample trays and the number of calibrators, quality controls, routine samples and emergency samples are usually fixed. These should be chosen according to the needs of the work.
(2) The racks for belt or track sampling are discontinuous, usually 65,438+00 racks. The conveyor belt is driven by a stepping motor, the racks move forward in turn, and then the racks move laterally to a fixed position one by one, and the samples are sampled by the sample distribution arm.
(3) The chain injection test tube is fixedly installed on the circulating transmission chain and horizontally moved to the sampling position, and then some instruments can clean the test tube.
Most dispensing and sampling devices consist of syringes, stepper motors or transfer pumps, sampling arms and sample probes. ① Violet sperm unit. According to the diameter of the syringe and the moving distance of the piston, the sample or reagent is inhaled quantitatively. Its accuracy determines the accuracy of sample addition, which can generally be as accurate as 1 microliter. When the syringe leaks, the first consideration is whether the probe is blocked, and the second is the wear of the syringe piston. Some liquid filling systems use volumetric injection pump and numerical control pulse stepping motor to improve accuracy. (2) The sample probe is connected with the sample adding arm to directly suck the sample. The probes are all equipped with liquid level sensors to prevent probe damage and reduce carrying pollution. Some are equipped with jam detection and alarm systems. When the blood clot and other substances in the probe sample are blocked, the instrument will automatically alarm to flush the probe, skip the current sample and add the sample to the next sample. Some also have intelligent anti-collision devices. When encountering obstacles, the probe immediately stops moving and gives an alarm. Even so, it is still a weak link in irregular operation. In order to protect the probe, the specifications, placement, liquid level height and other setting conditions of the sample container shall not be changed at will, unless it needs to be set in advance according to the height and minimum liquid level height of the sample container. On some instruments, the sampler and the liquid feeder are combined to complete the addition of samples and reagents or diluents at one time. ③ Sampling arm. Connect the probe and move between the sample cup (reagent bottle) and the reaction cup to complete sampling and sample addition (reagent addition). Its movement mode has a certain relationship with the working efficiency and working life of the instrument. (4) The valve is used to determine the direction of liquid flow. ⑤ Dilution system. Pre-dilution, post-dilution or double dilution of samples, serial dilution of standard reserve solution, etc. Different instruments have different dilution methods, so we should pay attention to identification. The reagent system also has a dilution function:
2. The reagent system generally consists of reagent storage, distribution and liquid addition devices.
(1) The reagent bin is usually combined with the reagent turntable. Most instruments set the reagent bin as a cold room to improve the stability period of on-line reagents.
(2) Distribution unit. Similar to the example system. The reagent probe can often preheat the reagent, and the initial amount of reagent 2(R2) probe in the double reagent system should be low to match the reagents with different ratios of R 1/R2.
(3) reagent bottle. There are different shapes and sizes. For example, COBAS Milla PLUS instrument has specifications such as 4, 10, 15 and 35ml, and the bottom of the bottle is concave. Olympus Au600 instrument has specifications such as 30, 60ml and Hitachi 7060 instrument has specifications such as 20, 50 and 100ml. The remaining dead volume and replacement frequency of reagent bottle should be reasonably selected according to the workload and reagent specifications. The specially designed cassette is small in size, evaporation-proof and easy to store.
(4) Matching reagents often have bar codes, and the instrument is equipped with a bar code inspection system, which can check the type, batch number, inventory, expiration date, calibration curve, etc. of reagents, such as BeckmanCX7.
(5) The reagent bottle cap automatic opening and closing system is more conducive to reagent preservation. Some instruments can be added and replaced during operation, while others must be suspended.
3. Bar code reading system
Generally, it consists of scanning system, signal shaping and decoder. The scanning system uses a light source to scan bar code symbols with black bars and blanks. Because the light reflected by bars and spaces is different, the reflected light duration of bar symbols with different widths is different, resulting in reflected light with different intensities, which is received by photoelectric conversion elements and converted into electrical signals with corresponding intensities. Finally, it is processed by signal shaping and interpreted by the decoder. The system automatically identifies sample racks and sample numbers, reagents, calibrators and their batch numbers and expiration dates, and some can also identify calibration curves and other information.
The commonly used barcode types in the laboratory are CODE 39, CODE 128, 2 of 5 Standard, Interleaved2of 5, etc. To edit the sample barcode, a barcode input device is needed, and the barcode reading system should match the barcode. There are automatic test tube distribution and barcode paste preparation systems.
4. Reaction system
(1) The reaction plate is equipped with a series of reaction cuvettes, mostly in the form of turntables. In the process of reaction determination, it rotates among the sample adding arm, the liquid adding arm, the stirring rod, the light path and the cleaning device according to a fixed procedure. Some instruments are sucked into the cuvette for color comparison after completing the reaction in the cuvette. Now it is more common to react and detect in a cuvette, which is more efficient and especially suitable for continuous monitoring. Colorimetric cups are mostly made of hard timely glass, hard glass and acrylic plastic that does not absorb ultraviolet rays. , different service life. Dimension series cuvettes are manufactured automatically in the machine, sealed automatically, free from cleaning and pollution. The flow cell type is mainly used for small analyzers. The volume is generally in the tens of microliters, but the pumping pipeline takes up more reaction liquid, and multiple samples are used continuously, which increases the chance of cross-contamination.
Peristaltic pump Semi-automatic biochemical analyzer needs peristaltic pump to pump the reaction solution into the flow colorimetric cell for determination. It is required to calibrate the peristaltic pump regularly, that is, to check whether the amount of liquid sucked by the pump is accurate by sucking a certain amount of water. Pump calibration function is usually provided.
(2) The mixing unit adopts multi-head rotary stirring rod (double-head and double-washing stirring system). Stirring rods are usually coated with Teflon non-stick coating to avoid liquid adhesion.
(3) Temperature Control Device The biochemical analyzer keeps the incubation temperature regulated and constant through a constant temperature control device, which is also controlled by a computer. The ideal incubation temperature fluctuation should be less than 0.65438 0℃. There are three ways to keep the temperature constant. ① Constant air bath temperature: that is, there is air between the cuvette and the heater. Air bath is characterized by convenience, rapidity and no need of special materials, but its stability and uniformity are slightly worse than that of water bath. Roche's cobas and 0lympus Au2700 systems adopt air bath constant temperature mode. ② Water bath circulation: that is, water is filled around the cuvette, and the heater controls the water temperature. The characteristic of constant temperature in water bath is constant temperature, but special preservatives are needed to ensure the cleanliness of water quality, and circulating water should be replaced regularly. Hitachi system biochemical analyzer adopts water bath circulating constant temperature device. ⑧ Constant temperature liquid circulation indirect heating type: The structural principle is that a special constant temperature liquid (tasteless, pollution-free, inert and non-evaporating) flows around the cuvette. There is a very small air slit between the cuvette and the thermostatic liquid, and the thermostatic liquid reaches a constant temperature by heating the air in the slit, so its temperature stability is better than that of dry type, and it does not need special maintenance compared with water bath circulation type.
Step 5 clean the system
The probe and the stirring rod are automatically cleaned by the rapids. The cleaning device usually consists of a liquid suction needle, a liquid discharge needle and a wiping brush. The cleaning workflow is to suck out the reaction, inhale the injected pure water, suck it dry and dry it. There are two kinds of cleaning solutions: alkaline and acidic. Generally speaking, after the reaction solution is sucked out, the instrument is cleaned with alkaline solution, then with acidic solution, and finally with deionized water for three times. The function of the wiping brush is to suck away the water hanging on the cup wall, and there is a negative pressure device inside the brush body. Pay attention to whether the wiping brush is worn during use.
It is worth noting that conventional washing can not remove the residue experiment, so special treatment should be carried out to reduce cross-contamination or residual pollution. For example, cholates in cholesterol determination reagents interfere with the determination of serum total bile acids. In the process of eliminating cross-contamination, a program can be input to instruct the total bile acid not to be determined in the colorimetric cup for testing cholesterol. If it is unavoidable, the instrument will specially clean the cuvette to prevent cross-contamination.
Automatically control the water temperature of washing water close to the temperature of the constant temperature reaction tank, ensure the constant temperature of the reaction system and increase the decontamination power. It seems that it is more efficient and economical to adopt targeted cleaning after emergency measurement than to adopt a fixed comprehensive cleaning procedure. The water consumption of different instruments varies greatly.
Abbott AEROSET automatic biochemical analyzer and other systems have intelligent cleaning function and optimal sample sequence selection function (OSS). That is, the instrument automatically changes the detection order according to the combination of cross-contamination items between reagents or samples to avoid the analysis items that affect each other; When it is really unavoidable, choose a special cleaning agent for automatic cleaning.
6. Chromaticity system
(1) most light sources are halogen lamps, and the working wavelength is 325 ~ 800 nm. Halogen lamps have a short life, generally only 1 000 ~ L 500 hours. When the luminous intensity of the lamp is insufficient, the instrument will automatically give an alarm and should be replaced in time. Some biochemical analyzers use long-life xenon lamps, which can work for several years in 24-hour standby, and the working wavelength is 285-750nm.
(2) Colorimetric cup The colorimetric cup of the automatic biochemical analyzer is also a reaction cup. The optical diameter of the cuvette varies from 0.5 cm to 0.7 cm, and it is usually made of timely or high-quality plastic. For reagents with small optical diameter, when the optical diameter of the cuvette is less than 1 cm, some instruments can be automatically corrected to 1cm. The automatic flushing device of the colorimetric cup of biochemical analyzer automatically washes and sucks up repeatedly after the colorimetric analysis of the instrument is completed, and the colorimetric cup continues to be recycled after the automatic detection is qualified. Unqualified cuvettes should be replaced in time. If a seasonal cuvette is used, it should be inspected and cleaned regularly.
(3) All kinds of automatic biochemical analyzers of monochromator and detector adopt visible-ultraviolet absorption spectrometry, that is, in the light region of 200-700nm, the change of absorbance of chromophore at a specific wavelength is monitored, and the microcomputer software system is assisted to calculate and complete the determination. The quantitative basis of visible ultraviolet absorption spectrum is Lambert-Beer law.
The traditional photometric measurement generally adopts pre-splitting, that is, the light between the light source lamp and the sample cup is split by using a filter, prism or grating, and the monochromatic light complementary to the sample is obtained through an adjustable slit, and then it is irradiated on the sample cup, and then the photoelectric tube or photoelectric tube is used as a detector to measure the absorption (absorbance) of the monochromatic light by the sample.
However, most modern biochemical analyzers use post-spectral measurement technology. Post-spectral measurement: first, a beam of white light (mixed light) is irradiated on the sample cup, then it is split by grating, and a row of light-emitting diodes are placed behind the grating as detectors. The advantage of post-splitting is that it does not need to move any parts in the colorimetric system of the instrument, and it can be determined at the same time at two or more wavelengths, which can reduce the noise of colorimetric analysis, improve the accuracy of analysis and reduce the failure rate.
The monochromator of biochemical instruments, that is, beam splitter, has two kinds: interference filter and grating beam splitter. There are two kinds of interference filters: plug-in and turntable. Plug-in is to insert the required filter into the filter slot. Disc type is to install all the filters equipped with the instrument in the disc, and rotate them to the required filters when using. Interference filter is cheap, but it is easy to get damp and moldy, which affects the accuracy of test results. This kind of filter is often used in semi-automatic biochemical analyzer.
Grating splitting can be divided into holographic reflection grating and etched concave grating. The former is made by covering a metal film on the glass, which is easy to be corroded, and there is a certain degree of difference; The latter is to carve the selected wavelength on concave glass, which is wear-resistant, corrosion-resistant and phase-free. Most automatic biochemical analyzers use grating light splitting.
7. Program control system
The computer is the brain of the automatic biochemical analyzer. The injection and identification of samples and reagents, bar code identification, constant temperature control, washing control, result printing, quality control monitoring and various fault alarms of instruments are all controlled by computers. The instrument is getting better from generation to generation, and the degree of automation is getting higher and higher. Some instruments can even complete some routine maintenance procedures. The data processing function of automatic biochemical analyzer is becoming more and more perfect, such as absorbance in the reaction process, indoor quality control results statistics of various determination methods and calibration methods, etc. , can be processed by biochemical analyzer. The computer can also adjust the patient's data, the performance index of the instrument and the running state of the instrument. Quality control and patient results in automatic biochemical analyzer can also be managed through the interface between instrument computer and laboratory information system (LIS).
The program controller is the hardware part of the system. Mainly includes:
(1) microprocessor and host. Used for all units and overall control of the instrument, it should have powerful functions such as program-controlled operation, fault diagnosis, various data processing and storage. Generally, it is configured according to the needs of instrument functions and the mainstream products in the computer hardware market.
(2) CRT monitor unit. Usually through the keyboard, mouse, touch screen and other operations.