Hematology analyzers, a type of hematological analysis equipment, are also known as blood analyzers, hemocytometers, or blood cell counters. They can test blood parameters including the counts of red blood cells, white blood cells, and platelets, hemoglobin concentration, hematocrit, mean corpuscular volume, etc. They can improve the accuracy of test results and are widely used in clinical testing. In the early days, blood routine tests were performed manually using microscopes, which had drawbacks such as long time consumption and high error rates. Hematology analyzers can replace manual operations, with more test parameters, faster speed, and higher accuracy, playing an important role in disease diagnosis and monitoring. They are widely used in various blood disease detection fields, including hemophilia, leukemia, malignant lymphoma, anemia, blood infections, etc. In 2022, the global market size of hematology analyzers was approximately 24.2 billion yuan. Currently, in the global hematology analyzer market, the North American region still accounts for the largest share of demand. However, emerging economies in the Asia-Pacific region are developing rapidly, with residents' income levels continuously rising, health awareness constantly increasing, and the diagnosis and treatment rate of patients with blood diseases keeping improving. Coupled with the growing market demand for fully automatic and high-precision hematology analyzers, the hematology analyzer market is growing more rapidly. Blood Cell Detection Technologies The main detection objects of hematology analyzers are the formed components in blood, including red blood cells, platelets, white blood cells, and hemoglobin in red blood cells. From the perspective of detection technology, they can be divided into three categories: impedance method, light scattering method, and colorimetry, each with different subdivided technologies, which are briefly described below. (1) Impedance method: The impedance method is based on the Coulter principle, that is, when non-conductive particles pass through a small hole with a constant current electric field applied at both ends, the change in pulse amplitude is proportional to their volume. In specific implementation, the aperture of the small hole is usually between 50 and 100 μm, and it is mostly processed with ruby, so it is also called a gem hole. When two or more particles pass through the small hole simultaneously or in close proximity, the obtained pulse amplitude will be distorted. Therefore, it is crucial to control the single passage of particles. In blood, the concentration of blood cells is very high, especially red blood cells, so they must first be diluted significantly. Thus, two specific technical routes have been developed: ordinary impedance method and sheath flow impedance method. Ordinary impedance method: A constant pressure is applied to the sample to be tested to make it flow slowly through the gem hole. The path of cells in the sample when passing through the hole is random and irregular. To ensure a low particle overlap interference rate, the dilution ratio is usually as high as about 20,000. This method is more suitable for red blood cells with a large number and large volume, but for platelets with a relatively small number and small volume, it has shortcomings such as few statistical data and easily interfered pulses, resulting in low repeatability and accuracy of platelet detection. Sheath flow impedance method: Using the principle of fluid focusing, the width of the sample flow is controlled to a scale equivalent to the cell diameter, so that cells pass through the gem hole in a straight line and one by one without mutual interference, thus obtaining extremely high-quality pulse signals. The dilution ratio of the sample by this method is usually between 300 and 500, with a large amount of statistical data and excellent performance. It also has characteristic capabilities such as dynamically detecting the system background and automatically identifying interfering substances. However, because it needs to establish a fluid focusing system, its complexity and cost are significantly higher than those of the ordinary impedance method. After lysing the red blood cells in the sample, the remaining white blood cells can be counted using the impedance method, and simple grouping can be done according to their volume, usually divided into lymphocyte group, intermediate cell group, and neutrophil group. Since the number of white blood cells is small, only about one-thousandth of that of red blood cells, a smaller dilution ratio and the ordinary impedance method can be used when measuring white blood cells. (2) Light scattering method: The light scattering method is based on the Mie scattering principle, that is, there is a proportional relationship between the internal complexity of particles and their scattered light intensity. This method was first applied to white blood cell detection, which can divide white blood cells into five categories: lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The excitation light source usually uses a monochromatic laser, and a very narrow light spot with uniform energy distribution is obtained through beam shaping technology to irradiate the optical flow cell. The flow cell is a transparent device with rectangular inner and outer parts. Using fluid focusing technology, cells in the sample fluid pass through one by one, and are irradiated by the light spot in the detection area to generate scattered light. The scattered light is received and converted into electrical signals using photoelectric devices. Depending on the signal strength, photodetectors or photomultiplier tubes can be used. The light scattering method can use at least two or more dimensions of information to obtain more accurate recognition capabilities. The composition of each dimension signal is as follows: Volume: A commonly used method is to use the forward scattered light signal at about 1°, or the 0° light absorption signal, or add a small hole in front of the optical flow cell to obtain volume information using the impedance method. Complexity: A commonly used method is to use side scattered signals, with optional collection angles such as medium angles around 10-20°, medium-high angles around 40°, or 90° side angles. Depolarized light information is also used to reflect differences in cell contents. Fluorescence information: By adding dyes with specific labeling capabilities, they enter the cell and combine with specific targets. After being excited by laser, the dyes release fluorescence with a specific wavelength different from the excitation wavelength, which is then filtered through a filter and detected by a highly sensitive photomultiplier tube. (3) Colorimetry: Colorimetry is based on the Lambert-Beer theorem, that is, the concentration of the target object is proportional to the amount of light absorption at a specific wavelength. This method is used for hemoglobin measurement. First, a specific lysing agent is used to lyse red blood cells, release hemoglobin, and form complexes. After irradiation with light of a specific wavelength, a photoelectric sensor is used to detect the attenuation of the absorbed light. The maximum absorption spectrum of the complexes formed by different lysing agents is slightly different, usually between 500 and 550 nm. Blood Cell Detection Methods The clinical detection of blood cells is closely related to the reagent treatment methods of blood cells. After blood cells are treated with supporting reagents, the above-mentioned detection technologies (such as sheath flow impedance technology, laser scattering technology, etc.) can be applied to realize counting and classification detection of white blood cells. The detection methods of blood cells are mainly divided into chemical method, chemical staining method, and fluorescent staining method. The chemical method is mainly used in three-part and five-part blood cell analyzers; the chemical staining method is mainly used in blood cell morphology detection, such as slide readers, and some manufacturers also apply chemical staining reagents to five-part blood cell analyzers; the fluorescent staining method is mainly used in high-end five-part blood cell analyzers and blood cell analysis modules equipped with assembly lines. (1) Chemical method: The chemical method generally uses chemical reagents to treat blood cells, and then combines with corresponding detection technologies to realize counting and classification detection of blood cells. There are two main types of reagents used in the chemical method: one is a special reagent containing surfactants; the other is a diluent reagent that maintains cell morphology and provides a corresponding ion environment. The special reagent contains surfactants, which show different effects when detecting different parameters: when detecting HGB, the special reagent mainly lyses red blood cells to expose hemoglobin; when counting cells and classifying white blood cells, the special reagent mainly performs differential treatment on cells, changing the cell density or cell size, providing a corresponding material basis for detection and classification. The diluent reagent can provide a suitable cell suspension environment, maintain cell morphology, and ensure the stability and reliability of the testing process. Due to the relatively low technical threshold and difficulty in technical implementation of the chemical method, many domestic and foreign manufacturers have supporting instruments and reagents. In addition to well-known foreign enterprises such as Sysmex, Abbott, and Beckman Coulter, domestic enterprises such as Mindray, Dimai, UriTest, and Landwind also apply this method to three-part lysing agents, such as Mindray's latest series of instruments BC-20, BC-30S, etc., and early products such as BC-2800, BC-3000Plus. Dimai's DH31, DH36, etc., and UriTest's URIT-2900, URIT-3000Plus also use chemical reagents. The application of the chemical method in five-part blood cell analyzers has high requirements for the detection system, and the technical development and implementation are difficult. However, many manufacturers apply this method, such as UriTest's URIT-5510, URIT-5380 series, Mindray's BC-5000 series, Dimai's DF55, Zhongyuan Huiji's Z5, Z3 series, etc., which use the chemical method for counting and classification detection of five-part blood cells. The chemical reagents used in three-part cell analyzers generally only have one special reagent with lysing effect, while the chemical reagents used in five-part blood cell detectors may contain one to three reagents to achieve accurate five-part detection. (2) Chemical staining method: The chemical dyes used in the chemical staining method can distinguish and stain different cell structures, and after staining and deposition, they have different optical properties. After blood cells are treated with chemical dyes and special reagent lysing, the cell size and cell structure density change. With these differential factors between different cells, the detection system can apply appropriate detection technologies to realize classification and counting of blood cells. The most typical application of this method in five-part blood cell analyzers is the supporting reagents used in Mindray's mid-range five-part blood cell analyzers, such as BC-5390 and BC-5390CRP series instruments. The chemical dyes in the supporting reagents stain and lyse blood cells to differentially classify different white blood cell subtypes, and the detection system can use these differential factors for counting and classification. This method is relatively mature, and most domestic five-part blood cell analyzers adopt this method. (3) Fluorescent staining method: The main difference between the fluorescent staining method and the above two methods is the introduction of fluorescent staining reagents. Fluorescent staining reagents are chemical substances that can target and combine with different cells or different components in cells, and such substances can emit excitation light (i.e., fluorescence) with corresponding wavelength energy when irradiated and excited by light of different energies. By collecting the intensity and quantity of fluorescence through a special detection device, classification detection and counting of different cells can be realized. In blood cells, different cells have different sizes and structures (for example, after white blood cells are treated with a special reagent containing surfactants, the cell structure density of neutrophils is greater than that of lymphocytes), or contain different cell components (for example, red blood cells and reticulocytes have different RNA contents), or have different contents of certain cell components (for example, abnormal granulocytes contain more DNA than neutrophils). The fluorescent staining method just uses these differences and the targeted binding characteristics of fluorescent dyes to realize more refined classification detection and counting, such as detecting NRBC which has a prompting effect on myeloproliferation through special dyes; detecting abnormal lymphocytes through the intensity of fluorescent signals, etc. For example, Mindray's BC-6000Plus, BC-6800Plus and other 6-series instruments, as well as BC-7500 CRP 7-series instruments, all use fluorescent staining reagents. The addition of fluorescent dyes provides another idea for the accurate detection of white blood cells and the counting and detection of some abnormal cells. Among them, M-6FD staining solution realizes the accurate detection of eosinophils, abnormal lymphocytes, immature granulocytes and other abnormal cells; RET channel staining solution and M-6FN staining solution respectively realize the classification detection of reticulocytes and nucleated red blood cells. The fluorescent staining method improves the accuracy and efficiency of clinical detection, and its technical threshold is high. At present, there are few manufacturers applying this method in the market. In addition to the above-mentioned Mindray models, domestic ones include迈克's F 800 series blood cell analyzers, Dirui's BF-7200 series blood cell analyzers, and foreign ones include Sysmex's XN, etc. Classification of Hematology Analyzers 1. Classification according to the classification of white blood cells: Three-part blood cell analyzer: It divides white blood cells into neutrophils, lymphocytes, and other white blood cells; Five-part blood cell analyzer: It divides white blood cells into neutrophils, lymphocytes, eosinophils, basophils, and monocytes. 2. Classification by automation degree: semi-automatic hematology analyzers, fully automatic hematology analyzers, hematology analysis workstations, and hematology analysis assembly lines. 3. Classification by detection principle: capacitive type, impedance type, laser type, photoelectric type, combined detection type, dry centrifugal stratification type, and non-invasive type. Current Situation of R&D and Production of Domestic Hematology Analysis Instruments and Reagents Hematology analysis is one of the three routine clinical tests. The traditional inspection method is to manually count red blood cells, white blood cells, and platelets in the blood with the help of a microscope, and classify white blood cells on stained blood smears, which is time-consuming and laborious, with few detection items, and poor accuracy and result consistency. With the advent and technological development of hematology analyzers (also known as blood cell analyzers, blood routine analyzers, hemocytometers, blood cell counters, etc.), with the characteristics of simple operation, convenience, and high degree of automation, they have been fully used in clinical blood analysis, becoming the necessary and most basic automated equipment in the laboratory department. At present, hematology analyzers and reagents have fully realized localization, with products covering three-part hematology analyzers, five-part hematology analyzers, and blood analysis assembly lines connected with slide staining machines, morphology analyzers (also known as slide readers), specific protein analyzers, and glycosylated hemoglobin analyzers, which are widely used in hospitals at all levels and serve as main equipment, accelerating import substitution. As mentioned earlier, hematology analysis instruments and reagents have fully realized localization. Five-part hematology analyzers and blood analysis assembly lines have become the main equipment in Chinese hospitals at all levels, while three-part hematology analyzers are mainly used in small medical and health institutions such as small private hospitals, private clinics, and township/community health stations. The industry of R&D and manufacturing of hematology analysis instruments and reagents has a high concentration. Although there are currently more than 20 manufacturers capable of manufacturing five-part hematology analyzers and hundreds of manufacturers capable of manufacturing three-part blood routine analyzers, only a few, including Mindray Medical,迈克 Biology, Changchun Dirui, Guilin UriTest, and Shenzhen Dimai, truly master core technologies, have innovative R&D capabilities, and realize large-scale production. In the first decade of the 21st century, the field of hematology analysis was dominated by imported brands. The "Kingdom of Hematology Analysis Standardization" - American Beckman Coulter and Japanese Sysmex competed with each other, monopolizing almost the entire market from five-part hematology analyzers to blood analysis assembly lines, and from secondary hospitals to tertiary hospitals. The pattern of domestic brands challenging import monopoly began in 2006 when Mindray Medical launched five-part hematology analyzers, which were widely used in major tertiary hospitals and continuously upgraded and improved. The real breakthrough of the monopoly of imported brands in the Chinese market began in the second decade of the 21st century. Mindray Medical independently developed a 6-series high-end hematology analyzer with three-dimensional nucleic acid fluorescent staining technology, which can detect white blood cell five classification, reticulocytes, and nucleated red blood cells, and further launched an 8-series blood analysis assembly line; Guilin UriTest digested and absorbed the four-angle laser scattering five classification technology to develop a 5-series five-part hematology analyzer; Shenzhen Dimai mastered the five-part blood analysis technology through the diffusion of cell chemical five classification technology, and integrated the CRP analysis function into the hematology analyzer, launching a D-series five-part CRP all-in-one machine; Jiashan Jiasideke Company in Zhejiang Province independently developed a 5-series five-part hematology analyzer using nucleic acid fluorescent staining technology (the company was acquired by迈克 Biology in 2015, becoming the technical source of迈克's five-part hematology analyzer); etc. At this stage, the domestic blood routine analysis industry has established a complete upstream and downstream industrial chain of instruments and reagents, completed the leap from three-part to five-part and then to blood analysis assembly lines, and achieved large-scale breakthroughs in top tertiary hospitals. In 2020, the first year of the third decade, China's hematology analyzer production capacity exceeded 60,000 units (sets), of which more than 30,000 units (sets) were installed in the domestic market, and more than half were "installed overseas"; the proportion of imported brands' installed units in the Chinese market dropped from absolute advantages in quantity and quality 10 years ago to less than 20% in 2020, fully reflecting the great achievements made by Chinese companies in the R&D and production of hematology analysis instruments and reagents. Introduction to Domestic Main Hematology Analysis Manufacturers, Products and Detection Principles (1) Mindray Medical: Shenzhen Mindray Biomedical Electronics Co., Ltd. (hereinafter referred to as "Mindray") was founded in 1991, is a world-leading medical device supplier, and is now the largest domestic IVD R&D, manufacturing, and production manufacturer, covering eight subdivided businesses. Mindray launched its first quasi-three-part analyzer in 1998, and produced China's first five-part blood cell analyzer BC-5500 in 2006, opening the era of localization of five-part hematology analyzers; in 2011, it once again led the development of China's hematology analyzers, launching the BC-6800 automatic hematology analyzer with functions such as reticulocyte and nucleated red blood cell measurement. This product uses sheath flow impedance method, laser scattering combined with fluorescent staining multi-dimensional analysis technology for cell counting and classification, and colorimetry for hemoglobin determination; in 2013, it launched the BC-6900 automatic blood routine and body fluid analyzer, which can measure the number of red blood cells, white blood cells, and nucleated cells in cerebrospinal fluid, pleural effusion, and peritoneal effusion, and can subdivide the number and proportion of mononuclear cells and multinuclear cells. Since then, BC-