Analysis Of Biochemical Diagnosis Technology And Product Development

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(1) Overview of Biochemical Diagnostic Instruments

The biochemical analyzer, also known as the biochemical instrument, is an instrument that uses photometric principles and biochemical analysis methods to measure specific chemical components in bodily fluids. Due to its fast measurement speed, high accuracy, and low reagent consumption, it has been widely used in hospitals, epidemic prevention stations, and family planning service stations at all levels.

The fully automatic biochemical analyzer is one of the most commonly used important analytical instruments in clinical testing, mainly used to determine various biochemical indicators in serum, plasma, or other body fluids, such as glucose, albumin, total protein, cholesterol, and transaminases. It plays an important role in auxiliary diagnosis, efficacy detection, health checks, and drug abuse detection, making it an essential clinical testing device for medical and disease control units at all levels, as well as a commonly used instrument for epidemic prevention, quarantine, and biological research. Its clinical application range is expanding, making it one of the fastest-growing fields in the global medical device industry today.

Biochemical analysis is one of the important means of modern medical clinical diagnosis and disease prevention. Automatic biochemical analyzers can monitor various types of reaction analyses continuously and at set intervals. In addition to general biochemical tests, they can also determine some special compounds such as hormones, immunoglobulins, and blood drug concentrations. By combining biochemical analysis results of blood and other bodily fluids with other clinical data for comprehensive analysis, they provide a basis for diagnosing diseases and making appropriate evaluations of organ functions, while also identifying complicating factors and determining future treatment benchmarks and measures.

In contemporary hospitals, the automatic biochemical analyzer is one of the most basic and indispensable medical devices for disease diagnosis, condition monitoring, efficacy observation, prognosis assessment, and prevention. The diagnosis of acute pancreatitis, diabetic ketoacidosis, myocardial infarction, uremia, and acid-base balance disorders or electrolyte disturbances caused by dehydration or edema in emergency situations cannot be separated from biochemical analyzers; the detection of liver function, kidney function, protein balance, lipid metabolism, glucose metabolism, potassium, sodium, chloride, calcium, phosphorus, magnesium, and trace elements is all performed by biochemical analyzers. The results obtained from biochemical analyzers affect the medical quality of the entire hospital and are crucial for patient safety.

(2) Principles of Biochemical Diagnostic Instruments

The automatic biochemical analyzer is a high-tech product that integrates optics, mechanics, electricity, and fluidics, roughly divided into four parts: the sample introduction system, optical system, control system, and data processing system. The sample introduction system is the prerequisite for analysis, the optical system is the core of the entire instrument, the control system ensures the analysis, and the data processing system extends its functionality. Currently, the vast majority of biochemical analyzers operate based on photometric principles. Their structure can be roughly seen as composed of a photometric device or spectrophotometer and a microcomputer.

In terms of structural composition, biochemical analyzers consist of a sample holder, sampling device, reaction chamber or reaction pipeline, heater, detector, microprocessor, printer, and functional monitor. The specific working principle is as follows: a monochromatic light beam illuminates the colored liquid in the cuvette, and the absorption of light energy by the sample is detected by a detector, which converts the light signal into a corresponding electrical signal. This signal is amplified, rectified, and converted into a digital signal, which is sent to the computer. Meanwhile, the computer controls the driving power to drive the filter wheel and sample tray. The computer then processes, calculates, analyzes, saves the measurement data according to the user’s selected operation mode, and the printer prints the corresponding results. Finally, after measuring each group of samples, the cuvette is cleaned.

Working Principle of Biochemical Analyzers

(3) Classification of Biochemical Diagnostic Instruments

Since Technicon in the United States successfully produced the world’s first fully automatic biochemical analyzer in 1957, various models and functions of fully automatic biochemical analyzers have emerged, marking a significant step towards the automation of clinical biochemical testing in hospitals. To date, the development of biochemical analyzers has been rapid, with diverse classification methods, which can generally be categorized as follows.

01

Classification by Level of Automation

(1) Semi-Automatic Biochemical Analyzers

In the analysis process, some operations need to be performed manually (such as sample addition, heating, colorimetric absorption, result recording, etc.), while other operations can be completed automatically by the instrument. These instruments are known as semi-automatic biochemical analyzers. Their characteristics are small size, simple structure, and high flexibility, with a low price.

(2) Fully Automatic Biochemical Analyzers

The entire process from sample addition to outputting test results is completely automated by the instrument. The operator only needs to place the sample in the designated position on the analyzer and start the program to obtain the test report without any manual intervention. This type of instrument is called a fully automatic biochemical analyzer. Since there are no manual operation steps in the analysis, subjective errors are minimal, and because such instruments generally have the function of automatically reporting abnormal situations and self-calibrating their working status, systematic errors are also small.

02

Classification by Structure and Principle

(1) Continuous Flow (Pipeline) Analyzers

Continuous flow analyzers refer to instruments where the chemical reactions of various samples to be tested mixed with reagents are completed while flowing through the same pipeline. These instruments can generally be divided into air-segmented systems and non-segmented systems. The air-segmented system refers to small segments of air separating each sample, reagent, and mixed reaction liquid in the inlet pipeline, while the non-segmented system relies on reagent blanks or buffer solutions to separate the reaction liquids of each sample. Among pipeline analyzers, the air-segmented system is the most common.

(2) Discrete Analyzers

Discrete analyzers are programmed in a way that mimics manual operation, and mechanical operations are rhythmically replaced with manual ones, with each step connected by conveyor belts operating sequentially. The chemical reactions of mixed samples and reagents are completed in their respective reaction cups.

(3) Centrifugal Analyzers

Centrifugal analyzers refer to instruments where each sample to be tested is mixed with reagents under the influence of centrifugal force in their respective reaction chambers, completing chemical reactions and measurements simultaneously, resulting in high analysis efficiency.

(4) Dry Slide Analyzers

Dry slide analyzers refer to instruments where reagents are solidified on carriers such as films or filter paper, and each sample to be tested is added to the corresponding test strip for reaction and measurement. Their advantages are quick operation and portability, and they are currently used more in emergencies and field tests.

(5) Bag-style Analyzers

Bag-style analyzers replace reaction cups and colorimetric cups with reagent bags, where each sample to be tested reacts and is measured within its respective reagent bag.

03

Classification by Reagent and Instrument Compatibility

(1) Closed Systems

Instruments and reagents are bundled for sale and use, generally with specified reagent brands designated by the instrument manufacturer, and other manufacturers’ reagents cannot be used.

(2) Open Systems

Instruments and reagents are sold and used separately, and the instrument manufacturer does not specify reagent brands, allowing users to choose freely.

04

Classification by International Testing Practices

(1) Small Instruments

Small instruments are generally single-channel and have slower testing speeds.

(2) Medium Instruments

Medium instruments are generally multi-channel, capable of testing 2-10 items simultaneously, with some instruments having fixed test items and others allowing free selection.

(3) Large Instruments

Large instruments are generally multi-channel and can test more than 10 items simultaneously, with freely selectable analysis items.

05

Classification by Testing Channels

(1) Single-channel Biochemical Analyzers

Single-channel biochemical analyzers can only test one item at a time, but the item can be changed, resulting in slower testing speeds.

(2) Multi-channel Biochemical Analyzers

Multi-channel biochemical analyzers can test multiple items simultaneously.

(4) Development History of Biochemical Diagnostic Instruments

Biochemical analyzers have gone through three stages from the earliest spectrophotometers to semi-automatic biochemical analyzers and now to the widely used fully automatic biochemical analyzers.

First generation: The spectrophotometer, which measures the absorption spectrum of substances using ultraviolet, visible, infrared light, and laser lights, is a method for qualitative and quantitative analysis of substances based on this absorption spectrum, and the instrument used is called a spectrophotometer. The advantages of the spectrophotometer include direct reading of absorbance, simple operation, and low cost; however, its disadvantages include the inability to directly calculate concentration values, large errors, and a limited number of test items.

Second generation: Semi-automatic biochemical analyzers, which require some operations (such as sample addition, heating, colorimetric absorption, result recording, etc.) to be performed manually during the analysis process, while other operations can be performed automatically by the instrument. These instruments are characterized by small size, simple structure, and high flexibility, and can be used separately or in combination with other instruments, at a low price.

Third generation: Fully automatic analyzers, in which the entire process from sample addition to outputting results is fully automated by the instrument. The operator only needs to place the sample in the designated position on the analyzer and start the program to obtain the test report. Fully automatic biochemical analyzers have more reagent and sample positions than semi-automatic ones, faster testing speeds, and eliminate errors caused by manual reagent addition, resulting in better accuracy and repeatability.

01

International Development History of Biochemical Analyzers

In the early 19th century, the most primitive manual methods were used to complete very few biochemical index tests on samples. During this stage, the methods for loading samples, reagents, and other liquids mainly used pipettes, and the work efficiency was extremely low with large errors. In the 1950s, with the advent of automatic diluters, the loading of liquids was automated or semi-automated, and semi-automatic colorimeters were gradually applied, completing sample colorimetric measurements using fixed flow colorimetric cups.

In 1957, Technicon Company in the United States manufactured the world’s first biochemical analyzer based on Professor Skeggs’ design, and various models and functions of fully automatic biochemical analyzers have continued to emerge, developing rapidly. In 1965, the discrete automatic analyzer was born, with a working principle similar to manual operation, where samples undergo reactions in separate reaction cups.

The 1970s saw the advent of reflective light analyzers paired with dry chemical reagents, improving the accuracy, precision, multifunctionality, and analysis speed of biochemical analysis. The application of analytical techniques such as spectrophotometry, centrifugation, chromatography, electrophoresis, radioactive isotopes, and immunology has strongly promoted the rapid development of various clinical biochemical testing instruments. In the early 1980s, TECHNICON Company in the United States invented a selectable measurement method that overcame cross-contamination between samples, raising the level of automatic biochemical analyzers to a new height. In the late 1980s, dry chemical analyzers using solid-phase enzymes, ion-specific electrodes, and multi-layer membranes were developed. Since the 1990s, with technological advancements, the technology of biochemical analyzers has developed in the direction of various functional improvements, the number of testing items has continuously increased, and the accuracy and precision of analyses have also improved, better meeting the different levels of requirements in laboratory management.

02

Development History of Biochemical Analyzers in China

In the mid-1970s, institutions such as the Shanghai Medical Device Research Institute, Beijing Medical Instrument Research Institute, Beijing Analytical Instrument Factory, and Beijing Biochemical Instrument Factory developed continuous flow, discrete, and centrifugal biochemical analyzers. Although domestic biochemical analyzers with independent intellectual property rights had been developed at that time, their quality was poor and unsatisfactory. Even those that had prototypes were not able to produce marketable products, and most of the instruments used domestically still relied on imports.

In 1972, the Italian Embassy in China donated a continuous flow automatic biochemical analyzer to Peking Union Medical College Hospital; in 1975, Tianjin Medical University Second Hospital introduced a two-channel continuous flow automatic biochemical analyzer from Italy’s Carlo Erba Company. Based on the study of these two instruments, Beijing Biochemical Instrument Factory launched a three-channel continuous flow automatic biochemical analyzer, which won a national science and technology conference award in 1978, but unfortunately did not see market effects.

During the widespread use of automatic biochemical analyzers in Chinese clinical chemistry laboratories, a significant impact occurred around 1986 when the Netherlands’ Vital Company introduced the MicroLab semi-automatic biochemical analyzer, with thousands of units introduced. To narrow the gap between domestic clinical laboratories’ automation processes and those in developed countries, developing fully automatic biochemical analyzers became the primary topic in domestic inspection medicine at that time.

Since the 1990s, through persistent efforts, a variety of semi-automatic and fully automatic biochemical analyzers have been independently developed in China. The development of automation in clinical chemistry testing in China can be summarized into seven periods, as shown in the diagram below.

(5) Main Circulating Products in the Biochemical Diagnostic Instruments Market

With the continuous development of fully automatic biochemical analyzers and the increasing speed of testing, we classify fully automatic biochemical analyzers based on testing speed, primarily into the following speed categories: ≤300T/H, 300-400T/H, 400-600T/H, 600-800T/H, and >800 T/H.

(6) Market Capacity of Biochemical Diagnostic Instruments

According to industry data and market sales statistics from various segmented companies, the biochemical market capacity was approximately 10.3 billion RMB in 2016 and about 11.3 billion RMB in 2017, with a growth rate of about 9%. In the domestic IVD segment, the traditional biochemical market share is gradually declining, and the growth rate is decreasing. As domestic biochemical testing matures and stabilizes, subsequent market growth is expected to slow down. Imported brands are mainly dominated by Roche and Beckman, accounting for about a quarter of the market, while the majority is domestic brands. The market growth expectation for the biochemical field in 2017 is around 10%, and the entire market has become a blue ocean market, with many brands experiencing sluggish growth for various reasons.

Looking at the domestic market, the domestic replacement rate for biochemical products is close to 50%, with many manufacturers. According to CFDA registration statistics, there are over 200 domestic companies related to clinical biochemistry. However, imported manufacturers still dominate high-quality clients such as large tertiary hospitals. Most fully automatic biochemical analyzers in tertiary hospitals are monopolized by foreign companies, mainly due to the complex technology involving optics, mechanics, electricity, software, fluidics, temperature control, and biochemical analysis, which requires a comprehensive technical foundation, strict control timing, and high reliability and accuracy. With the successful development of domestic biochemical diagnostic reagents and instruments, domestic biochemical analyzers have been rapidly promoted and applied in hospitals below the tertiary level. Currently, some quality domestic manufacturers have gradually penetrated into the high-end market of tertiary hospitals in China, such as Mindray, Kehua, and Dirui.

Foreign fully automatic biochemical analyzers have developed very mature technology over the years, with companies like Roche, Beckman, Abbott, Siemens, Johnson & Johnson, and Hitachi all launching high-performance, high-speed, modular biochemical instruments that can be linked with immunoassays. Domestic biochemical analyzers started late and have a weak technological foundation. Currently, domestic companies represented by Mindray, Kehua, and Dirui have successfully produced biochemical instruments that can compete with foreign companies, primarily targeting the mid-to-low-end market, while domestic enterprises such as InnoCare, Jinrui, Pukang, and Tekang focus on the low-end market. From the market situation, large hospitals and laboratories generally prioritize foreign brands of fully automatic biochemical analyzers due to their relatively high requirements for technical parameters, performance, and brand. In contrast, small and medium-sized hospitals, considering smaller sample volumes and cost factors, generally choose medium and small biochemical analyzers. Thus, it can be seen that the domestic high-end market is still dominated by foreign brands. As foreign brand product lines penetrate deeper, competition in the small and medium hospital market will become increasingly fierce.

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Source: China In Vitro Diagnostic Development Blue Book

Contributed by, Edited by: Yishui

Proofread by: Bonnie

Editor: Scorpion

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