The need for sophisticated integrated system urges the research and development of CLIA systems, which are able to integrate with other modules and have a larger test menu, are trending the IVD market.
With the combination of the basic principle of radioimmunoassay, high-sensitive chemiluminescence and high-specific immunoassay, the year 1977 saw the emergence of a new technology – chemiluminescence immunoassay (CLIA), which provided one of the best solutions for the quantification of specimens from a complex mixture with the non-radioactive nature, making it an advantage to replace RIA in multiple immunoassay applications in in-vitro diagnostic industry. Multiple factors have constituted the vast and rapid development of chemiluminescence immunoassays in the global IVD industry.
For many years, immunoassay had a narrow role in the clinical laboratory, and was performed by tedious manual methods in a specialized section of the laboratory. That situation has changed dramatically. The tremendous versatility of immunoassay, together with its increasing automation, has thrust it into a leading role in almost all areas of the laboratory. This in turn leads to continuous technical upgradation in immunoassay platforms or assays. Factors, such as rising incidences of infectious diseases, coupled with persistent product modifications, contribute toward the market growth. In addition, increasing incidences of endocrine disorders (diabetes, thyroid dysfunction), enhanced discovery of biomarkers (cancer and cardiovascular), and introduction of novel drugs are leading further augmentation of the market.
Advances on the new generation of small-molecule-detection technology
Vice Director, CLIA Reagent
Chemiluminescence immunoassay (CLIA) is an assay that combines the chemiluminescence technique with immunochemical reactions. In recent years, CLIA has gained increasing attention in different fields, including life science, and clinical diagnosis because of its high sensitivity, good specificity, and wide linear range. The CLIA can be used to either detect and quantify antibodies or measure the concentration of antigens in immunoassays.
Sandwich and competitive methods are the two main types used in diagnostics. For most small molecules, due to the structure of small molecules, their molecular mass and steric hindrance are limited. Small molecule analytes usually have only one epitope and no immunogenicity; so it is difficult to produce an immune response. Therefore, only competition methods are used. The principle of the competition method is that the antigen in the specimen competes with a certain number of labeled antigens and binds to solid-phase antibodies. However, the affinity between the antigenic analog and the natural small molecule antigen for the same antibody strain is often difficult to keep the same, which also leads to wrong results.
Recently, a new generation of small-molecule-detection technology is gaining attention, which is using the sandwich method instead of the traditional competitive method to complete the detection of small molecules. Differing from the usual sandwich method, which combines two antibodies to one antigen, the small-molecule sandwich method is achieved by developing antibodies against immune-complex, which consist of target antigen and primary antibody. The special antibody would not recognize either the target antigen or the coated antibody individually, only the complexes formed by them. Compared with a competitive method, the sandwich method has higher sensitivity, precision, and accuracy. Even in low-concentration sample, this technology also achieves precise results.
Nowadays, there are already manufacturers using this technology for 25-OH vitamin D testing and achieving good results consistent with the official reference measurement procedure (LC-MS). Relevant studies show that this breakthrough sandwich method can be used to measure vitamin D with greater accuracy than the competition method. In the future, with the advancement of technology, it is believed that this technology will be applied to the detection of smaller-molecule analytes.
The global immunoassays market is expected to reach USD 46.49 billion by 2028, at a CAGR of 7.5 percent during 2022–2028. Compared to conventional tests, immunoassays have been proven to provide highly accurate results even with very small samples. These immunoassays are considered to have a detection limit of 1 pg/mL, which can be attributed to the fact that immunoassays are based entirely on immunologic reactions. Immunologic reactions are highly specific, as they can take place only in the presence of proper immunologic agents. For instance, an antibody against a viral protein cannot bind with an antigen that is derived from bacteria. This high specificity indicates high accuracy in results, which enables high sensitivity in the detection of diseases. This high sensitivity not only helps in easy detection but also eliminates the need for secondary verifications, which ultimately saves a lot of costs. Thus, the high-sensitivity, specificity, and cost-saving nature of immunoassays are driving the growth of the immunoassays market.
In the absence of vaccine or specific therapy, diagnosis is the only way to control and manage the wide spreading of infectious disease, and immunoassays played this role significantly in curbing the spread of recent global pandemic condition of Covid-19. The massive research, validations, and approvals of several immunoassay consumables and analyzers have alleviated the issue of SARS CoV2 detection. There has been a surge in use of immunoassay, such as chemiluminescence, ELISA, and lateral flow base POCT rapid test.
Enzyme-linked immunoassay (ELISA) is the most widely used immunoassay technique for the diagnosis of infectious diseases. This technique is used to measure antibodies, antigens, proteins, and glycoproteins in biological samples. Some examples include diagnosis of HIV infection, pregnancy tests, and measurement of cytokines or soluble receptors in cell supernatant or serum. ELISA accounted for the second-largest market share after consumables. However, the introduction of high-throughput techniques and automation of screening processes is driving the demand for chemiluminescence assays. As a result, the segment is expected to grow at a significant growth rate from 2022 to 2028.
With the development of signal-generation methods, attention has now shifted to the development of immunochemical methods and instruments to provide convenient, high-performance systems. Important advances have been made in the design of immunochemical approaches that allow small molecules, such as metabolites and toxins, to substitute dynamic format assays with non-competitive formats, bringing advantages previously seen only with large molecular analytes. Further, the continuous development of new biomarkers, cost-benefit, and growing adoption of automated platforms for ELISA are expected to increase this technology’s adoption.
Bispecific antibodies and recombinant proteins are also beginning to impact immunodiagnostics. Due to the growing acceptance of smart devices, companies are developing automated lateral-flow readers connected to mobile phones or laptops. They can produce highly sensitive and quantifiable results and capture and transmit real-time data. Also, there has been high adoption of smart devices in healthcare systems for analysis and data management.
Integration of microfluidics technology in immunoassays offers lucrative growth opportunities. Immunoassays have long been widely used in various applications, such as medical diagnostics, pharmaceutical analysis, environmental, food safety testing, and basic scientific investigations, because of their simplicity, sensitivity, and specificity. However, most immunoassays include a series of washing, mixing, and incubation steps, which are labor-intensive and time-consuming.
Immunoagents used in immunoassays are relatively expensive. The consumption of the immunoagents can be greatly reduced once the system is miniaturized. Therefore, microfluidic systems, also known as a lab-on-a-chip or a micro-total-analysis-system, have attracted a lot of attention due to their advantages, such as miniaturization, integration, and automation.
Microfluidic devices are a new and diverse technology that uses fluids in micro-environments in a controlled manner, distinguishing them from conventional nitrocellulose lateral-flow tests. They can be regarded as the ultimate technical solution for miniaturizing protein biomarker immunoassays by uniquely combining the advantages of simplified fluidics, a reduced number of reagents, and much shorter assay times. These devices have used several methods for antibody immobilization, including passive adsorption, which is common with plastic surfaces, covalent binding, where salinization seems to be the base of most covalent binding techniques, and a combination of the two techniques together with some antibody-orientated techniques, which are still not widely used.
Microfluidic protein quantitation is a promising area for the POC diagnosis of non-communicable diseases and severe infections, such as sepsis. Diagnosing these health conditions requires the accurate quantitation of very small amounts of biomarkers present in biological samples. Thus, the integration of microfluidics technology in immunoassay is expected to provide lucrative opportunities for the growth of the immunoassays market.
Despite the long history of immunoassay IVD kits and reagents and maturity of the field, companies continue to develop new immunoassays and instrument platforms to improve assay sensitivity. New developments, expanding the future potential of immunoassays, include making multiplexing possible, miniaturizing platforms for POC testing, and identifying and developing assays for novel biomarkers.
The immunoassays market is large and, in some areas, locked up by large IVD companies, but there is a plenty of opportunity for innovators and for niche players developing antibody or antigen-based tests. Some of the leading players include Abbott, SNIBE Diagnostic, Thermo Fisher Scientific, Sysmex Corporation, Beckman Coulter, bioMérieux, Roche Diagnostics, Bio-Rad, Siemens Healthineers, Radiometer, DiaSorin, Fujirebio, and Ortho Clinical. More than 100 other companies compete for market share in immunoassays, while smaller players with ELISA tests serve local markets.
Strong niche competitors, including Thermo Fisher Scientific, bioMérieux, Sysmex Corporation, DiaSorin, and Wako, market their products worldwide. Other smaller companies have experienced remarkable growth, but their total revenues contribute only a small portion of the total market. As the average cost per test decreases with the migration of a number of immunoassays to integrated analyzers, the market’s capacity for growth becomes constrained.
In large-scale laboratories, integrated systems of biochemistry, CLIA, and electrolyte modules are appealing due to the increased demand for one system to handle a large number of samples for biochemistry, immunoassay, and electrolyte tests. The emerging need for sophisticated integrated system urges the research and development of CLIA systems, which are able to integrate with other modules and have a larger test menu, to become trending in the IVD market.