New analyzers based on multiplex detection would lead to better and sustained healthcare by enabling effective monitoring and management of disease, therapeutic regimen, and personalized or healthcare intervention.
Immunochemistry plays a critical role in various bioanalytical settings including clinical diagnostics, research laboratories, drug discovery, and biopharmaceutical analysis. Since its development, a wide range of analyzers have been developed to provide the quantitative, semi-quantitative, or qualitative detection of analytes that are critical to effectively diagnose, monitor, and manage the patients’ health. Immunochemistry has also shown prognostic applications in tumors, which has paved way for the implementation of preventive measures against various tumor developments. In addition, disease diagnoses have undergone improvement through the use of immunochemistry analyzers leading to the evolution of diagnostic markers that has significantly changed the clinical practices of surgical pathologists. Considering the prominent role that immunochemistry analyzers play in clinical decision-making, they are indispensable for healthcare settings.
Significant advances in immunochemistry formats and technologies during the last few decades have drastically shortened the duration of analysis manifold in comparison with conventional radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). ELISA is also difficult to develop for point-of-care (PoC) use and requires significant technical expertise. Furthermore, the immunochemistry analyzers are being simplified as many process steps are integrated and automated using dedicated instruments. The evolution of microfluidics and lab-on-a-chip (LOC) technologies based on automated microfluidic protocols has resulted in prospective semi- and fully automated immunoassays, enabling PoC testing of analytes at remote settings. There is also an emerging trend toward the development of multiplexed analyzers that holds tremendous potential in IVD and bioanalytical sciences.
There is currently a movement toward developing label free immunoassays. The new photonics field has the potential to launch the development of an entirely new generation of label free assays. This will lead to the development of miniature LOC label free immunoassay devices. These devices will be functionalized with capture antibodies and will have a resonance condition of light. This resonance wavelength will be shifted upon a reaction between the capture antibody and the target antigen due to the change in refractive index. Simply measuring the shift in resonance wavelength will provide a readout of a binding event – no label, just antibody-antigen interaction!
Indian market dynamics
The Indian immunochemistry market in 2017 is estimated at Rs 2170 crore. The instruments and reagents are estimated at Rs 1550 crore, ELISA kits at Rs 330 crore, and rapid tests at Rs 290 crore. The reagents in 2017 earned revenues of Rs 1385 crore, and the instruments Rs 165 crore.
Roche and Abbott continue to dominate this segment. On October 3, 2017, Alere became a subsidiary of Abbott. Siemens, J Mitra, and bioMérieux are equally aggressive, and have a considerable market share. Ortho, Tosoh, Beckman Coulter, Transasia, and Bio-Rad have presence in this segment.
Immunochemistry is the fastest growing area in the Indian IVD market. The segment’s growth is being fueled by the growing demand for automated diagnostics. The key contributory factors are increase in overall healthcare expenditure, rising healthcare spend from the government, decreasing morality rate, increasing aging population, and lifestyle related diseases.
The growth has also percolated down to Tier-II and Tier-III cities, as they too have started to move toward better medical and testing facilities. This is evident by the growing number of standalone hospitals and laboratories in smaller cities and towns, and the recent expansion of corporate hospital chains and chain labs from metros and A-towns to these areas. Small to medium privately owned laboratories of Tier-II and Tier-III cities make up 65–70 percent of India’s vast clinical diagnostic laboratory network, yet most IVD products have traditionally been designed for consolidated centers. Any approach to improving laboratory quality in India must include the implementation of reagents and instruments specifically designed to improve quality in Tier-II and Tier-III cities with ease-of-use, reduced consumption of consumables.
Responding to this development, the market over the last couple of years has become increasingly competitive. Vitality in this scenario is being ensured with clear understanding of the segment and the ability to provide products and services that fit. A breed of products which are faster, with better technology, have been launched. They offer advanced parameters, are modular and take up minimum bench space, and importantly, ensure excellent return on investment and affordability.
Manufacturers are designing new instruments to incorporate many additional capabilities and features, and are also actively engaged in discovering and validating new biomarkers, and creating assays for those biomarkers to extend the menus of their instruments.
The design and functionality of new instruments are predominantly customer-driven.
Automation. A number of semi-automated and fully automated analyzers are now commercially available for the performance of a variety of bacterial, viral, fungal, and parasitic antibody and/or antigen detection tests. The available automated platforms are either compact benchtop units that take up a limited amount of space in the laboratory, or free-standing units with larger footprints which require more space. The vast majority of the automated analyzers provide walk-away simplicity to perform assays from sample processing through interpretation and reporting of results. The majority of manufacturers of automated instruments also provide software for the analysis and management of patient data and for monitoring the quality of the testing being performed. Most of the instruments can also interface with computer-based, hospital laboratory information systems for seamless and accurate reporting of results. The number and selection of automated instruments used depends primarily on the volume of specimens being tested and the number of individual tests to be performed.
CLIA technology. Regardless of its current optimal analytical performance, CLIA (chemiluminescence immunoassay) technology is destined for further development. The new flow-injection CLIA (FI-CLIA) technology which is based on the fast injection of micro-bubbles into the reaction system with the aim of ensuring a more efficient reagent mixture and of reducing incubation times and increasing temperature control is able to improve the immunoreaction kinetics and therefore, significantly reduce analysis time. Further improvements are expected in the coming years with the development of new analytical platforms such as the two-dimensional resolution for chemiluminescence multiplex immunoassay and the magnetic nanoparticles CLIA, which will likely result in additional increases in the clinical efficacy of antibody tests.
Multiplexed assays. Recent advances have been made in the development of multiplex immunoassays, which allow for the simultaneous detection of multiple analytes in a single reaction by combining immunoassay chemistries with flow cytometric analysis. Part of the benefit of this technology arises from its ability to measure as many as 500 targets in a 50–100 µL sample. Moreover, multiplexing allows for a simple and easily automated, marker-guided tissue segmentation, and provides more information from each tissue section, which may be critically important for small samples, such as needle biopsies of tissues or small metastatic tumor samples. Although multiplexing aims primarily to get more from less, there is growing need to expand the technology even further by measuring not only multiple analytes present in a sample, but also the per cell output of each analyte.
Ultrasensitive immunoassays. The recent development of high-sensitivity immunoassays ushers in a new era for immunodiagnostics. Single molecule counting or detection technology, linked with traditional immunoassay technology, has made it possible to realize the holy grail of immunoassay development – specifically, improving the S/N ratio of an assay by up to a thousand fold. The evolution of high-sensitivity immunoassays has enabled detection of low-abundance molecules, approaching the clinical sensitivity accomplished with PCR. With a wide range of diagnostic opportunities, high-sensitivity immunoassays have the potential for a great and growing clinical impact. Their ability to rule out disease is critical for an accurate, safe, and cost-effective diagnostic workup. High-sensitivity immunoassays may allow for such a paradigm shift, not only in detecting and diagnosing disease, but also in ruling-out disease, thereby eliminating unnecessary testing, and ultimately improving patient care.
Undoubtedly, the future immunochemistry analyzers would be based on the multiplex detection of biomarkers for probing a particular disease using the effective clinical scoring algorithm. Single biomarkers often have inadequate predictive value, only about 70 percent for prostate-specific antigen, which is known as one of the better single biomarkers.
Thus, the highly reliable prediction of a specific cancer requires measuring a number of relevant biomarker proteins. New analyzers based on multiplex detection and clinical scoring would lead to better and sustained healthcare by enabling effective monitoring and management of disease, therapeutic regimen, and personalized or healthcare intervention.
The coming years would witness continuous innovation and breakthrough immunoassay formats, bioanalytical platforms, bio-sensing concepts, detection devices, and complementary technologies. The next-generation analyzers would be based on highly simplified immunoassay procedures, requiring minimal process steps and critically reduced sample volumes without any washing steps. They would be fully automated, cost-effective, and equipped with smart features such as mobile healthcare capabilities by interfacing or integration with SP and gadgets. They could be deployed and operated at centralized, decentralized, remote, and personalized settings with minimal or no requirement for power supply and skilled analysts.