For over 40 years, immunoassays have been used in hospitals, laboratory medicine, and research to improve health and well-being. Information gained by clinical immunoassay testing has shortened hospital stays and decreased the severity of illness by identifying and assessing the progression of disease, thereby leading to improved therapeutic choices.

The development of new immunoassays is proceeding more rapidly for some disease areas than for others as some pathogenic diseases, such as cancer and AIDS, present tough challenges to immunologists who are struggling to relate their fundamental research to the causes and cures of these and other devastating medical conditions. But the improved understanding of the immune system gained in research laboratories points the way to progress.

Keeping pace with emerging biomarkers and consolidating a broad test menu, are both important for developing new instruments and kits, or updating existing ones, with the aim of improving service and quality while decreasing costs. Manufacturers are designing new instruments to incorporate many additional capabilities and features. The design and functionality of new instruments are predominantly customer-driven. Factors like the available laboratory space for placing an instrument, throughput needs, and a range of workflows are considered in designing and including the components for providing a fully automated instrument. Manufacturers are also actively engaged in discovering and validating new biomarkers, creating assays for those biomarkers, and adding the assays to the menus of their instruments.

Increasing consolidation in laboratories and hospitals in the wake of healthcare reform to curb healthcare expenses is expected to stimulate market growth. Technological innovation for development of effective lab equipment along with new product launches with the ability to perform more than one test at a time are expected to drive the market globally.

India is expected to witness robust growth for automated instruments over the next sevenyears owing to increasing government focus toward development of healthcare infrastructure by encouraging public-private partnership to improve healthcare delivery into rural markets. Furthermore, increasing number of pathology laboratories and rising number of private and public hospitals is anticipated to fuel the market growth.

Technology Trends

Since they were first utilized, immunoassays have witnessed phenomenal growth in the range and scope of their applications. A vast array of different labels and assay strategies has been developed to meet the requirements of sensitivity, accuracy, and convenience that have drastically improved the sensitivity of immunoassay systems, allowing an ever-increasing range of analytes to be measured accurately.

Of course, the menu of tests is at the heart of labs' needs, and strengthening the menu is always going to be a top priority for manufacturers. But today labs highly value workflow solutions that can quickly deliver reliable, trustworthy results at the best possible value to the hospital. It is not just instruments. A new development opportunity is any solution that drives reliability of results and operational efficiency in the lab. In the past, this looked like the consolidation of assay technologies onto integrated instrument platforms. Today, it looks like open workflow solutions that automate off-instrument operations, reduce total cost of ownership, and enhance the interoperability of the lab's equipment. Meeting these demands for automation, scalability, and openness is a key focus.

Immunoaffinity assays. These assays are the workhorse for measuring individual proteins but have been limited for proteomic applications by long development times, cross-reactivity preventing multiplexing, specificity issues, and incomplete sensitivity to detect proteins in the lower range of the abundance spectrum. Emerging technologies to address these issues include nucleotide-labeled immunoassays and aptamer reagents that can be automated for efficient multiplexing of thousands of proteins at high sample throughput, coupling of affinity capture methods to mass spectrometry for improved specificity, and ultrasensitive detection systems to measure low-abundance proteins.

iPCR. Immuno-PCR is an extremely powerful tool that combines the specificity of ELISA with the signal amplification of PCR.While rtPCR provides exponential signal amplification, it cannot be used directly for antigen detection, and while ELISA is adaptable to any protein, its sensitivity is not adequate for the detection of analytes of low abundance. iPCR therefore offers a number of key advantages by combining them both, such as extremely low limit of detection, compatible with complex samples such as serum, amenable to multiplexing,higher assay reproducibility, and rapid time to results.

Digital pathology. Another transformative development is the advent of digital pathology. Instead of viewing and analyzing slides under a microscope, digital pathology systems scan the stained slides in their entirety, storing the resulting whole-slide images in a digital format that can then be viewed and manipulated on a computer. Whole-slide imaging also simplifies sample storage and retrieval by providing an easily accessible record of the slide (as opposed to physical slides), and facilitates data analysis and subsequent reanalysis. Another benefit of digital pathology is the ability to perform sophisticated image analyses.

Chemiluminescence technology. Chemiluminescent immunoassay (CLIA) instruments steadily infiltrated the immunometric assay domain, eventually being used to measure serum concentrations of hormones, drugs, vitamins, tumor markers, infectious disease markers, myocardial damage markers and, finally, autoantibodies. Today, autoantibody detection in immunochemiluminescence can be carried out on instruments specifically dedicated to the autoimmunology laboratory as stand-alone instrumentation or as part of an automated analytical platform.

Regardless of its current optimal analytical performance, CLIA technology is destined for further development:

FICLIA technology. Flow-injection CLIA ensures a more efficient reagent mixture, reduces incubation time, increases temperature control, and is also able to improve the immunoreaction kinetics and therefore significantly reduce analysis time.

Multi-parametric CLIA. Current CLIA consists of discrete tests, i.e. measures one autoantibody at a time. However, the need for multi-parametric tests that can identify all the components of a complex immunological picture in a single analytical step, efficiently and at reasonable cost. Use of the 2D resolution for CL multiplex immunoassay could open doors for the setting up of multiparametric CLIA tests.

CL-MBs-nano-immunoassay. Ultrasensitive chemiluminescence magnetic nanoparticles immunoassay technology further increases the analytic sensitivity of the CLIA method. In this non-competitive and direct-type immunoassay, where the solid phase is made up of magnetic beads, gold nanoparticles with double labelling are used. This amplifies the luminescent signal derived from the immunoreaction and the associated enzymatic reaction in an exponential manner.

Way Forward

Diagnostic technology is rapidly evolving, and over the last decade substantial progress has been made for the identification of antibodies, increasingly approaching this type of diagnostic to that of automated clinical chemistry laboratory. The wide dynamic range, greater than that of immune-enzymatic methods, the high sensitivity and specificity of the results expressed in quantitative form, the high degree of automation and the clinical implications related to the reduction in the turnaround time, and the ability to run a large number of antibody tests, directed toward large antigenic panels in random access mode, make immunochemistry one of the most advanced segments in the clinical laboratory, with enormous repercussions on the workflow and on the auto-immunology laboratory organization.

The evolutionary process of the CLIA method is, in all likelihood, merely beginning. In the coming years, new and more efficient analytical methods based on the principle of chemiluminescence will be introduced into autoimmune diagnostics, at a steadily reduced cost, which will likely result in additional increases in the clinical efficacy of antibody tests. This transformation will align antibody diagnostics with already consolidated biochemistry and immunoassay methods, with noticeable advantages in terms of both diagnostic accuracy and expediency, to great clinical benefit.

Alex Xu
Industry Speak
History of ABEI – A Chemiluminescence Immunoassay Label

Immunoassays employ a variety of labels to allow for detection of antibodies and antigens. Labels are typically chemically linked or conjugated to the desired antibody or antigen.

In chemiluminescence immunoassay (CLIA), there are some different small molecules or enzymes that have been used as labels by different CLIA system manufacturers, such as alkaline phosphatase (ALP), acridinium ester, luminol, and aminobutylethyl isoluminol (ABEI). snibe

Chemicalname of ABEI is N-(4-Aminobutyl)-N-ethylisoluminol. Like luminol, ABEI, as a derivative of isoluminol, is a chemical that exhibits chemiluminescence, with a blue glow when mixed with an appropriate oxidizing agent. This reaction is called luminal reaction. ABEI has been used as a label in some CLIA systems.

History of ABEI

  • In 1902, German chemist Schmitz synthesized luminol for the first time.
  • In 1928, German chemist Albrecht first found that luminol exhibited chemiluminescence properties in alkaline aqueous solution with existence of hydrogen peroxide.
  • In 1936, Gleu testified that hematin in blood can enhance the luminol luminescence.
  • lIn 1937, German forensic specialist Specht researched into the luminol chemiluminescence for application of blood test at crime scenes.
  • In 1968, Oleniacz applied luminol to detect the bacterial population in water as bacteria can activate luminol for luminescence in alkaline aqueous solution with existence of sodium borate.
  • In 1977, Halmann established chemiluminescence enzyme-linked immunoassay (CLEIA) that combines chemiluminescent reaction and enzyme-linked immunosorbent reaction, which provided a new approach for ultra-trace analysis of biological substances.
  • In 1978, Schroeder reported synthesis methods of ABEI and its analogues and established thyroxine (T4) chemiluminescence immunoassay. In the same year, he wrote in Analytical Chemistry-that in H2O2 - Hematin system, ABEI was almost equivalent to luminol with luminescent efficiency and detection sensitivity. In 1982, Cheng reported a solid - phase luminescent immunoassay method with sensitivity of analysis up to 1 ng. In this method, water soluble carbon 2 imine EDC [1 - (3 - dimethyl amino propyl) - 3 - ethyl carbon imide)] was used to label ABEI with rabbit-anti-human IgG, and immune microbeads were used as solid phase. In the same year, Patel synthesized the derivative of ABEIthe isothiocyanate of ABEI, which can directly label to antigen or antibody to achieve the detecting sensitivity of 10-17 to 10-16mol.
  • In 1984, Gadow synthesized the derivative of ABEIthe N-hydroxysuccinimide ester of ABEI hemisuccinate to label the protein directly.
  • In 2013, Palmioli reported a new derivative of ABEIthe macrolide of ABEI, which is more stable and more efficient to label than the N-hydroxysuccinimide ester of ABEI hemisuccinate and applied it to detecting HIV p24 antigen.

Although ABEI has been applied to the CLIA area for more than 10 years, it never fades. There is still a lot of research that could be done.

Alex Xu
Overseas Technical Director,
Snibe Co., Ltd.

Dharampal Sharma
Industry Speak
Emerging Trends in Indian Market

The Indian diagnostics sector has been witnessing immense progress. Major technological advancements and higher efficiency systems has taken the sector to new heights. Advanced cutting-edge technologies are being used to understand disease diagnosis and prognosis, thereby strengthening the sophistication level of the participants in the sector. Immunochemistry is one of the most rapidly growing fields in the Indian in vitro diagnostics (IVD) market. While immunochemistry is the fastest growing area in the Indian IVD market, the diagnostic lab services are also growing at a fast pace, in the public and private sector. The segment's growth is expected to be fuelled by the growing demand for automated diagnostics.

The factors which are fueling this growth are increase in overall healthcare expenditure; rising healthcare spend from Indian government, decreasing morality rate, increasing aging population, and life style related diseases. This growth has also percolate down to Tier II and Tier III cities, and they too have started to move towards better medical and testing facilities. This is evident by growing number of standalone hospital and laboratories in smaller cities and towns, and recently corporate hospital chains and chain labs have begun to step out of metros and A-towns to capitalize on this opportunity. This has impacted the overall market dynamics. The market has become increasing competitive and vitality in this scenario can only be ensured with clear understanding of the segment and the ability to provide product and services that fits. This has led to a breed of products which are faster, with better technology, offer advance parameters, modular and take-up minimum bench space, and importantly ensure excellent return on investment and affordability.

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 are 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.

As a of leading developer, manufacturer, and marketer in the field of in vitro diagnostics Mindray is committed to contribute to the improvement of public health. Scientific and technological innovation is at the heart of the Mindray strategy. It has enabled to extend Mindray's expertise to the fields of immunology through innovative chemiluminescence technology and the compact design of new immunoassay system is offering increases in the number of simultaneously measured parameters and processing capacity as well as enhanced usability has been specifically designed to fulfill the requirements across segments, and paving the way for affordable and high quality immunochemistry testing.

Mindray will meet increasingly sophisticated needs by providing a high-value-added testing environment comprising the compact and highly functional and unique reagents that deliver high clinical value. Going forward, Mindray aims to reduce the burden on patients and enhance the quality of testing, as well as instilling its customers with confidence.

Dharampal Sharma
Product Manager - Immunoassay,
Mindray Medical India Private Limited

Dharampal Sharma
Industry Speak
Early Diagnosis, Characterization, and Management

Currently the world is witnessing an unprecedented upsurge of a variety of deadly vector-borne diseases transmitted by an array of arthropods. In man's battle against these deadly and debilitating pathogens,,that often result in many kinds of infections for which neither vaccinations nor specific drug-based treatments are in place . Obviously, therefore the most important question arising alludes to whether our laboratories are adequately equipped to their real capacities and help timely respond to public health emergencies such as those erupted during the dengue and other arboviral disease outbreaks, the Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus epidemic in Africa, and more recently the Zika virus in the Americas, Europe, Africa, and Asia. To meet the ever growing demand, laboratories need high performance instruments which are compatible to human understanding and interpretation for an early and robust application at the end user.

Many laboratories and institutions in India are helping generate knowledge on different aspects of infections that the arthropods cause to humans. These institutes are healthily equipped with instruments such as polymerase chain reaction (PCR), real time PCR (RT-PCR), high performance liquid chromatography (HPLC), fluorescent microscope, laminar flow, and many more sophisticated tools and equipment. These institutions have in recent years made great strides in the research arena pertaining to dengue, chikungunya, Japanese encephalitis, to mention a few, and have made best use of instruments and appliances with easy-to-handle calibration.

These institutions, aided by both the government and their own efforts to generate funds, have a healthy and reasonable budgetary allocation for purchase of instruments, and hope to continue to further equip their laboratories. These institutes are aware that the Indian market is currently most liberal in supplying tools and equipment from any place across the world with minimum import hassles and therefore plan to add to their lists a variety of new material that will be useful in their genetic, physiological, molecular, and biotechnological research programs such as the DNA sequencers, atomic ionizer, GC, and GC-MS etc.

Prof. Dr B.K. Tyagi
President, Society of Medical Arthropodology,
President, Indian Dragonfly Society


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