The immunochemistry market is heavily impacted by rapid replacement trends, which affect the clinical chemistry market. The market is increasingly seeing the entry of chemiluminescence immunoassay (CLIA) systems, which are replacing older versions. Smaller labs still opt for fluorescent immunoassay (FIA) systems or semi-automated CLIA systems. Enzyme-linked immunosorbent assay (ELISA) systems and open systems are exhibiting some growth because of their open platform capabilities and larger test menus and affordability. FIA and CLIA systems tend to be more expensive, which works in favor of ELISA systems.

ELISA systems will eventually experience erosion because of their lack of sensitivity and low specificities, especially as most laboratories are now consolidating and converting to high throughput systems. As a result, vendors are using this opportunity to offer immunoassay or standalone clinical chemistry systems for a high discounted price. Demand for immunochemistry systems seems to work negatively for vendors. Because of this, the retention of the installed base is crucial. Some strategies adopted by vendors include offering large discounts/upgrades, adding automation capabilities to existing modules, and having long reagent rental contracts.

The market has undergone a massive change from a handful of participants offering only ELISA, CLIA, radioimmunoassay (RIA), and FIA as well as multiparametric assays such as microarrays, flow cytometry-based platforms, recombinant immunoassays, and indirect immunofluorescence assays (IFA). Tier-I participants mainly focus on providing the chemistry and the immunoassay on the same instrument in the combination of chemistry - ELISA and chemistry - CLIA.

Future growth in this area includes broadening the assays on the same platform and detecting biomarkers, even at low levels, for some high-growth segments such as infectious disease testing, autoimmune testing, and oncology markers.

Indian Market

immunochemistry-market-pie

In 2015, the Indian immunochemistry instruments and reagents market is valued at Rs.1000 crore. Reagents accounted for 90 percent of the market. The ELISA kits demand for this segment in 2015 is estimated at Rs.325 crore and rapid tests at Rs.250 crore.

Chemiluminescent systems are gaining momentum, especially in tier I cities where the installation base and replacement market is increasing. On the other hand, tier II and III cites are opting for fluorescent and manual chemiluminescent systems. The purchasing power of the customer has increased. ELISA kits, albeit a declining segment continue to have relevance for their large test menu and affordability.

Based on application, test for hepatitis C virus (HCV) dominates the Indian immunoassay market in 2015, with its increasing application in the diagnosis of infectious diseases.

In 2016, on the global front, Abbott has announced a definitive agreement to acquire Alere, significantly advancing Abbott's global diagnostics presence and leadership. Companies are developing solutions that are likely to improve the speed, accuracy, and reliability of lab testing through automation, workflow integration, as well as information management. They are enabling labs to better handle expanding testing and data volumes. Future development will undoubtedly include more micro-scale instrumentation with ultrasensitive detection, rapid and faster turnaround time, as well as increased relevance in clinical laboratories.

Global Market

The global immunochemistry instruments and reagents market is expected to reach USD 24.5 billion by 2019, growing at a CAGR of 7.2 percent from 2014 to 2019, estimates MarketsandMarkets. There is a rising focus on biomarker development across the globe as they help in detection of various diseases in their initial stage.

North America dominates the immunochemistry instruments and reagents market, with the U.S. accounting for a major market share. Government funding is a major factor for the growth of the U.S. market. Furthermore, presence of advanced immunochemistry instruments in the country is another major factor for the high share of the U.S. market. The Asian market is poised to grow at the highest CAGR during the forecast period owing to increasing government investments in the life science sector and improving healthcare facilities in the region. The rising focus of prominent players on the Asian immunochemistry market is another factor driving its growth. Increasing number of baby boomers that require frequent health checkups is also a main driver for this market. China's growing rural hospital market lacks basic diagnostics laboratory infrastructure and represents an untapped opportunity for affordable immunochemistry analyzers.

Currently, the companies that are operating in immunochemistry are entering into mergers and acquisitions with other companies to expand their immunochemistry business. In addition, new product launches also help the market to grow. Abbott Laboratories launched a new instrument to complete the product line of Architect immunochemistry analyzers.

High incidences of cancer, infectious diseases, and cardiovascular diseases, along with a global aging population will fuel demand for immunochemistry-based tests. The immunochemistry market will also benefit from strong growth in emerging countries, as these markets remain relatively under-penetrated. India offers huge opportunities, especially due to its vast patient population.

Despite the market being dominated by a few large medical devices manufacturers, there are several small companies manufacturing niche and innovative products. Market growth will be driven by an increasing demand for automated systems, especially from developing nations. The most obvious benefit of increasing automation is the reduction of human error and overall costs. Automation has become important in the context of budget restriction and staff reduction. However, the immunochemistry diagnostic market will face increasing competition from other diagnostic technologies and so future growth will depend on the availability of more clinical evidence to prove effectiveness of immunochemistry tests. The increasing competition from other technologies will also require market participants to differentiate their products to remain competitive.

Technology Trends

Following the development of new techniques in the field of immunochemistry, attention has shifted to the development of immunochemical methods and instrumentation to provide convenient systems of high performance. Important advances have been made in the design of immunochemical approaches that permit the replacement of competitive format assays for small molecules, such as drugs, metabolites, and pollutants, with non-competitive formats, bringing advantages previously seen only with large molecular analytes. Biospecific antibodies and recombinant proteins are also beginning to impact immunodiagnostics, with the promise of even more highly specified reagents. Improvements in automation have brought the facility of homogeneous systems to high-throughput and high-performance heterogeneous systems. Similarly, point-of-need testing continues to progress. Through all of these advances, systems are evolving according to the needs of users in terms of operator convenience, accuracy, specificity, speed, robustness, and sensitivity.

Advances in automation have led to a new generation of clinical chemistry analyzers, with advanced software and hardware solutions. These analyzers can offer laboratories fast, reportable, cost-effective and accurate results. Modern clinical chemistry analyzers can usually test for a variety of specific analytes such as proteins, electrolytes, and enzymes as well as general chemistries. They use a number of different measurement technologies including absorbance photometry, turbidimetry, ion-selective potentiometry, latex agglutination, and homogeneous EIA (enzyme immunoassay). A range of samples can be analyzed including serum, urine, plasma, and cerebrospinal fluid.

Recent improvements to the design of multiwell microplates, including use of membranes with reduced background fluorescence, have bolstered the widespread application of Elispot assays. Considering the sensitivity, ease-of-use, and cost, the Elispot platform is likely to be the superior choice for the development of multifunctional T-cell assays for the research, therapeutic, and diagnostic communities. By virtue of this assay's unsurpassed sensitivity, frequency analyses of rare cell populations (e.g., antigen-specific responses) which were not possible before are now relatively easy.

Multiplex immunoassays confer several advantages over widely adopted singleplex immunoassays including increased efficiency at a reduced expense, greater output per sample volume ratio, and higher throughput predicating more resolute, detailed diagnostics, and facilitating personalized medicine. Nonetheless, to date, relatively few protein multiplex immunoassays have been validated for in vitro diagnostics in clinical/point-of-care settings. Different platforms are used to perform this type of analysis including bead-based flow cytometry and planar assays containing a defined array of capture microspots deposited in the bottom of the well. While these platforms have shown great utility in multiplexing quantitation, the microfluidics platform offers several advantages by its design. Despite all the potential advantages, multiplex immunoassays based on microfluidic technology have yet to be generally employed in translational research for measurement of protein biomarkers.

CLIA offers several potential advantages and has applications in clinical chemistry, bioanalyses, and environmental analyses. Chemiluminescence is widely used for immunoassay for its high sensitivity, selectivity, and rapid and simple analysis. Automation and high-throughput techniques offered by CLIA systems are replacing older versions.

Different methods developed are not without their weaknesses, and as a result much study is still being performed to tackle these differences and also to delve in more complicated areas that are yet to attain important improvements.

Drivers and Restraints

Under the strong rules and regulations, laboratories find it difficult to have good revenues. Thus, it is very important to find ways to sustain in such a cost-crunched environment. Due to the cost-cutting in clinical lab fees, profitability per test is decreasing, which makes it necessary for the laboratories to focus on the volume rather than the value. There is also heavy pressure for quality, error-free results to ensure patient satisfaction. This forces labs to lean toward more automated systems with effective workflow solutions.

Globally, laboratories are encouraged for automation due to the heavy influx of patients with insurance coverage. But with limited workforce in the clinical labs, it is difficult to manage the huge inflow of patients. On the other hand patients need prompt and error-free results. Thus, this scenario demands laboratories to seek the help of systems that have a high accuracy, with managing high growing volumes and also offer remote data-acquisition capabilities.

Future of Immunodiagnostics

There have been tremendous advances in immunodiagnostics during the last five decades, which have led to the emergence of potential diagnostic technologies, new immunoassay formats, and diagnostic platforms. Radioimmunoassay and ELISA were the predominant techniques during the initial era of immunodiagnostics. The strenuous research efforts during the last three decades have enabled the development of potential antibodies for a wide range of analytes.

There have also been some major advances in lateral flow immunoassays (LFIA), which have been developed for a large number of analytes. Researchers have started looking into the development of quantitative LFIA instead of the conventional qualitative ones.

Moreover, various signal-enhancement strategies have also been developed during the last decade using nanomaterials, nanocomposites, dendrimers, polymers, and nanostructured substrates. They have led to ultrasensitive immunoassays with lower limit of detection and superior analytical performance. The use of magnetic beads/particles in magnetic immunoassays has led to truly remarkable applications that take into account the convenience of handling the magnetic beads/particles.

Despite tremendous advances, there is a critical need for rapid and cost-effective immunoassay procedures and novel diagnostic platforms in order to increase the outreach of immunodiagnostics to remote settings and developing countries. The most prospective development in this regard is the use of smartphones for immunodiagnostics. Various smartphone-based immunoassays and smartphone-based integrated readers for (LFIAs) have already been developed during the last few years. The current generation of smartphones is equipped with high-resolution camera, advanced processor, GPRS, connectivity, and iCloud computing, which make them the ideal next-generation devices for point-of-care immunodiagnostics, telemedicine, and mobile healthcare. Taking into account ~6.8 billion cellphone users worldwide, there will be a huge market for smartphone-based immunodiagnostics. Moreover, it will lead to tremendous cost-savings due to automated data analysis, highly centralized operations, telemedicine, and personalized healthcare. The integration of smartphones with cheap paper-based immunoassays will be highly useful in developing low-cost immunodiagnostics for the developing world.

Raymond Morrill, Marketing Manager, Medica Corporation USA
Industry Speak
EasyRA - The Easy Choice

Actively engaged in developing new technology, Medica specifically designs products to enhance productivity and the quality of care in small- to medium-size in vitro diagnostic laboratories. The company's clinical chemistry, blood gas, electrolyte, and hematology analyzers are focused on the global need to lower the healthcare costs.

Medica's EasyRA analyzer is a fully automated clinical chemistry analyzer that accommodates the diverse needs of small laboratories. Lab technicians become experts with minimal training, thanks to a simple and intuitive user interface. Four color-coded icons guide the technician through all analyzer functions. EasyRA is quickly operational and ready to run samples. Friendly displays clearly signal the progress of a run and easily allow changes. Technicians can analyze stat samples in less than 8 minutes. The system saves valuable time by programming the next work list while another work list is running, or simply check reagent and cuvette inventories to prepare for the next run.

The clinical chemistry analyzer offers unprecedented access to all replaceable components. Its unique, slide-out drawer makes maintenance quick and easy. RFID technology eliminates the need to manually program reagents. When the smart reagent wedge is placed anywhere in the reagent area, EasyRA identifies location, number of samples remaining, sample volumes, and expiration dates.

With 150 tests per hour (>300 with integrated ISE), 24 sample positions, 24 reagents on board, and more, the analyzer is an easy choice for the laboratory's clinical chemistry analysis needs.

Today, globally Medica has more than 1000 satisfied EasyRA users. The pathologists appreciate the ease-of-use of the analyzer as it has helped them to rule out the manual errors considerably and has assisted in giving accurate and reliable results, each time - every time.

Raymond Morrill
Marketing Manager,
Medica Corporation USA

Louis Liao, Vice Director, SNIBE
Industry Speak
Chemiluminescence Immunoassay Principle

Chemiluminescence immunoassay (CLIA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody or immunoglobulin. It offers several advantages and has applications in clinical laboratories for diagnoses use. The principle of CLIA system is based on antigen-antibody reaction by combining a patient sample, control, or calibrator in a reaction module. The two key technologies in CLIA system are nano-magnetic microbeads and label material.

Nano-Magnetic Microbeads. The outer layer of microbeads is formed by organic polymer material and the core is made of nano-size iron oxide material. There are a lot of active groups on the microbead surface; in proper condition they can conjugate with varied molecules by a stable chemical bond. In CLIA system, the microbeads can be coated with anti-FITC or other antibody or antigen.

Nano-magnetic microbeads can be magnetized by a magnetic field, so they can be gathered quickly and separated from liquid. After external magnet field is removed, microbeads return to their initial state without remanence, which helps to separate them again for measuring.

Chemiluminescence Label Material. Chemiluminescence label material can be labeled with both antibody and antigen. ABEI, stable in acid and alkaline solutions, one of the famous isoluminol label material, is easier to label the antibody. Luminol, isoluminol, and ABEI are chemiluminescence label materials and share the same reaction principle during chemiluminescence process.

The system is capable of sandwich immunoassay and competitive immunoassay. The sample, chemiluminescence label, and nano-magnetic microbeads are added in the reaction module and incubated, upon which they form an immune complex. After washing, only immune complex stays, and then the substrate is added. This results in generation of light, the intensity of which is directly proportional to the amount of labeled complexes present, which indirectly aids in quantification of the analyte of interest. The intensity of light is measured in terms of relative light units (RLUs). The main advantages of CLIA technology include sensitivity, stability, and its ability to remain unaffected by background signals.

Louis Liao
Vice Director, SNIBE

Dr Abhipsa Dharia, Sr. Manager-Medical Affairs, Transasia Bio-Medicals Ltd.
Industry Speak
Immunochemical Methods and Trends

All immunochemical methods are based on a highly specific and sensitive reaction between an antigen and an antibody. Immunochemistry offers simple, rapid, robust yet sensitive, and in most cases, easily automated methods which are applicable to routine analyses in clinical laboratories. Immunochemical methods do not usually require extensive sample preparation. Infact, most methods are based on simple photo, fluoro, or luminometric detection. These methods have rapidly replaced chromatographic techniques in clinical diagnostics, offering fast detection of antibodies associated with specific diseases, disease biomarkers, and hormones.

The assays most often used in clinical immunochemistry involve either quantitative or qualitative formats using enzyme-linked immunosorbent assays (ELISAs), immunochromatography in the form of lateral-flow devices like dip-sticks, and test strips or Western Blot assays used to interpret data from protein analysis with gel electrophoresis. Immunohistochemistry, one of the main diagnostics tools in today's clinical laboratories, is also based on the principles of antigen-antibody binding.

Immunohistochemistry (IHC) detects the presence of critical marker proteins in tissue samples while in situ hybridization (ISH) detects target RNA or DNA sequences. When morphology and routine staining cannot provide all the diagnostic answers, pathologists turn to these advanced staining techniques. Both techniques are commonly used for cancer diagnosis, where the presence or absence of particular proteins or sequences helps pathologists make an accurate diagnosis and differentiate between disease states that look morphologically similar. IHC uses primary antibodies that bind to the target protein and detection systems that link to the primary antibody to provide a visual indication of the protein's presence and location using bright-field microscopy. ISH uses probes that bind to the target RNA or DNA sequence. Different detection systems are then used to visualize the presence of the target sequence - FISH uses fluorescent dyes and fluorescent microscopy while CISH uses chromogenic dyes and bright field microscopy.

IHC is identified as the most lucrative sub-segment of the tissue diagnostic market majorly owing to increasing incidences of cancer diagnostic. North America is the leading tissue diagnostic market owing to rising prevalence of cancer, supportive reimbursement facilities, and growing demand for personalized medicines. Europe is expected to be the second-most profit-generating region owing to rising patient awareness levels, especially in Western European countries. The emerging economies of Asia-Pacific such as India and China are expected to witness lucrative growth over the forecast period owing to increasing geriatric population base, increasing disposable income, rapid innovation in diagnostic testing, rising research funding for cancer and a large pool of patients.

Dr Abhipsa Dharia
Sr. Manager-Medical Affairs,
Transasia Bio-Medicals Ltd.

Nitin Srivastava, National Sales Manager-IVD, Nihon Kohden India Private Limited
Industry Speak
Automation in Open Segment

The continuous attempt to excel has brought the company to a fortunate position of being the catalyst of change in IVD sector. It has been our endeavor to drive the company and its business to the next level with the changing market dynamics to achieve all these. The company adopts innovative ideas, technologies, and stronger business process with the support of a professional team. In continuation of this, Nihon Kohden India has joined hands with Tokyo Boeki Medisys Inc., Japan, to provide innovative product auto analyzer model Biolis 24i Premium to Indian customers. Now, Nihon Kohden India is the exclusive distributor for sales and marketing for Biolis 24i Premium.

It smartly minimizes the errors which occur in existing automation like carryover due to stirrer or probe mixing; it is rectified by using Biolis 24i patented technology contactless mixing (air-pressure mixing). It also avoids more water consumption due to extra washing. Cross-reagent contamination due to single probe is rectified by separate two probes for reagents and one for the sample.

Key features of the analyzer are:

  • Fixed-grating technology with 12 wavelengths avoids frequent filter maintenance and replacement.
  • Various calibration curves.
  • Flexibility of assigning reagent with 1 ┬╡L step and sample with 0.1 ┬╡L step.
  • Low reaction volume requirement only 140 ┬╡L.
  • Voice prompt makes it a walkaway system.
  • Internal printer to avoid any data loss due to accidently PC off.
  • Detachable reagent tray and separate function for reagent station makes it convenient to maintain temperature in off time.
  • Reaction cuvette washing with heated water and two kinds of washing solutions (alkaline and acidic) and heated water washing for all probes.
  • Sample pre-dilution ratio and auto-rerun dilution ratio can be set in advance.
  • Carryover protection program for reaction cuvettes and probes.
  • Sample cup and primary tube (5, 7, and 10 mL) can be used.

Open system and user-friendly software gives flexibility-to-use to perform specialized parameters with their reliable chemistry and economical cost per test.

Nitin Srivastava
National Sales Manager-IVD,
Nihon Kohden India Private Limited

Vaibhav Garud, Product Manager-Immunoassays, bioMérieux
Industry Speak
Need for High Sensitivity Troponin Assay

Cardiovascular disease is still the number one killer in the world and almost half of those deaths are due to ischemic heart disease. Chest pain is a common symptom for an emergency admission to hospital and is a large burden on healthcare resources. Most of the patients who are in emergency department with chest pain do not have acute myocardial infarction (MI). Hence, there is a need of a biomarker such as cardiac troponin to safely and very early rule out acute MI. Implementation of this approach would reduce avoidable hospital admission and have major benefits for both patients and healthcare providers.

With advances in technology, a new era in troponin assays is approaching. The new high-sensitivity troponin assays will reduce the threshold for the diagnosis of MI, as specified in the 2012 third universal definition of MI. These new high sensitivity troponin assays could have several distinct roles in clinical practice including facilitation of earlier diagnosis and ruling out of MI, risk stratification in acute cardiac conditions, and prognostic information in stable disease states. Interpretation of troponin results will be in combination with a full assessment of the clinical context.

A contemporary cTn assay results can provide clear evidence for a directional trend after the second 3-hour value, with supporting ECG or imaging findings, to rule-in acute MI in a patient. With a high sensitivity troponin on the other hand, a 2-hour algorithm can be used to rule-out acute MI, in an otherwise low-risk patient; providing the ability to cancel subsequent testing at 6-and 9-hour orders. In this way, an earlier rule-out can mean significant savings for the hospital through the possibility of an earlier discharge from the emergency department. Thus, the high-sensitivity cTn is needed to move from conventional troponin to the new generation of high-sensitivity troponin assays.

Vaibhav Garud
Product Manager-Immunoassays,
bioMérieux 

Sunitha KG, Product Specialist, CPC Diagnostics
Industry Speak
An Insight into the Algorithmic Approach for ANA Diagnosis

A healthy human body is equipped with a powerful system for fighting off disease. Unfortunately, this system can sometimes go awry and cause the body to attack itself, a phenomenon known as autoimmunity. Autoimmune diseases are a spectrum of diseases ranging from organ-specific, in which the immune system reacts against self-antigens in a particular tissue, to systemic, in which the immune response takes place against a specific antigen or antigens of multiple tissues. The etiology is unknown but many theories were put forward to describe the development of these diseases. Heredity, infections, chemical toxicity, and stress are some of the causes that are implicated.

Autoimmune diseases (AIDs) are accompanied by autoantibodies, which act as early reliable markers essential for diagnosis. One such marker is anti-nuclear antibodies (ANAs), which are the hallmark of many autoimmune connective tissue diseases. ANA testing is used extensively for diagnosing and monitoring various AIDs such as systemic lupus erythematosus (SLE), scleroderma, Sjogren's syndrome, mixed connective tissue disease (MCTD), polymyositis, and dermatomyositis.

The methodologies for measuring ANA have changed substantially over the years in recognition of a wider spectrum of potentially relevant autoantibodies and a sensible requirement to improve test performance and efficiency. The combination of a sensitive screening test (indirect immunofluorescence) with a specific confirmatory test ensures the reliable determination of ANA.

For serological investigation of ANA screening, indirect immunofluorescence (IIF) slides with BIOCHIPs is the method of choice and is considered the gold standard. Each test field contains a combination of human epithelial cells (HEp 2 or HEp 20-10) and frozen section of primate liver. By comparing the fluorescence patterns of both substrates, many ANAs can be pre-differentiated and the results verified reciprocally. The primate liver allows clinicians to identify a range of additional autoantibodies, thus helping to make important unexpected diagnosis.

Additionally, antibodies against ANA can be distinguished semi-quantitatively through a multi-parametric approach in a single test protocol. The line immunoassay test is the method of choice. The plastic strip (EUROLINE) contains membrane strips with antigens purified by affinity chromatography and applied as thin parallel lines. The bound-serum antibodies are made visible by an enzyme-immune reaction. The EUROLineScan system developed by EUROIMMUN provides computer-based evaluation of the strips (EURO-LINE) and enables electronic archiving of the data. The automation of the entire process is made possible through PlexMat - a high precision multiplex line immunoassay processor.

Sunitha KG
Product Specialist,
CPC Diagnostics


 

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