Microarray is an important tool used in functional genomics for understanding biological data. Advancements in technology have led to the development of more sophisticated techniques, instruments, data analysis, and management tools for studying genetics. The recent advances in microarray technology aid doctors in accurate and rapid diagnosis of diseases. Microarray is an integral part of effective disease management. Since diagnostic microarrays are useful for genotyping and determination of disease-relevant genes, mutation analysis, and SNP screening, they allow doctors to detect specific subtypes within a disease category based on differences in gene expression. Thus, the extensive use of microarray technology for disease diagnosis will positively affect the market for microarrays in coming years.

The current market is rapidly evolving with companies making substantial investments on research and development to develop new technologies and identify new therapies and diagnostic tests. With the latest development of nanoarrays, researchers can efficiently print thousands of binding sites on a single conventional microarray spot. Also, advanced and specialized methods to express and purify proteins help companies build recombinant proteins' library. The rising demand for microarrays will bolster this market's growth over the next 5 years.

Indian Market

Major Vendors in Indian Clinical Microarray Instruments and Consumables Market 2015The Indian clinical microarray instruments and consumables market was valued at Rs.12 crore in 2015, with consumables dominating with a 70 percent share. The government, which is a major buyer, did not place any orders in 2015. Three vendors are driving the segment in India: Illumina marketed by Premas Biotech; Affymetrix marketed by Imperial Life Sciences; and Agilent Technologies.

The segment may be viewed in three dimensions:

  • Cytogenetics, where the microarrays leverage the investigative power of SNP genotypes to reliably detect chromosomal imbalances of copy number and allelic homozygosity, which are commonly associated with genetic constitutional disorders.
  • Agrigenomics, which transforms the future of agriculture with genomics. It has and will continue to help drive sustainable productivity and offer solutions to the mounting challenges of feeding the world's growing population. Agrigenomics technologies help plant and animal breeders and researchers identify desirable traits, leading to healthier and more productive crops and livestock.
  • Personal genomics is important for identifying the genetic predisposition of an individual for common diseases, carrier status for inherited diseases, familial traits and efficacy, and adverse reactions to common drugs.

Fast gaining popularity in India is chromosomal microarray analysis, a technique that can identify major chromosomal aneuploidy as well as submicroscopic abnormalities that are too small to be detected by conventional karyotyping. In contrast to the conventional karyotype, which detects primarily genetic abnormalities resulting from large changes in the number or structure of chromosomes, microarray analysis also can provide information at the submicroscopic level throughout the human genome. There are two types of microarrays used in clinical prenatal testing: comparative genomic hybridization (CGH) and SNP arrays. Although both of these techniques detect copy number variants, they identify different types of genetic variation. With each of these technologies, DNA from a fetal sample is hybridized to a DNA chip or array containing DNA fragments of a known identity (known sequences). The fetal DNA to be studied is typically derived from aminocytes or chorionic villi samples.

Imperial Lifesciences has had good success with leading diagnostic centers as Lal Pathlabs, Metropolis, Gangaram, AIIMS, SRL, SGPGI (Sanjay Gandhi Postgraduate Institute of Medical Sciences), and Manipal in adopting chromosomal microarray analysis in 2015. The ACMG guidelines, which recommend replacing karyotyping with chromosomal microarrays as first-line postnatal test, have contributed to their acceptance.

Advancing breakthroughs have been made with genomic solutions in noninvasive prenatal tests (NIPT). Evolving noninvasive screening options offer early genetic screening for chromosomal conditions using just one tube of blood - as early as 10 weeks into a patient's pregnancy. Other types of prenatal screening and diagnostic tests may require more than one office visit, multiple blood draws, or carry a higher risk of false positive results. Diagnostic tests, such as amniocentesis, provide definite results for most chromosome conditions but have an associated risk of miscarriage.

Illumina has recently launched the GSA, a highly economical tool for genetic risk screening of large global populations. It offers genomic coverage and imputation performance across 26 continental populations and features approximately 50,000 hand-curated variants relevant to clinical research, including markers for pharmacogenomics, newborn screening research, risk profiling, and confirmation of putative clinical associations. Leveraging the 24-sample Infinium format, the array includes 660,000 markers, and allows for the cost-effective addition of up to 50,000 custom markers. It has found great acceptance in India. In USA, where it was first launched, the company received orders for more than 3 million samples of the new consortia-developed array. Initial customers include human disease researchers at The Broad Institute and deCODE Genetics, health systems Avera Health, Codigo46, Diagnomics, Eone Diagnomics Genome Center (EDGC), Sanford Health, and UCLA Health System, genomic service providers Centre National de Genotypage, Human Genomics Facility HuGeF, Erasmus MC, Life and Brain, and consumer genomics company 23andMe, Inc. The early adoption of the GSA, represented by these deals, illustrates the widespread market demand for genotyping products and the continued relevance of arrays in human disease and translational research. The value of the content on this array will lead to widespread use in clinical research, including precision medicine programs, predictive risk screening, large-scale genome-wide association studies, and in biobank sample characterization and quality control.

Premas Biotech, Illumina's Indian counterpart, too has had good success with GSA. The company is focused on microarrays for pre-natal genetic screening, and NIPT. Some of the clinics and translational research centers, which were its leading customers in 2015, were The National Institute of Biomedical Genomics (NIBMG), National Design and Research Foundation (NDRF); Sandor Life Sciences; Positive Bioscience, Lal Path Labs; and service providers as Genotypic Technology.

Agilent delivers industry-leading CGH and NGS solutions for pre-implantation and human genetics.

Global Market

The global array instruments market stood at USD 1 billion in 2015 and is predicted to reach USD 1.12 billion in 2020, representing a compound annual growth rate (CAGR) of 4.3 percent between 2015 and 2020.

In terms of technology, the array instruments market is segmented into DNA, protein, tissue, and cellular microarrays. The global DNA microarray market is expected to grow at a CAGR of 15.16 percent during 2016 to 2020. Growing popularity of personalized medicines will be a key trend for market growth. The popularity of DNA microarray technology is growing as it helps in the early detection of diseases, and selection of accurate treatment methods can reduce mortality rates. DNA microarray technology enables researchers to analyze critical biological complications such as the genomic variations and nature of inherited syndromes that cause cardiovascular diseases and cancers. Advances in technology will be a key driver for market growth. Rapid advances in technology related to DNA microarray have equipped related solutions to produce results with high efficiency, accuracy, specificity, and reproducibility in target identification, primary screening, and toxicity study in drug discovery and research. Technological advances in DNA microarray have also enabled solutions to be applied in clinics, commercial laboratories and research institutions, and hospitals to detect DNA and proteins with the motive of disease diagnosis, drug discovery, and disease monitoring that has significantly increased the acceptance and adoption of these solutions.

The laws and regulations of the approval process for diagnostic devices vary across all countries, which is a major challenge faced by MNCs. In addition, any change in regulatory policies by different governing bodies including National Institutes of Health (NIH), National Human Genome Research Institute (NHGRI), and FDA during the product development period could delay the entry of potential products into the market. Many developed countries such as the US, the UK, Germany, France, Japan, Singapore, and South Korea have strict regulations regarding the approval and marketing of diagnostics products.

The segment of protein microarray emerged as the second-largest and most-swiftly developing segment of the market. Increased accuracy in identification of protein-protein interactions, high sensitivity, and high resolution are amongst the chief factors fuelling the demand for protein microarrays. The segments of tissue microarray and cellular microarray are presently in their early stages and thus have certain limitations. The major factors that limit the use of tissue microarray are tissue heterogeneity and high cost. Expensive nature of array instruments limits the use in general practice in several countries. Hence, researchers are working on constructing cost-effective tissue microarrays. Certain drawbacks with the use of cellular microarray are related to sensitivity. Moreover, there is further need for development of automated image analysis and data acquisition.

The market is highly competitive owing to the presence of well-established players. The competitive environment is expected to increase due to factors like the discovery of new applications and advances in technologies, growth in the personalized medicine market, and increased government spending and private investment in the healthcare sector and R&D. Major global vendors are Affymetrix, Agilent Technologies, Cellix, Illumina, and PerkinElmer. Other prominent players include Bio-Rad Laboratories, EMD Millipore, Fluidigm, Cepheid, US Biomax, Biochain Institute, and SuperBioChips Laboratories.

Market Trends

  • Emerging markets for biochips in diagnostics are beginning to gain traction. The main biochips platforms are undergoing a transition.
  • In 2015, the microarrays segment dominated the global biochips market and accounted for a market share of nearly 70 percent.
  • DNA microarrays are being influenced by next-generation sequencing (NGS) applications, as well as exciting new applications in rapid DNA analysis and diagnostics. Protein microarrays continue to make progress in the market, as well as emerging microarray classes (tissue/cell and glycomics).
  • Lab-on-a-chip (LOAC) applications are becoming more important in point-of-care diagnostics applications, as well as in drug discovery and development.
  • NGS applications continue to increase as a result of lowered costs and better informatics support.
  • Increasing advancement in the protein-chip technology is resulting in improved economies of some of the regions such as Asian countries. This factor is expected to create a lot of opportunities for the enlargement and expansion of the market.

Hybridizing the Past and Present

The field of medicine is in the process of being profoundly transformed by new technologies; much of this transformation comes from exciting advances in genomics.

Genomics technologies have developed at a very fast pace, especially in the last decade. Microarrays, once the most cutting-edge technology, are rapidly losing their leading position as a discovery tool to a newer and superior technology - next-generation sequencing (NGS). Despite some predictions that NGS - due to crucial advantages - would have replaced microarrays completely by this time, their use remains significant. The reasons for continued use of microarrays include their proven track record for almost two decades; lower costs and higher throughput in the case of very large-scale studies; lack of well-established molecular biology solutions for NGS platforms for difficult samples (low input, FFPE, etc.); streamlined bioinformatics; and the necessity to validate NGS results with an alternative high-throughput technology, among others.

Early array technology had done an excellent job of working out the methodology for isolating, hybridizing, and detecting genes of interest, and at the same time making substantial progress with high-throughput workflows. However, there was one main area of arrays that needed to be addressed - the micro portion. Shrinking arrays down to more microscopic levels would allow scientists to cram thousands of gene sequences into more manageable sizes and so cut sample input requirements, reagent usage, and overall costs.

In 1995, Stanford researchers published a seminal paper in the journal, Science (Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray) introducing the first miniaturized microarray that printed samples from microtiter plates onto a standard glass microscope slide (3.5 mm × 5.5 mm). A year later molecular biologist and Howard Hughes Medical Institute investigator Joseph DeRisi and a group of investigators at Stanford described a method that allowed higher-density arrays to be printed onto the same microscope slide area.

These newer arrays were also improved through their replacement of radiolabeled probes with fluorescently tagged oligonucleotides. The importance of using fluorescence detection cannot be overstated, because the technique is not only quite sensitive with a broad dynamic range, but it also allows for the labeling of two or more samples with different colors within the same array. This two-color approach enabled researchers to measure the ratio of signals on the same array, thereby creating a more reproducible technique.

Way Forward

Microarrays have expanded far beyond their early uses as simple gene-expression profiling tools and now have applications that span the genomic gamut. While broad-based arrays are still attractive, such as those designed to look at genome-wide single-nucleotide polymorphisms (SNPs), biotech companies are creating focused arrays that contain subsets of genes known to be involved in various human diseases. These targeted approaches allow clinical researchers to use multiple microarrays as molecular diagnostic tests for a number of different disorders.

The greatest challenge the microarray industry faces is from the bourgeoning NGS market. Although NGS technology has some distinct advantages over microarrays, many researchers still depend on arrays' proven, validated technology over the generation of NGS data. Because most scientists are concerned with the finances of their laboratory, microarrays come out on top in this category in comparison to the expenditures required for NGS analyses methods.

A quick perusal of the scientific and pop-sci literature will ultimately yield a number of articles with a relatively regular periodicity predicting the ultimate demise of microarrays, often to be replaced by some newer, advanced technology. Yet, here we are in 2016, assembling a 40-year or so retrospective. Seemingly the sky is still the limit for the technology that had some very simple beginnings and blossomed into a fundamental laboratory tool.

Neeraj Gupta, Director Sales and Marketing, Imperial Life Sciences (P) Limited
Industry Speak
Microarray Evolution in New Landscape

Microarray has been a gold standard technology since many years for applications like gene expression profiling, miRNA analysis, and SNP genotyping. However, new applications like pharmacogenomics and molecular cytogenetics have recently brought a paradigm shift in the utility of microarray technology. Microarray has in fact done a fantastic comeback in different aspects of research and diagnostics all across India with high growth in clinical diagnostics, population studies for human genetic screening, personalized medicine projects, and agri-genomics.

Due to high resolution, cytogenetic microarray (CMA) is moving to replace the traditional karyotyping for the evaluation of individuals with intellectual disability, autism, and congenital malformations. The diagnostic yield of CMA adds extra 15 to 20 percent to the existing information and is more than any other investigation for evaluation of developmental disabilities. Several studies showed that compared to conventional karyotyping, prenatal diagnosis with Cytosure and PrenataSure arrays reveals 8-35 percent extra diagnoses in abnormal ultrasound pregnancies.

Confirming the above findings, The American College of Medical Genetics has recently published guidelines that support the use of chromosomal microarrays as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or multiple congenital anomalies (MCAs). Also, ACOG guidelines recommend prenatal microarray testing to be used as confirmation of NIPS as once an invasive procedure is offered.

Microarrays have been preferred by leading biobanks worldwide for population-based screening (including the UK Biobank). A new precision medicine research array has also been launched. This array offers a genome-wide imputation grid from Phase-III of the 1000 Genomes Project and from the NHGRI-EBI GWAS catalog published as of May 2016, providing the most up-to-date content, broadest coverage, and highest accuracy for disease association studies across populations.

Neeraj Gupta
Director Sales and Marketing,
Imperial Life Sciences (P) Limited


 

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