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Pharmaceutical Microarrays glossary & taxonomy
Evolving terminology for emerging technologies

Comments? Suggestions? Revisions? Questions? Mary Chitty mchitty@healthtech.com
Last revised March 04, 2014 

 



Microarray technologies have become an invaluable tool for drug discovery as well as for diagnostics. Microarrays are being used to find new drug targets as well as developing personalized medicine in a fast and affordable manner. However, many challenges of the technology remain --  quality control, expression arrays and pharmacokinetics will be addressed as well as new developments in the field, such as microRNA arrays and DNA methylation.

There is still a great deal of volatility in the area of microarray terminology. See FAQ question # 3 for a methodology for investigating and quantitating use of various terms.  Note that names and definitions for arrays - chips- and/or  microarrays vary widely in the literature and are far from standard yet.

Technologies map   Finding guide to terms in these glossaries   Site Map
Sub-categories are Microarrays categories Other related glossaries include 
Applications  Molecular Medicine  Drug discovery & development  Pharmacogenomics
Informatics Algorithms, Bioinformatics  
Technologies Labels, Signaling & Detection,
Gene Amplification & PCR; Nanoscience & Miniaturization  Protein arrays/microarrays are in the Protein technologies  Cell and tissue arrays are in Cell & Tissue Technologies  
Biology Expression, SNPs & genetic variations 

applications - microarrays: See Expression gene expression analysis  disease classification; Sequencing genotyping, diagnosis, drug efficacy and toxicity,  sequencing - mutation detection.

array technology See microarray.  “Array technology” in a broader context may refer to computer science, engineering and/ or telecommunications. 

Array technologies include 2D gel electrophoresis, CCDs Charged Coupled Devices, CCD cameras, detection technologies, fiber optics. imaging, ink jetting, mass spectrometry, photolithography, phosphorimagers, piezoelectric, semiconductors, spotting robots.

arrayed library: Individual primary recombinant clones (hosted in phage, cosmid, YAC, or other vector) that are placed in two- dimensional arrays in microtiter dishes. Each primary clone can be identified by the identity of the plate and the clone location (row and column) on that plate. Arrayed libraries of clones can be used for many applications, including screening for a specific gene or genomic region of interest … Information gathered on individual clones from various genetic linkage and physical map analyses is entered into a relational database and used to construct physical and genetic linkage maps  simultaneously; clone identifiers serve to interrelate the multilevel maps. [DOE]  Broader terms: Cell biology library, genomic library; Drug discovery & development

arrays: Microarrays categories Narrower terms include BAC microarrays, bead arrays, bead based arrays, bioarrays, biochips, bioelectronic arrays, cDNA arrays, cell arrays, DNA arrays, encoded bead arrays, gel pad arrays, gene arrays, gene expression arrays, genome arrays, genomic arrays,  high density oligonucleotide arrays, high density protein arrays, hybridization arrays, in situ arrays, low density arrays,  microelectronic arrays, multiplex DNA hybridization arrays,  nanoarrays, nylon macroarrays, oligo arrays, oligonucleotide arrays, oligosaccharide arrays, peptide arrays, planar arrays, protein arrays, solution arrays, spotted arrays, tissue arrays, exon arrays, filter arrays, macroarrays, small molecule microarrays, suspension arrays, theme arrays, tiling arrays, transcript arrays; Expression  gene expression arrays;   Related terms include arrayed library.  See also chips, microarrays.

bioassays: Assays & screening See second definition 

blotting: A technique used for transferring DNA, RNA, or protein from gels to a suitable binding matrix, such as nitrocellulose or nylon paper, while maintaining the same physical separation. [IUPAC Biotech] Narrower terms: Northern blotting, Southern blotting, Western blotting.

clones: Cell biology  Related term: arrayed library.

competitive hybridization: Gene Amplification & PCR

cross hybridization: One of the challenges in measuring mRNA levels on microarrays is that genes can cross- hybridize, depending on whether the probes target unique or common regions. [George Church Lab, "S. cerevisiae cross- hybridization and unique regions", Harvard Medical School, 1999]  http://arep.med.harvard.edu/labgc/adnan/projects/YeastCrossHyb/

Incorrect hybridization that occurs in microarray experiments by virtue of the fact that the number of incorrect molecules in a target is so much greater than the number of correct ones. This phenomenon adds a small amount of noise to every measurement. Cross-hybridization is more of a problem with cDNA arrays than with oligonucleotide arraysRelated terms: Gene Amplification & PCR  

density of microarrays: Low (200-5000 genes): low-density arrays (Clontech, Research Genetics) —Medium: microarrays (14,000 cDNAs/ array; Agilent), spotted oligos (8000; Clontech)  —High (>10,000 genes): high- density oligo arrays (Affymetrix)  CHI, GenomeLink 14.1 http://www.chidb.com/newsarticles/issue14_1.asp

The entire yeast genome (6,000+ genes) has been put on a chip. See proteome chip.  Narrower terms: high density oligonucleotide arrays, high density protein arrays, macroarrays, ultra high density. Related terms: Expression

deprotection: During the chemical synthesis of DNA and RNA, branching is prevented by ensuring that only one chemically reactive group is present in the growing oligonucleotide and one in the nucleoside 3′-phosphoramidite. This is achieved by blocking other reactive groups within the sugars and bases (e.g. exocyclic amines) with protecting groups. The removal of the protecting groups that block exocyclic amines, commonly known as deprotection, occurs only after synthesis.  Assessing incomplete deprotection of microarray oligonucleotides in situ, Holly K. Dressman, Lise Barley-Maloney,1 Laura-Leigh Rowlette, Paul F. Agris,1* and Mariano A. Garcia-Blanco2 Nucleic Acids Research v.34(19); Nov 2006   detection technologies: Labels, signaling & detection
External RNA Control Consortium ERCC:
http://www.cstl.nist.gov/biotech/workshops/ERCC2003/ 

FDA draft guidelines - multiplex tests: Regulatory Affairs Primarily considers nucleic acid arrays, but principles apply to protein arrays and tissue arrays. Related term: analyte specific reagent

fluorescence scanners: A fluorescence- based detection method used with microarrays, high- density oligonucleotide arrays, and microelectronic chips. Fluorescence is generally detected with a confocal scanning microscope.  Related terms:  Imaging  Labels signaling & Detection

ink jetting technologies: The most advanced of these [‘drop- on- demand’ delivery] approaches are adaptations of the ink- jetting technologies, which utilize piezoelectric and other forms of propulsion to transfer biochemical substances from miniature nozzles to solid surfaces. .. [these] allow high- density gridding of virtually any biomolecule of interest, including cDNAs, genomic DNAs, antibodies and small molecules … not currently as robust as photolithography or microspotting, this approach has been used to prepare microarrays of single cDNAs at a density of 10,000 spots cm-2. Because ink jetting does not require direct surface contact, piezoelectric delivery is theoretically amenable to very high throughput.  Mark Schena et al “Microarrays: biotechnology’s discovery platform for functional genomics” Trends in Biotechnology 16(7): 301- 306 July 1998   See also note under probes- microarrays

lithography: Primary enabling technology for semiconductor manufacturing Intel Lithography Roadmap, Intel Research, US ftp://download.intel.com/technology/itj/2002/volume06issue02/art06_lithographyroadmap/vol6iss2_art06.pdf    Narrower terms: photolithography, soft lithography

mask: Device which acts as a barrier to the passage of a reagent (often light - see photolithography). A pattern of holes in the mask allows selective passage of reagent and results in a corresponding pattern of reagent deposition or photodeprotection on a surface placed behind the mask. This allows the generation of spatially addressable libraries. [IUPAC Combinatorial Chemistry]

mass spectrometry: Mass Spectrometry  can be used to both measure and analyze the molecules contained in microarray spots. It involves introducing enough energy into a target molecule to cause its ionization and disintegration. The resulting fragments are then analyzed, based on the mass/ charge ratio to produce a "molecular fingerprint. [CHI Microarrays report] Mass spectrometry

matrix: 1) From the Latin word for womb (in turn from mater or mother), a matrix is either the intercellular substance of a tissue, the material in which a fossil is embedded, or a mold from which a relief surface is made in printing or phonograph manufacturing. 2) In mathematics and computer science, a matrix is a set of numbers laid out in tabular form (in rows and columns). From this meaning, a less formal meaning is derived of a complex of lines intersecting at right angles. [whatis.com] Related term: substrates.

measurement error: Has two components: variance and bias. Variance results from uncontrolled (or uncontrollable) variation that occurs in biological samples, experimental procedures, and arrays themselves. These factors cause measurements of expression level to vary in an apparently random fashion between replicas. Bias is a systematic error that causes the measurement to differ from the correct value. Since bias is systematic, it affects all replicas the same way. 

microarray technology:  A developing technology used to study the expression of many genes at once. It involves placing thousands of gene sequences in known locations on a glass slide called a gene chip. A sample containing DNA or RNA is placed in contact with the gene chip. Complementary base pairing between the sample and the gene sequences on the chip produces light that is measured. Areas on the chip producing light identify genes that are expressed in the sample. NHGRI Glossary http://www.genome.gov/glossary/index.cfm?id=125 

microarrays:  I will keep this term for DNA arrays [regardless of the support] in which the spacing between spots is less than 500 um. This translates into densities of at least 400 genes per cm2. S Granjeaud "Expression profiling: DNA arrays in many guises" BioEssays 21: 781-790 Sept. 1999

A microscopic, ordered array of nucleic acids, proteins, small molecules, cells or other substances that enables parallel analysis of complex biochemical samples. Mark Schena et al. "Quantitative monitoring of gene expression patterns with a complementary DNA microarray" Science 270, 467-470 Oct. 20 1995

The term microarray originally referred to spotted cDNA arrays, but now we and others use it for any hybridization- based array. [When the term microarray was first introduced, the prefix micro served to distinguish this new generation of arrays from their predecessors, which came to be called macroarrays. Traditionally, microarrays differ from macroarrays based on the physical size of the surface and the spots. 

Microarrays  were developed in large part by Patrick O. Brown and colleagues at Stanford University. The major characteristics of microarrays - under the strictest definition of this term - are that they have a glass or plastic slide as a matrix, use fluorescent dye labeling for the detection of hybridization, and are created with robots that deposit probes on the slides. Microarrays also tend to have a large number and high density of probes; however, their probe density is less than that of high- density oligonucleotide arrays. The probes used on these arrays can be made from clones, PCR amplicons, or oligonucleotides.   The market for DNA microarrays has grown significantly since its inception in the mid- 1990s. New players have entered the market in recent years, driving improvements in product quality and a search for new market opportunities. The prospect of participation in the $20 billion in vitro diagnostics industry serves as a further incentive to current and emerging industry players, creating a fiercely competitive environment.  Narrower terms: Microarrays- categories Related terms: density of microarrays  

micron: One one thousandth of a millimeter; 10,000 angstroms. [NIGMS] Represented by u.

microspotting: An original version of mechanical microspotting was developed by [Dari] Shalon and [Pat] Brown [at Stanford] and later commercialized at Synteni [now Incyte Genomics] …a miniaturized version of earlier DNA spotting techniques, encompasses a family of related deposition technologies that enable automated microarray production by printing small quantities of premade biochemical substances onto solid surfaces. Printing is accomplished by direct surface contact between the printing substrate and a delivery mechanism that contains an array of tweezers, pins or capillaries that serve to transfer the biochemical samples to the surface. M Schena et al “Microarrays: biotechnology’s discovery platform for functional genomics” Trends in Biotechnology 16(7): 301- 306 July 1998 Related terms: Stokes shift,  spotted arrays, spotting robots.

microwell chips: Narrower term: nanowells

Northern blotting: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES. MeSH, 1991

oligonucleotide: Biomolecules

phosphorimagers: Instruments used to quantify the radioactive signal (an indication of the level of hybridization) produced by macroarrays.

photolithography: Process by which selective masking generates light patterns which direct chemical transformations to certain areas of a photosensitive surface. Coupling of different building blocks to discrete sites may give rise to spatially addressable arrays of compounds. [IUPAC Combinatorial Chemistry] 

Unlike droplet- printing technology, which allows microarrays to be created with relatively inexpensive and user- friendly equipment, photolithography requires expensive equipment and particular expertise and is also protected by patents. Related term: soft lithography

physical bioassay: See under Assays & screening bioassay

piezoelectric: A material that generates an electric charge when mechanically deformed. ..[About.com http://chemistry.about.com/library/glossary/bldef700.htm

printing:  The placing of probes on an array - a process often called printing - is accomplished by automated machinery that can produce very small spots and place them quite close to one another with high precision. With modern equipment, spot diameters are in the range of 100 mm, and it is possible to place 10,000- 30,000 probes on a standard 1" x 3" glass slide. The large number of probes is a bit misleading in that it is often necessary to represent each gene by two different probes to achieve adequate reproducibility. Thus, an array with 30,000 probes might represent only 15,000 genes.

probes - microarray: In this paper "probe" refers to the (labeled) material that is hybridised with the array of cDNA inserts or oligonucleotides ("targets"). The oligonucleotide chip community tends to use the reverse terminology. S Granjeaud "Expression profiling: DNA arrays in many guises" BioEssays 21: 781-790, Sept. 1999

We use the term probe for the DNA affixed to the array, and target for the DNA or RNA being hybridized to the array. This usage is fairly common, although some authors reverse the meanings of probe and target. CHI Microarray Informatics report

Two technologies are available for placing the DNA probes on the array. The traditional and most popular approach involves contact spotting, in which the DNA is loaded into a print tip and deposited by physically tapping the tip on the surface. There is also a newer noncontact method in which DNA is sprayed onto the surface using technology adapted from computer ink- jet printers. [The ink- jet method is sometimes called indirect because the DNA is sprayed onto the surface rather than being directly placed.] The ink- jet method is capable of producing smaller spots, and because it avoids physical contact with the surface may prove to be more reliable. (The physical contact can introduce more variability into spots.)   Can be made from clones, PCR amplicons or oligonucleotides. See also probes Gene amplification & PCR

protein arrays, protein chips, protein microarrays: Protein technologies  
RNA expression arrays: Expression 

sample: In microarray work, this term often refers to the biological material from which mRNA is extracted (e.g., tissue or serum from patients or laboratory animals). However, sample is also an important term in statistics, where it means the subset of a population that is surveyed for the purpose of estimating properties of the entire population. See also Drug discovery & developmen sample 

scanning technologies: See fluorescent scanners, laser scanning phosphorimagers Related term: image analysis - microarrays See also Imaging, Mass Spectrometry
solution arrays: Labels, signaling & detection

Southern blotting: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane. MeSH, 1989

The Southern blot was the first array. Eric Lander "Array of hope" Nature Genetics 21 (1s): 3-4 Jan 1999

spots:   Parts of the image corresponding to the DNA probes on the microarray.  

spotting robots: Most spotting robots use an X-Y-Z robot arm (one that can move in three dimensions) mounted on an antivibration table. Pins held by the arm are dipped into the first microtiter plate to pick up the fluid (probe solution) to be delivered. The tips of the pins are then moved to the array matrix and allowed to touch the surface only minimally; the probe solution is then transferred. The pins are then washed and moved to the next set of wells and probes. This process is repeated until hundreds or thousands of probes are deposited. Currently, solid pins, quills, and pin- and- ring configurations of pins are available. Related terms: Stokes shift,  microspotting, spotted arrays.

Stokes shift: The difference (usually in frequency units) between the spectral positions of the band maxima (or the band origin) of the absorption and luminescence arising from the same electronic transition. Generally, the luminescence occurring at a longer wavelength than the absorption is stronger than the opposite. The latter may be called an anti- Stokes shift.  [IUPAC Photo] Related terms: microspotting, spotted arrays, spotting robots.

substrates: In hybridization arrays, the particular materials onto which probes are deposited. Substrate materials include glass, nylon, silicon, and ceramic. Traditionally, arrays have been prepared using plastic multiwell plates. As the need for more reaction "vessels" per unit area has increased dramatically, users have turned to flatter supports such as glass slides, which provide greater surface areas.    Different from substrate Pharmaceutical biology  Related term: matrix

Western blotting: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes MeSH, 1989

Bibliography
BioChipNet Glossary, 2002, 150 + definitions  http://www.biochipnet.com/glossary 
Chipping Forecast III, Nature Genetics, 37 (65): June 2005 http://www.nature.com/ng/journal/v37/n6s/index.html 
Chipping Forecast II, Nature Genetics 32 (supp): 509- 514, 2002  http://www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/v32/n4s/index.html
“Chipping Forecast”, Nature Genetics supplement 21 (1s), Jan 1999 http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v21/n1s/index.html
MicroArray Explorer Glossary, NCI, Lab of Experimental & Computational Biology http://www.lecb.ncifcrf.gov/searchframes.html about 50 definitions.
Profiling Microarrays, Nature Genome Gateway - Post- Genomics http://www.nature.com/genomics/post-genomics/microarrays.html
Microarray related activities at the EBI, European Bioinformatics Institute, UK http://www.ebi.ac.uk/microarray/
MGuide, [Pat] Brown Lab’s Guide to Microarraying, Stanford Univ., US http://cmgm.stanford.edu/pbrown/mguide/
MIAME Glossary, MGED, 2005 about 80 terms  http://www.mged.org/Workgroups/MIAME/miame_glossary.html 

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