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Labels, signaling & detection glossary & taxonomy
Evolving terminology for emerging technologies
Comments? Questions? Revisions?
Mary Chitty MSLS
mchitty@healthtech.com
Last revised July 10, 2019



Related glossaries include   Drug Discovery & Development   Molecular Diagnostics  
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Assays & screening,   Cell & tissue technologies    Gene Amplification & PCR,    Molecular Imaging,   Mass spectrometry,   Microarrays & protein chips, Nanoscience & MiniaturizationSequencingUltrasensitivity    Technologies term index

actuator: A  peripheral [output] device which translates electrical signals into mechanical actions; e.g., a stepper motor which acts on an electrical signal received from a computer instructing it to turn its shaft a certain number of degrees or a certain number of rotations. See: servomechanism. FDA, Glossary of Computerized System and Software Development Terminology last updated 2014  http://www.fda.gov/iceci/inspections/inspectionguides/ucm074875.htm 

An actuator, the reverse of a sensor, is a device that converts an electrical signal to an action. Actuators are further divided into three categories: simple actuators that move valves or beams using one simple physical law, micromotors, more complex in the design and the possibilities, and microrobots which are the latest release in microtechnology.  Materials Research: Current Scenario and Future Projections 2003 https://books.google.com/books?id=a3EWH_vGQp0C&printsec=frontcover#v=onepage&q&f=false 

a component of a machine that is responsible for moving and controlling a mechanism or system, for example by opening a valve. In simple terms, it is a "mover". An actuator requires a control signal and a source of energy. The control signal is relatively low energy and may be electric voltage or current, pneumatic or hydraulic pressure, or even human power. Its main energy source may be an electric currenthydraulic fluidpressure, or pneumatic pressure. When it receives a control signal, an actuator responds by converting the signal's energy into mechanical motion. An actuator is the mechanism by which a control system acts upon an environment.   Wikipedia accessed 2018 Nov 8 https://en.wikipedia.org/wiki/Actuator  Narrower term: biosensor Broader terms: sensors, transducers

amplification: See signal amplification, target amplification (and gene amplification).

avidin: Protein found in raw egg white which binds to biotin (etymology is from its avidity to biotin). The interaction of biotin and Avidin or Streptavidin has been exploited for use in many protein and nucleic acid detection and purification methods. Because the biotin label is stable and small, it rarely interferes with the function of labeled molecules enabling the Avidin-biotin interaction to be used for the development of robust and highly sensitive assays. Thermo Fisher Avidin-Biotin interaction https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/avidin-biotin-interaction.html

bioluminescence: Luminescence produced by living systems. IUPAC Photochemistry

biosensor: A device that uses specific biochemical reactions mediated by isolated enzymes, immunosystems, tissues, organelles or whole cells to detect chemical compounds, usually by electrical, thermal or optical signals. IUPAC Bioinorganic Narrower terms: electrochemical biosensor, spore based biosensor  Related term: sensor web

biotinylation:  the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin (MW = 244.31 g/mol). Biotin binds to streptavidin and avidin with an extremely high affinity, fast on-rate, and high specificity, and these interactions are exploited in many areas of biotechnology to isolate biotinylated molecules of interest. Biotin-binding to streptavidin and avidin is resistant to extremes of heat, pH and proteolysis, making capture of biotinylated molecules possible in a wide variety of environments. Also, multiple biotin molecules can be conjugated to a protein of interest, which allows binding of multiple streptavidin, avidin or neutravidin protein molecules and increases the sensitivity of detection of the protein of interest. There is a large number of biotinylation reagents available that exploit the wide range of possible labelling methods. Due to the strong affinity between biotin and streptavidin, the purification of biotinylated proteins has been a widely used approach to identify protein-protein interactions and post-translational events such as ubiquitylation[1] in molecular biology. Wikipedia accessed 2018 Sept 18 https://en.wikipedia.org/wiki/Biotinylation

To label a probe with biotin.

blinking: See under green fluorescent protein

Catalyzed Reporter Deposition CARD: See Tyramide Signal Amplification TSA.


chemiexcitation:
Generation, by a chemical reaction, of electronically excited molecular entities from reactants in their ground electronic states. IUPAC Photo

chemiluminescence:  Emission of light as a result of a chemical reaction without an apparent change in temperature. MeSH, 1993

Luminescence arising from chemiexcitation. IUPAC Photochemistry

colorimetry: The methods used to measure color and to define the results of the measurements. Photonics

competitive hybridization: Gene amplification & PCR

detection: The Oxford English Dictionary points out that detecting involves finding what is otherwise apt to elude notice, particularly that which is "artfully concealed".  Narrower terms: gated detection;  Ultrasensitivity: single molecule detection

detector technologies: Include direct detection, electrochemical, fluorescence, fluorescence polarization, colorimetry, mass spectrometry, luminescence, optical, primer extension and minisequencing. Michael Phillips, CHI Nucleic Acids Technologies conference, June 7-9, 2000  Detector instrumentation includes CCD cameras and lasers.

differential labeling: When comparing the proteomes of two cell states (e.g. diseased vs. normal), gel- to- gel variability in spot position and protein yield often places the results of such experiments in question. Differential labeling  enables one to analyze both states on a single gel, thus enabling direct comparison of protein levels. In this method, cells are treated with normal media, or media enriched in 15N. Corresponding proteins from each state will migrate to the same location on the gel, but analysis by mass spectrometry will distinguish the metabolically labeled peptides and thus quantify the two sets of proteins separately. This can have significant impact on reproducibility when comparing experiments. 

dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. MeSH, 1963. Related terms: labels, reagents Narrower term: spectroscopic dyes

electrochemical biosensor: A self- contained integrated device, which is capable of providing specific quantitative or semi- quantitative analytical information using a biological recognition element (biochemical receptor) which is retained in direct spatial contact with an electrochemical transduction element. Because of their ability to be repeatedly calibrated, we recommend that a biosensor should be clearly distinguished from a bioanalytical system, which requires additional processing steps, such as reagent addition. A device which is both disposable after one measurement, i.e., single use, and unable to monitor the analyte concentration continuously or after rapid and reproducible regeneration should be designated a single use biosensor. IUPAC Commission on Electroanalytical Chemistry, Electrochemical Biosensors: Recommended Definitions and Classification, 1999 https://www.iupac.org/publications/pac/71/12/2333/index.html   Broader term: biosensor

electrochemiluminescence: See Electrogenerated Luminescence ECL. IUPAC Photo

electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. MeSH, 1966  Related terms:  electrochemiluminescence, Electrogenerated Luminescence ECL, electroluminescence
Electrochemistry Dictionary, 1000 definitions http://knowledge.electrochem.org/ed/dict.htm
Electrochemistry Encyclopedia http://knowledge.electrochem.org/encycl/

Electrogenerated Luminescence ECL: Luminescence produced by electrode reactions. Also called electroluminescence or electrochemiluminescence. IUPAC Photo

electroluminescence: See electrogenerated chemiluminescence.  IUPAC Photo

electronic nose: a device intended to detect odors or flavors. Over the last decades, "electronic sensing" or "e-sensing" technologies have undergone important developments from a technical and commercial point of view. The expression "electronic sensing" refers to the capability of reproducing human senses using sensor arrays and pattern recognition systems. Since 1982,[2] research has been conducted to develop technologies, commonly referred to as electronic noses, that could detect and recognize odors and flavors. The stages of the recognition process are similar to human olfaction and are performed for identification, comparison, quantification and other applications, including data storage and retrieval. However, hedonicevaluation is a specificity of the human nose given that it is related to subjective opinions. These devices have undergone much development and are now used to fulfill industrial needs.  Wikipedia accessed 2018 Oct 26 https://en.wikipedia.org/wiki/Electronic_nose

A device used to detect airborne odors, gases, flavors, volatile substances or vapors. MeSH Year introduced: 2013

electronic tongues:  For liquid analysis, based on the organizational principles of biological sensory systems, developed rapidly during the last decade. ... The exciting possibility of establishing a correlation between the output from an electronic tongue and human sensory assessment of food flavour, thereby enabling quantification of taste and flavour, is described. Application areas of electronic tongue systems including foodstuffs, clinical, industrial, and environmental analysis are discussed in depth. Y. Vlasov et. al., "Electronic tongues and their analytical application" Analytical Bioanalytical Chem. 2002 Jun;373 (3): 136- 146, June 2002   Broader term: sensors

excitation emission spectrum: The three-dimensional spectrum generated by scanning the emission spectrum at incremental steps of excitationwavelength ( axis = emission wavelength,  axis = excitation wavelength,  axis = emission flux) is called a (fluorescencephosphorescence) excitation-emission spectrum (or EES). The spectra are particularly useful for investigating samples containing more than one emitting species. Corrected EES are obtained if (a) the emission is corrected for instrumental response with wavelength, and (b) the exciting radiation flux in photons  is held constant for all excitation wavelengths.  IUPAC Gold Book https://goldbook.iupac.org/html/E/E02249.html 
Narrower terms: chemiexcitation, photoexcitation Related terms: quencher, quenching, scintillation

Fluorescence Recovery After Photobleaching FRAP: A method used to study the lateral movement of MEMBRANE PROTEINS and LIPIDS. A small area of a cell membrane is bleached by laser light and the amount of time necessary for unbleached fluorescent marker- tagged proteins to diffuse back into the bleached site is a measurement of the cell membrane's fluidity. The diffusion coefficient of a protein or lipid in the membrane can be calculated from the data. (From Segen, Current Med Talk, 1995). MeSH 2003

fluorescence: Luminescence which occurs essentially only during the irradiation of a substance by electromagnetic radiation. IUPAC Compendium

The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. MeSH  Narrower terms: FISH Fluorescence In Situ Hybridization, Fluorescence Resonance Energy Transfer FRET, green fluorescent protein GFP;  FRAP Fluorescence Recovery After Photobleaching, fluorescence polarization, LIF Laser Induced Fluorescence Related terms: fluorophore

Fluorescence In Situ Hybridization: See Gene Amplification & PCR FISH 

Fluorescence Resonance Energy Transfer FRET: A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING. MeSH 2003
Narrower term: single-pair FRET spFRET

fluorophore: May refer to either the fluorescent label or marker, or to the atoms which make the label fluorescent.

green fluorescent protein GFP: As a label for reporting cellular events in situ has been explored by a large number of laboratories. GFP and its mutants offer a powerful advantage as clonable markers for use in living tissue. However, photoisomerization and flickering of the emission signal ('blinking') create a challenge in single molecule experiments for both types of probe. Studies are in progress by W.E. Moerner and others (for example, see 6,7) to understand the basis for the long- lived dark states that lead to fluctuations in the emission spectra from these molecules, and to develop improved probes with reduced photoisomerization and blinking. [NIGMS  Single Molecule Detection and Manipulation Workshop" Single Molecule Fluorescence of Biomolecules and Complexes Protein Folding April 17-18, 2000] http://www.nigms.nih.gov/news/reports/single_molecules.html#examples  Broader term: fluorescent proteins

Isotope Coded Affinity Tags (ICAT): See under differential labeling
in situ
hybridization ISH: Gene amplification & PCR
indirect detection: See under reporter gene

isothermal: Isothermal conditions are important in immunoassays, immunohistochemistry, in situ amplification and in cell- based assays, in which one wants to retain the morphology and viability of the cells. The relative simplicity of an isothermal reaction also indicates greater utility for point of care diagnostic applications. Having a constant temperature.

label: A marker, tag or indicator distinguishable by the observer but not by the system and used to identify a tracer. IUPAC Nomenclature for Radioanalytical Chemistry, Pure & Applied Chemistry: 2514- 2576, 1994 https://www.iupac.org/publications/pac/pdf/1994/pdf/6612x2513.pdf

There is a need to develop better methods for inserting site- specific labels in the samples for detection, as well as mechanical handles for manipulation. Site- directed mutagenesis, approaches using chimeras, clonable tags, reporter genes, protection/ deprotection protocols, and protein modification using derivatized amines and thiols, such as His tags, are currently used, but flexibility in the placement of chemical handles in the sample remains a limitation. NIGMS, Single Molecule Detection and Manipulation Workshop "Single Molecule Fluorescence of Biomolecules and Complexes Protein Folding, April 17-18, 2000 http://www.nigms.nih.gov/news/reports/single_molecules.html#examples   Narrower terms: nanolabels, biotin, differential labelling, ICAT, optical tagging, streptavidin, target labelling  Related terms: assays, dyes, reagents, staining and labeling, target labelling, tracer; Ultrasensitivity

label free: In the journey of a molecule from its origins in a compound library to candidate drug status, a large variety of profiling must occur to define activity, selectivity, potency, adverse effects, pharmacology and in vivo efficacy. Advances in biophysical methods that can analyse drug interactions with a molecular target, a whole cell, or even ex vivo tissue have enabled many of these studies to be carried out without the need for reporter-based or ‘labelled’ assays. Label-free screening in high-throughput mode can be used as a pathway independent screening tool with whole cells, or in low-throughput mode with individual receptors to define interaction kinetics and thermodynamics.  European Pharmaceutical review, What is label free screening and why use it in drug discovery? https://www.europeanpharmaceuticalreview.com/article/16213/what-is-label-free-screening-and-why-use-it-in-drug-discovery/

luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. MeSH

Spontaneous emission of radiation from an electronically or vibrationally excited species not in thermal equilibrium with its environment. IUPAC Compendium  Narrower terms:  bioluminescence, chemiluminescence, electrochemiluminescence, Electrogenerated Luminescence ECL. 

luminometer: Light measuring instrument.

molecular biosensors: Devices of molecular size that are designed for sensing different analytes on the basis of biospecific recognition. They should provide two coupled functions - the recognition (specific binding) of the target and the transduction of information about the recognition event into a measurable signal. Fluorescence sensing of intermolecular interactions and development of direct molecular biosensors DaniŔle Altschuh 1 *, Sule Oncul 2, Alexander P. Demchenko 2 Journal of Molecular Recognition: `9 (6): 459-477 published online 6 Nov 2006 http://www3.interscience.wiley.com/cgi-bin/abstract/113445627/ABSTRACT?CRETRY=1&SRETRY=0 .

molecular combing: A method ... which can straighten and align molecules of genomic DNA on a solid surface. The technology also includes a battery of novel statistical methods developed for analyzing the large amounts of data obtained from FISH analyses made on individual DNA molecules.
Wikipedia https://en.wikipedia.org/wiki/Chromosome_combing  also known as molecular combing or DNA combing

nanolabel: A novel double-codified nanolabel (DC-AuNP) based on gold nanoparticle (AuNP) modified with anti-human IgG peroxidase (HRP)-conjugated antibody is reported. It represents a simple assay that allows enhanced spectrophotometric and electrochemical detection of antigen human IgG as a model protein. Ambrosi A, Casta˝eda MT, Killard AJ, Smyth MR, Alegret S, Merkoši A. Double-codified gold nanolabels for enhanced immunoanalysis,  Analytical Chemistry 2007 Jul 15;79 (14): 5232- 5240. Epub 2007 Jun 19. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17579481&ordinalpos=1&itoo...  

photoexcitation: Luminescence arising from photoexcitation. IUPAC Photo

primed in situ labeling: A technique that labels specific sequences in whole chromosomes by in situ DNA chain elongation or PCR (polymerase chain reaction). MeSH, 1999

Quantum Dots (QD): very small semiconductor particles, only several nanometres in size, so small that their optical and electronic properties differ from those of larger LED particles. They are a central theme in nanotechnology. Many types of quantum dot will emit light of specific frequencies if electricity or light is applied to them, and these frequencies can be precisely tuned by changing the dots' size,[1][2]shape and material, giving rise to many applications. In the language of materials science, nanoscale semiconductor materials tightly confine either electrons or electron holes. Quantum dots are also sometimes referred to as artificial atoms, a term that emphasizes that a quantum dot is a single object with bound, discrete electronic states, as is the case with naturally occurring atoms or molecules.[3][4] Wikipedia accessed 2018 Nov 11 https://en.wikipedia.org/wiki/Quantum_dot Biology applications https://en.wikipedia.org/wiki/Quantum_dot#Biology

quencher: A molecular entity that deactivates (quenches) an excited state of another molecular entity, either by energy transfer, electron transfer, or by a chemical mechanism. IUPAC Photo

quenching: 1. Arresting the course of a chemical reaction by chemical or physical means. (in photochemistry) 2. The deactivation of an excited molecular entity intermolecularly by an external environmental influence (such as a quencher) or intramolecularly by a substituent through a nonradiative process. 3. (in radiation chemistry) The process of inhibiting continuous or multiple discharges following a single event in certain types of radiation detectors. [IUPAC Compendium]

reactant: A  substance that is consumed in the course of a chemical reaction.  It is sometimes known, especially in the older literature, as a reagent, but this term is better used in a more specialized sense as a test substance that is added to a system in order to bring about a reaction or to see whether a reaction occurs (e.g. an analytical reagent). IUPAC Compendium Related term: reagents

reagents:  Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. .. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents.   MeSH ‘indicators and reagents’  Related term: reactant

scintillation: Burst of luminescence of short duration caused by an individual energetic particle. IUPAC Radioanalytical

sensitivity: 100% sensitivity = 100% true positives, 0% false positives.

sensor:  In the broadest definition, a sensor is a device, module, or subsystem whose purpose is to detect events or changes in its environment and send the information to other electronics, frequently a computer processor.
Wikipedia accessed 2018 March 22  https://en.wikipedia.org/wiki/Sensor
 Related terms: actuators, labels, nanoparticles, sensor model language, transducers Narrower terms:  biosensor, electrochemical biosensors, electronic biosensor, electronic nose, electronic tongues, molecular biosensors, nanosensors,  neurally inspired sensor, spore based biosensors 

sensor model language SensorML:  Sensor Model Language (SensorML) for In-situ and Remote Sensors. Edited by Mike Botts (University of Alabama in Huntsville). Open GIS Discussion Paper [not an adopted standard]. Open GIS Consortium Inc. Issued by the OGC Natural Resources and Environment (NRE) Working Group. Publication Date: 2002-12-20. Reference number: OGC 02-026r4. Version 0.7. 118 pages. With associated XML Schemas. http://xml.coverpages.org/ni2003-01-31-b.html With definitions of sensors.

sensor web: An independent network of wireless, intra- communicating sensor pods, deployed to monitor and explore a limitless range of environments. This adaptable instrument can be tailored to whatever conditions it is sent to observe. Jet Propulsion Lab, NASA "Sensor Web Project" http://sensorwebs.jpl.nasa.gov/

Sensors Global Summit 2018 Dec  10-12 San Diego CA Emerging technological innovations enabled by next generation sensors will define the landscape for the future commercialization of life changing products. The exponential growth of the global sensors market and the demand for next generation integrated systems is expected to reach $154 billion by 2020, the latest technological advancements of real-world applications within healthcare and emerging markets http://www.sensorsglobalsummit.com/

signal amplification: PCR

signal to noise: Ratio which can interfere with detection. Can also refer to data analysis. Biological data is often very "noisy". This is particularly seen when trying to look at low abundance biomolecules.

signals: Produced by dyes, fluorescence or radioactivity. (Non- radioactive materials, because of disposal and other problems, and improvements in other technologies) are increasingly in demand.  Related terms: detection, reagents, actuators

single cell, single molecule: Ultrasensitivity

single-pair FRET spFRET: Designed to overcome the averaging effects of ensemble studies because measurements are made on single molecules freely diffusing in solution. This method limits the observation period to the diffusion time of each molecule through the focal spot of a laser on the order of a few hundred milliseconds, but it permits the rapid gathering of data at single- molecule resolution on a large number of molecules in a short time period. SpFRET can be used to study intramolecular conformational changes by placing the donor and acceptor fluorescent tags on two different sites of the same macromolecule, or alternatively, intermolecular interactions can be studied by attaching the donor and acceptor tags to two different macromolecules.  NIGMS, Single Molecule Detection and Manipulation Workshop "Single Molecule Fluorescence of Biomolecules and Complexes Protein Folding April 17- 18, 2000 http://www.nigms.nih.gov/news/reports/single_molecules.html#examples 

spectroscopic dyes: These dyes—in particular, nanoparticles — are emerging as alternatives to fluorescent dyes. Because the emission spectra of nanoparticles vary according to these particles’ specific size and shape, these nanostructures can be used in multicolor detection formats, potentially offering much greater multiplexing than is currently achievable. The fact that chemists have been able to create a great variety of structures (and properties) in nanoparticles suggests that these particles might be more "finely tunable" than organic dyes, allowing better results from biological assays CHI High- Content Analysis Market Outlook report, 2004  

staining and labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts. MeSH, 2001 Related terms: label, tags

streptavidin:  A 60 kD extracellular protein of Streptomyces avidinii with four high-affinity biotin binding sites. Unlike AVIDIN,  streptavidin has a near neutral isoelectric point and is free of carbohydrate side chains. MeSH, 1998

Surface Plasmon Resonance SPR: Technologies overivew

TSA Tyramide Signal Amplification: TSA - also known as Catalyzed Reporter Deposition (CARD) - is a signal- amplification technology designed to enhance detection sensitivity in DNA arrays, in situ hybridization (ISH) assays, and other applications.  Kerstens HM, Poddighe PJ, Hanselaar AG. "A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine." Journal of Histochemistry & Cytochemistry. 1995. 43:347-352.

tag: See label, capture tag, Isotope Coded Affinity Tags ICAT, optical tagging. This is different from tagging for information retrieval

target labelling: Drug & disease Targets 

tracer: Labelled members of a population used to measure certain properties of that population.  IUPAC Radioanalytical

transducer: A transducer is a device that converts energy from one form to another. Usually a transducer converts a signal in one form of energy to a signal in another.[1] Transducers are often employed at the boundaries of automationmeasurement, and control systems, where electrical signals are converted to and from other physical quantities (energy, force, torque, light, motion, position, etc.). The process of converting one form of energy to another is known as transduction.[2]  Wikipedia accessed 2018 Nov 9 http://en.wikipedia.org/wiki/Transducers  Narrower terms: actuators, sensors

Labels Signaling Detection Resources
IUPAC Commission on Electroanalytical Chemistry, Electrochemical Biosensors: Recommended Definitions and Classification, 1999 https://www.iupac.org/publications/pac/71/12/2333/index.html
IUPAC Glossary of Terms used in Photochemistry, 3rd ed. 2006  http://iupac.org/publications/pac/79/3/0293/
IUPAC Nomenclature for Radioanalytical Chemistry, Pure & Applied Chemistry: 2514- 2576, 1994 https://www.iupac.org/publications/pac/pdf/1994/pdf/6612x2513.pdf
IU
PAC Terminology for Biomolecular Screening  2011 http://iupac.org/publications/pac/83/5/1129/
Molecular Probes the Handbook http://www.thermofisher.com/us/en/home/references/molecular-probes-the-handbook.html

How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

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