Microbead (research)
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Microbeads, also called Ugelstad particles after the Norwegian
chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe t ...
, professor Dr. John Ugelstad, who invented them in 1977 and patented the method in 1978,Rangnes 1997:4–5 are uniform polymer particles, typically 0.5 to 500 micrometres in diameter. Bio-reactive molecules can be absorbed or coupled to their surface, and used to separate biological materials such as
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s,
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, or nucleic acids.
Microbeads Microbeads are manufactured solid plastic particles of less than one millimeter in their largest dimension. They are most frequently made of polyethylene but can be of other petrochemical plastics such as polypropylene and polystyrene. They are ...
have been used for isolation and handling of specific material or molecules, as well as for analyzing sensitive molecules, or those that are in low abundance, e.g. in miniaturized and automated settings.


Background

Microbeads Microbeads are manufactured solid plastic particles of less than one millimeter in their largest dimension. They are most frequently made of polyethylene but can be of other petrochemical plastics such as polypropylene and polystyrene. They are ...
were created when John Ugelstad managed to form polystyrene beads of the same spherical sizes at the Norwegian University of Science and Technology (NTNU) in 1977. A few years later he created superparamagnetic microbeads ( Dynabeads), which exhibit magnetic properties when placed in a magnetic field. When they are removed from the magnetic field, there is no residual magnetism, which led to the development of magnetic separation technology. Other processes such as centrifugation, filtration, columns or
precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls under gravitational pull from clouds. The main forms of precipitation include drizzle, rain, sleet, snow, ice pellets, graupel and hail. ...
, are not needed. Microbeads display a large surface area per volume. This together with uniformity of size and shape provides for very good accessibility and fast liquid-phase reaction kinetics, and rapid and efficient binding.


Use

Black polyethylene microspheres can have magnetic or conductive functionality, and have uses in electronic devices, EMI shielding and microscopy techniques. Fluorescent polyethylene microspheres are commonly used to run
blind test In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...
s on laboratory and industrial processes, in order to develop proper methods and minimize cross-contamination of equipment and materials. Microspheres that appear to be invisible in the daylight can be illuminated to display a bright
fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, ...
response under
UV light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
. Colored polyethylene microspheres are used for fluid
flow visualization Flow visualization or flow visualisation in fluid dynamics is used to make the flow patterns visible, in order to get qualitative or quantitative information on them. Overview Flow visualization is the art of making flow patterns visible. M ...
to enable observation and characterization of flow of particles in a device or be used as visible markers in microscopy and biotechnology.


Applications

Microbeads serve as the main tool for bio-magnetic separations. A range of patented processes and applications have been developed based on the use of microbeads in academic and industrial research. Microbeads are pre-coupled with a
ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...
; a biomolecule such as
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, streptavidin,
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
,
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
, DNA/ RNA or other molecule. There are three steps involved in the magnetic separation process: # Bind – Microbeads bind to the desired target, relative to the specific
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...
of the
ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...
on the surface of the beads. # Wash – Microbeads will move to the side of the tube in response to a magnetic field, along with the bound material. This happens quickly and efficiently because of the magnetic field and the micro-sized particles. The un-bound and un-wanted material that is left behind in the sample is removed by pipetting/aspiration. The bead-bound material is washed using the appropriate buffers, by applying the magnet. # Elute – Once the bead-bound target is isolated and washed, it can be released in the appropriate solution and desired volume. It can then be used for any downstream application directly, or the microbeads can be released and removed. Microbeads are used for cell isolation and cell expansion. Proteins and protein complexes can be separated, e.g. in immunoprecipitation protocols. Molecular studies and diagnostics also benefit from microbeads (e.g.
immunoassay An immunoassay (IA) 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 (usually) or an antigen (sometimes). The molecule detected by the immunoass ...
IVD and nucleic acid IVD). When microbeads are coupled with streptavidin, they offer a very efficient way to isolate any biotinylated molecule. This is frequently used in DNA/ RNA binding protein studies, sequencing, and to prepare single stranded templates. Gene expression analysis also benefits from microbeads, such as isolating
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
for transcriptional analysis. There are many uses for microbeads, mostly for
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
and biomedical research. Microbeads and magnetic separation technology have enabled a range of innovative methods to benefit research on disease prevention, medicine, and other fields to improve the human condition.


See also

* Microspheres


References

*Kemshead, JT, Ugelstad, J (1985). "Magnetic separation techniques:their application to medicine", ''Mol Cell Biochem'', 67(1):11-8. *Vetvicka, V, Fornusek, L (1987). "Polymer microbeads in immunology", ''Biomaterials'', 8(5)341-5. *Arshady, R (1993). "Microspheres for biomedical applications: preparation of reactive and labelled microspheres", ''Biomaterials'', 14(1):5-15. *Fonnum, G, Johansson, C, Molteberg, A, Morup, S, Aksnes, E (2005). "Characterization of Dynabeads by magnetization measurements and Mössbauer spectroscopy", ''Journal of Magnetism and Magnetic Materials'', 293:41-47. * {{Cite book, last=Rangnes, first=Per, title=John Ugelstad : the man behind the beads, publisher=Scandinavian University Press, year=1997, isbn=8200376737


External links


Dynabeads
Biotechnology Polymers