
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 ...
, professor
Dr. John Ugelstad
John Ugelstad (31 March 1921 – 3 April 1997) was a Norwegian chemical engineer and inventor, known for discovering a process to manufacture monodisperse micropellets or Microbead (research), microbeads and dynabeads. He was a professor at t ...
, 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
cells,
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, respon ...
s, or
nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
s.
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
Polystyrene (PS) is a synthetic polymer made from monomers of the aromatic hydrocarbon styrene. Polystyrene can be solid or foamed. General-purpose polystyrene is clear, hard, and brittle. It is an inexpensive resin per unit weight. It is ...
beads of the same spherical sizes at the
Norwegian University of Science and Technology (NTNU) in 1977.
A few years later he created
superparamagnetic
Superparamagnetism is a form of magnetism which appears in small ferromagnetic or ferrimagnetic nanoparticles. In sufficiently small nanoparticles, magnetization can randomly flip direction under the influence of temperature. The typical time betw ...
microbeads (
Dynabeads Dynabeads are superparamagnetic spherical polymer particles with a uniform size and a consistent, defined surface for the adsorption or coupling of various bioreactive molecules or cells.
Description
Dynabeads were developed after John Ugelstad m ...
), which exhibit magnetic properties when placed in a magnetic field. When they are removed from the magnetic field, there is no residual
magnetism
Magnetism is the class of physical attributes that are mediated by a magnetic field, which refers to the capacity to induce attractive and repulsive phenomena in other entities. Electric currents and the magnetic moments of elementary particle ...
, which led to the development of magnetic separation technology. Other processes such as
centrifugation
Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...
,
filtration
Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filte ...
, 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 hai ...
, 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
Kinetics ( grc, κίνησις, , kinesis, ''movement'' or ''to move'') may refer to:
Science and medicine
* Kinetics (physics), the study of motion and its causes
** Rigid body kinetics, the study of the motion of rigid bodies
* Chemical k ...
, 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, th ...
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 ele ...
; a
biomolecule
A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include larg ...
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 Viral disease, viruses. The antibody recognizes a unique m ...
,
streptavidin
Streptavidin is a 66.0 (tetramer) kDa protein purified from the bacterium ''Streptomyces avidinii''. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin (also known as vitamin B7 or vitamin H). With a dissociation c ...
,
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, respon ...
,
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 response. ...
,
DNA/
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
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 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 ele ...
on the surface of the beads.
# Wash – Microbeads will move to the side of the tube in response to a
magnetic
Magnetism is the class of physical attributes that are mediated by a magnetic field, which refers to the capacity to induce attractive and repulsive phenomena in other entities. Electric currents and the magnetic moments of elementary particles ...
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
Immunoprecipitation (IP) is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a sam ...
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
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
IVD). When microbeads are coupled with
streptavidin
Streptavidin is a 66.0 (tetramer) kDa protein purified from the bacterium ''Streptomyces avidinii''. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin (also known as vitamin B7 or vitamin H). With a dissociation c ...
, they offer a very efficient way to isolate any biotinylated molecule. This is frequently used in
DNA/
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
binding protein studies,
sequencing
In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succi ...
, and to prepare single stranded templates.
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...
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 b ...
and
biomedical research
Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from " basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scienti ...
. 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