Sterilization refers to any process that removes, kills, or deactivates all forms of
life
Life is a quality that distinguishes matter that has biological processes, such as signaling and self-sustaining processes, from that which does not, and is defined by the capacity for growth, reaction to stimuli, metabolism, energ ...
(particularly
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s such as
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
,
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
spore
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
s, and
unicellular
A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells. Organisms fall into two general categories: prokaryotic organisms and ...
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
organisms) and other
biological agent
A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, or toxin that can be used purposefully as a weapon in bioterroris ...
s such as
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
s present in or on a specific surface, object, or fluid. Sterilization can be achieved through various means, including
heat
In thermodynamics, heat is defined as the form of energy crossing the boundary of a thermodynamic system by virtue of a temperature difference across the boundary. A thermodynamic system does not ''contain'' heat. Nevertheless, the term is al ...
,
chemical
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...
s,
irradiation
Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve ...
,
high pressure
In science and engineering the study of high pressure examines its effects on materials and the design and construction of devices, such as a diamond anvil cell, which can create high pressure. By ''high pressure'' is usually meant pressures of th ...
, and
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 filter ...
. Sterilization is distinct from
disinfection
A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
, sanitization, and
pasteurization
Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life.
The ...
, in that those methods reduce rather than eliminate all forms of life and biological agents present. After sterilization, an object is referred to as being sterile or
aseptic
Asepsis is the state of being free from disease-causing micro-organisms (such as pathogenic bacteria, viruses, pathogenic fungi, and parasites). There are two categories of asepsis: medical and surgical. The modern day notion of asepsis is deriv ...
.
Applications
Foods
One of the first steps toward modernized sterilization was made by
Nicolas Appert
Nicolas Appert (17 November 1749 – 1 June 1841) was the French inventor of airtight food preservation. Appert, known as the " father of Food Science", was a confectioner. Appert described his invention as a way "of conserving all kinds of food ...
, who discovered that application of heat over a suitable period slowed the decay of foods and various liquids, preserving them for safe consumption for a longer time than was typical.
Canning
Canning is a method of food preservation in which food is processed and sealed in an airtight container (jars like Mason jars, and steel and tin cans). Canning provides a shelf life that typically ranges from one to five years, although u ...
of foods is an extension of the same principle and has helped to reduce
food borne illness ("food poisoning"). Other methods of sterilizing foods include
food irradiation
Food irradiation is the process of exposing food and food packaging to ionizing radiation, such as from gamma rays, x-rays, or electron beams. Food irradiation improves food safety and extends product shelf life (preservation) by effectively ...
and high pressure (
pascalization
Pascalization, bridgmanization, high pressure processing (HPP) or high hydrostatic pressure (HHP) processing is a method of preserving and sterilizing food, in which a product is processed under very high pressure, leading to the inactivation of ...
).
Medicine and surgery
![Joseph Lister c1855](https://upload.wikimedia.org/wikipedia/commons/7/7b/Joseph_Lister_c1855.jpg)
In general, surgical instruments and medications that enter an already
aseptic
Asepsis is the state of being free from disease-causing micro-organisms (such as pathogenic bacteria, viruses, pathogenic fungi, and parasites). There are two categories of asepsis: medical and surgical. The modern day notion of asepsis is deriv ...
part of the body (such as the bloodstream, or penetrating the skin) must be sterile. Examples of such instruments include
scalpel
A scalpel, lancet, or bistoury is a small and extremely sharp bladed instrument used for surgery, anatomical dissection, podiatry and various arts and crafts (either called a hobby knife or an X-acto knife.). Scalpels may be single-use disposa ...
s,
hypodermic needle
A hypodermic needle (from Greek ὑπο- (''hypo-'' = under), and δέρμα (''derma'' = skin)), one of a category of medical tools which enter the skin, called sharps, is a very thin, hollow tube with one sharp tip. It is commonly used w ...
s, and
artificial pacemaker
An artificial cardiac pacemaker (or artificial pacemaker, so as not to be confused with the natural cardiac pacemaker) or pacemaker is a medical device that generates electrical impulses delivered by electrodes to the chambers of the heart eith ...
s. This is also essential in the manufacture of
parenteral
A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance is applied. ...
pharmaceuticals.
Preparation of injectable medications and intravenous
solution
Solution may refer to:
* Solution (chemistry), a mixture where one substance is dissolved in another
* Solution (equation), in mathematics
** Numerical solution, in numerical analysis, approximate solutions within specified error bounds
* Soluti ...
s for
fluid replacement
Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous ...
therapy requires not only sterility but also well-designed containers to prevent entry of
adventitious agents after initial product sterilization.
Most medical and surgical devices used in healthcare facilities are made of materials that are able to go under
steam
Steam is a substance containing water in the gas phase, and sometimes also an aerosol of liquid water droplets, or air. This may occur due to evaporation or due to boiling, where heat is applied until water reaches the enthalpy of vaporization ...
sterilization. However, since 1950, there has been an increase in medical devices and instruments made of materials (e.g., plastics) that require low-temperature sterilization.
Ethylene oxide
Ethylene oxide is an organic compound with the chemical formula, formula . It is a cyclic ether and the simplest epoxide: a three-membered Ring (chemistry), ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless a ...
gas has been used since the 1950s for heat- and moisture-sensitive medical devices. Within the past 15 years, a number of new, low-temperature sterilization systems (e.g.,
vaporized hydrogen peroxide Vaporized hydrogen peroxide (trademarked VHP, Retrieved February 2016. also known as hydrogen peroxide vapor, HPV) is a vapor form of hydrogen peroxide (H2O2) with applications as a low-temperature antimicrobial vapor used to decontaminate enclosed ...
,
peracetic acid
Peracetic acid (also known as peroxyacetic acid, or PAA) is an organic compound with the formula CH3CO3H. This peroxy acid is a colorless liquid with a characteristic acrid odor reminiscent of acetic acid. It can be highly corrosive.
Peracetic a ...
immersion,
ozone
Ozone (), or trioxygen, is an inorganic molecule with the chemical formula . It is a pale blue gas with a distinctively pungent smell. It is an allotrope of oxygen that is much less stable than the diatomic allotrope , breaking down in the lo ...
) have been developed and are being used to sterilize medical devices.
Spacecraft
There are strict international rules to
protect the contamination of Solar System bodies from biological material from Earth. Standards vary depending on both the type of mission and its destination; the more likely a planet is considered to be
habitable
Habitability refers to the adequacy of an environment for human living. Where housing is concerned, there are generally local ordinances which define habitability. If a residence complies with those laws it is said to be habitable. In extreme e ...
, the stricter the requirements are.
Many components of instruments used on spacecraft cannot withstand very high temperatures, so techniques not requiring excessive temperatures are used as tolerated, including heating to at least , chemical sterilization, oxidization, ultraviolet, and irradiation.
Quantification
The aim of sterilization is the reduction of initially present microorganisms or other potential pathogens. The degree of sterilization is commonly expressed by multiples of the decimal reduction time, or
D-value, denoting the time needed to reduce the initial number
to one tenth (
) of its original value. Then the number of microorganisms
after sterilization time
is given by:
:
.
The D-value is a function of sterilization conditions and varies with the type of microorganism,
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer.
Thermometers are calibrated in various temperature scales that historically have relied o ...
,
water activity
Water activity (''aw'') is the partial vapor pressure of water in a solution divided by the standard state partial vapor pressure of water. In the field of food science, the standard state is most often defined as pure water at the same tempera ...
,
pH etc.. For steam sterilization (see below) typically the temperature, in degrees
Celsius
The degree Celsius is the unit of temperature on the Celsius scale (originally known as the centigrade scale outside Sweden), one of two temperature scales used in the International System of Units (SI), the other being the Kelvin scale. The ...
, is given as an index.
Theoretically, the likelihood of the survival of an individual microorganism is never zero. To compensate for this, the overkill method is often used. Using the overkill method, sterilization is performed by sterilizing for longer than is required to kill the
bioburden Bioburden is normally defined as the number of bacteria living on a surface that has not been sterilized.
The term is most often used in the context of bioburden testing, also known as microbial limit testing, which is performed on pharmaceutical ...
present on or in the item being sterilized. This provides a
sterility assurance level In microbiology, sterility assurance level (SAL) is the probability that a single unit that has been subjected to sterilization nevertheless remains nonsterile.
It is never possible to prove that all organisms have been destroyed, as the likelihoo ...
(SAL) equal to the probability of a non-sterile unit.
For high-risk applications, such as medical devices and injections, a sterility assurance level of at least 10
−6 is required by the United States
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA).
Heat
Steam
Steam sterilization, also known as moist heat sterilization, uses heated
saturated steam
Steam is a substance containing water in the gas phase, and sometimes also an aerosol of liquid water droplets, or air. This may occur due to evaporation or due to boiling, where heat is applied until water reaches the enthalpy of vaporization ...
under
pressure
Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country and e ...
to inactivate or kill microorganisms via
denaturation of macromolecules, primarily proteins. This method is a faster process than dry heat sterilization. Steam sterilization is performed using an
autoclave
An autoclave is a machine used to carry out industrial and scientific processes requiring elevated temperature and pressure in relation to ambient pressure and/or temperature. Autoclaves are used before surgical procedures to perform sterilizat ...
, sometimes called a converter or steam sterilizer. The article is placed in the autoclave chamber, which is then sealed and heated using pressurized steam to a temperature set point for a defined period of time. Steam sterilization cycles can be categorized as either pre-vacuum or gravity displacement. Gravity displacement cycles rely on the lower density of the injected steam to force cooler, denser air out of the chamber drai
In comparison, pre-vacuum cycles draw a vacuum in the chamber to remove cool dry air prior to injecting saturated steam, resulting in faster heating and shorter cycle times. Typical steam sterilization cycles are between 3 and 30 minutes at at , but adjustments may be made depending on the
bioburden Bioburden is normally defined as the number of bacteria living on a surface that has not been sterilized.
The term is most often used in the context of bioburden testing, also known as microbial limit testing, which is performed on pharmaceutical ...
of the article being sterilized, its resistance (
D-value) to steam sterilization, the article's heat tolerance, and the required sterility assurance level. Following the completion of a cycle, liquids in a pressurized autoclave must be cooled slowly to avoid boiling over when the pressure is released. This may be achieved by gradually depressurizing the sterilization chamber and allowing liquids to evaporate under a negative pressure, while cooling the contents.
Proper autoclave treatment will inactivate all resistant bacterial
spore
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
s in addition to
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
, bacteria, and viruses, but is not expected to eliminate all
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
s, which vary in their resistance. For prion elimination, various recommendations state for 60 minutes or for at least 18 minutes. The 263K
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
prion is inactivated relatively quickly by such sterilization procedures; however, other strains of scrapie, and strains of
Creutzfeldt-Jakob disease (CKD) and
bovine spongiform encephalopathy
Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of t ...
(BSE) are more resistant. Using
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
as test animals, one experiment showed that heating BSE positive
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
tissue at for 18 minutes resulted in only a 2.5
log
Log most often refers to:
* Trunk (botany), the stem and main wooden axis of a tree, called logs when cut
** Logging, cutting down trees for logs
** Firewood, logs used for fuel
** Lumber or timber, converted from wood logs
* Logarithm, in mathe ...
decrease in prion infectivity.
Most autoclaves have meters and charts that record or display information, particularly temperature and pressure as a function of time. The information is checked to ensure that the conditions required for sterilization have been met.
Indicator tape is often placed on the packages of products prior to autoclaving, and some packaging incorporates indicators. The indicator changes color when exposed to steam, providing a visual confirmation.
Biological indicators can also be used to independently confirm autoclave performance. Simple biological indicator devices are commercially available, based on microbial spores. Most contain spores of the heat-resistant microbe ''
Geobacillus stearothermophilus
''Geobacillus stearothermophilus'' (previously ''Bacillus stearothermophilus'') is a rod-shaped, Gram-positive bacterium and a member of the phylum Bacillota. The bacterium is a thermophile and is widely distributed in soil, hot springs, ocean s ...
'' (formerly ''Bacillus stearothermophilus''), which is extremely resistant to steam sterilization. Biological indicators may take the form of glass vials of spores and liquid media, or as spores on strips of paper inside
glassine
Glassine is a smooth and glossy paper that is air, water, and grease resistant. It is usually available in densities between . It is translucent unless dyes are added to color it or make it opaque. It is manufactured by supercalendering: after ...
envelopes. These indicators are placed in locations where it is difficult for steam to reach to verify that steam is penetrating there.
For autoclaving, cleaning is critical. Extraneous biological matter or grime may shield organisms from steam penetration. Proper cleaning can be achieved through physical scrubbing,
sonication
A sonicator at the Weizmann Institute of Science during sonicationSonication is the act of applying sound energy to agitate particles in a sample, for various purposes such as the extraction of multiple compounds from plants, microalgae and seawe ...
,
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
, or pulsed air.
Pressure cooking
Pressure cooking is the process of cooking food under high pressure steam and water or a water-based cooking liquid, in a sealed vessel known as a ''pressure cooker''. High pressure limits boiling, and creates higher cooking temperatures which c ...
and
canning
Canning is a method of food preservation in which food is processed and sealed in an airtight container (jars like Mason jars, and steel and tin cans). Canning provides a shelf life that typically ranges from one to five years, although u ...
is analogous to autoclaving, and when performed correctly renders food sterile.
To sterilize waste materials that are chiefly composed of liquid, a purpose-built
effluent decontamination system
An effluent decontamination system (EDS) is a device, or suite of devices, designed to decontaminate or sterilise biologically active or biohazardous materials in fluid and liquid waste material. Facility types that may utilise an EDS include h ...
can be utilized. These devices can function using a variety of sterilants, although using heat via steam is most common.
Dry
![2003-12-03-Heissluft-Sterilisator](https://upload.wikimedia.org/wikipedia/commons/c/c5/2003-12-03-Heissluft-Sterilisator.JPG)
Dry heat was the first method of sterilization and is a longer process than moist heat sterilization. The destruction of microorganisms through the use of dry heat is a gradual phenomenon. With longer exposure to lethal temperatures, the number of killed microorganisms increases. Forced ventilation of hot air can be used to increase the rate at which heat is transferred to an organism and reduce the temperature and amount of time needed to achieve sterility. At higher temperatures, shorter exposure times are required to kill organisms. This can reduce heat-induced damage to food products.
The standard setting for a hot air oven is at least two hours at . A rapid method heats air to for 6 minutes for unwrapped objects and 12 minutes for wrapped objects. Dry heat has the advantage that it can be used on powders and other heat-stable items that are adversely affected by steam (e.g. it does not cause rusting of steel objects).
Flaming
Flaming is done to
inoculation loop
An inoculation loop (also called a smear loop, inoculation wand or microstreaker) is a simple tool used mainly by microbiologists to pick up and transfer a small sample of microorganisms called inoculum from a microbial culture, e.g. for streakin ...
s and straight-wires in microbiology labs for
streaking
Streaking is the act of running, often naked, through a public area for publicity, as a prank, a dare, or a form of protest. Streaking is often associated with sporting events, but can occur in more secluded areas. Streakers are often pursued b ...
. Leaving the loop in the flame of a
Bunsen burner
A Bunsen burner, named after Robert Bunsen, is a kind of ambient air gas burner used as laboratory equipment; it produces a single open gas flame, and is used for heating, sterilization, and combustion.
The gas can be natural gas (which is main ...
or
alcohol burner
An alcohol burner or spirit lamp is a piece of laboratory equipment used to produce an open flame. It can be made from brass, glass, stainless steel or aluminium.
Uses
Alcohol burners are preferred for some uses over Bunsen burners for safety p ...
until it glows red ensures that any infectious agent is inactivated. This is commonly used for small metal or glass objects, but not for large objects (see
Incineration
Incineration is a waste treatment process that involves the combustion of substances contained in waste materials. Industrial plants for waste incineration are commonly referred to as waste-to-energy facilities. Incineration and other high ...
below). However, during the initial heating, infectious material may be sprayed from the wire surface before it is killed, contaminating nearby surfaces and objects. Therefore, special heaters have been developed that surround the inoculating loop with a heated cage, ensuring that such sprayed material does not further contaminate the area. Another problem is that gas flames may leave carbon or other residues on the object if the object is not heated enough. A variation on flaming is to dip the object in a 70% or more concentrated solution of
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
, then briefly touch the object to a
Bunsen burner
A Bunsen burner, named after Robert Bunsen, is a kind of ambient air gas burner used as laboratory equipment; it produces a single open gas flame, and is used for heating, sterilization, and combustion.
The gas can be natural gas (which is main ...
flame. The ethanol will ignite and burn off rapidly, leaving less residue than a gas flame
Incineration
Incineration
Incineration is a waste treatment process that involves the combustion of substances contained in waste materials. Industrial plants for waste incineration are commonly referred to as waste-to-energy facilities. Incineration and other high ...
is a waste treatment process that involves the combustion of organic substances contained in waste materials. This method also burns any organism to ash. It is used to sterilize medical and other
biohazardous waste before it is discarded with non-hazardous waste. Bacteria incinerators are mini furnaces that incinerate and kill off any microorganisms that may be on an inoculating loop or wire.
Tyndallization
Named after
John Tyndall
John Tyndall FRS (; 2 August 1820 – 4 December 1893) was a prominent 19th-century Irish physicist. His scientific fame arose in the 1850s from his study of diamagnetism. Later he made discoveries in the realms of infrared radiation and the p ...
, Tyndallization is an obsolete and lengthy process designed to reduce the level of activity of sporulating bacteria that are left by a simple boiling water method. The process involves boiling for a period (typically 20 minutes) at atmospheric pressure, cooling, incubating for a day, and then repeating the process a total of three to four times. The incubation periods are to allow heat-resistant spores surviving the previous boiling period to germinate to form the heat-sensitive vegetative (growing) stage, which can be killed by the next boiling step. This is effective because many spores are stimulated to grow by the heat shock. The procedure only works for media that can support bacterial growth, and will not sterilize non-nutritive substrates like water. Tyndallization is also ineffective against prions.
Glass bead sterilizers
Glass bead sterilizers work by heating glass beads to . Instruments are then quickly doused in these glass beads, which heat the object while physically scraping contaminants off their surface. Glass bead sterilizers were once a common sterilization method employed in
dental offices as well as biological laboratories,
but are not approved by the
U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) and
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) to be used as a sterilizers since 1997. They are still popular in
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
an and
Israel
Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...
i dental practices, although there are no current
evidence-based
Evidence-based practice (EBP) is the idea that occupational practices ought to be based on scientific evidence. While seemingly obviously desirable, the proposal has been controversial, with some arguing that results may not specialize to indivi ...
guidelines for using this sterilizer.
Chemical sterilization
![2003-12-03-Chemiclav](https://upload.wikimedia.org/wikipedia/commons/d/d3/2003-12-03-Chemiclav.JPG)
Chemicals are also used for sterilization. Heating provides a reliable way to rid objects of all transmissible agents, but it is not always appropriate if it will damage heat-sensitive materials such as biological materials,
fiber optic
An optical fiber, or optical fibre in Commonwealth English, is a flexible, transparent fiber made by drawing glass (silica) or plastic to a diameter slightly thicker than that of a human hair. Optical fibers are used most often as a means to ...
s, electronics, and many
plastic
Plastics are a wide range of synthetic or semi-synthetic materials that use polymers as a main ingredient. Their plasticity makes it possible for plastics to be moulded, extruded or pressed into solid objects of various shapes. This adaptab ...
s. In these situations chemicals, either in a gaseous or liquid form, can be used as sterilants. While the use of gas and liquid chemical sterilants avoids the problem of heat damage, users must ensure that the article to be sterilized is chemically compatible with the sterilant being used and that the sterilant is able to reach all surfaces that must be sterilized (typically cannot penetrate packaging). In addition, the use of chemical sterilants poses new challenges for
workplace safety, as the properties that make chemicals effective sterilants usually make them harmful to humans. The procedure for removing sterilant residue from the sterilized materials varies depending on the chemical and process that is used.
Ethylene oxide
Ethylene oxide
Ethylene oxide is an organic compound with the chemical formula, formula . It is a cyclic ether and the simplest epoxide: a three-membered Ring (chemistry), ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless a ...
(EO, EtO) gas treatment is one of the common methods used to sterilize, pasteurize, or disinfect items because of its wide range of material compatibility. It is also used to process items that are sensitive to processing with other methods, such as radiation (gamma, electron beam, X-ray), heat (moist or dry), or other chemicals. Ethylene oxide treatment is the most common chemical sterilization method, used for approximately 70% of total sterilizations, and for over 50% of all
disposable
A disposable (also called disposable product) is a product designed for a single use after which it is recycled or is disposed as solid waste. The term is also sometimes used for products that may last several months (e.g. disposable air filter ...
medical devices.
Ethylene oxide treatment is generally carried out between with
relative humidity
Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present.
Humidity depe ...
above 30% and a gas concentration between 200 and 800 mg/L. Typically, the process lasts for several hours. Ethylene oxide is highly effective, as it penetrates all
porous materials
A porous medium or a porous material is a material containing pores (voids). The skeletal portion of the material is often called the "matrix" or "frame". The pores are typically filled with a fluid (liquid or gas). The skeletal material is usua ...
, and it can penetrate through some plastic materials and films. Ethylene oxide kills all known microorganisms, such as bacteria (including spores), viruses, and fungi (including yeasts and moulds), and is compatible with almost all materials even when repeatedly applied. It is flammable, toxic, and
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
ic; however, only with a reported potential for some adverse health effects when not used in compliance with published requirements. Ethylene oxide sterilizers and processes require biological
validation
Validation may refer to:
* Data validation, in computer science, ensuring that data inserted into an application satisfies defined formats and other input criteria
* Forecast verification, validating and verifying prognostic output from a numerica ...
after sterilizer installation, significant repairs or process changes.
The traditional process consists of a preconditioning phase (in a separate room or cell), a processing phase (more commonly in a vacuum vessel and sometimes in a pressure rated vessel), and an aeration phase (in a separate room or cell) to remove EO residues and lower by-products such as
ethylene chlorohydrin
2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...
(EC or ECH) and, of lesser importance,
ethylene glycol
Ethylene glycol (IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an odo ...
(EG). An alternative process, known as all-in-one processing, also exists for some products whereby all three phases are performed in the vacuum or pressure rated vessel. This latter option can facilitate faster overall processing time and residue dissipation.
The most common EO processing method is the gas chamber method. To benefit from
economies of scale
In microeconomics, economies of scale are the cost advantages that enterprises obtain due to their scale of operation, and are typically measured by the amount of output produced per unit of time. A decrease in cost per unit of output enables ...
, EO has traditionally been delivered by filling a large chamber with a combination of gaseous EO either as pure EO, or with other gases used as diluents; diluents include chlorofluorocarbons (
CFCs
Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F), produced as volatile derivatives of methane, ethane, and propan ...
), hydrochlorofluorocarbons (HCFCs), and
carbon dioxide
Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
.
Ethylene oxide is still widely used by medical device manufacturers. Since EO is explosive at concentrations above 3%, EO was traditionally supplied with an
inert carrier gas, such as a CFC or HCFC. The use of CFCs or HCFCs as the carrier gas was banned because of concerns of
ozone depletion
Ozone depletion consists of two related events observed since the late 1970s: a steady lowering of about four percent in the total amount of ozone in Earth's atmosphere, and a much larger springtime decrease in stratospheric ozone (the ozone l ...
. These
halogenated hydrocarbon
The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely us ...
s are being replaced by systems using 100% EO, because of regulations and the high cost of the blends. In hospitals, most EO sterilizers use single-use cartridges because of the convenience and ease of use compared to the former plumbed gas cylinders of EO blends.
It is important to adhere to patient and healthcare personnel government specified limits of EO residues in and/or on processed products, operator exposure after processing, during storage and handling of EO gas cylinders, and environmental emissions produced when using EO.
The U.S.
Occupational Safety and Health Administration
The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...
(OSHA) has set the
permissible exposure limit
The permissible exposure limit (PEL or OSHA PEL) is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent such as high level noise. Permissible exposure limits are established by the Occupational S ...
(PEL) at 1 ppm – calculated as an eight-hour time-weighted average (TWA) – and 5 ppm as a 15-minute excursion limit (EL). The
National Institute for Occupational Safety and Health
The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
's (NIOSH) immediately dangerous to life and health limit (IDLH) for EO is 800 ppm.
The
odor threshold
The odor detection threshold is the lowest concentration of a certain odor compound that is perceivable by the human sense of smell. The threshold of a chemical compound is determined in part by its shape, polarity, partial charges, and molecu ...
is around 500 ppm, so EO is imperceptible until concentrations are well above the OSHA PEL. Therefore, OSHA recommends that continuous gas monitoring systems be used to protect workers using EO for processing.
Nitrogen dioxide
Nitrogen dioxide
Nitrogen dioxide is a chemical compound with the formula . It is one of several nitrogen oxides. is an intermediate in the industrial synthesis of nitric acid, millions of tons of which are produced each year for use primarily in the producti ...
(NO
2) gas is a rapid and effective sterilant for use against a wide range of microorganisms, including common bacteria, viruses, and spores. The unique physical properties of NO
2 gas allow for sterilant dispersion in an enclosed environment at room temperature and atmospheric pressure. The mechanism for lethality is the degradation of
DNA in the spore core through
nitration
In organic chemistry, nitration is a general class of chemical processes for the introduction of a nitro group into an organic compound. The term also is applied incorrectly to the different process of forming nitrate esters between alcohols and ...
of the phosphate backbone, which kills the exposed organism as it absorbs NO
2. This degradations occurs at even very low concentrations of the gas. NO
2 has a boiling point of at sea level, which results in a relatively highly saturated
vapour pressure
Vapor pressure (or vapour pressure in English-speaking countries other than the US; see spelling differences) or equilibrium vapor pressure is defined as the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phases ...
at ambient temperature. Because of this, liquid NO
2 may be used as a convenient source for the sterilant gas. Liquid NO
2 is often referred to by the name of its
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
,
dinitrogen tetroxide
Dinitrogen tetroxide, commonly referred to as nitrogen tetroxide (NTO), and occasionally (usually among ex-USSR/Russia rocket engineers) as amyl, is the chemical compound N2O4. It is a useful reagent in chemical synthesis. It forms an equilibrium ...
(N
2O
4). Additionally, the low levels of concentration required, coupled with the high vapour pressure, assures that no
condensation
Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...
occurs on the devices being sterilized. This means that no aeration of the devices is required immediately following the sterilization cycle.
NO
2 is also less
corrosive
A corrosive substance is one that will damage or destroy other substances with which it comes into contact by means of a chemical reaction.
Etymology
The word ''corrosive'' is derived from the Latin verb ''corrodere'', which means ''to gnaw'', ...
than other sterilant gases, and is compatible with most medical materials and adhesives.
The most-resistant organism (MRO) to sterilization with NO
2 gas is the spore of ''
Geobacillus stearothermophilus
''Geobacillus stearothermophilus'' (previously ''Bacillus stearothermophilus'') is a rod-shaped, Gram-positive bacterium and a member of the phylum Bacillota. The bacterium is a thermophile and is widely distributed in soil, hot springs, ocean s ...
'', which is the same MRO for both steam and hydrogen peroxide sterilization processes. The spore form of ''G. stearothermophilus'' has been well characterized over the years as a
biological indicator
A bioindicator is any species (an indicator species) or group of species whose function, population, or status can reveal the qualitative status of the environment. The most common indicator species are animals. For example, copepods and other sma ...
in sterilization applications. Microbial inactivation of ''G. stearothermophilus'' with NO
2 gas proceeds rapidly in a
log-linear fashion, as is typical of other sterilization processes. Noxilizer, Inc. has commercialized this technology to offer contract sterilization services for
medical devices
A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...
at its Baltimore, Maryland (U.S.) facility. This has been demonstrated in Noxilizer’s lab in multiple studies and is supported by published reports from other labs. These same properties also allow for quicker removal of the sterilant and residual gases through aeration of the enclosed environment. The combination of rapid lethality and easy removal of the gas allows for shorter overall cycle times during the sterilization (or decontamination) process and a lower level of sterilant residuals than are found with other sterilization methods.
Eniware, LLC has developed a portable, power-free sterilizer that uses no electricity, heat or water. The 25 liter unit makes sterilization of surgical instruments possible for austere forward surgical teams, in health centers throughout the world with intermittent or no electricity and in disaster relief and humanitarian crisis situations. The four hour cycle uses a single use gas generation ampoule and a disposable scrubber to remove nitrogen dioxide gas.
Ozone
Ozone
Ozone (), or trioxygen, is an inorganic molecule with the chemical formula . It is a pale blue gas with a distinctively pungent smell. It is an allotrope of oxygen that is much less stable than the diatomic allotrope , breaking down in the lo ...
is used in industrial settings to sterilize water and air, as well as a disinfectant for surfaces. It has the benefit of being able to
oxidize
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
most organic matter. On the other hand, it is a toxic and unstable gas that must be produced on-site, so it is not practical to use in many settings.
Ozone offers many advantages as a sterilant gas; ozone is a very efficient sterilant because of its strong oxidizing properties (
E=2.076 vs
SHE
She most commonly refers to:
*She (pronoun), the third person singular, feminine, nominative case pronoun in modern English.
She or S.H.E. may also refer to:
Literature and films
*'' She: A History of Adventure'', an 1887 novel by H. Rider Hagga ...
) capable of destroying a wide range of pathogens, including prions, without the need for handling hazardous chemicals since the ozone is generated within the sterilizer from medical-grade
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
. The high reactivity of ozone means that waste ozone can be destroyed by passing over a simple
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
that reverts it to oxygen and ensures that the cycle time is relatively short. The disadvantage of using ozone is that the gas is very reactive and very hazardous. The NIOSH's immediately dangerous to life and health limit (IDLH) for ozone is smaller than the IDLH for ethylene oxide. NIOSH and OSHA has set the PEL for ozone at , calculated as an time-weighted average. The sterilant gas manufacturers include many safety features in their products but prudent practice is to provide continuous monitoring of exposure to ozone, in order to provide a rapid warning in the event of a leak. Monitors for determining workplace exposure to ozone are commercially available.
Glutaraldehyde and formaldehyde
Glutaraldehyde
Glutaraldehyde is an organic compound with the formula . The molecule consists of a five carbon chain doubly terminated with formyl (CHO) groups. It is usually used as a solution in water, and such solutions exists as a collection of hydrates, c ...
and
formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
solutions (also used as
fixatives) are accepted liquid sterilizing agents, provided that the immersion time is sufficiently long. To kill all spores in a clear liquid can take up to 22 hours with glutaraldehyde and even longer with formaldehyde. The presence of solid particles may lengthen the required period or render the treatment ineffective. Sterilization of blocks of tissue can take much longer, due to the time required for the fixative to penetrate. Glutaraldehyde and formaldehyde are
volatile, and toxic by both skin contact and inhalation. Glutaraldehyde has a short shelf-life (<2 weeks), and is expensive. Formaldehyde is less expensive and has a much longer shelf-life if some
methanol
Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
is added to inhibit
polymerization
In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer, monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are ...
to
paraformaldehyde
Paraformaldehyde (PFA) is the smallest polyoxymethylene, the polymerization product of formaldehyde with a typical degree of polymerization of 8–100 units. Paraformaldehyde commonly has a slight odor of formaldehyde due to decomposition. Paraf ...
, but is much more volatile. Formaldehyde is also used as a gaseous sterilizing agent; in this case, it is prepared on-site by depolymerization of solid paraformaldehyde. Many vaccines, such as the original
Salk polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chil ...
, are sterilized with formaldehyde.
Hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
, in both liquid and as
vaporized hydrogen peroxide Vaporized hydrogen peroxide (trademarked VHP, Retrieved February 2016. also known as hydrogen peroxide vapor, HPV) is a vapor form of hydrogen peroxide (H2O2) with applications as a low-temperature antimicrobial vapor used to decontaminate enclosed ...
(VHP), is another chemical sterilizing agent. Hydrogen peroxide is a strong
oxidant
An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxid ...
, which allows it to destroy a wide range of pathogens. Hydrogen peroxide is used to sterilize heat- or temperature-sensitive articles, such as rigid
endoscope
An endoscope is an inspection instrument composed of image sensor, optical lens, light source and mechanical device, which is used to look deep into the body by way of openings such as the mouth or anus. A typical endoscope applies several modern t ...
s. In medical sterilization, hydrogen peroxide is used at higher concentrations, ranging from around 35% up to 90%. The biggest advantage of hydrogen peroxide as a sterilant is the short cycle time. Whereas the cycle time for ethylene oxide may be 10 to 15 hours, some modern hydrogen peroxide sterilizers have a cycle time as short as 28 minutes.
Drawbacks of hydrogen peroxide include material compatibility, a lower capability for penetration and operator health risks. Products containing cellulose, such as paper, cannot be sterilized using VHP and products containing
nylon
Nylon is a generic designation for a family of synthetic polymers composed of polyamides ( repeating units linked by amide links).The polyamides may be aliphatic or semi-aromatic.
Nylon is a silk-like thermoplastic, generally made from petro ...
may become brittle. The penetrating ability of hydrogen peroxide is not as good as ethylene oxide and so there are limitations on the length and diameter of the lumen of objects that can be effectively sterilized. Hydrogen peroxide is a primary irritant and the contact of the liquid solution with skin will cause
bleaching
Bleach is the generic name for any chemical product that is used industrially or domestically to remove color (whitening) from a fabric or fiber or to clean or to remove stains in a process called bleaching. It often refers specifically, to ...
or
ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
depending on the concentration and contact time. It is relatively non-toxic when diluted to low concentrations, but is a dangerous oxidizer at high concentrations (> 10% w/w). The vapour is also hazardous, primarily affecting the eyes and respiratory system. Even short term exposures can be hazardous and NIOSH has set the IDLH at 75 ppm,
less than one tenth the IDLH for ethylene oxide (800 ppm). Prolonged exposure to lower concentrations can cause permanent lung damage and consequently, OSHA has set the permissible exposure limit to 1.0 ppm, calculated as an eight-hour time-weighted average. Sterilizer manufacturers go to great lengths to make their products safe through careful design and incorporation of many safety features, though there are still workplace exposures of hydrogen peroxide from gas sterilizers documented in the FDA MAUDE database. When using any type of gas sterilizer, prudent work practices should include good ventilation, a continuous gas monitor for hydrogen peroxide and good work practices and training.
Vaporized hydrogen peroxide Vaporized hydrogen peroxide (trademarked VHP, Retrieved February 2016. also known as hydrogen peroxide vapor, HPV) is a vapor form of hydrogen peroxide (H2O2) with applications as a low-temperature antimicrobial vapor used to decontaminate enclosed ...
(VHP) is used to sterilize large enclosed and sealed areas, such as entire rooms and aircraft interiors.
Although toxic, VHP breaks down in a short time to water and oxygen.
Peracetic acid
Peracetic acid
Peracetic acid (also known as peroxyacetic acid, or PAA) is an organic compound with the formula CH3CO3H. This peroxy acid is a colorless liquid with a characteristic acrid odor reminiscent of acetic acid. It can be highly corrosive.
Peracetic a ...
(0.2%) is a recognized sterilant by the FDA for use in sterilizing medical devices such as
endoscope
An endoscope is an inspection instrument composed of image sensor, optical lens, light source and mechanical device, which is used to look deep into the body by way of openings such as the mouth or anus. A typical endoscope applies several modern t ...
s. Peracetic acid which is also known as peroxyacetic acid is a chemical compound often used in disinfectants such as sanitizers. It is most commonly produced by the reaction of
acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
and
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
with each other by using an acid catalyst. Peracetic acid is never sold in unstabilized solutions which is why it is considered to be environmentally friendly. Peracetic acid is a colorless liquid and the molecular formula of peracetic acid is C
2H
4O
3 or CH3COOOH. More recently, peracetic acid is being used throughout the world as more people are using fumigation to decontaminate surfaces to reduce the risk of Covid-19 and other diseases.
Potential for chemical sterilization of prions
Prions are highly resistant to chemical sterilization. Treatment with
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
s, such as formaldehyde, have actually been shown to increase prion resistance. Hydrogen peroxide (3%) for one hour was shown to be ineffective, providing less than 3 logs (10
−3) reduction in contamination.
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
, formaldehyde, glutaraldehyde, and peracetic acid also fail this test (one hour treatment). Only
chlorine
Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...
,
phenolic compounds,
guanidinium thiocyanate
Guanidinium thiocyanate (GTC) or guanidinium isothiocyanate (GITC) is a chemical compound used as a general protein denaturant, being a chaotropic agent, although it is most commonly used as a nucleic acid protector in the extraction of DNA and RN ...
, and sodium hydroxide reduce prion levels by more than 4 logs; chlorine (too corrosive to use on certain objects) and sodium hydroxide are the most consistent. Many studies have shown the effectiveness of sodium hydroxide.
Radiation sterilization
Sterilization can be achieved using
electromagnetic radiation
In physics, electromagnetic radiation (EMR) consists of waves of the electromagnetic field, electromagnetic (EM) field, which propagate through space and carry momentum and electromagnetic radiant energy. It includes radio waves, microwaves, inf ...
, such as
ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...
light
Light or visible light is electromagnetic radiation that can be perceived by the human eye. Visible light is usually defined as having wavelengths in the range of 400–700 nanometres (nm), corresponding to frequencies of 750–420 tera ...
,
X-rays
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 Picometre, picometers to 10 Nanometre, nanometers, corresponding to frequency, ...
and
gamma rays
A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
, or irradiation by
subatomic particle
In physical sciences, a subatomic particle is a particle that composes an atom. According to the Standard Model of particle physics, a subatomic particle can be either a composite particle, which is composed of other particles (for example, a pr ...
s such as by
electron beam
Cathode rays or electron beam (e-beam) are streams of electrons observed in discharge tubes. If an evacuated glass tube is equipped with two electrodes and a voltage is applied, glass behind the positive electrode is observed to glow, due to ele ...
s. Electromagnetic or particulate radiation can be energetic enough to ionize atoms or molecules (
ionizing radiation
Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
), or less energetic (
non-ionizing radiation
Non-ionizing (or non-ionising) radiation refers to any type of electromagnetic radiation that does not carry enough energy per quantum (photon energy) to ionize atoms or molecules—that is, to completely remove an electron from an atom or molec ...
).
Non-ionizing radiation sterilization
Ultraviolet light irradiation (UV, from a
germicidal lamp
A germicidal lamp (also known as disinfection lamp or sterilizer lamp) is an electric light that produces ultraviolet C (UVC) light. This short-wave ultraviolet light disrupts DNA base pairing, causing formation of pyrimidine dimers, and lead ...
) is useful for sterilization of surfaces and some transparent objects. Many objects that are transparent to
visible light
Light or visible light is electromagnetic radiation that can be perceived by the human eye. Visible light is usually defined as having wavelengths in the range of 400–700 nanometres (nm), corresponding to frequencies of 750–420 te ...
absorb UV. UV irradiation is routinely used to sterilize the interiors of
biological safety cabinet
A biosafety cabinet (BSC)—also called a biological safety cabinet or microbiological safety cabinet—is an enclosed, ventilated laboratory workspace for safely working with materials contaminated with (or potentially contaminated with) pathogen ...
s between uses, but is ineffective in shaded areas, including areas under dirt (which may become polymerized after prolonged irradiation, so that it is very difficult to remove). It also damages some plastics, such as
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 a ...
foam if exposed for prolonged periods of time.
Ionizing radiation sterilization
![E-beam-x-ray-gamma-efficiency](https://upload.wikimedia.org/wikipedia/commons/a/a5/E-beam-x-ray-gamma-efficiency.jpg)
The safety of irradiation facilities is regulated by the
International Atomic Energy Agency
The International Atomic Energy Agency (IAEA) is an intergovernmental organization that seeks to promote the peaceful use of nuclear energy and to inhibit its use for any military purpose, including nuclear weapons. It was established in 1957 ...
of the
United Nations
The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...
and monitored by the different national
Nuclear Regulatory Commission
The Nuclear Regulatory Commission (NRC) is an independent agency of the United States government tasked with protecting public health and safety related to nuclear energy. Established by the Energy Reorganization Act of 1974, the NRC began operat ...
s (NRC). The radiation exposure accidents that have occurred in the past are documented by the agency and thoroughly analyzed to determine the cause and improvement potential. Such improvements are then mandated to retrofit existing facilities and future design.
Gamma radiation
A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically s ...
is very penetrating, and is commonly used for sterilization of disposable medical equipment, such as syringes, needles,
cannula
A cannula (; Latin meaning 'little reed'; plural or ) is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of samples. In simple terms, a cannula can surround the inner or outer surfaces ...
s and IV sets, and food. It is emitted by a
radioisotope
A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...
, usually
cobalt-60
Cobalt-60 (60Co) is a synthetic radioactive isotope of cobalt with a half-life of 5.2713 years. It is produced artificially in nuclear reactors. Deliberate industrial production depends on neutron activation of bulk samples of the monoisoto ...
(
60Co) or
caesium-137
Caesium-137 (), cesium-137 (US), or radiocaesium, is a radioactive isotope of caesium that is formed as one of the more common fission products by the nuclear fission of uranium-235 and other fissionable isotopes in nuclear reactors and nucl ...
(
137Cs), which have
photon
A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they always ...
energies of up to 1.3 and 0.66
MeV
In physics, an electronvolt (symbol eV, also written electron-volt and electron volt) is the measure of an amount of kinetic energy gained by a single electron accelerating from rest through an Voltage, electric potential difference of one volt i ...
, respectively.
Use of a radioisotope requires shielding for the safety of the operators while in use and in storage. With most designs, the radioisotope is lowered into a water-filled source storage pool, which absorbs radiation and allows maintenance personnel to enter the radiation shield. One variant keeps the radioisotope under water at all times and lowers the product to be irradiated in the water in hermetically-sealed bells; no further shielding is required for such designs. Other uncommonly used designs use dry storage, providing movable shields that reduce radiation levels in areas of the irradiation chamber. An incident in
Decatur, Georgia
Decatur is a city in, and the county seat of, DeKalb County, Georgia, which is part of the Atlanta metropolitan area. With a population of 24,928 in the 2020 census, the municipality is sometimes assumed to be larger since multiple ZIP Codes in ...
, US, where water-soluble caesium-137 leaked into the source storage pool, requiring NRC intervention has led to use of this radioisotope being almost entirely discontinued in favour of the more costly, non-water-soluble cobalt-60. Cobalt-60 gamma
photon
A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they always ...
s have about twice the energy, and hence greater penetrating range, of caesium-137-produced radiation.
Electron beam processing
Electron-beam processing or electron irradiation (EBI) is a process that involves using electrons, usually of high energy, to treat an object for a variety of purposes. This may take place under elevated temperatures and nitrogen atmosphere. Poss ...
is also commonly used for sterilization.
Electron beams
Cathode rays or electron beam (e-beam) are streams of electrons observed in discharge tubes. If an evacuated glass tube is equipped with two electrodes and a voltage is applied, glass behind the positive electrode is observed to glow, due to el ...
use an on-off technology and provide a much higher dosing rate than gamma or X-rays. Due to the higher dose rate, less exposure time is needed and thereby any potential degradation to polymers is reduced. Because
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no kn ...
s carry a charge, electron beams are less penetrating than both gamma and X-rays. Facilities rely on substantial concrete shields to protect workers and the environment from radiation exposure.
High-energy X-rays
High-energy X-rays or HEX-rays are very hard X-rays, with typical energies of 80–1000 keV (1 MeV), about one order of magnitude higher than conventional X-rays used for X-ray crystallography (and well into gamma-ray energies over 120 k ...
(produced by ''
bremsstrahlung
''Bremsstrahlung'' (), from "to brake" and "radiation"; i.e., "braking radiation" or "deceleration radiation", is electromagnetic radiation produced by the deceleration of a charged particle when deflected by another charged particle, typicall ...
'') allow irradiation of large packages and
pallet
A pallet (also called a skid) is a flat transport structure, which supports goods in a stable fashion while being lifted by a forklift, a pallet jack, a front loader, a jacking device, or an erect crane. A pallet is the structural foundat ...
loads of medical devices. They are sufficiently penetrating to treat multiple pallet loads of low-density packages with very good dose uniformity ratios. X-ray sterilization does not require chemical or radioactive material: high-energy X-rays are generated at high intensity by an
X-ray generator
An X-ray generator is a device that produces X-rays. Together with an X-ray detector, it is commonly used in a variety of applications including medicine, X-ray fluorescence, electronic assembly inspection, and measurement of material thickness ...
that does not require shielding when not in use. X-rays are generated by bombarding a dense material (target) such as
tantalum
Tantalum is a chemical element with the symbol Ta and atomic number 73. Previously known as ''tantalium'', it is named after Tantalus, a villain in Greek mythology. Tantalum is a very hard, ductile, lustrous, blue-gray transition metal that is ...
or
tungsten
Tungsten, or wolfram, is a chemical element with the symbol W and atomic number 74. Tungsten is a rare metal found naturally on Earth almost exclusively as compounds with other elements. It was identified as a new element in 1781 and first isolat ...
with high-energy electrons, in a process known as ''bremsstrahlung'' conversion. These systems are energy-inefficient, requiring much more electrical energy than other systems for the same result.
Irradiation
Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve ...
with X-rays, gamma rays, or electrons does not make materials
radioactive
Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is consid ...
, because the energy used is too low. Generally an energy of at least 10 MeV is needed to
induce radioactivity in a material.
Neutron
The neutron is a subatomic particle, symbol or , which has a neutral (not positive or negative) charge, and a mass slightly greater than that of a proton. Protons and neutrons constitute the nuclei of atoms. Since protons and neutrons beh ...
s and very high-energy particles can make materials radioactive, but have good penetration, whereas lower energy particles (other than neutrons) cannot make materials radioactive, but have poorer penetration.
Sterilization by irradiation with gamma rays may however affect material properties.
Irradiation is used by the
United States Postal Service
The United States Postal Service (USPS), also known as the Post Office, U.S. Mail, or Postal Service, is an independent agency of the executive branch of the United States federal government responsible for providing postal service in the U ...
to sterilize mail in the
Washington, D.C.
)
, image_skyline =
, image_caption = Clockwise from top left: the Washington Monument and Lincoln Memorial on the National Mall, United States Capitol, Logan Circle, Jefferson Memorial, White House, Adams Morgan, ...
area. Some foods (e.g. spices and ground meats) are
sterilized by irradiation.
Subatomic particles may be more or less penetrating and may be generated by a radioisotope or a device, depending upon the type of particle.
Sterile filtration
Fluids that would be damaged by heat, irradiation or chemical sterilization, such as drug solution, can be sterilized by
microfiltration
Microfiltration is a type of physical filtration process where a contaminated fluid is passed through a special pore-sized membrane filter to separate microorganisms and suspended particles from process liquid. It is commonly used in conjunction ...
using
membrane filter
Membrane technology encompasses the scientific processes used in the construction and application of membranes. Membranes are used to facilitate the transport or rejection of substances between mediums, and the mechanical separation of gas and li ...
s. This method is commonly used for heat labile pharmaceuticals and
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, respo ...
solutions in medicinal drug processing. A microfilter with pore size of usually 0.22
µm will effectively remove
microorganisms
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
.
[
] Some
staphylococcal
''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultative ...
species have, however, been shown to be flexible enough to pass through 0.22 µm filters. In the processing of
biologics
A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, th ...
,
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es must be removed or inactivated, requiring the use of
nanofilters with a smaller pore size (20–50
nm). Smaller pore sizes lower the flow rate, so in order to achieve higher total throughput or to avoid premature blockage, pre-filters might be used to protect small pore membrane filters.
Tangential flow filtration
In chemical engineering, biochemical engineering and protein purification, crossflow filtration (also known as tangential flow filtration) is a type of filtration (a particular unit operation). Crossflow filtration is different from dead-end filtra ...
(TFF) and alternating tangential flow (ATF) systems also reduce particulate accumulation and blockage.
Membrane filters used in production processes are commonly made from materials such as mixed
cellulose ester or
polyethersulfone
Polysulfones are a family of high performance thermoplastics. These polymers are known for their toughness and stability at high temperatures. Technically used polysulfones contain an aryl- SO2-aryl subunit. Due to the high cost of raw material ...
(PES). The filtration equipment and the filters themselves may be purchased as pre-sterilized disposable units in sealed packaging or must be sterilized by the user, generally by autoclaving at a temperature that does not damage the fragile filter membranes. To ensure proper functioning of the filter, the membrane filters are integrity tested post-use and sometimes before use. The nondestructive integrity test assures the filter is undamaged and is a regulatory requirement.
Typically, terminal pharmaceutical sterile filtration is performed inside of a
cleanroom
A cleanroom or clean room is an engineered space, which maintains a very low concentration of airborne particulates. It is well isolated, well-controlled from contamination, and actively cleansed. Such rooms are commonly needed for scientif ...
to prevent contamination.
Preservation of sterility
![Curette in sterile packaging](https://upload.wikimedia.org/wikipedia/commons/2/28/Curette_in_sterile_packaging.jpg)
Instruments that have undergone sterilization can be maintained in such condition by containment in sealed packaging until use.
Aseptic technique is the act of maintaining sterility during procedures.
See also
*
Antibacterial soap
Antibacterial soap is a soap which contains chemical ingredients that purportedly assist in killing bacteria. The majority of antibacterial soaps contain triclosan, though other chemical additives are also common. The effectiveness of products bra ...
*
Asepsis
Asepsis is the state of being free from disease-causing micro-organisms (such as pathogenic bacteria, viruses, pathogenic fungi, and parasites). There are two categories of asepsis: medical and surgical. The modern day notion of asepsis is deriv ...
*
Aseptic processing
Aseptic processing is a processing technique wherein commercially thermally sterilized liquid products (typically food or pharmaceutical) are packaged into previously sterilized containers under sterile conditions to produce shelf-stable products ...
*
Contamination control
Contamination control is the generic term for all activities aiming to control the existence, growth and proliferation of contamination in certain areas. Contamination control may refer to the atmosphere as well as to surfaces, to particulate matte ...
*
Electron irradiation
Electron-beam processing or electron irradiation (EBI) is a process that involves using electrons, usually of high energy, to treat an object for a variety of purposes. This may take place under elevated temperatures and nitrogen atmosphere. Poss ...
*
Food packaging
Food packaging is a packaging system specifically designed for food and represents one of the most important aspects among the processes involved in the food industry, as it provides protection from chemical, biological and physical alterations ...
*
Food preservation
Food preservation includes processes that make food more resistant to microorganism growth and slow the oxidation of fats. This slows down the decomposition and rancidification process. Food preservation may also include processes that inhibit ...
*
Food safety
Food safety (or food hygiene) is used as a scientific method/discipline describing handling, preparation, and storage of food in ways that prevent food-borne illness. The occurrence of two or more cases of a similar illness resulting from t ...
*
Spaulding classification
*
Sterilant gas monitoring
References
Other references
WHO - Infection Control Guidelines for Transmissible Spongiform Encephalopathies Retrieved Jul 10, 2010
*
Control of microbes*
Innovative Technologies for the Biofunctionalisation and Terminal Sterilisation of Medical DevicesSterilization of liquids, solids, waste in disposal bags and hazardous biological substances*Pharmaceutical Filtration - The Management of Organism Removal, Meltzer TH, Jornitz MW, PDA/DHI 1998
*"Association for Advancement of Medical Instrumentation ANSI/AAMI ST41-Ehylene Oxyde Sterilization in Healthcare facilities: Safety and Effectiveness. Arlington, VA: Association for Advancement of Medical Instrumentation; 2000."
*“US Department of Labor, Occupational Safety and Health Administration.29 CFR 1910.1020. Access to Employee Medical Records.". October 26, 2007.
*Perioperative Standards and Recommended Practices, AORN 2013,
{{DEFAULTSORT:Sterilization (Microbiology)
Biocides
Electron beam
Hygiene
Microbiology