Medical Device Sterilization: Methods Explained, Compared & Contrasted

Sensors nowadays are used in a growing number of products, including medical devices.

The need to keep medical products sterile, free of harmful contaminants such as fungi, bacteria, viruses, and spore forms, is a particular challenge. Although there is a lot of information regarding sterilization processes and equipment, there isn’t much information about how sterilization affects sensors and electronics

In this article, we will examine and contrasts common sterilization methods for medical devices, as well as their compatibility for sensors and electronics.

We will discuss sterilization techniques, how are medical devices sterilized during each method, and what the advantages and disadvantages of each method are.

• Physical Sterilization
  • Autoclave Steam Sterilization
• Chemical Sterilization
  • Ethylene Oxide Sterilization (ETO)
  • Chlorine Dioxide Gas Sterilization (CD)
  • Hydrogen Peroxide Sterilization
• Radiation Sterilization
  • Gamma Ray Sterilization
  • Electron Beam Sterilization
• Sterilization of medical instruments: a summary
  • Sterilization Methods and Their Compatibility

What are the methods of sterilization?

Here are the 3 main types of sterilization we will be covering:

• Physical
• Chemical
• Radiation

1st method of medical sterilization: Physical Sterilization

There are several physical sterilization methods, the most efficient of which combines heat, humidity and high pressure in a device called an autoclave.

Autoclave Steam Sterilization

The autoclave is a pressure cooker-like container. During the sterilization process, the autoclave is sealed after being filled with the items to be sterilized. Then, under high pressure, high-temperature steam is pumped in, displacing air. Microorganisms are essentially killed through moist heat sterilization, which causes permanent coagulation and denaturation of enzymes and structural proteins.

Autoclave sterilization temperature & time

Under normal circumstances, autoclave sterilization time can take anywhere from fifteen to sixty minutes for a complete cycle.

However, when it comes to autoclave sterilization temperature and time and pressure, these depend on the type of microorganisms to be cleaved.

At the end of the process, the steam is released, and the sterilized objects are removed when the required time has passed.

Objects that can withstand humidity, high pressure (up to 3.5 bar gauge), and high temperature (up to 148°C) should be sterilized in an autoclave. Surgical instruments are a good example. Semiconductor devices can normally withstand temperatures of up to 125°C.

Sterilization of medical instruments using an autoclave – things to know

Please note that exposing integrated batteries to high temperatures diminishes their lifespan dramatically. EEPROMs, for example, are susceptible to high temperatures because they use floating-gate technology. However, if the data retention is stated as 10 years at 125°C, no data integrity loss should be expected. Sensors based on MEMS technology can typically tolerate temperatures of up to 125°C and can be protected from steam via encapsulation or coating.

2nd method of medical sterilization: Chemical Sterilization

There are multiple types of chemical sterilization in the medical field. The most commonly used are:

• Ethylene Oxide (ETO) Sterilization
• Chlorine Dioxide (CD) Gas Sterilization
• Vaporized Hydrogen Peroxide (VHP) Sterilization

Chemical sterilization procedures can be combined with physical sterilization procedures.

Let’s see their individual characteristics and when each method can be used.

Ethylene Oxide Sterilization (ETO)

Ethylene oxide (ETO) became important in industry in the early 1900s. In 1938, ETO sterilization for spice preservation was patented. ETO sterilization process became popular when there were few other options for sterilizing heat- and moisture-sensitive medical instruments.

ETO sterilization process: time and temperature

The ETO sterilizer is a container that is first filled with the sterilized objects. The basic ETO sterilization cycle has five phases. These are:

1. evacuation with humidification
2. gas introduction
3. exposure
4. evacuation
5. air washes

ETO sterilization takes two to three hours, aeration time (removal of ETO) not included.

Aeration by mechanical means requires eight to twelve hours at 50° to 60°C. Passive aeration takes seven days.

The sterilized objects are removed after the aeration is finished. To impede microbial reproduction, ETO reacts chemically with amino acids, proteins, and DNA.

Ethylene Oxide sterilization of medical devices – what you need to know

ETO treatment is appropriate for devices that cannot withstand the high temperatures and humidity required by autoclave sterilization.

The ETO sterilization procedure is particularly suited for medical devices with embedded electronics thanks to its low (up to 60°C) temperature conditions. However, for medical devices with embedded batteries, the vacuum may not be acceptable.

Furthermore, this sterilization process has a major drawback: ETO is a highly combustible, petroleum-based gas that is also a carcinogen.

Chlorine Dioxide Gas Sterilization (CD)

Chlorine dioxide (CD) was discovered in 1811 and quickly became popular in the paper industry as a bleaching agent. The Environmental Protection Agency (EPA) designated chlorine dioxide as a sterilant in 1988. This opened the possibility of medical uses

CD gas sterilization process: time and temperature

The CD sterilizer is a container that is first filled with the medical devices to be sterilized. The typical CD sterilization process has five stages. These are:

1. preconditioning with humidification
2. conditioning
3. generation and delivery of chlorine dioxide gas
4. exposure
5. aeration

CD gas sterilization takes two to three hours to complete including aeration (removal of CD) time.

The sterilized objects are removed after the aeration is finished. Chlorine dioxide (ClO2) is an oxidizing chemical that reacts with a variety of biological components, including microbial cell membranes. CD destroys their chemical connections leading in the death of the organism due to cell disintegration.

Because CD changes the structure of microorganisms, the enzymatic function is disrupted, resulting in fast bacterial death. CD’s efficacy is due to the simultaneous oxidative attack on several proteins, which prevents the cells from evolving into a resistant form. Furthermore, because chlorine dioxide has a lower reactivity, its antibacterial action lasts longer in the presence of organic matter.

Chlorine Dioxide sterilization for medical devices – what you need to know

CD gas sterilization is approved by the FDA. It is ideal for products that can’t withstand the high temperatures and humidity required for autoclave sterilization. The CD sterilization procedure is particularly suited for medical devices with embedded electronics and sensors due to the low temperature of 15° to 40°C. CD gas is nonflammable and noncarcinogenic at the doses utilized in this procedure. To achieve sporicidal effects, low doses are required.

Hydrogen Peroxide Sterilization

In the pharmaceutical business, hydrogen peroxide has a long history of use and is a popular alternative to ethylene oxide (ETO).

There are two ways to use hydrogen peroxide. These are:

• Vaporized hydrogen peroxide sterilization
• Hydrogen peroxide plasma sterilization

Vaporized Hydrogen Peroxide Sterilization (VHP)

So, what is VHP and how does it work?

In short, H2O2 causes oxidative stress by creating reactive oxygen species such hydroxyl radicals, which damage a variety of molecular targets including nucleic acids, enzymes, cell wall proteins, and lipids. VHP’s specific mechanism of action is unknown, and it most likely differs depending on the microbe.

VHP sterilization process – time and temperature

The medical devices to be sterilized are first placed in the VHP sterilizer. The typical hydrogen peroxide sterilization process has three stages. These are:

1. Conditioning
2. H2O2 injection
3. Aeration

VHP sterilization takes one to two hours to complete, including aeration (removal of H2O2) time.

The sterilized objects are removed after the aeration is finished.

VHP sterilization for medical devices – what you need to know

VHP sterilization is suitable for devices that cannot withstand the high temperatures and humidity required for autoclave sterilization.

The VHP sterilization procedure is particularly suited for medical equipment with embedded electronics and sensors – the machine used is considered a low temperature sterilizer thanks to its low temperature operation of 25° to 50°C. The vacuum required for the procedure of VHP might deem the process unsuitable for medical devices with embedded batteries.

Regarding the disadvantages of hydrogen peroxide sterilization, the method has small disinfecting and oxidizing abilities, making VHP’s penetrating capabilities inferior to ETO’s.

Hydrogen Peroxide Plasma Sterilization

Sterilization through hydrogen peroxide gas plasma incorporates both chemistry and physics. The medical devices to be sterilized are firstly placed in the hydrogen peroxide plasma sterilizer.

Hydrogen peroxide plasma sterilization procedure – time and temperature

The basic hydrogen peroxide plasma sterilization process consists of four steps. These are:

1. vacuum creation
2. H2O2 injection
3. diffusion
4. plasma discharge

Hydrogen peroxide sterilization takes one to three hours and consists of four steps. There is no need for aeration. The sterilized objects are removed after the cycle is completed.

During the plasma phase of the cycle, hydrogen peroxide plasma sterilization inactivates bacteria primarily by combining the usage of hydrogen peroxide gas with the formation of free radicals (hydroxyl and hydroproxyl free radicals). Plasma sterilization with hydrogen peroxide should not be confused with systems that use ultrasound to create a mist and so do not require an electric plasma discharge.

Hydrogen peroxide plasma sterilization for medical devices – what you need to know

Hydrogen peroxide plasma treatment is ideal for products that can’t withstand the high temperatures and humidity required by autoclave sterilization. When compared to VHP sterilization, the required vacuum is not as high. The low process temperature of 40° to 65°C is enticing, but the 13.56MHz RF energy of 200W to 400W during the plasma discharge phase is problematic for embedded devices. For medical devices containing semiconductors, hydrogen peroxide plasma sterilization should not be employed.

3rd method of medical sterilization: Radiation Sterilization

There are two common processes used for radiation sterilization. These are:

• Gamma Ray Sterilization
• Electron Beam Sterilization

Let’s see their individual characteristics, advantages, and disadvantages.

Gamma Ray Sterilization

When scientists were researching the radiation emitted by radium around 1900, they found gamma radiation. Other sources, such as technetium-99m and cobalt-60, were identified later. The use of cobalt-60 as a source of gamma radiation in industry began in the 1950s. Cobalt-60 does not occur naturally; it is synthesized in a reactor. Cobalt-60 has a half-life of 5.2714 years.

Gama radiation sterilization process

The sterilized objects are placed on a conveyor that delivers them to a powerful gamma radiation source, such as cobalt-60.

The conveyor constantly transfers devices on to expose while stopping in the radiation field to ensure the object receives the required dose. Instead of stopping and starting, the conveyor could move at a constant speed that ensures that the correct dosage is received per medical device. Ionizing radiation generates excitations, ionizations, and the creation of free radicals in the presence of water.

Free radicals are highly reactive oxidizing (OH, HO2) and reducing (H) chemicals that can harm vital components in living cells. As a result, these three steps contribute to the disintegration of vital cell components such as enzymes and DNA. Cell death occurs as a result of this reaction.

Radiation sterilization is faster than physical and chemical procedures, and it takes place at normal air pressure and at higher ambient temperature. To protect the environment from the radiation, the irradiator is a massive structure with 2m thick concrete walls.

To maintain a constant radiation dose, the exposure time must be modified on a regular basis due to radioactive decay. Gamma radiation impacts polymers and semiconductors in addition to biological cells. The effect on electronics is determined by the dose and pace of delivery. In the extreme, a complete ionization in silicon of more than 5000 rads delivered over seconds to minutes damages semiconductor materials over time.

Gama ray sterilization for medical devices – what you need to know

The medical devices exposed are deeply penetrated by gamma radiation.

In practice, sterilization levels in the 250 to 500 rads range are used in the medical industry to sanitize instruments and products, where specially designed semiconductor devices can reliably operate.

As a result, gamma ray sterilization can be employed at medical devices containing compatible semiconductor electronics and sensors and while under the correct conditions.

Electron Beam Sterilization

Electron beams were initially known as cathode rays because they were emitted from the cathode of an electron tube (also known as a vacuum tube). In 1897, the cathode ray tube (CRT) was designed, which produces and deflects an electron beam to scan a fluorescent screen. With the emergence of television, it became a common home appliance.

When electrons in a television CRT are accelerated with a 10kV (black and white) or 25kV (color) anode voltage, they return to a metallic conductor when they contact the screen.

A CRT is similar to an electron beam generator. Their main differences are that the acceleration voltage can be up to 1000 times greater, and the screen is replaced by a window constructed of titanium foil that allows electrons to escape the vacuum while keeping gas molecules out.

Electron beam sterilization process

Gamma radiation penetrates well beyond electron beam radiation.

However, electron beam radiation:

• is faster than gamma ray sterilization
• produces no radioactive waste
• occurs at a higher room temperature at normal atmospheric pressure.

Compared to gamma radiation, electron beam radiation is more compatible with materials. The electron beam, when aimed at electronic components, can produce charge build-up (ESD), which can lead to damage. As a result, electron beam sterilization should only be used on semiconductor-containing products that are specifically engineered to withstand both the electron beam radiation level and ESD build-up.

Electron beam sterilization for medical devices – what you need to know

The medical device sector established the first commercial application of electron beams for sterilization in 1956.

The sterilized objects are placed on a conveyor that moves them gently past the window where the electron beam exits the generator. The conveyor speed is set to ensure that the dosage is correct. Energy levels of 5MeV to 10MeV are required to achieve the penetration required for sterilization.

Free radicals produced by electron beam radiation react with macromolecules, causing DNA damage and cell death. All pathogens, including viruses, fungus, bacteria, parasites, spores, and molds, are destroyed using this procedure. 

Sterilization of medical instruments: a summary

As one can easily tell, sterilizing medical equipment is of utmost importance.

Sterilization techniques for medical devices include physical, chemical, and radiation procedures.

Each sterilization process has unique properties that may or may not be compatible with semiconductor devices. When deciding on a process, it’s important to think about the possible negative effects, especially when electronics and sensors are involved.

The sterilization procedures mentioned in this article and their compatibility with embedded electronics are summarized in the table below.

Sterilization Methods and Their Compatibility

Here are the key takes:

• Chlorine dioxide has no known negative effects on electronic components, making it the greatest overall choice for electronic component compatibility.
• For electronic medical devices without batteries, ethylene oxide and vaporized hydrogen peroxide are also effective sterilizing procedures.
• Chemical sterilizing agents do not damage the epoxy packing material used to package ICs, hence it is unaffected.
• Specially designed and appropriate ICs must be used if irradiation immunity is required.