Cleanrooms are designed to control particles, microorganisms and chemical contaminants in environments where even invisible contamination can compromise a product, a process or a patient. But filtration and compliance with standards are only part of the equation. Human behaviour, airflow, equipment positioning and the behaviour of bioaerosols all influence real-world performance. Today, research is moving towards a more dynamic approach combining microbiology, fluid mechanics, numerical simulation and, eventually, digital twins.

From pharmaceuticals and microelectronics to hospitals, cosmetics, food production and the space industry, cleanrooms have become essential to many sectors.

Their purpose may appear straightforward: create an environment in which contamination is maintained below a predefined level.

In practice, the challenge is far more complex.

During a session presented at Forum LABO, experts from ASPEC explored both the fundamental principles of contamination control and the technologies now emerging to improve the performance of controlled environments.

Three major families of contaminants must be considered in controlled environments.

The first is particulate contamination: inert particles and dust suspended in the air.

The second is microbiological contamination, including bacteria, fungi, yeasts, moulds and viruses.

The third is chemical and molecular contamination, which may originate from outdoor pollution, industrial activities, materials or even the people working inside the controlled environment.

One of the main difficulties is that much of this contamination is invisible to the naked eye.

A human hair is around 100 micrometres in diameter, while the human eye can generally distinguish particles only down to approximately 50 micrometres. Many of the particles of interest in contamination control are therefore far smaller.

Viruses take this challenge even further, with some respiratory viruses measuring around 0.1 micrometres.

Contamination control is therefore largely about detecting and managing what cannot be seen.

The environment itself is not the only source of contamination.

People are among the most significant contributors inside cleanrooms.

Even when sitting relatively still, a person continuously releases particles. As activity increases, so does particle generation, through movement, clothing and the resuspension of material deposited on surfaces.

The human body also continuously sheds skin cells.

This explains why cleanroom clothing is not simply protective workwear. Its purpose is to create a barrier between the operator and the controlled environment.

Depending on the level of risk, this may involve coveralls, gloves, masks, hair covers, overshoes and other specialised equipment.

But clothing alone is not enough.

Movement, hygiene, working practices and behaviour all directly influence contamination levels.

Even everyday objects such as glasses, phones or computers can become contamination sources if they enter a controlled environment without appropriate cleaning procedures.

Contamination control begins with risk analysis.

A cleanroom used for microelectronics does not have the same purpose as a hospital operating theatre or a laboratory handling highly pathogenic viruses.

For particulate contamination, ISO cleanroom classes define maximum concentrations of airborne particles according to particle size.

In microbiological containment laboratories, the approach is different. BSL or containment levels are determined according to the biological hazards being handled.

Pressure management then becomes particularly important.

In some environments, the aim is to protect the product or process from external contamination. The room is maintained at positive pressure so that air flows outwards when an opening occurs.

In containment laboratories, the objective may be exactly the opposite: prevent a dangerous biological agent from escaping.

The room is therefore maintained at negative pressure, drawing air inward.

The technical solution changes according to the risk, but the principle remains the same: understand what needs to be protected, from what, and then design the environment accordingly.

Air handling systems are one of the central components of a cleanroom.

Air handling units filter incoming air while controlling parameters such as temperature, humidity, airflow rate and pressure.

Depending on the application, systems may operate using 100% fresh air or recirculate part of the treated air.

High-efficiency filtration then removes particles according to the required level of performance.

But achieving the required air-change rate or particle concentration does not necessarily mean that every part of the room is equally protected.

The position of supply and extract vents, furniture, equipment, operators and other obstacles can all influence airflow.

A room may therefore comply with its overall specifications while still containing poorly ventilated areas or local zones where contamination behaves differently.

This is one of the areas in which contamination-control research is currently evolving.

Rather than controlling an entire room to the highest possible standard, laboratories can also create highly controlled local environments.

Fume cupboards, laminar airflow systems, microbiological safety cabinets, isolators and other mini-environments can be selected according to the risk.

Some are designed primarily to protect the operator.

Others protect the product.

Some protect the external environment.

And certain systems are designed to protect all three.

This approach reflects an increasingly important principle in cleanroom design: the objective is not necessarily to maximise performance everywhere, but to apply the appropriate level of control exactly where it is required.

Cleaning is another essential part of the contamination-control strategy.

But cleaning a cleanroom is not simply a matter of applying a disinfectant.

Its effectiveness depends on several interacting parameters: the product used, mechanical action, contact time and, where relevant, temperature.

Poorly designed or poorly executed cleaning procedures can actually become a source of contamination.

Monitoring is therefore essential.

Surface sampling, particle measurements and other control techniques can be used to compare conditions before and after cleaning and detect abnormal trends.

Trend monitoring can also reveal recurring problems.

During the session, one example showed contamination peaks appearing approximately every two weeks. Investigation eventually linked them to the intervention of an external cleaning company.

The lesson is simple: cleaning must itself be treated as a controlled process.

While cleanroom standards and monitoring techniques are well established for particles and many microorganisms, viruses remain more difficult to characterise.

Unlike bacteria, viruses are not living organisms capable of independently multiplying in an environmental sample.

Collecting them from the air, determining whether they remain infectious and quantifying the actual biological risk therefore require specific approaches.

This became particularly visible during the COVID-19 pandemic.

Research teams developed systems capable of generating atmospheres containing infectious respiratory viruses in order to evaluate air-treatment technologies and bioaerosol collection systems under controlled conditions.

This work highlighted a broader issue: measuring particles alone does not fully describe the behaviour of infectious bioaerosols.

Air purifiers and other air-treatment technologies can display very different levels of performance.

Evaluating them therefore requires more than checking their technical specifications.

Researchers presented the development of a 30 m³ experimental test chamber designed to evaluate air-treatment devices against real microbiological bioaerosols, including bacteria, viruses and moulds.

Such facilities make it possible to reproduce realistic temperature and humidity conditions while studying airflow throughout the test environment.

This distinction is important.

A highly efficient filtration or air-treatment device may still provide poor protection if it is positioned in the wrong location.

The effectiveness of the technology and the way it is deployed must therefore be considered together.

This is where fluid mechanics becomes increasingly important.

Bioaerosols do not simply appear and disappear according to the theoretical performance of a filter. They move through complex environments shaped by ventilation, thermal effects, equipment, obstacles and human activity.

Computational fluid dynamics can help map these air movements and simulate how contaminants may travel through a room.

Researchers can then use experimental measurements to improve and validate the models.

The ambition is to combine microbiology, experimental aerosol science and fluid dynamics in order to better predict contamination risk.

However, there is still a scientific challenge.

Existing simulation tools are generally designed to model physical particles or gases. A bioaerosol is more complex: it may contain biological fluids, microorganisms and particles whose physical and infectious properties change over time.

Better characterising this behaviour could therefore make future simulations considerably more representative of real biological risk.

The next step is to move from occasional simulation towards dynamic management.

Digital twins could eventually provide virtual representations of cleanrooms, hospital rooms, operating theatres or production areas.

Data from the physical environment could then feed the model in real time.

Combined with contamination sensors, air-quality monitoring and predictive modelling, such systems could potentially adjust air handling, purification or extraction according to actual conditions.

Instead of operating continuously at maximum capacity, a controlled environment could become responsive to its real level of activity and risk.

This approach could also contribute to another major challenge: energy consumption.

Cleanrooms require large quantities of energy to filter, move, heat, cool and condition air.

Historically, many installations were designed according to a "more is better" philosophy: high airflow rates and continuous operation provided additional safety margins.

Today, the objective is increasingly to find the right level of performance for the actual requirement.

One example is the use of standby or reduced-operation modes when an environment is not being used.

An operating theatre, for example, does not necessarily need to operate overnight under exactly the same airflow conditions as during surgery, provided that contamination remains controlled and the room can return to nominal conditions when required.

The challenge is therefore not simply to reduce ventilation.

It is to demonstrate that energy consumption can be reduced without compromising contamination control.

Monitoring, modelling and a better understanding of airflow could play an important role in achieving this balance.

The future of cleanrooms is therefore not simply about stronger filters, more powerful ventilation or increasingly restrictive procedures.

It is moving towards a more integrated understanding of contamination.

Particles, microorganisms, bioaerosols, airflow, human behaviour, equipment, room geometry and energy consumption all interact.

Managing them effectively requires combining engineering and microbiology with measurement, modelling and risk analysis.

Ultimately, the objective is not to create the cleanest environment technically possible.

It is to create the right controlled environment for the right risk — and to maintain that performance throughout its lifetime.

Because in contamination control, standards and technology provide the framework, but real-world performance depends on how the entire system behaves together.

Article based on the session dedicated to contamination control in laboratories and cleanrooms, presented by ASPEC at Forum LABO.