Medical Laboratory Cleanroom System
Section 1 Medical Laboratory Cleanroom System
I. Definition of a Cleanroom
A cleanroom is a space in which the air cleanliness reaches a specified class and in which people can work. Its function is to control particulate contamination.
In order to achieve the specified cleanliness class, effectively control particulate contamination, and allow people to carry out precise scientific experiments in it, a cleanroom is by no means merely "clean"; it must be a multifunctional integrated whole with considerable requirements for temperature, humidity, pressure differential, noise, illuminance, and so on—a product that integrates multiple professional technologies such as architectural decoration, cleanroom air conditioning, purified water and purified gas, and electrical control.
II. Classification of Cleanrooms
1. Classification by Airflow
1.1 Unidirectional-flow cleanroom
[Figure: Fig. 6-1 Principle of a unidirectional-flow cleanroom — schematic of various unidirectional airflow patterns in which air is supplied through a HEPA-filtered ceiling and returned via a gridded floor and return air ducts]
1.2 Non-unidirectional-flow cleanroom (turbulent-flow cleanroom)
[Figure: Fig. 6-2 Principle of a turbulent-flow cleanroom; multiple supply air outlets are arranged on the top of a rectangular cleanroom, with a grille return air outlet at the lower-left corner; dashed arrows show the air forming numerous vortices, recirculation, and backflow in the room, in a turbulent state]
1.3 Radial (vector) flow cleanroom
[Figure: Fig. 6-3 Vector-flow airflow pattern; an angled HEPA supply air outlet is placed at the upper-left corner of the room, and the airflow spreads fan-wise and radially from the supply outlet toward the lower opposite side; the top and right side connect to return/exhaust ducts]
1.4 Mixed-flow (locally unidirectional-flow) cleanroom
[Figure: Fig. 6-4 Mixed-flow airflow pattern; multiple FFUs are suspended from the cleanroom ceiling and deliver localized vertical unidirectional flow downward, while the surrounding and lower air rises along the side walls and corridor to return, forming an overall mixed flow]
2. Classification by the Main Controlled Object of the Cleanroom
2.1 Industrial cleanroom
The main controlled objects of an industrial cleanroom are dust particles (whether living or non-living); certain processes also require control of molecular contaminants (AMC).
Industrial cleanrooms are mainly used in the electronics, aerospace, aviation, machinery, chemical, pharmaceutical, energy, and nanotechnology industries. The electronics and optoelectronics industries in particular cannot do without cleanrooms and cleanroom technology.
2.2 Biological cleanroom
The main controlled objects of a biological cleanroom are living microbial particles, such as bacteria and viruses that are harmful to humans, animals, and the environment.
Biological cleanrooms can be further divided into general biological cleanrooms, which mainly control the contamination of the work object by living particles and are generally maintained at positive pressure internally (e.g., the food industry, biopharmaceuticals, clean operating rooms);
and biosafety cleanrooms, which mainly control the contamination of the outside environment and people by living particles from the work object and are maintained at negative pressure internally (e.g., bacteriological/biological clean laboratories and health, epidemic-prevention, and quarantine facilities).
Our current clinical laboratory departments and pathology departments belong to the category of biological cleanrooms.
III. Cleanroom Classification Standards
Every country in the world has its own classification standards for cleanroom classes, but international standards (ISO) are now gradually being unified.
Table 6-1 Airborne Particulate Cleanliness Classes for Cleanrooms
| Air cleanliness class (N) | Maximum concentration limits (pc/m³) for particles equal to or larger than the sizes listed | |||||
|---|---|---|---|---|---|---|
| 0.1 μm | 0.2 μm | 0.3 μm | 0.5 μm | 1 μm | 5 μm | |
| 1 | 10 | 2 | ||||
| 2 | 100 | 24 | 10 | 4 | ||
| 3 | 1000 | 237 | 102 | 35 | 8 | |
| 4 | 10000 | 2370 | 1020 | 352 | 83 | |
| 5 | 100000 | 23700 | 10200 | 3520 | 832 | 29 |
| 6 | 1000000 | 237000 | 102000 | 35200 | 8320 | 293 |
| 7 | 352000 | 83200 | 2930 | |||
| 8 | 3520000 | 832000 | 29300 | |||
| 9 | 35200000 | 8320000 | 293000 |
IV. Technical Elements of Cleanrooms
- Supply air shall pass through at least three stages of filtration (primary, medium, and high efficiency), and the HEPA filter shall be installed at the terminal of the system.
Air filters are the most important equipment in an air cleaning system. There are three major categories of filters: primary filters, medium-efficiency filters, and high-efficiency filters (or sub-high-efficiency filters).
Primary filters mainly block settleable dust particles larger than 10 micrometers and various foreign matter. Most such filters use metal wire mesh, iron filings, coarse-pore glass-fiber polyurethane foam, and various synthetic fibers as filter media.
Medium-efficiency air filters first filter out dust of 1–10 micrometers. The filter media used in medium-efficiency filters mainly include polyester non-woven fabric, polypropylene non-woven fabric, medium-pore foam plastic, fine-pore foam plastic, and medium-efficiency glass-fiber filter paper.
HEPA filters are mainly used to capture particulate dust below 0.5 μm and various suspended matter, serving as the terminal filtration of various filtration systems. They use ultra-fine glass-fiber paper as the filter medium, with offset paper, aluminum foil, and other materials folded as separator plates, sealed with new polyurethane sealant, and framed in galvanized sheet, stainless-steel sheet, or aluminum-alloy profiles.
-
The cleanroom shall have sufficient supply air volume for purification and air conditioning.
-
The cleanroom shall maintain the necessary pressure gradient (positive or negative pressure gradient).
-
The cleanroom shall have a rational airflow organization.
[Figure: Fig. 6-5 Layout plan of high-throughput air outlets — floor plan of a molecular laboratory (electrophoresis area, sequencing area, library testing area, amplification area 1, WGA preparation area, reagent preparation area, hybridization capture area, DNA fragmentation area, specimen and library preparation area, etc.), showing the arrangement of HEPA supply outlets GKF-5/GKF-10 and exhaust louver outlets (320×250, 400×300), with legend and axis dimensions]
Fig. 6-6 Layout plan of high-throughput supply and return air
[Figure: Layout plan of high-throughput supply and return air — floor plan arrangement of HEPA supply outlets (GKF-5, GKF-10) and return air outlets in each room of the molecular laboratory, with duct routing and dimension annotations]
Legend:
| No. | Material Name |
|---|---|
| 1 | HEPA supply outlet GKF-5 |
| 2 | HEPA supply outlet GKF-10 |
| 3 | Opposed multi-blade regulating damper |
| 4 | 70°C fire damper with regulation |
- Note: Each HEPA supply outlet is equipped with a manual opposed multi-blade regulating damper.
- Each return air branch is equipped with a manual opposed multi-blade regulating damper.
Fig. 6-7 Layout plan of high-throughput exhaust air
[Figure: Layout plan of high-throughput exhaust air — arrangement of exhaust branch ducts and exhaust outlets in the molecular laboratory, including the locations of 5500 m³/h and 6000 m³/h exhaust fan units, check valves, and fire dampers with regulation]
Legend:
| No. | Material Name |
|---|---|
| 1 | HEPA supply outlet GKF-5 |
| 2 | HEPA supply outlet GKF-10 |
| 3 | Opposed multi-blade regulating damper |
| 4 | 70°C fire damper with regulation |
| 5 | Check valve |
| 5500 m³/h exhaust fan unit | |
| 6000 m³/h exhaust fan unit |
- Note: Each exhaust branch is equipped with a manual opposed multi-blade regulating damper.
V. Airflow Organization in Cleanrooms
A laboratory must maintain certain temperature and airflow conditions. Under normal circumstances, the laboratory area is kept at negative pressure relative to corridors and non-laboratory areas, with airflow moving from low-risk zones to high-risk zones; the entire building must be kept at positive pressure relative to the outside to prevent the infiltration of harmful, unfiltered air.
Laboratory design must consider not only the direction of airflow but also the flow rate and the pressure differentials between rooms of different cleanliness classes or different functions—typically 5–10 Pa; for biosafety laboratories, the pressure differential between adjacent rooms with different functions is typically 10–15 Pa. The routes of personnel and material flows must be fully considered to minimize indoor air backflow and turbulence, and to prevent contaminants from spreading indoors and endangering personnel and environmental safety. Special attention must be paid to the influence of fume hoods on indoor airflow organization; turbulence should be avoided as far as possible in areas near laboratory fume hoods and biosafety cabinets, as the influence of turbulence at the side of the hood is far greater than at the front. Basic airflow patterns are shown in Figures 6-8 through 6-24.
[Figure: Room section; a filter with a diffuser outlet at the center of the ceiling supplies air downward; the indoor airflow diverges downward, forms recirculation on both sides, and returns at the lower sides]
| Main Feature | Increases the effective range of the clean airflow supplied from the ceiling-mounted filter. More prone to dust accumulation than plain ceiling supply; after long shutdown, the diffuser outlet must be wiped clean before restarting |
|---|
Fig. 6-8 Ceiling supply via filter with diffuser outlet
[Figure: Section of a tall room; two filters with diffuser outlets (spacing d₀) at the top supply air downward, with the lower height h and total height hw marked; the airflow descends to the bottom and returns at the lower sides]
| Main Feature | Suitable for rooms with high ceilings; suitable for cleanrooms with air-conditioning requirements |
|---|
Fig. 6-9 Ceiling supply via filter with diffuser outlet
[Figure: Section of sidewall supply; air is supplied into the room from an outlet on the right side, the airflow recirculates in the room, and returns at the lower right]
Section
| Main Feature | Even simpler than ceiling filter supply; especially suitable for rooms without ceiling space; the corridor can be used, with ducts installed in the corridor ceiling; suitable for cleanrooms with general air-conditioning requirements |
|---|
Fig. 6-10 Sidewall outlet supply
[Figure: Section of angled outlet supply; in the left figure, angled supply outlets are arranged on both sides of the room top, sending air downward; in the right figure, an angled supply outlet is arranged on one side of the room top, sending air obliquely toward the lower part of the room]
Section
| Main Feature | Used where the room is not long enough for sidewall supply or where backflow is not permitted (e.g., operating rooms) |
|---|
Fig. 6-11 Angled outlet supply
[Figure: Horizontal unidirectional flow with straight return; (a) section — air enters from the left, the right side is a return air filter wall, and the airflow moves horizontally and unidirectionally; (b) axonometric — recirculated and conditioned air is connected at the top, with a HEPA filter wall and fan at the end, plus a mesh or perforated plate and an air shower door]
(a) Section (b) Axonometric
| Main Feature | A typical horizontal unidirectional flow; cleanliness varies along the airflow direction; streamlines may slope slightly downward; because few particles settle on surfaces, it is especially suitable for operating rooms |
|---|
Fig. 6-12 Horizontal unidirectional flow with straight return
[Figure: Fig. 6-13 (a) plan — an air-handling unit on the left sends air horizontally to the right, which U-turns back at the right end; (b) plan — a return air filter at the top, with downward and oblique return airflows visible]
| Main Feature | Can shorten the room length; the return airflow can be used for the preparation room |
|---|
Fig. 6-13 Horizontal unidirectional flow with one-side return
[Figure: Fig. 6-14 (a) plan — a return air filter on the left, marked "top-to-bottom return air outlet", with airflow roughly from left to right and turning back; (b) plan — a filtered supply air wall on the left, with two horizontal airflows to the right that U-turn back at the right end, forming two-side return]
| Main Feature | Same as horizontal unidirectional flow with one-side return, but with more uniform airflow |
|---|
Fig. 6-14 Horizontal unidirectional flow with two-side return
[Figure: Section — full-ceiling filter supply, airflow vertically downward through a gridded floor and return air filters]
| Main Feature | A typical vertical unidirectional flow; highest cost; can achieve the highest cleanliness |
|---|
Fig. 6-15 Vertical unidirectional flow with full gridded-floor return and full-ceiling filter supply
[Figure: Section — full-ceiling filter supply, airflow vertically downward, with peripheral push-out return]
| Main Feature | The easiest vertical unidirectional-flow cleanroom; airflow parallelism inferior to the two-side lower-return type; the pushed-out airflow helps improve the cleanliness of the surrounding environment |
|---|
Fig. 6-16 Vertical unidirectional flow with peripheral push-out return and full-ceiling filter supply
[Figure: Section of local vertical unidirectional flow without air curtain]
| Main Feature | Forms local unidirectional flow only where parallel flow is needed; greatly reduces investment |
|---|
Fig. 6-17 Local vertical unidirectional flow without air curtain
[Figure: Section of local vertical unidirectional flow with enclosing walls]
| Main Feature | Extends the effective length of the vertical unidirectional flow, equivalent to widening the supply outlet or shortening the distance from the supply outlet to the work zone |
|---|
Fig. 6-18 Local vertical unidirectional flow with enclosing walls
[Figure: Section — a fan-filter unit at the upper left; air passes through the top supply plenum and forms a vertical unidirectional flow downward; the clean booth is supported by columns with curtains hung around, and air flows out downward from the booth]
Section
| Main Feature | Flexible and inexpensive; can prevent contamination ingress, but creates obstructions |
|---|
Fig. 6-19 Column-and-curtain clean booth
[Figure: Section — filter supply units on the left and right sides of the work surface; the airflow crosses the work surface (the first work plane) in a horizontal unidirectional flow and returns at the lower edge of the surface, with lighting at the top]
Section
| Main Feature | Places the work surface directly on the first work plane of the horizontal unidirectional flow, making it more compact and economical |
|---|
Fig. 6-20 Bench-top local horizontal unidirectional flow
[Figure: Section — radial-flow cleanroom; air is supplied from the upper left and sweeps across the room in radiating/near-unidirectional streamlines, returning and exhausting toward the lower right]
Section
| Main Feature | Streamlines flow approximately in one direction; performance close to horizontal unidirectional flow, but simpler to construct and lower in cost; often used in pharmaceutical plants in the United States |
|---|
Fig. 6-21 Radial-flow cleanroom
[Figure: Section — tunnel-type cleanroom; Class 100, Class 1000, and Class 10000 zones are delineated within a lower-cleanliness background, with exhaust, drainage, and gas/water/electricity piping facilities marked]
Section
| Main Feature | Can achieve the highest cleanliness; offers maximum flexibility to adapt to process changes; cheaper than full parallel-flow cleanrooms; especially suitable for large-scale integrated circuit production |
|---|
Fig. 6-22 Tunnel-type cleanroom
[Figure: (a) Wall type — air enters from the left, constrained into a horizontal unidirectional flow by sliding enclosure walls, with a medium-efficiency filter exhaust at the right end; (b) Clean-unit type — a clean unit with enclosure walls on the left, horizontal unidirectional flow from left to right in the middle, and recirculating airflow above and below]
| Main Feature | Extends the effective length of the horizontal unidirectional flow, equivalent to widening the supply face |
|---|
Fig. 6-23 Local horizontal unidirectional flow with enclosing walls, clean-unit type or wall type
[Figure: Schematic of a clean tunnel (clean duct)]
| Main Feature | Suitable where cleanliness requirements are extremely high and the clean zone is very small, allowing automated continuous production; achieves the highest cleanliness at the lowest cost |
|---|
Fig. 6-24 Clean tunnel
VI. Technical Parameters of Cleanrooms
-
Temperature and relative humidity: the temperature and humidity of the cleanroom (zone) shall suit its production and process requirements (in the absence of special requirements, a temperature of 18–26°C and a relative humidity of 45–65% are advisable).
-
Static pressure differential: the static pressure differential between a cleanroom and a non-cleanroom shall be greater than 10 Pa; the differential between adjacent cleanrooms of different classes shall be greater than 5 Pa; the differential between the clean zone and the outdoors shall be greater than 12 Pa.
-
Air volume and air velocity
3.1 For non-unidirectional-flow cleanroom systems, the measured air volumes and air change rates shall be greater than their respective design values, but shall not exceed them by more than 20%; the difference between the air volume at each outlet and its design value shall not exceed ±15% of the design volume.
3.2 For unidirectional-flow cleanrooms, the measured average indoor air velocity shall be greater than the design velocity, but shall not exceed it by more than 15%.
- Illuminance: the illuminance of clean zones without daylighting is 200–500 lx; auxiliary rooms, personnel and material airlocks... (truncated at bottom of page)
...material airlocks, airlock rooms, corridors, etc. should preferably be 150–300 lx. GMP requires not less than 300 lx.
-
Noise: in the as-built (unoccupied) state, the noise of non-unidirectional-flow cleanrooms shall not exceed 60 dB(A); the noise of unidirectional-flow and mixed-flow cleanrooms shall not exceed 65 dB(A).
-
Recovery time (self-cleaning time): a recovery time within 10 min is preferable for unidirectional-flow cleanrooms, while for non-unidirectional-flow cleanrooms the recovery time shall not exceed 30 min.
VII. Pressure Differential Control
For safety measures against biological hazards, the most important thing is to establish and constantly maintain a certain negative pressure according to the hazard level.
There are six main causes of external disturbance to negative-pressure control, listed in Table 6-2.
Table 6-2 Causes of External Disturbance to Negative Pressure
| No. | Disturbance Item | Remarks (speed and magnitude of disturbance) |
|---|---|---|
| 1 | Changes in outdoor pressure (mainly wind pressure) | Slow disturbance speed, small changes, relatively easy to control |
| 2 | Increase/decrease of duct system resistance (clogging of HEPA filters after a period of operation) | |
| 3 | Biosafety cabinet shutdown | |
| 4 | Door opening and closing | With airlock |
| Without airlock | ||
| 5 | Start and stop of supply/exhaust fans | |
| 6 | Valve closure due to sterilization operations | Fast disturbance speed, large changes, difficult even with automatic control |
Table 6-3 Control of Negative-Pressure Systems
| No. | System | Characteristics |
|---|---|---|
| 1 | [Figure: Supply air VD (volume damper) → HEPA filter → room → HEPA filter → VD exhaust system schematic] | Negative-pressure operation can be achieved by adjusting only the VD; however, it is susceptible to all disturbances in Table 6-2, and the room pressure fluctuates easily. VD: volume damper |
| 2 | [Figure: Supply air CAV (constant air volume valve) → HEPA filter → room → HEPA filter → VD exhaust system schematic] | Compared with No. 1, disturbances 1, 3, and 4 in Table 6-2 have less influence on it; it is affected by disturbances 2, 5, and 6. CAV: constant air volume valve |
Continued Table 6-3
| No. | System | Characteristics |
|---|---|---|
| 3 | [Figure: Room ventilation system schematic with supply air via CAV and HEPA filter, exhaust via HEPA filter and CAV] | Compared with No. 2, disturbances 1–4 in Table 6-2 have less influence on it; however, variation occurs due to mutual interference and lag between the two CAVs, and maintenance is required |
| 4 | [Figure: Room ventilation system schematic with VAV supply via HEPA filter, exhaust via HEPA filter and VD, with ΔP detection] | Disturbances 1–4 in Table 6-2 have less influence on it; however, air volume decreases as filter performance changes over extended operation. VAV: variable air volume valve |
| 5 | [Figure: Room ventilation system schematic with VAV supply via HEPA filter, CAV exhaust via HEPA filter, with ΔP detection] | Disturbances 1–5 in Table 6-2 have less influence on it; can adapt to changes in filter performance |
| 6 | [Figure: Energy-saving negative-pressure and air-volume control system schematic with inverter on supply air, exhaust via HEPA filter, and ΔP detection in the room] | An energy-saving example taking into account both negative-pressure control and air-volume control; this system has various applications; reliability must be thoroughly checked |
| 7 | [Figure: Air-volume and negative-pressure control system schematic with inverters and HEPA filters on both supply and exhaust, ΔP detection in the room, and a microprocessor controlling the valves and supply fan speed] | To meet the requirement of controlling and regulating all disturbances in Table 6-2, a microprocessor controls each valve and the supply fan speed — the optimal control of air volume and negative pressure |
To prevent pressure differential reversal, the supply fan may only be started after the exhaust of the biosafety cleanroom has been turned on, and the exhaust fan may only be turned off after the supply fan has stopped; likewise, only after the exhaust fan of the biosafety cabinet has been started may the room's exhaust and supply fans be started.
VIII. Special Provisions for Cleanroom Air-Conditioning Design
- Independent supply and exhaust air systems shall be adopted to prevent aerosol cross-infection.
- Areas that generate harmful gases (reagent preparation, specimen handling, experimental apparatus, etc.) shall use negative-pressure clean benches.
- Operations that generate aerosols harmful to humans shall be performed in Class II (or higher) biosafety cabinets.
- The heat output of dedicated medical examination equipment shall be considered.