Infectious disease diagnosis strips developed at new facility

South African mineral research organisation Mintek launched a R13-million manufacturing facility last month to produce lateral-flow diagnostics test strips for infectious diseases, such as malaria, the human immunodeficiency virus (HIV) and tuberculosis (TB).

The facility, located at Mintek’s Nanotechnology Innovation Centre, in Johannesburg, was designed by consulting engineering firm Royal HaskoningDHV. It comprises ISO class 3 and ISO class 5 cleanrooms, as well as a biosafety level (BSL) 3 laboratory, with each area performing an important function in the development of the diagnostic strips.

The ISO class 5 cleanroom is used to manufacture the test strips, during which gold nanoparticle technology is used. The gold nanoparticles react with colourless antibodies or antigens on the surface of the strip, producing either two red lines for a positive result or one line for a negative result.

Mintek ISO class 5 cleanroom scientist Hendriëtte van der Walt tells Engineering News that gold particles are the best material for conducting nanodiagnostic tests and generally provide the best test results.

The ISO class 3 cleanroom is used to construct electronic, nano- and micro-electromechanical systems (NEMS and MEMS), as well as micro- and nanoscale microfluidic devices. “The ability to fabricate nanostuctured devices under the correct conditions significantly increases Mintek’s capacity to discover and study new properties exhibited at nanoscale, including quantum phenomena,” says Mintek water technology research principal scientist Richard Moatloali.

Meanwhile, Royal HaskoningDHV associate and mechanical engineer Walter van der Linde explains that the cleanliness of cleanrooms is rated according to the number of particles in a cubic meter of air, with ISO class 9 having the highest presence of particulates and ISO class 1 the lowest.

An ISO class 3 cleanroom was required for the nanoparticle technology of this specific manufacturing process, as the diagnostic strips could provide false positive or negative test results if contaminated by particles such as moisture and dust.

“ISO class 3 cleanrooms are typically used for material research, from which scientists are trying either to get very specific properties – which could be compromised if contaminated – or fabricate materials used in the construction of sensitive devices such as electronics.

“These cleanrooms are used to ensure that the contaminants do not interfere with the material research being conducted or the equipment being manufactured,” explains Mintek nanominerals and nanotechnology director and ISO class 3 cleanroom principal scientist Lucky Sikhwivhizu.

Royal HaskoningDHV advisory group director and mechanical engineer Cobus van Deventer points out that to limit the amount of particulates in the air, the ISO class 3 cleanroom uses an environmental control system (ECS), which employs ultralow particulate air (ULPA) filtration to capture any particulates to maintain the appropriate particulate count, the correct room temperature, relative humidity and pressure.

Meanwhile, the BSL 3 facility, which is situated in the ISO class 5 cleanroom, is used to validate the performance of the completed diagnostics strips using samples of malaria, HIV and TB.

The ISO class 5 cleanroom employs high-efficiency particulate arrestance (HEPA) filtered ECS systems to ensure no particulates contaminate the test samples.

Van Deventer explains that the ECS systems are used not only to ensure that the particulate count is maintained through adequate filtration in the two ISO rooms but also to provide sufficient air pressure differentials between the spaces or rooms to avoid contamination of the clean areas.

“The rationale is that scientists working in the facility will move from a less clean zone to a cleaner zone. The pressure created by the ECS will ensure the less clean air is flushed out of the clean zone,” explains Van der Linde. The BSL 3 laboratory, on the other hand, is designed to confine the air to the room, to avoid the escape of any airborne pathogens in the BSL 3 laboratory.

He points out that to reach the cleanliness levels of ISO class 3 cleanrooms, unidirectional airflow is required to limit air turbulence, which could cause uncontrolled dust movement and contaminate the rooms.

To achieve this, Royal HaskoningDHV designed special unidirectional airflow system (UDAF). The UDAF plenums are ceiling-mounted above the working surface and recirculate the air in the room using HEPA and ULPA filters in the ISO class 5 and ISO class 3 cleanrooms respectively.

The unidirectional airflow systems supply air downwards in parallel streams and force contaminated air out of the working area where the highest risk of contaminants exists. A portion of the room air is then returned to the air-handling unit through grills installed into the raised floor of the facility.