The second half of the 20th century can be characterized and named as the ‘plasma era’, as the plasma gathered scientific interest because of its special physical behaviour. Thus, it was considered as the fourth material state and the plasma physics began to form consequently. In addition to this, many important applications of plasma were discovered and put to use. Especially, in last few decades, there has been an increased interest in the use of cold atmospheric plasma in bio-chemical applications. Until now, thermal plasma has been commonly used in many bio-medical and other applications; however, more recent efforts have shown that plasma can also be produced at lower temperature (close to the environment temperature) by using ambient air in an open space (in atmospheric pressure). However, two aspects remain neglected: firstly, low-temperature plasma production with a large area, and secondly, acquiring the necessary knowledge and understanding the relevant interaction mechanisms of plasma species with microorganisms. These aspects are currently being investigated at the ‘Demokritos’ Plasma Laboratory in Athens, Greece with radio frequency (27.12 MHz and it integer harmonics)-driven sub-atmospheric pressure plasma (100 Pa). The first aspect was achieved with atmospheric plasma being produced at a low temperature (close to the environment temperature) and in a large closed space systems. Regarding the plasma effect on living microorganisms, preliminary experiments and findings have already been carried out and many more have been planned for the near future.