## 1 Introduction  
Mammalian cell cultures play a crucial role in the biopharmacy industry and are an efficient way to obtain pharmaceutical protein, which is in increasing demand. bioreactors are an important piece of equipment for mammalian cell cultivation, which indicates that the development of the bioengineeringindustry is largely determined by bioreactors capability. There are several types of bioreactors with different agitating principles. Stirred-tank bioreactors (STRs) are the most traditional bioreactor design, which has been fully developed and its largest scale can be up to 20,000 L. Air lift bioreactors employ moving gas bubbles with a high speed to agitate the fluid in the bioreactor, which can produce a high shear stress resulting in mammalian cell death. Wave bioreactors can mix the fluid efficiently, but this type of bioreactor is difficult to scale up due to the cumbersome mechanical system and its largest scale is only about 500 L. Recently, orbitally shaken bioreactors (OSRs) have become increasingly popular in processing cell cultures because of its simple agitating principle, low-cost, ease of operation and suitability for single use experiments. Nowadays, the CHO cells cultivation with 2000 L in OSRs was reported and this type of bioreactor is considered as the most promising candidate to take the place of STRs. Prior to their general adoption by industry, large-scale industrial mixing tanks were used in the early stages of bioprocess development, such as microbial fermentation, biotransformation and recycling technologies. A microscale method depends on the utilization of shaken microtiter plates. On a shaken microtiter plate, full mixing is accomplished by shaking, rather than stirring. Shake flask bioreactors are cost-effective and simple to operate. They are available in 25-mL to six-liter volume sizes, different geometries and materials of construction [1], but limited to batch system, mass transfer, scale-up and real-time monitoring [2]. [PERSON] et al. [3] identified the specific growth rate to shake flask process parameters of specific power consumption, mixing time, maximum fluid velocity and Reynolds number. High-throughput shaking bioreactors are more flexible than conventional stirred-tank bioreactors, which are less automated and restricted to off-line sampling due to their small volume capacity [4]. Table 1 summarizes the relation between the experimental throughput and the level of monitoring and control required for an effective cell cultivation process. Mixing and oxygen-mass transfer are both enhanced by shaking. The rate of both processes is influenced by the geometry of the flask, the fill volume and the intensity of shaking (frequency and amplitude of shaking) [5]. Compared to conventional stirred-tank bioreactors [4], the advantages of shaking bioreactors are ease of operation, lower material requirement and capital investment, higher throughput and lower labor requirement. However, the disadvantages are lower oxygen-mass transfer efficiency, less accessible to monitoring and control, scale-up criteria not well established and lower information content per experiment. Shaken bioreactors were comprehensively utilized in the early stages of bioprocess development and microscale plates (24-, 48-, 96- or 384-orifice discs) facilitated a significant number of experiments. The shaker (25 mL-6 L) was the most widely used orbitally shaken bioreactor (OSB) type, providing a cost-effective system that is effective for a broad range of applications [8; 9; 10; 11; 12; 13; 14]. Orbital-shake bioreactors are universally utilized for small-scale screening and process adjustment. Complicated mechanical and electronic components of the shaken table drive, the power supply and the control unit are integrated into the shaken plate and are therefore independent of the reactor. This makes the reactor design simple and cost-effective, not only for many small-scale parallel experiments, but also for general one-time applications. [PERSON] et al.