The development and application of high throughput cultivation technology in bioprocess development.
This review focuses on recent progress in the technology of high throughput (HTP) cultivation and its increasing application in quality by design (QbD) -driven bioprocess development. Several practical HTP strategies aimed at shortening process development (PD) timelines from DNA to large scale processes involving commercially available HTP technology platforms, including microtiter plate (MTP) culture, micro-scale bioreactors, and in parallel fermentation systems, etc., are critically reviewed in detail. This discussion focuses upon the relative strengths and weaknesses or limitations of each of these platforms in this context. Emerging prototypes of micro-bioreactors reported recently, such as milliliter (mL) scale stirred tank bioreactors, and microfludics integrated micro-scale bioreactors, and their potential for practical application in QbD-driven HTP process development are also critically appraised. The overall aim of such technology is to rapidly gain process insights, and since the analytical technology deployed in HTP systems is critically important to the achievement of this aim, this rapidly developing area is discussed. Finally, general future trends are critically reviewed.
Jiangnan University, Jiangsu, Wuxi, 214122, PR China.
Quan
Q
Long
Jiangnan University, Jiangsu, Wuxi, 214122, PR China.
Xiuxia
X
Liu
Jiangnan University, Jiangsu, Wuxi, 214122, PR China.
Yankun
Y
Yang
Jiangnan University, Jiangsu, Wuxi, 214122, PR China.
Lu
L
Li
University of Strathclyde, Glasgow G1 1XQ, UK.
Linda
L
Harvey
University of Strathclyde, Glasgow G1 1XQ, UK. Electronic address: b.mcneil@strath.ac.uk.
Brian
B
McNeil
Jiangnan University, Jiangsu, Wuxi, 214122, PR China. Electronic address: baizhonghu@jiangnan.edu.cn.
Zhonghu
Z
Bai
D019149:Bioreactors; D018929:Cell Culture Techniques; D057166:High-Throughput Screening Assays; D046210:Microfluidic Analytical Techniques
HTP culture strategy; High throughput culture; Micro-bioreactor; Process development