What are the upstream, midstream and downstream technologies of fermentation? What is the relationship between them?

In a broad sense, fermentation engineering consists of three parts, which are upstream engineering, midstream engineering and downstream engineering. Among them, the upstream engineering includes the selection and breeding of excellent breeding strains, the determination of optimum fermentation conditions (pH, temperature, dissolved oxygen and nutrient composition), the preparation of nutrients and so on. The midstream engineering mainly refers to the engineering technology for mass cultivation of cells and production of metabolites in fermenters under optimal fermentation conditions. A strict aseptic growth environment is required here, including the technology of sterilizing the fermentation raw materials and fermenters as well as various connecting pipelines using high temperatures and pressures prior to the start of fermentation. Downstream engineering refers to the technology of separating and purifying products from the fermentation broth, including solid-liquid separation technology (centrifugal separation, filtration separation, sedimentation separation, and other processes), and cell-breaking technology.