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Microalgae are considered to be a promising renewable resource to manufacture both low-value bulk commodities and high added-value fine chemicals. However, on a large scale, these products in the context of microalgae biorefinery face several obstacles, which make commercial competitiveness unfeasible. Therefore, the central objective of this chapter is to present the technological bottlenecks in establishing microalgal biorefineries. Firstly, we provide an overview of these facilities, emphasizing unit processing operations of the upstream and downstream stages. The core of the chapter is a critical discussion of the hottest spots, usually attributed to the technical-economic aspects found in a microalgae biorefinery. In the end, recent developments, some potential solutions, and a patent landscape, in an attempt to resolve such bottlenecks, are addressed.

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