# Analysis of Sequential Pretreatments to Enhance the Early-Stage Biorefinery Designs
## 1 Introduction  
As the world shifts from relying on fossil fuels to natural resources and with a growing population, it becomes necessary to suggest strategies that encourage the effective utilization and conversion of biomass to fulfill global demands. Biorefineries are alternatives that could be applied for the economic and social development of regions where biodiversity coexists as a source of feedstocks with the demand for bioproducts constituted by energy, food, and chemicals. Some authors suggest that biorefineries promote biodiversity through a sociotechnical transition toward bioeconomy, improving energy security, and industrial development [1]. Indeed, the valorization of exotic and wild fruit residues from tropicalforests for small communities has been studied through small-scale biorefineries [2] or the implementation of biorefinery schemes involving multi-feedstock analysis using plantain and avocado residues [3]. Thus, second-generation biorefineries could be an industrial-scale processing strategy since they use raw material residues, most of which are poorly managed. Recent biorefinery assessments involve a sustainability analysis through economic, environmental, and social pillars [4]. Therefore, designs are critical for the overall biorefinery performance, as the pretreatment stage can contribute at least 20% of the total investment costs [5]. Although reaction has been identified as the first stage of biorefinery design through the onion diagram [6], pretreatments are key for upstream and downstream processes. Pretreatment will allow easy future access to primary platforms during the reaction stages, subsequently affecting conversion, selectivity, and reaction rates. Lignocellulosic residues are considered the future of sustainable energy sources and for the manufacture of biomaterials, as they are economical and the most abundant worldwide [7; 8]. Moreover, lignocellulosic material is a renewable resource from agricultural waste, forestry residues, and dedicated energy crops, being an environmentally friendly alternative to non-biodegradable materials, such as plastics. Lignocellulosic biomass can be converted into biofuels or other chemicals, but highlight again the reduction of climate change impact. Lignocellulose consist of cellulose, hemicellulose, and lignin through a three-dimensional configuration that is difficult to access and exerts recalcitrance for decomposition. Therefore, treatments are important prior to transformation. Pretreatments hydrolyze complex organic molecule bonds into simpler molecules, which are more easily further transformed in bioconversions. The efficacy of pretreatments has been discussed and described when they meet a series of sustainable indicators related to operational, economic, environmental, and social considerations [9]. Pretreatments should also involve structural analyses toward the cellulose cleanliness, as it is the main source of biofuels, described as specific surface area, crystallinity, degree of polymerization, hemicellulose, and lignin coating, and the influence of acetyl groups [10]. Consequently, the physical and chemical changes of the biomass following pretreatment will affect subsequent processes, and their variation will increase through process scale-up. The constant increase of publications related to biomass pretreatment suggests a need to be realized for full scale-up in biorefineries. Schemes should be proposed depending on the industrial application of the platform product or the commercial bioproduct. Most pretreatment studies focus on single-step schemes, especially the valorization of a lignocellulosic fraction, as it minimizes technological complexity and total costs compared to full-scale valorization. However, biorefineries should be proposed based on maximum feedstock utilization to enhance economic viability while minimizing environmental impact by reducing waste streams [11].