• Downstream-Processing
    In Bioprocesses
    A Key Part of The Process


Downstream Processing

Bioprocesses often involve a series of steps focused on the conversion of biomass to the targeted biobased products. For example, a bioprocess focused on the simultaneous saccharification and fermentation ( SSF) of a lignocellulosic feedstock (e.g. corn stover) to bioethanol may involve milling and pretreatment steps prior to the main SSF process. While the target of the process is bioethanol, the output of the SSF stage would be a slurry containing the fermentation broth and the solid enzymatic hydrolysis residue.

Downstream-processing in bioprocesses concerns the ways in which such output streams (e.g. solid, liquid, slurry etc.) are handled and the means for the recovery and purification of the targeted products. As such, downstream processing is crucial for bioprocess development. However, it is often overlooked, especially in early stages of research and development, where much of the focus tends to be on optimising the bioconversion process itself. This is a critical oversight given that downstream processing can account for a large portion (sometimes up to 80%) of the total production costs, particularly in processes dealing with dilute concentrations of the target product or complex mixtures.

Importance in Bioprocesses

Using again the example of lignocellulosic bioethanol, the downstream process here involves separating ethanol from the fermentation broth, which also contains unfermented sugars, residual enzymes, and other byproducts. This is typically done through distillation, a process that requires a significant amount of energy, especially considering that the ethanol concentration in the broth is usually low. Further purification steps may be necessary to meet the specifications for fuel-grade ethanol, adding more to the costs. In this case, optimising the downstream process to increase the yield and purity of ethanol and to reduce energy consumption can significantly improve the economic viability of the process.

Similarly, in the production of lactic acid from lignocellulosic sugars, the downstream process again involves the separation of lactic acid from the fermentation broth, followed by its concentration and purification. Conventional methods like precipitation, evaporation, and ion exchange can be costly and have a high environmental impact. Newer methods like membrane-based separations offer potential advantages but also require optimisation to handle the challenges posed by these complex feedstocks, such as membrane fouling and degradation of the product.

Hence, giving due importance to downstream processing in bioprocess development can not only lead to better product recovery and quality but also to significant cost savings and improved sustainability. This is especially important in processes concerning the valorisation of lignocellulosic feedstocks, where the complexity of the feedstock and the need for high-purity end products can make the downstream process a significant factor in the overall economic viability of the process.

Targets of Downstream Processing

Solid/Liquid Separation

In bioprocesses involving lignocellulosic feedstocks, solid/liquid separation is a critical downstream processing step. The choice of separation method depends on several factors, including the nature of the solids and the liquid, the required separation efficiency, and the cost and energy requirements of the method. Some of the techniques used for solid-liquid separation are described below. Sometimes a combination of methods is used to achieve the desired separation.
  • Filtration - This can be done using filter presses, filter-dryers, rotary vacuum filters, or membrane filters, among other equipment. The choice of filter depends on the characteristics of the solids and liquid, as well as the desired separation efficiency.
  • Centrifugation - Centrifuges can effectively separate solids from liquids based on their differences in density.
  • Sedimentation - In some cases, solids can be left to settle at the bottom of a vessel due to gravity, then removed from the liquid. This is often used in combination with other separation methods.
  • Flotation - This involves the introduction of air bubbles into the liquid, which attach to the solid particles and cause them to float to the surface, where they can be removed.

Product Recovery

Product recovery in bioprocesses is a critical step that often dictates the economic viability of the entire process. Some of the downstream-processing approaches used are detailed below:
  • Distillation - A widely-used technology for product recovery in bioprocesses, particularly for volatile products. For example, distillation is used to separate bioethanol from the fermentation broth due to its lower boiling point. For fuel-grade ethanol, azeotropic distillation may be needed.
  • Gas Stripping and Liquid-Liquid Extraction - These techniques are often used to recover products that are toxic to the producing organisms or have higher boiling points. For example, in biobutanol production from lignocellulosic feedstocks, butanol recovery from the fermentation broth is challenging due to its toxicity to the microorganisms and its higher boiling point. Gas stripping and liquid-liquid extraction are among the techniques that have been explored for butanol recovery.
  • Membrane-Based Separations - These techniques, which include ultrafiltration, electrodialysis, pervaporation, and Tangential Flow Filtration (TFF), are used when traditional methods are not efficient or generate large amounts of waste. One example of a product that can be recovered using this approach is lactic acid, derived from the fermentation of biomass-derived sugars. For this product membrane-based processes, such as ultrafiltration and electrodialysis, have been explored as alternatives to traditional methods like precipitation and ion exchange.
  • Centrifugation and Chromatography - These techniques are commonly used for the recovery and purification of non-volatile products like enzymes. Using lignocellulosic feedstocks as a carbon source, enzymes such as cellulases and xylanases can be produced. The recovery process uses a combination of centrifugation to remove the microbial cells, ultrafiltration to concentrate the enzymes, and chromatography for further purification if needed.

Solvent Recovery

In certain bioprocesses solvents can be used in several steps, such as in: the pretreatment of the biomass, the extraction of certain compounds, or as a part of the product recovery process. The recovery and reuse of these solvents is crucial for both economic and environmental reasons. Some of the downstream-processing approaches used for solvent recovery are detailed below:
  • Distillation - This involves the separation of substances based on their different boiling points. For instance, in the organosolv process, organic solvents such as ethanol or acetone are used to pretreat lignocellulosic biomass. Post-pretreatment, these solvents are typically recovered via distillation and then reused. Distillation is also used to recover ionic liquids in ionic liquid pretreatment, and in the separation of butanol and solvents in biobutanol production.
  • Evaporation - This technique is used when the solvents are more volatile compared to the other components in the mixture. By supplying heat, the solvents evaporate, leaving the other components behind. The solvent vapours are then condensed and collected. An example of its application can be seen in certain processes that use organic solvents to extract lignin from lignocellulosic biomass.
  • Liquid-Liquid Extraction - This method is used when the solvent forms two immiscible phases with water or other solvents. After creating two phases, they can be easily separated, which allows for the recovery of the solvent. A prominent example of this technique can be seen in biobutanol production. In the recovery phase, liquid-liquid extraction is often used, involving a solvent that can extract butanol from the fermentation broth. This solvent-butanol mixture is then subjected to distillation for the separation and recovery of both butanol and the solvent.

Product Purification

Product purification is the final stage of downstream processing in bioprocesses and is crucial to obtaining a product of the desired quality and specifications. The specific techniques used for product purification can vary depending on the nature of the product and the impurities present. Here are some examples of product purification in the context of bioprocesses focused on lignocellulosic feedstocks:
  • Membrane Filtration - Membrane filtration technologies, such as microfiltration, ultrafiltration, nanofiltration, and Tangential Flow Filtration (TFF), can be used to separate the desired product based on size or molecular weight. For example, in the production of biofuels or biochemicals from lignocellulosic feedstocks, ultrafiltration can be used to concentrate the product and remove small impurities.
  • Chromatography - Chromatography is a powerful technique for the separation and purification of products based on their different affinities for a stationary phase. For example, in the production of high-value chemicals or proteins from lignocellulosic feedstocks, chromatography can be used to purify the product to a high degree. Different types of chromatography, such as ion-exchange, affinity, or size-exclusion chromatography, can be used depending on the nature of the product and the impurities.
  • Crystallization - Crystallization is often used for the purification of solid products. The product is first dissolved in a suitable solvent, and then conditions are set to allow the product to crystallize out, leaving impurities in the solvent. For example, in the production of organic acids from lignocellulosic feedstocks, crystallization can be used to purify the acid.
  • Distillation - Distillation, as mentioned earlier, is not only used for product recovery but also for product purification. For example, bioethanol produced from lignocellulosic feedstocks often needs to be distilled multiple times to achieve the required purity for use as a fuel.
  • Extraction - Liquid-liquid extraction can also be used for product purification, where the product is selectively dissolved in a solvent, separating it from impurities.

Challenges in Downstream Processing

  • Complexity - The product stream in a bioprocess often contains a complex mixture of the product, other metabolites, proteins, cells, and medium components. The product may also be present in very low concentrations. This complexity and the need for high purity often requires multiple downstream steps, each of which needs to be optimised and coordinated.
  • Product Stability - Many bioproducts, such as proteins or enzymes, are sensitive to changes in temperature, pH, or shear stress, which can lead to product degradation during downstream processing. Maintaining the stability of the product throughout the downstream process can be challenging and may require the use of gentle separation techniques, stabilizing agents, or specific temperature and pH conditions.
  • Scale-Up - While a downstream process might work well at a laboratory scale, scaling up to an industrial scale can pose several challenges. For example, the efficiency of a separation technique may decrease at a larger scale, or it may be more difficult to maintain consistent temperature or pH conditions. The cost of downstream processing can also increase significantly with scale.
  • Cost - Downstream processing can account for a significant proportion of the total cost of a bioprocess, particularly for high-purity products. The use of expensive consumables, such as chromatography resins or membranes, and the energy cost of operations like distillation or centrifugation, can contribute to high downstream costs. Reducing these costs while maintaining product quality is a key challenge.
  • Environmental Impact - Many downstream processes use solvents or generate waste streams that can have a significant environmental impact. Reducing this impact, through the use of green solvents, waste minimisation, or waste valorization strategies, is another important challenge.
  • Regulatory Compliance - For bioproducts used in food, pharmaceutical, or medical applications, the downstream process needs to comply with strict regulatory standards. These may relate to the purity of the product, the removal of specific contaminants, or the validation of the downstream process. Meeting these standards can be technically challenging and add to the cost of the process.

Downstream Processing Facilities and Services at Celignis

At Celignis we understand that downstream processing is a key component in the devleopment of a bioprocess. Our bioprocess development projects usually incorporate tasks related to downstream-processing activities and we often formulate and optimise upstream processes (e.g. pretreatment, hydrolysis etc.) considering the effects on the subsequent downstream steps.

As well as being part of a wider bioprocess project, we can also work with clients on specific bioprocess development projects focused on downstream processing steps. For example, we can receive a slurry sample from a client and design a project around optimising its downstream processing considering a variety of different metrics (e.g. final product yield, purity, chemical consumption, energy cost etc.).

We have a wide-array of equipment and infrastructure that allow us to handle downstream processing activities up to TRL6. Some of the relevant equipment we have are detailed below.

Tangential Flow Filtration (TFF)

Tangential Flow Filtration (TFF), also known as crossflow filtration, is a widely used technique in bioprocess development for the separation and concentration of biomolecules. Unlike traditional filtration, where the feed solution flows perpendicularly towards the filter, in TFF, the feed solution flows tangentially along the surface of the membrane. This tangential flow prevents the rapid buildup of a concentrated layer ("cake layer") of the retained species on the surface of the membrane, which can lead to membrane fouling and reduced filtration performance.

At Celignis we have several items of TFF equipment, suitable for different TRL levels, from lab-scale to TRL6. Our higher-TRL equipment are made by Millipore and can process 10's of litres of liquid per hour.

Click below for more on TFF and its use in bioprocess development.

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Filter Press

A filter press is a piece of equipment used in various industries, including bioprocessing, to separate solids and liquids. It consists of multiple filter plates arranged in a frame, which create a series of chambers. The feed slurry (a mixture of liquid and solids) is pumped into these chambers, and the liquid phase passes through the filter cloth, leaving the solid materials behind.

At Celignis we have several items of filter press equipment, suitable for different TRL levels up to TRL6. Our higher-TRL equipment can process 10's of litres of liquid per hour.

Click below for more info on filter presses and their use in bioprocess development.

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Filter Dryer

A filter dryer is a piece of equipment used in the pharmaceutical and chemical industries, including in some bioprocessing applications, for solid-liquid separation and subsequent drying of the solid. This device combines filtration and drying in a single unit, which can be beneficial in terms of process integration and reduction of product handling.

At Celignis we have a Sweco PharmASep PH30 Filter Dryer, suitable for pilot-scale operations.

Click below for more info on filter dryers and their use in bioprocess development.

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Supercritical CO2 Extraction System

Supercritical CO2 is CO2 (carbon dioxide) maintained at a temperature and pressure above its critical point, resulting in a state of matter that has properties of both a gas and a liquid. Its density is comparable to that of a liquid, while it diffuses into materials like a gas and has a low viscosity. These properties make supercritical CO2 an excellent solvent for many substances, making it a versatile tool in bioprocess development.

At Celignis we have a 5-litre supercritical CO2 extraction system which can be used in higher-TRL projects.

Click below for more info on supercritical CO2 and its use in bioprocess development.

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Distillation Equipment

Distillation is a widely-used separation technique in many bioprocesses. It involves heating a liquid mixture to create vapour and then cooling and condensing the vapour to create a separate liquid phase. Different components in the mixture have different boiling points, which allows them to be separated through distillation.

At Celignis we have a 20-litre vacuum distillation system which can be used in higher-TRL projects.

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Technoeconomic Analysis of Downstream Processing Options


Techno-economic analysis (TEA) is a model-based methodology that evaluates both the technical aspects (e.g., process design, performance, and yield) and economic aspects (e.g., capital investment, operating costs, and product selling price) of a process. It is a critical tool for assessing the economic feasibility and technical challenges of a bioprocess through its development stages. TEA is particularly important for downstream processing activities, for the reasons outlined below:
  • Informed Process Design Decisions - Downstream processing often presents a significant challenge due to the complexity of the mixture obtained after conversion processes. This mixture includes the desired products and a variety of byproducts, unreacted feedstock, and impurities. TEA allows for comparisons to be made between different options for downstream processing, including product recovery, separation, and purification. By identifying the most cost-effective and technically feasible methods, TEA can inform critical design decisions that can influence the efficiency and economics of the overall process.
  • Evaluation of Innovative Technologies - Technological innovation often plays a vital role in improving the efficiency and reducing the costs of downstream processing. However, these new technologies also come with risks, particularly related to scalability, performance stability, and regulatory acceptance. TEA can provide an objective assessment of these novel technologies by quantifying their potential economic benefits and associated risks, aiding in the decision-making process.
  • Assessing Commercial Feasibility - Downstream processing can significantly impact the overall economics of a lignocellulosic bioprocess. It directly influences the cost of producing the final product, which in turn determines the product selling price. TEA allows the estimation of the product's market price based on the overall processing costs. The comparison of this price with existing market prices can provide insights into the commercial feasibility of the bioprocess.
  • Guiding Future Research Directions - TEA provides a systematic way to identify the most expensive or technically challenging stages in downstream processing. By pointing out the areas that significantly impact the process economics or efficiency, it can guide the direction of future research and development efforts. This can lead to the generation of solutions that improve the overall process, enhance the product yield and quality, and reduce the associated costs.
Click below to read more about our bioprocess TEA activities and expertise.

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Approach at Celignis

We can incorporate technoeconomic analysis (TEA) at various stages in a project targeting the development or improvement of downstream processes. Such an inclusion can provide valuable insights and inform decisions throughout the development process. Below are detailed the stages of how we can structure such a downstream bioprocess project with the integration of TEA:

  1. Initial TEA: At the beginning of the project, an initial TEA is conducted to evaluate the existing downstream processing options. This analysis includes an assessment of the technical challenges, performance, cost, and potential environmental impacts associated with each option. This stage provides an overview of the different strategies available and their relative merits and shortcomings, thereby setting the stage for informed decision-making.
  2. Experimental Selection: Based on the outcomes of the initial TEA, a subset of promising downstream processing options is selected for further investigation. These options are then subjected to experimental testing in the laboratory to evaluate their performance under controlled conditions. This stage provides empirical data on each option’s efficacy and potential for optimisation.
  3. Secondary TEA: - Following the experimental testing, a second TEA is conducted based on the results obtained. This analysis provides a refined understanding of the costs and performance of each option when applied in a real-world context. The findings from this secondary TEA inform the selection of the most appropriate downstream processing option for further development.
  4. Process Optimisation: Once the most promising downstream processing option has been selected, further experimental work is carried out to optimise this process. These experiments aim to maximize efficiency, minimize costs, and ensure a high-quality end product. The optimisation phase is informed by the data and insights gathered from the previous experimental and TEA stages.
  5. Validation at Higher TRLs: After optimising the selected process, it is then tested at higher Technology Readiness Levels (TRLs). These tests aim to validate the process under conditions that more closely resemble those of full-scale industrial operations. This stage can identify potential scale-up issues and provide data on how the process performs under realistic operating conditions.
  6. Final TEA: In the final stage of the project, a detailed TEA is conducted based on the results obtained from the higher TRL testing. This final analysis evaluates the commercial-scale viability of the developed downstream process, taking into account all associated costs, potential revenues, and environmental impacts. This final TEA can help stakeholders make informed decisions about whether to invest in further development or commercial deployment of the process.

Contact Celignis Bioprocess

With regards to the development of downstream stages of bioprocesses, the Celignis Bioprocess team members with the most experience in undertaking such projects are listed below. Feel free to contact them to discuss potential projects.

Lalitha Gottumukkala

Founder of Celignis Bioprocess, CIO of Celignis


Has a deep understanding of all biological and chemical aspects of bioproceses. Has developed Celignis into a renowned provider of bioprocess development services to a global network of clients.

Oscar Bedzo

Bioprocess Project Manager & Technoeconomic Analysis Lead


A dynamic, purpose-driven chemical engineer with expertise in bioprocess development, process design, simulation and techno-economic analysis over several years in the bioeconomy sector.

Dan Hayes

Celignis CEO And Founder

PhD (Analytical Chemistry)

Dreamer and achiever. Took Celignis from a concept in a research project to being the bioeconomy's premier provider of analytical and bioprocessing expertise.

Other Celignis Services for Bioprocess Development

Global Recognition as Bioprocess Experts

Celignis provides valued services to over 1000 clients. We understand how the focus of bioprocess projects can differ between countries and have advised a global network of clients. We also have customs-exemptions for samples sent to us allowing us to quickly get to work no matter where our clients are based.

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Biomass can be rich in bioactive compounds of high value for food, feed, cosmetic, and pharmaceutical applications. We develop bespoke extraction methods suitable for your needs with high selectivity, efficiency and low environmental impact.

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The choice of pretreatment method varies with the type of biomass and the end-product requirements. At Celignis we can determine the most suitable pretreatment for your feedstock and determine the optimum conditions in lab-scale trials followed by higher TRL scale-ups.

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For the hydrolysis of lignocellulosic biomass to monomeric sugars either chemical or biological approaches can be used. At Celignis Bioprocess we can use both methods at scales ranging from flask-level to 100-litres. We have particular expertise in the optimisation of conditions for enzymatic hydrolysis.

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Enzymes are biological catalysts that have a wide variety of applicaitons in the bioeconomy, ranging from the liberation of sugars from lignocellulosic biomass to the functionalisation of biomass-derived chemicals and materials for higher-value applications. We are experts in the design and use of enzymatic approaches.

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Development of fermentation processes requires knowledge of an array of important factors including: biomass, the microbes used, nutrient media, and fermentation conditions. We're experienced in many fermentations and can help you determine and optimise yields of an array of different fermentation products.

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Lab-Scale Optimisations

We consider that optimising a bioprocess at the lab-scale is the most cost-effective approach to explore a range of different scenarios in search of optimal process conditions. Based on the outputs of these experiments we can then test the chosen set of conditions at higher TRL levels.

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TRL Scale-Up

At our dedicated Celignis Bioprocess laboratories we have all the necessary upstream and downstream apparatus to undertake bioprocess projects up to a tehcnology readiness level (TRL) of 6, with reactor and processing capacities of up to 100 litres.

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Technoeconomic Analyses

Our technoeconomic experts can evaluate your bioprocess, considering various scale, technology, and feedstock options. We apply accurate costing models to determine CAPEX/OPEX of simulated and pilot-scale processes which are then used to determine key economic indicators (e.g. IRR, NPV).

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Biobased Chemicals

A large array of chemicals and materials are possible from biomass and wastes. These can involve chemical or biological approaches, or a combination of the two. Based on your desired end-product we can design and test the most appropriate bioprocess.

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From Process Refinements to an Entire New Process

We work closely with you to understand your objectives and timelines. We then propose a project, usually covering a series of deliverables and stage-gates. Often our projects involve optimising conditions at the lab-scale before replicating the conditions at higher TRL levels.

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Research Collaborations

Celignis is active in several bioprocess research projects. These include projects funded by the EU's CBE-JU, with Celignis being a Full Industry Member of the BIC. We're open to participating in future collaborative research projects where our extensive infrastructure and expertise in bioprocesses can be leveraged.

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