• Improving a Bioprocess
    Through Evaluation
    And Experimental Work


Bioprocesses are defined as any technology that is used to process biomass feedstocks (e.g. hemp, straws, hardwoods, sugarcane bagasse etc.), biomass-derived wastes and residues (e.g. waste papers, composts, municipal waste etc.), or compounds/chemicals obtained or derived from biomass (e.g. lignin, glucose, ethanol etc.).

The bioprocess can be a fully vertically-integrated process, involving every stage of processing and conversion, starting from the original feedstock (e.g. corn stover) and ending at the final product (e.g. bioethanol). Alternatively, the bioprocess can be considered to a specific node within a larger sequence of processing steps, for example the pretreatment applied to the corn stover prior to the subsequent hydrolysis and fermentation stages.

Bioprocess Development is a project undertaken to either develop a new bioprocess or to improve an existing one. There are many criteria for assessing a bioprocess and, hence, metrics for determining whether it is a viable new process or an improvement over the prior art. Some of the most common critera include: sustainability, cost & profitability, yield and quality of the targeted product(s), feedstock flexibility, efficiency of biomass conversion, amount of by-products and their treatment or disposal options.

Development of a Full Vertically-Integrated Bioprocess

At Celignis we can work on the development of an entirely new bioprocess for our clients, covering all of the stages and aspects of processing described below. These projects can be focused on the production of a particular product, the valorisation of a particular feedstock, or on a combination of these two approaches (i.e. the targeted production of a certain product from an already-selected feedstock).

At Celignis we have undertaken such full bioprocess development work for a number of clients. Click below to read more about our activities and projects in this area.

Get more info...Full Bioprocess Development

Bioprocess Improvement Focused on a Particular Stage

It is also possible for bioprocess development to focus on just one, or on a selected subset, of the Stages outlined below. Such work is often undertaken when an existing bioprocess already exists but certain aspects of the technology require improvement.

Alternatively, work on one process node can be exploratory, considering new options for bioprocess development and a particular node of the wider value chain.

At Celignis we have undertaken such process improvement/refinement work for a number of clients covering a wide variety of different feedstocks and processing technologies.

Improvement of a Bioprocesses - How Celignis Works With Our Clients

1. Audit of Existing Process

Our first Stage of the project involves us learning from our clients about their targets and as to whether there are any restrictions or requirements that may need to form the boundaries of the work that we undertake.

We then undertake a study of the client's existing bioprocess under the context of these targets and requirements. At this Stage it is to the benefit of the project for us to receive as much information and data as possible about the existing bioprocess, particularly with regards to the specific process nodes that the project is seeking to improve.

Depending on the amount of data provided to us, we may also undertake a preliminary technoeconomic analysis of the process at this Stage. This provides us with a useful baseline against which to compare the improvements made during the bioprocess development project.

2. Detailed Compositional Analysis

Compositional data, of the inputs and outputs of any particular node of a bioprocess, is of key importance in assessing it and in formulating approaches for its improvement. At this Stage of the project we typically request a number of different samples from the client, covering the various input and output streams of the Stages of the bioprocess that the project is seeking to improve.

We then undertake detailed compositional analyses, for any parameters considered to be relevant to the development of the bioprocess, of all these inputs, outputs, and sidestreams. The resulting data are provided to the client and used to formulate our experimental plan for process improvement (Stage 3).

3. Experimental Plan

At this point of the project, the Celignis Bioprocess team typically meet to discuss and prepare a project proposal for the improvement of the bioprocess. This will involve us defining the number and scope of lab-scale optimisation experiments, formulated according to our chosen Design of Experiments (DoE).

This work will most likely involve several different experimental datasets, focused on each of the stages of the bioprocess that the project is seeking to improve and, potentially, on iterative improvements/refinements based on prior experiments.

In the former case it is possible that these different sets of experiments could be undertaken in parallel (in order to achieve the project's objectives more quickly) while, in the latter case, the next set of experiments would need to follow the prior set, as the information learnt from earlier work would be needed to set the specific conditions for the follow-up work.

After this proposal is reviewed by the client, and revised if needed, we are then ready to start the lab-work.

4. Undertake Experiments

This stage of the project will involve us undertaking the lab-scale experimental work agreed in Stage 3.

It is possible for the work in this Stage to be phase-gated where the experimental work is broken-up into smaller subsections which, once completed, lead to the provision of reports/deliverables to the clients providing an update on the results and observations. Once a phase-gate is completed, in accordance with the requirements and expectations outlined in Stage 3, then we can proceed to work on the next phase.

In many cases these phases are based on the sequential nodes associated with the processing of the feedstock along the selected nodes of the value chain. For example, our first phase of work can be focused upon optimising the pretreatment conditions for the feedstock with the second phase focused on optimising the hydrolysis of the pretreated sample.

The division of projects in this manner allows for them to be managed and evaluated more effectively and gives ample opportunities for our clients to provide feedback.

Stage 4 of the project will be completed once the DoE, formulated in Stage 3, has been completed and the final reports issued.

5. Validation at Higher TRLs

This is an optional Stage of the bioprocess development project. It involves the validation of the optimal process conditions, determined in Stage 4 at the lab-scale, at higher technology readiness levels (TRLs). The scales at which we can operate are dependent on the type of technology employed, but can reach up to 100 litres.

We have all of the necessary downstream equipment to efficiently handle the solid and liquid streams arising from these scaled-up activities.

If we find that there are differences between the yield and compositions of the different streams, compared with our lab-scale experiments, then we can explore the potential reasons for these and work on final tweaks to optimise the bioprocess for higher TRLs.

6. Technoeconomic Analysis (TEA)

This is also an optional Stage of the bioprocess development. It involves the Celignis team, including Oscar our chief TEA expert, undertaking a detailed technoeconomic analysis of the improved process. We apply accurate and realistic costing models to determine the CAPEX and OPEX of simulated and pilot scale processes which are then used to determine key economic indicators such as IRR, NPV and payback periods. A key metric in this Stage will be the comparison between such values for the improved bioprocess versus those for the exisiting bioprocess, based on the audit in Stage 1.

Within these TEAs we can also undertake sensitivity analyses to assess the effect of variable costs and revenues on the commercial viability of the process.

Click here to read more about the technoeconomic analysis (TEA) services offered by Celignis.

Bioprocess Improvment Projects - Case Studies

Oligomers from Biomass

We have undertaken a number of projects, for different clients, focused on obtaining oligomeric sugars from biomass, or biomass-derived polymers. The bioprocess development work focused on achieving improved product characteristcs, according to the client's specifications, over the existing bioprocess. Such characteristics included the oligomer chain length and the ratio of monomeric to oligomeric sugars in the final liquid output.

Improving the bioprocess required a carefully-formulated DoE considering relevant factors (e.g. temperature, enzymes, pretreatment) in the context of the chosen feedstock and the final product requirements. In all such projects that we have undertaken to date we developed an improved bioprocess that allowed for greater proportions of the total carbohydrates in the liquid phase being in the client's targeted product range.

Pectin from Agricultural Residues

We have also worked on a number of bioprocess development projects that involve the incorporation of a pectin extraction step as a first-stage process node to be incorporated within an existing bioprocess. The extraction of pectin is complex and challenging and requires careful bioprocess development in order to ensure that the product is obtained in high yields and high purities.

Our work involved the evaluation of a number of different processes for pectin extraction, covering how variations in key process parameters influenced the yield and quality of the final pectin. This initial work led to a core extraction process being selected with additional experimental work then undertaken to optimise the process. Additional tasks in the project included pectin recovery and detailed analysis of the final product(s) in order to ascertain suitable end-use applications. The project also involved the optimised conditions being tested in larger reactors in order to evaluate the scale-up potential of the process.

Stages of a Bioprocess that Can be Improved

The route involved in progressing from a starting biomass feedstock to the targeted outputs, for example biobased-chemicals or biomaterials, typically involves a number of different processing Stages. Below these Stages are described, in general terms, with links provided to other sections of the Celignis Database where these process operations are described in more detail.

The improvement of an existing bioprocess can focus on one or more of the Stages outlined below. However, it should be noted that improvements that are made for process nodes early-on in the value-chain may, in some cases, have implications with regards to the subsequent process nodes. For this reason we often recommend that small-scale tests of certain later processing activities are undertaken using the output streams of the Stage focused-on for process improvement.

1. Feedstock Preparation

In many cases the feedstock may be in a physical state that is not suitable for direct conversion in subsequent Stages of the process. For example, the moisture content may not be suitable for the main conversion process or the feedstock may be too bulky.

Hence, the first step of the bioprocess may involve the processing of the feedstock, for example drying and/or mechanical pretreatment (e.g. millimg) for particle-size reduction, in order that it may be more efficiently processed in the subsequent stages.

2. Extraction Processes

Extractives are defined as are defined as extraneous components that may be separated from the insoluble cell wall material by their solubility in water or neutral organic solvents. In some cases there may be valuable chemicals in the extractives that warrant their removal and subsequent recovery. In other cases, the extractives can interfere-with the dyanmics of, and the quality of the product streams from, the subequent processing stages.

As a result, it is sometimes necessary for a separate stage focused on the removal of extractives, depending on the particular chemistry of the feedstock and the conversion processes selected for subsequent stages.

Click below to read more about bioprocess development for the removal and valorisation of extractives.

Get more info...Extractions

3. Pretreatment

Depending on the technology selected for the primary conversion of the biomass, a pretreatment stage may be needed to make the feedstock more amenable for subsequent stages of the bioprocess.

For example, in bioprocesses focused on the hydrolysis of lignocellulosic feedstocks, pretreatments are often used to break apart the lignocellulosic matrix (and in particular the associations between lignin and cellulose), reduce cellulose crystallinty, and (in some instances) hydrolyse hemicelluloses.

A wide variety of different pretreatment technologies can be used, including: mechanical pretreatments, steam pretreatments, hydrothermal (Liquid Hot Water) pretreatment, dilute-acid pretreatment, alkali-pretreatment, organosolv pretreatments, and ionic-liquid pretreatments, among others. Click below to read more about bioprocess development biomass pretreatment.

Get more info...Pretreatment

4. Main Conversion Stage

This Stage focuses on the primary conversion process of interest with regards to the targeted product(s) of the bioprocess.

For example, if the focus of the bioprocess is on the production of bioethanol from cellulose via chemical or biological processing, then this Stage would focus on the hydrolysis of the pretreated biomass with the target of efficient, high-yielding, production of monomeric glucose from cellulose.

In some cases this primary conversion stage may involve a number of conversion steps within the same reactor. For example, if Simultaneous Saccharification and Fermentation (SSF), or Simultaneous Saccharification and Co-Fermentation (SSCF), are the hydrolysis technologies being optimised then this Stage will also involve the concurrent fermentation of the sugars liberated during the hydrolysis.

Click below to read more about bioprocess development for biomass hydrolysis technologies.

Get more info...Hydrolysis

5. Subsequent Conversions

In some bioprocesses the output streams from the prior Stages of the process may not yet provide the final targeted products. In that case there will be subsequent processing activities focused on the the downstream conversions of the outputs from selected process nodes. There may be a number of different separate downstream conversion processes undertaken, using different outputs and side-streams of the prior Stages (e.g. extraction, pretreatment, primary conversion etc.).

For example, a bioprocess that incorporates a dilute-acid pretreatment step to remove hemicellulose followed by an enzymatic hyrolysis step for the hydrolysis of the residual solids will have a separate solid and liquid stream output from each of these stages. For the liquid side-stream of the pretreatment, downstream conversion could, for example, focus on the production of xylitol from the hyrolysed hemicellulose sugars. The solid output stream of the pretreatment would be the substrate for hydrolysis in the primary conversion step. In a scenario where a Separate Hydrolysis and Fermentation (SHF) process would be used for this hydrolysis stage then the liquid output would be the hydrolysate, containing monomeric sugars, and the solid output would consist of the unhydrolysed polysaccharides and lignin. The downstream conversion process for the hydrolysate could involve its fermentation to bioethanol using yeasts whilst the downstream conversion process for the solid residue could involve its combustion to provide process heat and energy.

6. Downstream Processing

Downstream-processing in bioprocesses concerns the ways in which the output streams (e.g. solid, liquid, slurry etc.) are handled and the means for the recovery and purification of the targeted products. The targets of a particular downstream processing step can include one or more of the following: Downstream processing can take place at several stages within a bioprocess with each downstream process selectively focused on the outputs stream(s) of a particular stage of the bioprocess. It is also possible, in some cases, for output streams from different stages of the bioprocess to be combined in a downstream processing step.

Downstream processing is a critical component of 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. Click below to read more about bioprocess development for downstream processing

Get more info...Downstream Processing

7. Waste Side/Stream Handling

An ideal bioprocess would find viable means of valorising all components of a feedstock, resulting in no waste. In practice, the elimination of waste is rarely possible but various strategies can be considered throughout the conversion processes to reduce and minimise the formation of wastes. Those wastes that do arise need to be properly characterised and there should be approaches developed for their sustainable handling, treatment, and disposal.

The effective utilisation of waste heat/energy from process nodes should also be considered, with process integration tools examined for the conservation of energy across the entire bioprocess.

Bioprocess development concerning this stage of the bioprocess can involve analytical and experimental work as well as the technoeconomic modelling of the integrated technologies. Appropriate considerations should be given to regulatory requirements with regards to the production and handling of wastes.



Contact Celignis Bioprocess

With regards to the improvement of existing 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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Downstream Processing

How the various outputs (solid and liquid) of a bioprocess are dealt with is often overlooked until later in bioprocess development, leading to excessive costs and complications. We consider and tackle these issues, and others such as product recovery, early-on as being integral to the bioprocess.

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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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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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