• Lab-Scale Optimisations
    The Crucial First Step in
    Bioprocess Development


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.

Importance of Lab-Scale Optimisations

Bioprocesses, especially those incorporating the valorisation of lignocellulosic feedstocks, present a complex interplay of many variables. Factors such as feedstock characteristics, the efficiency of pretreatment, enzymatic or microbial conversion, and various downstream processing steps (e.g. product recovery, purification etc.) are some of the many elements that can substantially impact the overall process performance. It is for this reason that developing and optimizing these processes at lower technology readiness levels (TRLs) (i.e., the lab-scale) is a critical first step. At this scale, process variables can be manipulated and monitored with more flexibility and precision, enabling a detailed understanding of the process.

Starting at the lab-scale also allows for the screening of numerous operating conditions and the rapid identification of optimal ones. The smaller volumes at this scale also minimize the amount of materials needed, reducing costs and waste. Furthermore, potential challenges or bottlenecks that could hinder scaling-up can be identified and addressed early in the development process.

Additionally, from the standpoint of downstream processing, which is often one of the most complex and costly stages of a bioprocess, lab-scale experimentation can help identify the most efficient methods for product separation, recovery, and purification.

On the other hand, if one were to commence process development directly at higher TRLs, the resources needed would be significantly higher, the risk of failure would be increased, and any process optimisation or troubleshooting would be more complex and costly. Without an understanding of the process at a smaller scale, inefficiencies and suboptimal conditions might not be detected until they result in significant losses at the larger scale.

Design of Experiments (DoE) - for Bioprocess Optimisations


The Design of Experiments (DoE) approach is a systematic, rigorous procedure used to understand the influence of various factors affecting a process and their interactive effects. It is a statistical tool that aims to optimise processes by not only focusing on the relationship between input parameters and output response but also considering the interdependencies between input variables. The statistical methodology underlying DoE allows for the more efficient and effective exploration of the design space and helps in developing empirical models for process understanding and optimisation.

One of the primary advantages of the DoE approach is its efficiency. Rather than conducting numerous experiments that alter one variable at a time, DoE uses a more holistic approach that varies multiple factors simultaneously. This enables researchers to understand how factors interact with each other to influence the process, yielding more comprehensive insights into the process. Moreover, it reduces the number of experiments needed, saving time, effort, and resources.

Another advantage of the DoE approach is its ability to identify optimal process conditions. By systematically varying the factors and examining the process output, DoE can identify the conditions that yield the best result. For a bioprocess this could mean maximizing product yield, purity, or overall process efficiency.


The implementation of DoE in bioprocess optimisation at the lab-scale involves a sequence of steps. First, the process parameters (factors) and their potential ranges are identified. Then, an experimental design is chosen. This can be a full-factorial design, where all possible combinations of factors are tested, or a fractional factorial design, where only a subset of the possible combinations is tested. After performing the experiments, the data is analysed, often using regression analysis, to develop an empirical model of the process.

In some cases several sequential DoE can be undertaken in order to fully optimise a bioprocesses. For example, there may initially be an uncertainty with regards to which type of pretreatment technology would be most suitable for valorising a particular feedstock. Simply testing each of the candidate pretreatment processes once, using only one set of conditions, may not give the correct answer with regards to which pretreatment is the most suitable since the selected conditions may not be appropriate for that feedstock. Hence, an initial DoE could involve testing a number of different pretreatments with each type of pretreatment being tested over a number of different conditions.

The outputs of these experiments would provide crucial data with regards to the dynamics and efficiency of biomass processing for each pretreatment over a range of conditions. Such data may then be sufficient to allow for a final decision to be made with regards to the selected pretreatment technology. There could then follow a second DoE where, informed by the results from the prior experiments, a more detailed investigation and optimisation of the chosen pretreatment can be undertaken. A further DoE may be possible in some cases and would involve fine-tuning the optimal conditions, based on the relationships elucidated in the prior experiments.

Validation of Optimised Conditions at Higher TRLs

Starting bioprocess development at lower technology readiness level (e.g. TRL 3-4) is the most cost-effective and efficient approach for developing and optimising a new bioprocess or for improving an existing one. However, the ultimate target of bioprocess development is a process that performs well, and hence is commercially-viable, at much higher TRLs. Hence, it is important that the outputs of the lower-TRL optimisation work are then validated at the larger scale.

Factors such as mass and heat transfer, mixing, and the behavior of materials often change with scale, and these changes can influence the process performance. alidation at higher TRLs ensures that these factors are taken into account, thereby ensuring the robustness and reliability of the process.

In bioprocess development the general approach is that, after optimising the process at the lab-scale (i.e TRL 3/ 4), the process is then validated at pilot-scale TRLs (e.g. TRL5 or TRL6).

Celignis is able to develop, validate, and optimise bioprocesses at these technology readiness levels. Click below to read more about our facilities and services for pilot-scale bioprocesses.

Get more info...Pilot-Scale

Lab-Scale Optimisation of Bioprocesses - How Celignis Works With Our Clients

1. Understanding Your Requirements

Prior to undertaking bioprocess projects we learn from our clients what their targets are from the process as well as whether there are any restrictions or requirements that may need to form the boundaries of the work that we undertake. These help to guide us to then prepare a potential bioprocess development project.

2. Detailed Feedstock Analysis

In cases where you have already selected a feedstock for the bioprocess, we would then undertake a detailed compositional analysis (P10 or, ideally, P19) of representative samples of that feedstock.

In cases where the feedstock has not yet been selected we can review your list of candidate feedstocks, selecting top candidates based on our prior experience in their analysis and bioprocessing. If you do not have a list of candidate feedstocks then we can provide one, based on your location and the requirements outlined in Stage 1. We would then analyse in detail these priority feedstocks and come to a decision, based on the compositional data and other relevant factors (e.g. price, supply, consistency etc.) on a selected feedstock for the project.

3. Formulation of DoE

At this point of the project, the Celignis Bioprocess team typically meet to discuss and prepare a project proposal for the development 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).

It is possible that the work may involve several different experimental datasets, either focused on different stages of the bioprocess (e.g. pretreatment, primary-conversion, product recovery etc.) or 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 particular 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.

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 developed 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.

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

Our preferred approach is to include TEA studies at each stage of the development of the bioprocess, so that the process can be optimised in a commercially-relevant way, followed by a more detailed TEA after the process has been optimised and tested at higher TRL levels.

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

Contact Celignis Bioprocess

With regards to the lab-scale optimisation 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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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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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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