• Scaling-Up
    At Celignis Biomss Lab


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.

Technology Readiness Levels (TRLs)

Technology Readiness Levels (TRLs) are a system used to estimate the maturity level of a particular technology. The scale was developed by NASA and has since been adopted by many industries. It ranges from 1 to 9, with 1 being the lowest and 9 the highest. Below is a general breakdown of the TRLs in the context of a bioprocess:

  1. TRL 1 (Basic principles observed and reported): Here the basic principles underlying the technology are understood. Research is starting to link the principles to potential applications.
  2. TRL 2 (Technology concept and/or application formulated): Researchers consider potential applications of the basic principles and theoretical studies start to investigate process feasibility.
  3. TRL 3 (Analytical and experimental critical function and/or characteristic proof-of-concept): Laboratory studies are conducted to validate the concept, and critical technical parameters are identified.
  4. TRL 4 (Component and/or breadboard validation in a laboratory environment): The technology is developed to the extent that key components can be tested in a laboratory environment. The basic technological components are integrated to establish that the pieces will work together.
  5. TRL 5 (Component and/or breadboard validation in a relevant environment): The basic technological components are tested in a relevant environment, e.g. a small-scale bioreactor.
  6. TRL 6 (System/subsystem model or prototype demonstration in a relevant environment): A model or prototype of the system or subsystem is tested in a relevant environment. For a bioprocess, this could mean a pilot-scale demonstration.
  7. TRL 7 (System prototype demonstration in an operational environment): A system prototype must be demonstrated in an operational environment. In a bioprocess context, this typically means using the technology under industry-relevant conditions.
  8. TRL 8 (Actual system completed and qualified through test and demonstration): The technology is incorporated into a complete system and tested, demonstrating that it works in its final form under the expected conditions.
  9. TRL 9 (Actual system proven through successful mission operations): The technology is in its final form and has been proven to work in real-world operations. In the context of a bioprocess, this would mean the process has been successfully implemented at full industrial scale.
The image below is the NASA TRL Meter, drawn-up by the National Aeronautics and Space Administration.

Higher TRL Bioprocesses at Celignis

If we are developing a new bioprocess, or looking to improve an existing one, we generally recommend that these activities are first undertaken at lab-scale TRLs (e.g TRL 3-4). This is because lower-TRL activities generally take less time and are less costly than higher-TRL activities, meaning that, by focusing on process optimisations at TRL 3/4, we can undertake more experiments, in a shorter timeframe, and so can improve the chances of developing a well-optimised bioprocess for a given budget.

However, once we have optimised the bioprocess at lower TRLs we recommend that the processes are validated at higher TRLs. Doing so will help to ascertain whether the bioprocess can be easily scaled-up, with product yields and quality comparable to the lab-scale experiments, or whether modifications need to be made to the process to ensure it is viable at enhanced TRLs.

Moving up the TRL meter also highlights the importance of developing and testing commercially-viable downstream processing steps (e.g. solids/liquid separations, product recoveries, and waste treatment). These can often be overlooked in bioprocess development projects even though they can often represent a significant proportion of CAPEX and OPEX costs in real-world operations.

At Celignis we are able to scale bioprocesses up to TRL6. This scaling-up can be part of a larger bioprocess development project, where the conditions are first optimised in lab-scale activities, or we can use process conditions specified by our clients based on their own lower-TRL research that they are now looking to upscale using the Celignis Bioprocess facilities.

We have a wide-array of higher-TRL equipment and infrastructure that allow us to handle these TRL6 projects. Some of the relevant equipment we have are detailed below.

TRL6 Bioreactors

We have dozens of different bioreactors with capacities ranging from 1 litre to 100 litres. Our 100-litre system is manufactured by Sartorius and allows full and precise control of the bioprocess. When using such a system for fermentations we often also use one or more smaller-scale bioreactors (of around 20-litres capacity) to provide the culture seed-train.

Please get in touch with us if you would like us to involve our TRL6 bioreactors in a bioprocess development project or for the scale-up of your existing bioprocess.


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 up 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.

Get more info...TFF


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.

Get more info...Filter Press


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.

Get more info...Filter Dryers


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.

Get more info...Supercritical CO2


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.

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

Get more info...Distillation


Contact Celignis Bioprocess

With regards to the scale-up 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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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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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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