CLASSY: Cell‑inspired compartmentalisation and the push toward self‑regulating chemical reaction systems

Brussels, June 10th 2024
Summary
  • CLASSY used cell inspired compartmentalisation to explore self regulating chemical synthesis and produced a microfluidic microreactor platform and several proof of concept advances.
  • Consortium teams reported progress on peptide catalysis, combined peptide and biocatalyst one pot reactions, chemical reaction networks and microfluidic catalytic reactors.
  • Research spawned follow on projects including CORENET and contributed to new collaborations that attracted Horizon Europe and other grants.
  • Complementary investment in automation arrived with a separate 97 million euro Dutch grant to build an autonomous robot lab aimed at AI driven molecular discovery.
  • Claims about near term industrial waste reduction and green manufacturing remain prospective and will require scale up, reproducibility and integration with industrial processes.

CLASSY: cell like molecular assembly lines for programmable reactions

Over four years the multidisciplinary project known as CLASSY, funded under Horizon 2020 Future and Emerging Technologies and later aligned with EIC Pathfinder priorities, developed a body of work that explores how strategies used by living cells can be applied to synthetic chemical synthesis. The premise is straightforward. Living cells manage complex, multistep chemistry reliably and with minimal waste by organising reactions in compartments and using networks of catalysts. CLASSY set out to copy elements of that architecture at the lab scale with the goal of producing more efficient, adaptive and lower waste synthetic routes.

What the project set out to prove and why it matters

CLASSY was motivated by sustainability arguments that are now common in chemical research. Traditional industrial synthesis often requires multiple, separate reaction steps with intermediate purification. Each step can consume solvent, energy and reagents and produce waste. The project asked whether compartmentalisation and networked catalytic strategies borrowed from biology could reorganise synthesis so that sequences of transformations run in a regulated and productive way. The hope is that such architectures could reduce process mass intensity and energy use but that outcome depends on many engineering, scale and economic factors that the project did not aim to resolve fully.

Compartmentalisation strategy in brief:Biological cells use membrane bound or otherwise separated compartments to keep incompatible chemistries apart and to route intermediates efficiently. In a synthetic context compartmentalisation can mean physical microreactors, phase separation or supramolecular assemblies that control which catalysts and substrates interact and when. The intent is to mimic metabolic flow control rather than simply combining reagents in one flask.

Key technical advances reported

The consortium reported several technical advances across systems chemistry, catalysis and microfluidics. Partners emphasised progress rather than claims of ready industrial deployment. Notable themes were peptide based catalysis that is robust across conditions, the tandem use of peptide catalysts with enzymes in single pot transformations, studies of dynamic chemical networks, and the construction of a microfluidic microreactor platform to host compartmentalised reactions.

Peptide catalysis and enzyme cooperation:Teams led by Helma Wennemers at ETH Zurich and Wolfgang Kroutil at Universität Graz demonstrated peptides that function as efficient and robust catalysts. They showed that peptide catalysts can operate alongside enzymes in a single reaction mixture to complete a two step biocatalytic transformation. Such combinations are scientifically interesting because peptides can offer synthetic flexibility while enzymes can provide high selectivity. The practical challenge is maintaining enzyme activity and managing competing reaction conditions in the same pot.
Chemical reaction networks and microreactors:Wilhelm Huck's group at Radboud University focused on dynamic chemical networks and leveraged microfluidic fabrication, working with company Micronit Micro Technologies B.V. to develop microfluidic chips that host catalytic microreactors. Microfluidic systems allow precise control of flow, gradients and compartment volumes. They are suited to studying reaction dynamics and to prototyping compartmentalised schemes, but moving microfluidic methods to industrial scale requires addressing throughput, fouling and integration with bulk chemical processing.

Beyond specific catalysts and devices CLASSY partners reported insights into the self organisation of multi component synthetic systems. These are fundamental science contributions that help map how far systems chemistry can approach cell like behaviours such as feedback, adaptation and hierarchical organisation.

Collaborations, dissemination and derivative projects

CLASSY was an explicitly multidisciplinary consortium. The project host and coordinator was the Biohybrid Materials and Systems Chemistry Group at Universidad Autónoma de Madrid led by Andrés de la Escosura. Partners included academic groups in Switzerland, the Netherlands, Austria and Israel and two companies providing microfluidic technology and project management. The project culminated in a final symposium on 15 March 2024 titled Catalysis in chemical networks and supramolecular assemblies. The online event attracted more than 50 participants from 42 organisations and served as a platform to present findings and to discuss future directions with external experts.

Partner or ProjectRole or FocusFunding instrument or note
Biohybrid Materials and Systems Chemistry Group, Universidad Autónoma de MadridCoordinator, systems chemistryHorizon 2020 FET grant agreement No 862081
Laboratory for Systems Chemistry, Ben Gurion UniversitySystems chemistry and networksConsortium partner
Laboratory of Organic Chemistry, ETH ZürichPeptide catalysisConsortium partner
Physical-Organic Chemistry Research Group, Radboud UniversityChemical networks and microfluidics researchConsortium partner
Biocatalytic Synthesis Group, Universität GrazEnzyme catalysis and one pot transformationsConsortium partner
Micronit Micro Technologies B.V.Microfluidic chip developmentIndustry partner
accelopment Schweiz AGProject management, dissemination and funding scoutingIndustry partner

Some collaborations that grew from CLASSY have already led to new funded projects under Horizon Europe and other schemes. These include CORENET, an EIC Pathfinder Open effort coordinated by Andrés de la Escosura that started in April 2022 and aims to construct brain mimicking chemical computing devices made from networks of reactions. Other follow on actions include DarChemDN, a MSCA doctoral network, and MiniLife, an ERC Synergy project. These trajectories show how early stage projects can seed more ambitious programmes but they also underline that each further step is a new funding and technical challenge.

Chemical computing and CORENET explained:CORENET proposes to use networks of chemical reactions as information processing systems. The basic idea is that input molecules and environmental conditions drive reaction networks to produce patterns of product molecules that encode computation. Monitoring would combine analytical chemistry, cheminformatics and artificial intelligence. Chemical computing is conceptually different from electronics because it uses concentration patterns and reaction pathways as signals. The technology faces hurdles such as speed, reproducibility, error correction and interfaces to electronic systems.

Automation and the push toward autonomous discovery

An important external development that complements CLASSY research is the large Dutch government investment of 97 million euro awarded to a project led by Wilhelm Huck to build a fully autonomous robot lab. This Robotlab initiative funded by the National Growth Fund aims to assemble hardware for automated experiments with closed loop design driven by artificial intelligence.

Autonomous robot lab concept:The robot lab model envisages robots performing pipetting, mixing and measurements, integrated analytical instruments and AI software that suggests new experiments based on results. The intended cycle is problem definition by researchers, automated experiment execution, data analysis by algorithms and autonomous proposal of next experiments. This approach promises speed and exploration at scale. The caveat is that interpretation of complex chemical data and transfer of automated lab routines to other contexts can be difficult. Validation and reproducibility remain central concerns.

Proponents argue that automation plus AI can accelerate discovery and help tackle climate related problems by speeding up the development of greener materials and processes. Critics caution that automation amplifies existing biases in experimental design and that the collection of large experimental datasets does not by itself guarantee conceptual breakthroughs. Both perspectives matter for assessing the likely impact of the Robotlab and of AI enabled chemical research generally.

Challenges, limitations and the path from lab to industry

CLASSY faced expected challenges including disruptions from the pandemic and shifting research priorities over the project period. The science itself is complex. Demonstrating a concept at small scale does not automatically translate into reduced industrial waste or cost. Microfluidic and compartmentalised systems must be engineered for throughput, robustness and regulatory compliance before they can disrupt existing manufacturing processes. Enzyme and peptide combinations will need to prove stability, reuse and economic viability at scale.

Funding scouting and exploitation planning are active parts of the consortiums strategy. The presence of a company specialised in research funding services indicates an explicit route to chase further grants and to explore commercial pathways. That work is necessary but it does not guarantee commercial uptake.

Outlook and concluding assessment

CLASSY delivered meaningful scientific outputs and strengthened networks between systems chemistry, microfluidics and biocatalysis groups in Europe and beyond. It helped spawn new projects that probe chemical computation and aim to combine advanced automation with AI. The work sits at the intersection of promising scientific trends. At the same time the translation claims should be read as prospectus rather than proof. To move from demonstration to impact the field will need sustained engineering, reproducible scale up, robust automation that handles chemical complexity and evidence that new workflows improve environmental and economic metrics in production settings.

For policymakers and funders the CLASSY story is familiar. Early stage, multidisciplinary research builds knowledge and networks that can be leveraged. Long timelines and risk remain intrinsic to this kind of deep innovation. The investment in autonomous labs and in chemical computing reflects an appetite to accelerate the pipeline from discovery to application. How much acceleration results will be visible only after further validation and real world deployment.