Pub Date : 2026-01-03DOI: 10.1016/j.copbio.2025.103422
Tingyuan Xiao, Timothy P Durrett
Oilseeds provide a renewable platform to produce lipids and other valuable biomolecules. While conventional crops accumulate a limited set of fatty acids, advances in synthetic biology now enable exogenous pathways to expand oil diversity. The oilseeds camelina (Camelina sativa) and pennycress (Thlaspi arvense) have emerged as powerful platforms for this work due to their efficient transformation methods. Recent breakthroughs have come from genome-editing rewiring of endogenous lipid metabolism to remove competing pathways, which, when combined with bioprospecting to identify more efficient enzymes, delivers the greatest gains in product yield. Overcoming challenges such as achieving cell-type–specific expression and developing scalable strategies for pathway gene expression control will ensure these crops realize their potential as versatile platforms for next-generation bioproducts.
{"title":"Advances in tailoring camelina and pennycress oilseeds for specialty metabolites","authors":"Tingyuan Xiao, Timothy P Durrett","doi":"10.1016/j.copbio.2025.103422","DOIUrl":"10.1016/j.copbio.2025.103422","url":null,"abstract":"<div><div>Oilseeds provide a renewable platform to produce lipids and other valuable biomolecules. While conventional crops accumulate a limited set of fatty acids, advances in synthetic biology now enable exogenous pathways to expand oil diversity. The oilseeds camelina (<em>Camelina sativa</em>) and pennycress (<em>Thlaspi arvense</em>) have emerged as powerful platforms for this work due to their efficient transformation methods. Recent breakthroughs have come from genome-editing rewiring of endogenous lipid metabolism to remove competing pathways, which, when combined with bioprospecting to identify more efficient enzymes, delivers the greatest gains in product yield. Overcoming challenges such as achieving cell-type–specific expression and developing scalable strategies for pathway gene expression control will ensure these crops realize their potential as versatile platforms for next-generation bioproducts.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103422"},"PeriodicalIF":7.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1016/j.copbio.2025.103424
Claudia Beraldo, Alessandro Alboresi, Tomas Morosinotto
Photosynthesis is a fundamental biological process, and optimizing its efficiency is crucial for increasing crop yields without expanding cultivated land. Photosynthesis is finely regulated, and plants employ photoprotective mechanisms such as non-photochemical quenching (NPQ) and alternative electron pathways to dissipate excess energy and avoid potential damage.
In field conditions, light availability fluctuates rapidly due to environmental variability and canopy architecture, creating alternating periods of saturating illumination and shade, a context where photoprotection mechanisms are essential but also generate energy losses. Promising improvements in light-use efficiency have been obtained by optimizing NPQ response to field conditions, though impacts vary across species. These results highlight the need for strategies tailored to species and environment and for exploration of complementary approaches targeting other mechanisms.
{"title":"Photoprotective-based strategies to enhance crop yield under fluctuating light conditions","authors":"Claudia Beraldo, Alessandro Alboresi, Tomas Morosinotto","doi":"10.1016/j.copbio.2025.103424","DOIUrl":"10.1016/j.copbio.2025.103424","url":null,"abstract":"<div><div>Photosynthesis is a fundamental biological process, and optimizing its efficiency is crucial for increasing crop yields without expanding cultivated land. Photosynthesis is finely regulated, and plants employ photoprotective mechanisms such as non-photochemical quenching (NPQ) and alternative electron pathways to dissipate excess energy and avoid potential damage.</div><div>In field conditions, light availability fluctuates rapidly due to environmental variability and canopy architecture, creating alternating periods of saturating illumination and shade, a context where photoprotection mechanisms are essential but also generate energy losses. Promising improvements in light-use efficiency have been obtained by optimizing NPQ response to field conditions, though impacts vary across species. These results highlight the need for strategies tailored to species and environment and for exploration of complementary approaches targeting other mechanisms.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103424"},"PeriodicalIF":7.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.copbio.2025.103417
Zachary L Budimir , Elizabeth I Parkinson
Cyclic peptides are promising drug candidates, but their synthesis, especially the synthesis of small, strained rings, remains challenging. Penicillin-binding protein-type thioesterases (PBP-TEs) have emerged as versatile biocatalysts that catalyze head-to-tail macrocyclization of nonribosomal peptides. Unlike canonical thioesterase domains, which catalyze diverse offloading outcomes, PBP-TEs exclusively promote head-to-tail cyclization, offering predictable reactivity. Their ability to act on diverse substrates in vitro further underscores their potential as tools for peptide drug discovery. This review highlights PBP-TE discovery and substrate scope investigation, along with recent advances in structural characterization and engineering, establishing these enzymes as a promising platform for the biocatalytic synthesis of cyclic peptides.
{"title":"Discovery and development of penicillin-binding protein-type thioesterases as biocatalysts","authors":"Zachary L Budimir , Elizabeth I Parkinson","doi":"10.1016/j.copbio.2025.103417","DOIUrl":"10.1016/j.copbio.2025.103417","url":null,"abstract":"<div><div>Cyclic peptides are promising drug candidates, but their synthesis, especially the synthesis of small, strained rings, remains challenging. Penicillin-binding protein-type thioesterases (PBP-TEs) have emerged as versatile biocatalysts that catalyze head-to-tail macrocyclization of nonribosomal peptides. Unlike canonical thioesterase domains, which catalyze diverse offloading outcomes, PBP-TEs exclusively promote head-to-tail cyclization, offering predictable reactivity. Their ability to act on diverse substrates <em>in vitro</em> further underscores their potential as tools for peptide drug discovery. This review highlights PBP-TE discovery and substrate scope investigation, along with recent advances in structural characterization and engineering, establishing these enzymes as a promising platform for the biocatalytic synthesis of cyclic peptides.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103417"},"PeriodicalIF":7.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.copbio.2025.103421
Jeffrey L Moseley , Sabeeha S Merchant
Homologous recombination (HR) is an essential tool for complex metabolic engineering in yeast, but transgene integration into plant and green algal nuclear genomes predominantly occurs by non-homologous end-joining. Species of the closely related, oleaginous trebouxiophytes Auxenochlorella and Prototheca, are unusual among the green algae in that HR is the favored mechanism for DNA integration into the nuclear genome. This property enables locus-specific targeting of gene cassettes encoding multiple enzymes for manipulating existing biochemical pathways or introducing new functions. Genetic malleability, and regulatory approval for human consumption, coupled with robust fermentation performance at industrial scale, establishes Auxenochlorella and Prototheca as prime candidates for algal production of biochemicals and biomaterials. The examples presented here highlight strain improvement and engineering for synthesis of hydroxylated fatty acids for biomaterials, structured triglycerides resembling human milk fat for infant nutrition, very-long-chain mono- and polyunsaturated fatty acids with nutraceutical or therapeutic potential, and cannabinoids for pharmacological applications.
{"title":"Genetically pliable green algae for bioproduction of modified fatty acids, nutritional therapeutic oils, and biopharmaceuticals","authors":"Jeffrey L Moseley , Sabeeha S Merchant","doi":"10.1016/j.copbio.2025.103421","DOIUrl":"10.1016/j.copbio.2025.103421","url":null,"abstract":"<div><div>Homologous recombination (HR) is an essential tool for complex metabolic engineering in yeast, but transgene integration into plant and green algal nuclear genomes predominantly occurs by non-homologous end-joining. Species of the closely related, oleaginous trebouxiophytes <em>Auxenochlorella</em> and <em>Prototheca</em>, are unusual among the green algae in that HR is the favored mechanism for DNA integration into the nuclear genome. This property enables locus-specific targeting of gene cassettes encoding multiple enzymes for manipulating existing biochemical pathways or introducing new functions. Genetic malleability, and regulatory approval for human consumption, coupled with robust fermentation performance at industrial scale, establishes <em>Auxenochlorella</em> and <em>Prototheca</em> as prime candidates for algal production of biochemicals and biomaterials. The examples presented here highlight strain improvement and engineering for synthesis of hydroxylated fatty acids for biomaterials, structured triglycerides resembling human milk fat for infant nutrition, very-long-chain mono- and polyunsaturated fatty acids with nutraceutical or therapeutic potential, and cannabinoids for pharmacological applications.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103421"},"PeriodicalIF":7.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/j.copbio.2025.103420
Bruno Pok Man Ngou , Yasuhiro Kadota , Ken Shirasu
Cell-surface receptors perceive environmental cues and trigger appropriate responses. In plants, these receptors comprise ectodomain, juxta-membrane, and cytosolic regions that define ligand specificity, modulate co-receptor associations, and fine-tune downstream signaling, respectively. Here we highlight the mechanistic principles underlying each module and discuss strategies to reprogram them. By integrating structural insights with illustrative examples, we provide a blueprint for designing cell-surface receptors with customized recognition specificity and programmable outputs, offering new opportunities to enhance plant resilience in the face of rapid climate change.
{"title":"A guide to designing cell-surface receptors in plants","authors":"Bruno Pok Man Ngou , Yasuhiro Kadota , Ken Shirasu","doi":"10.1016/j.copbio.2025.103420","DOIUrl":"10.1016/j.copbio.2025.103420","url":null,"abstract":"<div><div>Cell-surface receptors perceive environmental cues and trigger appropriate responses. In plants, these receptors comprise ectodomain, juxta-membrane, and cytosolic regions that define ligand specificity, modulate co-receptor associations, and fine-tune downstream signaling, respectively. Here we highlight the mechanistic principles underlying each module and discuss strategies to reprogram them. By integrating structural insights with illustrative examples, we provide a blueprint for designing cell-surface receptors with customized recognition specificity and programmable outputs, offering new opportunities to enhance plant resilience in the face of rapid climate change.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103420"},"PeriodicalIF":7.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cereal pan-genomics, powered by long-read sequencing and multi-omics integration, provides high-resolution maps of structural variants, regulatory elements, and adaptive alleles across cultivated and wild germplasm. Here, we review how these comprehensive resources uncover trait-associated variation inaccessible to single-reference approaches, enabling haplotype-informed breeding, pathway engineering, and targeted introgression of wild alleles. Integration with regulatory genomics — the study of noncoding elements controlling gene expression — and 3D genome architecture further enables precision editing of noncoding elements for phenotypic fine-tuning. Together, these advances position cereal pan-genomics as a foundational platform for predictive crop design, accelerating the development of high-yielding, climate-resilient varieties while providing actionable guidance for breeding strategies.
{"title":"Functional cereal pan-genomics: harnessing structural and regulatory variation for precision crop design","authors":"Zihao Zhu , Srijan Jhingan , Erwang Chen , Nils Stein","doi":"10.1016/j.copbio.2025.103418","DOIUrl":"10.1016/j.copbio.2025.103418","url":null,"abstract":"<div><div>Cereal pan-genomics, powered by long-read sequencing and multi-omics integration, provides high-resolution maps of structural variants, regulatory elements, and adaptive alleles across cultivated and wild germplasm. Here, we review how these comprehensive resources uncover trait-associated variation inaccessible to single-reference approaches, enabling haplotype-informed breeding, pathway engineering, and targeted introgression of wild alleles. Integration with regulatory genomics — the study of noncoding elements controlling gene expression — and 3D genome architecture further enables precision editing of noncoding elements for phenotypic fine-tuning. Together, these advances position cereal pan-genomics as a foundational platform for predictive crop design, accelerating the development of high-yielding, climate-resilient varieties while providing actionable guidance for breeding strategies.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103418"},"PeriodicalIF":7.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.copbio.2025.103419
Priscila O Giuseppe , Nadia MV Sampaio , Tassia L Junqueira, Fernanda Mandelli, Leticia M Zanphorlin, Gabriela F Persinoti, Mario T Murakami
Biofoundries are transforming biotechnology by automating design–build–test–learn (DBTL) cycles that accelerate biological design and innovation. While globally recognized as strategic infrastructures for the bioeconomy, they remain underrepresented in Latin America. This perspective highlights opportunities and challenges for establishing biofoundries across the region, emphasizing the need for open-access infrastructures, interdisciplinary networks, sustainability-assisted developments, and regulatory convergence. We discuss the advancement of integrated biofoundry models that combine multi-omics and synthetic biology approaches with sustainability assessments and bioprocess scale-up capabilities. This integrative framework, spanning from bioprospection to bioprocess scale-up, offers a key strategy to bridge biodiversity and industrial innovation, serving as a potential blueprint for expanding biofoundry initiatives across Latin America. Harnessing the regional biodiversity, scientific capacity, and growing innovation networks can establish a collaborative, sustainable biofoundry landscape capable of converting biological resources into high-value biotechnological solutions to address global challenges.
{"title":"Challenges and opportunities for establishing biofoundries in Latin America","authors":"Priscila O Giuseppe , Nadia MV Sampaio , Tassia L Junqueira, Fernanda Mandelli, Leticia M Zanphorlin, Gabriela F Persinoti, Mario T Murakami","doi":"10.1016/j.copbio.2025.103419","DOIUrl":"10.1016/j.copbio.2025.103419","url":null,"abstract":"<div><div>Biofoundries are transforming biotechnology by automating design–build–test–learn (DBTL) cycles that accelerate biological design and innovation. While globally recognized as strategic infrastructures for the bioeconomy, they remain underrepresented in Latin America. This perspective highlights opportunities and challenges for establishing biofoundries across the region, emphasizing the need for open-access infrastructures, interdisciplinary networks, sustainability-assisted developments, and regulatory convergence. We discuss the advancement of integrated biofoundry models that combine multi-omics and synthetic biology approaches with sustainability assessments and bioprocess scale-up capabilities. This integrative framework, spanning from bioprospection to bioprocess scale-up, offers a key strategy to bridge biodiversity and industrial innovation, serving as a potential blueprint for expanding biofoundry initiatives across Latin America. Harnessing the regional biodiversity, scientific capacity, and growing innovation networks can establish a collaborative, sustainable biofoundry landscape capable of converting biological resources into high-value biotechnological solutions to address global challenges.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103419"},"PeriodicalIF":7.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gut microbiome plays a crucial role in maintaining health by supporting digestion, immunity, and overall well-being. Disruptions to the gut microbiome can result in dysbiosis, which is correlated with disease states. Recent advances in engineering the gut microbiome, functional ingredients designed through prebiotics, probiotics, and synbiotics have progressed together with synthetic microbial communities (SynComs), which influence the modulation of microbiome composition and functional role, offering a promising strategy to restore balance and enhance health. This field is rapidly advancing with broad applications focused on improving animal and human health. This review explores the significance and current applications of the engineering microbiome and its impact on gut health, as well as the challenges and sustainable future.
{"title":"Engineering the gut microbiome and its impact on human health","authors":"Amornthep Kingkaw , Kevin Mok , Massalin Nakphaichit , Mattheos Koffas , Wanwipa Vongsangnak","doi":"10.1016/j.copbio.2025.103415","DOIUrl":"10.1016/j.copbio.2025.103415","url":null,"abstract":"<div><div>The gut microbiome plays a crucial role in maintaining health by supporting digestion, immunity, and overall well-being. Disruptions to the gut microbiome can result in dysbiosis, which is correlated with disease states. Recent advances in engineering the gut microbiome, functional ingredients designed through prebiotics, probiotics, and synbiotics have progressed together with synthetic microbial communities (SynComs), which influence the modulation of microbiome composition and functional role, offering a promising strategy to restore balance and enhance health. This field is rapidly advancing with broad applications focused on improving animal and human health. This review explores the significance and current applications of the engineering microbiome and its impact on gut health, as well as the challenges and sustainable future.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103415"},"PeriodicalIF":7.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.copbio.2025.103416
Joshua Ricouvier , Aurore Dupin , Matthaeus Schwarz-Schilling , Ferdinand Greiss , Shirley S. Daube , Roy H. Bar-Ziv
Recent efforts in bottom-up synthetic biology focus on fabricating programmable biological units that can be viewed as synthetic cells. Combining microfluidic techniques with cell-free protein expression systems defines the geometrical limits of the synthetic cell (e.g. microfluidic compartments, droplets, vesicles) and facilitates communication pathways to distribute functions over an assembly of synthetic cells. In this review, we describe and compare the different strategies implemented to reconstitute cell–cell communication among synthetic cells. We focus especially on various experimental setups of microcompartmentalization containing a cell-free expression system and genetic material. We highlight efforts to develop and engineer different modes of communication among the synthetic cells in different forms, varying by the degree of permeability, resource renewal, stability, and scalability, and how these influence the trade-off between programmability and biomimicry. We then summarize recent progress in the realization of different stages of communication (signaling, processing, and output generation) by genetic circuits, holding great promise for applications in synthetic biology and biotechnology.
{"title":"Cell-free protein synthesis in microcompartments towards cell–cell communication","authors":"Joshua Ricouvier , Aurore Dupin , Matthaeus Schwarz-Schilling , Ferdinand Greiss , Shirley S. Daube , Roy H. Bar-Ziv","doi":"10.1016/j.copbio.2025.103416","DOIUrl":"10.1016/j.copbio.2025.103416","url":null,"abstract":"<div><div>Recent efforts in bottom-up synthetic biology focus on fabricating programmable biological units that can be viewed as synthetic cells. Combining microfluidic techniques with cell-free protein expression systems defines the geometrical limits of the synthetic cell (e.g. microfluidic compartments, droplets, vesicles) and facilitates communication pathways to distribute functions over an assembly of synthetic cells. In this review, we describe and compare the different strategies implemented to reconstitute cell–cell communication among synthetic cells. We focus especially on various experimental setups of microcompartmentalization containing a cell-free expression system and genetic material. We highlight efforts to develop and engineer different modes of communication among the synthetic cells in different forms, varying by the degree of permeability, resource renewal, stability, and scalability, and how these influence the trade-off between programmability and biomimicry. We then summarize recent progress in the realization of different stages of communication (signaling, processing, and output generation) by genetic circuits, holding great promise for applications in synthetic biology and biotechnology.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103416"},"PeriodicalIF":7.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.copbio.2025.103401
Yannick Scholz, Boris Yermakov, Alexander Grünberger
Microfluidic cultivation systems have transformed the study of cellular physiology by enabling high spatial and temporal analysis under precisely controlled environmental conditions. However, the successful application of these systems is hindered by technical challenges, including the lack of systematic characterization of key operational parameters and their interdependencies, which limits experimental reproducibility within a given setup and hampers the rational design of new systems. Here, we propose adapting ‘Windows of Operation’ — a framework originating from bioprocess engineering to visualize how different parameters define design limits — as a qualitative operational design tool for microfluidic cultivation, here further denoted as microfluidic window of operation (MWO). Through selected case studies, we demonstrate how defining MWOs can guide the identification and optimization of key experimental parameters. This provides a foundation for robust experimental design that links device function with operating parameters, thereby advancing feasibility, robustness, and comparability, while minimizing experimental bias.
{"title":"Windows of operation as qualitative early-stage design tool for microfluidic (single-cell) cultivations","authors":"Yannick Scholz, Boris Yermakov, Alexander Grünberger","doi":"10.1016/j.copbio.2025.103401","DOIUrl":"10.1016/j.copbio.2025.103401","url":null,"abstract":"<div><div>Microfluidic cultivation systems have transformed the study of cellular physiology by enabling high spatial and temporal analysis under precisely controlled environmental conditions. However, the successful application of these systems is hindered by technical challenges, including the lack of systematic characterization of key operational parameters and their interdependencies, which limits experimental reproducibility within a given setup and hampers the rational design of new systems. Here, we propose adapting ‘Windows of Operation’ — a framework originating from bioprocess engineering to visualize how different parameters define design limits — as a qualitative operational design tool for microfluidic cultivation, here further denoted as microfluidic window of operation (MWO). Through selected case studies, we demonstrate how defining MWOs can guide the identification and optimization of key experimental parameters. This provides a foundation for robust experimental design that links device function with operating parameters, thereby advancing feasibility, robustness, and comparability, while minimizing experimental bias.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103401"},"PeriodicalIF":7.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}