ArticleProceedings of the National Academy of Sciences of the United States of America2016
Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
154 citing papers in PubMed, 1 synthesis or guideline pooled it, 342 citations in OpenAlex.
- A quantitative meta-analysis comparing cell models in perfused organ on a chip with static cell cultures.Scientific reports · 2023Pooled it
- Beyond Detection Limits: Integrated Biosensors for Molecular Diagnostics, Longitudinal Monitoring, and Clinical Translation.Biosensors · 2026Review
- Article
- Methodological innovations in perfusable vascular networks: Advancing high-density tissue models.Regenerative therapy · 2026Article
- Engineering Organ-on-a-Chip Systems for Cancer Immunotherapy: Strategies and Assay Integration.Bioengineering (Basel, Switzerland) · 2026Review
- Microengineering the Liver: Strategies for Constructing Functional Liver-on-a-Chip Devices.Exploration (Beijing, China) · 2026Review
- Review
- Strategies to control cellular spatial organization in microphysiological systems.Microsystems & nanoengineering · 2026Review
- Recent advances in microfluidics and bioelectronics for three-dimensional organoid interfaces.Biomicrofluidics · 2026Article
- Toward continuous monitoring systems: emerging trends of on-chip sensors in organ-on-a-chip.Microsystems & nanoengineering · 2026Review
- Organ-on-a-Chip Technology and Global Multi-Omics: Current Applications and Future Directions.MedComm · 2026Review
- Transducer Systems Integrated into Organ-on-a-Chip Devices: From Detection to Fabrication.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Functional material probes and advanced technologies in organ-on-a-chip characterization.Theranostics · 2026Review
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Primary Human Tissue Models for Metabolic Dysfunction-Associated Liver Disease - toward Streamlining Drug Discovery with Patient-Derived Assays.Advanced biology · 2025Review
- Development of a sensor-compatible vascular microphysiological system for metabolic monitoring during drug-induced endothelial injury.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Article
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- Advanced 3D In Vitro Liver Fibrosis Models: Spheroids, Organoids, and Liver-on-Chips.Biomimetics (Basel, Switzerland) · 2025Review
- Lessons Learned from Liver-on-Chip Platform.Annals of biomedical engineering · 2025Review
- Overview of methods that determine mitochondrial function in human disease.Metabolism: clinical and experimental · 2025Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing, but thus far has demonstrated few advantages over traditional methods. Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity, as well as pluripotency and disease processes. However, current methods to evaluate mitochondrial activity still rely on end-point assays, resulting in limited kinetic and prognostic information. Here, we present a liver-on-chip device capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. A computer-controlled microfluidic switchboard allowed contiguous electrochemical measurements of glucose and lactate, providing real-time analysis of minute shifts from oxidative phosphorylation to anaerobic glycolysis, an early indication of mitochondrial stress. We quantify the dynamics of cellular adaptation to mitochondrial damage and the resulting redistribution of ATP production during rotenone-induced mitochondrial dysfunction and troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts metabolic fluxes at concentrations previously regarded as safe, suggesting a mechanism for its observed idiosyncratic effect. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to mitochondrial damage, a unique advantage of organ-on-chip technology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.