Emerging Standards for Organ on a Chip
Introduction
Organ-on-a-chip (OOAC) and microphysiological systems (MPS) are revolutionising in vitro biology by recreating key aspects of human organ function on miniature platforms. These systems offer far greater physiological fidelity than static 2-D cell cultures or animal models, which often fail to predict human outcomes because of species differences and oversimplified environments. The promise of OOAC/MPS technology spans drug development, toxicology and disease modelling—for example, a well-designed liver-on-a-chip can metabolise drugs and reveal toxicity that traditional assays might miss. However, with this innovation comes new challenges in consistency and trust. Early MPS prototypes have been developed in diverse ways, leading to inconsistent performance; many models “do not possess critical levels of baseline performance” required for pharmaceutical use [1]. Such variability in materials, protocols and read-outs has made it difficult to reproduce results across labs and to compare data from different platforms.
Stakeholders across industry and academia increasingly agree that standardisation is an urgent next step for broader OOAC adoption [2]. In short, without common standards and validation practices it is hard for end-users and regulators to fully trust and integrate these novel systems. This white paper examines the push for standardisation in the OOAC field and demonstrates how the Quasi Vivo® system—particularly the latest QV1200 model—aligns with emerging standards to deliver reliable, user-friendly organ-on-chip solutions.
Why MPS and OOAC Need Standardised Protocols and Benchmarks
A core motivation for standards is to improve reproducibility between laboratories and comparability between different MPS platforms. Today, groups often use custom in-house protocols—varying in everything from cell sourcing and culture media to fluid-flow rates and read-out assays—which means that two “liver-on-chip” models may produce divergent results for the same drug. As one review noted, most MPS developers perform some form of internal validation, but these ad-hoc approaches are “limited in scope and often overlook important aspects of performance.” The lack of standardised characterisation means even similar devices are hard to compare objectively, and it is difficult to judge which system truly meets the requirements of a given application. Clearly, there is a need to define common performance metrics, quality benchmarks and validation principles for MPS. These should cover basic functionality (e.g. tissue viability, key protein outputs), technical stability (e.g. flow control, sensor calibration) and biological relevance (e.g. proper metabolic capacity for liver models). A consensus-based process involving developers, end-users and regulators is recommended to establish such qualification standards [3].
Encouragingly, several initiatives are under way: for example, the ORCHID consortium in Europe identified standardisation as “a fundamental pillar for advancement of organ-on-chip technologies” [4], and a 2019 trans-Atlantic workshop of 46 experts concluded that standards are critical tools to support MPS qualification and eventual regulatory acceptance [5]. Only recently has the community begun actively working with Standards Development Organisations—for instance, the US-based ASTM International now has a working group on microphysiological systems, and in Europe a CEN-CENELEC Focus Group has published a roadmap prioritising MPS standardisation need [3][6].
Regulators will only accept data from MPS and organ-on-chip models if they are confident the models are reliable, reproducible and relevant. Thus, standardised protocols and reference materials are essential to build that confidence. A recent European Commission report highlighted that, for organ-on-chips to be used in drug development and chemical safety, standards are needed to ensure that devices are reliable and effective [6].
Defining reference models and controls
A separate aspect of standardisation is establishing reference models and control materials for MPS. In pharmaceutical research every new assay or instrument is typically qualified using reference compounds—a set of well-characterised drugs or chemicals that produce predictable outcomes. The same approach is being applied to OOAC and MPS systems. For instance, a pharma-led consortium published “Liver microphysiological-system development guidelines for safety risk assessment,” which outline a three-tiered characterisation process along with a panel of 20 reference compounds to benchmark new liver-chip models [1].
Material standards
In addition to chemical benchmarks, material standards are coming under scrutiny. Many early devices were made of PDMS silicone, which is convenient but can absorb small hydrophobic drugs and skew experimental results. Recent studies quantify small-molecule sorption into device materials and encourage the use of low-binding plastics instead [7].
Case Study – Liver Models: Challenges and Progress
One of the most impactful applications of OOAC technology is the liver-on-a-chip, used to assess drug metabolism and hepatotoxicity in a human-relevant context. Conventional animal tests have limited predictive value for human liver toxicity, and static 2-D hepatocyte cultures lose function rapidly [1]. Likewise, primary human hepatocytes in static 2-D culture lose polarity and CYP450 expression within 1–2 weeks [8].
Introducing continuous perfusion culture significantly improves physiological relevance. Flow-conditioned microenvironments support extended viability and function of primary hepatocytes [9]; perfused liver chips have maintained detectable CYP3A4 and other functions for more than three weeks, whereas 2-D cultures do not [8].
A blinded study of 27 drugs found that a human multi-cell liver microphysiological platform identified clinical DILI with 87% sensitivity and 100% specificity, outperforming 3D hepatic spheroids (47% sensitivity) and conventional animal data (0% in this set) [10][11].
Many early devices used simple microfluidic chambers and channels [12]. Although adequate for cell viability, they failed to recreate full liver morphology or CYP450 activity, possibly owing to poor oxygen control, lack of non-parenchymal cells or excessive shear stress. Liu et al. emphasised that all these factors must be addressed to build physiologically relevant models [15].
An example that meets these criteria is the multizonal liver model of Tomlinson, Hyndman et al. [14], which uses computational fluid dynamics to create oxygen gradients and demonstrates periportal–perivenous metabolic differences.
Quasi Vivo® technology supports emerging standards
Quasi Vivo chambers are available in both PDMS and low-sorption plastics, the latter preferred for pharmacokinetic studies because of minimal small-molecule binding [7]. The QV1200 design accommodates standard Transwell™ inserts, enabling co-culture or barrier models recommended by recent guidelines. By pairing sealed chambers with peristaltic pumps, the system delivers low-shear flow while reducing contamination risk and prevents harmful pressure spikes seen with injection pumps.
Validation
The validation workflow proposed by Liu et al. remains our working standard for advanced in vitro liver systems [15]. To functionally qualify hepatocyte models under flow, we map endpoints to the CYP gene and protein read-outs described by Ewart et al. for engineering-grade microphysiology assays [10]. Comparable long-term functional maintenance has been demonstrated in Quasi Vivo® perfusion platforms: primary human hepatocytes cultured in the QV900 flow system retained viability and albumin secretion for ≥3 weeks and supported metabolic readouts relative to static sandwich controls [9].
Manufacturer and user data further document month-long (≥28 day) hepatocyte cultures in Quasi Vivo liquid/liquid configurations with preservation of phenotype and CYP expression, supporting realistic repeat-dosing study designs [16].
Additional work using Quasi Vivo perfusion with primary rat hepatocytes shows improved functional readouts (zonation markers, albumin, toxin response) under low-shear flow versus static culture, underscoring the system’s ability to sustain differentiated hepatocyte behaviour [14].
Conclusion
Robust standards—spanning reference compounds, material specifications and validation metrics—are essential for the wider adoption of OOAC and MPS. Platforms such as Quasi Vivo, designed with these standards in mind, will accelerate the translation of sophisticated microphysiological engineering into dependable biomedical tools, benefiting drug development and reducing reliance on animal testing [2][4][6].
References
[1] Baudy, A.R., Otieno, M.A., Hewitt, P. et al. (2020) ‘Liver microphysiological systems development guidelines for safety risk assessment in the pharmaceutical industry’, Lab on a Chip, 20, 215–225. https://doi.org/10.1039/C9LC00768G
[2] Meneses, J., Conceição, F., van der Meer, A.D. et al. (2024) ‘Guiding organs-on-chips towards applications: a balancing act between integration of advanced technologies and standardization’, Frontiers in Lab on a Chip Technologies, 3, 1376964. https://doi.org/10.3389/frlct.2024.1376964
[3] Piergiovanni, M., Leite, S.B., Corvi, R. and Whelan, M. (2021) ‘Standardisation needs for organ-on-chip devices’, Lab on a Chip, 21(15), 2857–2868. https://doi.org/10.1039/D1LC00241D
[4] ORCHID Consortium (2019) ORCHID – Organ-on-a-Chip in Development project overview. Available at: https://h2020-orchid.eu (Accessed 25 June 2025).
[5] National Academies of Sciences, Engineering, and Medicine (2021) Microphysiological Systems: Bridging Human and Animal Research – Proceedings of a Workshop-in-Brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/26124
[6] Joint Research Centre (2025) ‘Setting out a roadmap for standardisation of organ-on-chip technology’, JRC News and Updates, 13 January. Available at: https://joint-research-centre.ec.europa.eu/ (Accessed 25 June 2025).
[7] Grindulis, K., Matusevica, N.G., Kozlova, V. et al. (2025) ‘Sorption and release of small molecules in PDMS and COC for organs on chip’, Scientific Reports, 15, 14012. https://doi.org/10.1038/s41598-025-97111-2
[8] Mugaanyi, J., Huang, J., Fang, J. et al. (2025) ‘Developments and applications of liver-on-a-chip technology—current status and future prospects’, Biomedicines, 13(6), 1272. https://doi.org/10.3390/biomedicines13061272
[9] Buesch, S. et al. (2018) ‘A novel in vitro liver cell culture flow system allowing long-term metabolism and hepatotoxicity studies’, Applied in Vitro Toxicology, 4(3), 152–164. https://doi.org/10.1089/aivt.2018.0009
[10] Ewart, L., Apostolou, A., Briggs, S.A. et al. (2022) ‘Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology’, Communications Medicine, 2, 154. https://doi.org/10.1038/s43856-022-00209-1
[11] Wilkinson, J.M. (2023) ‘A review of complex in vitro cell culture stressing the importance of fluid flow and illustrated by organ-on-a-chip liver models’, Frontiers in Toxicology, 5, 1170193. https://doi.org/10.3389/ftox.2023.1170193
[12] Tonon, F., Giobbe, G.G., Zambon, A. et al. (2019) ‘In vitro metabolic zonation through oxygen gradient on a chip’, Scientific Reports, 9, 13557. https://doi.org/10.1038/s41598-019-49412-6
[13] Lee, P.J., Hung, P.J. and Lee, L.P. (2007) ‘An artificial liver sinusoid with a microfluidic endothelial-like barrier’, Biotechnology and Bioengineering, 97(5), 1340–1346. https://doi.org/10.1002/bit.21360
[14] Tomlinson, L., Hyndman, L., Firman, J.W. et al. (2019) ‘In vitro liver zonation of primary rat hepatocytes’, Frontiers in Bioengineering and Biotechnology, 7, 17. https://doi.org/10.3389/fbioe.2019.00017
[15] Liu et al. (2025) ‘Standard: human liver-on-a-chip’ Cell Regeneration 14:9 https://doi.org/10.1186/s13619-025-00226-0
[16] Lonza Scientific Poster. “Long-Term Culture of Primary Human Hepatocytes in the Quasi Vivo® QV900 Flow System Enables Repeat Dosing Toxicity Studies.” (Heps-and-QuasiVivo poster; Lonza/Kirkstall collaboration)