Organ-on-Chip in 2025: In the Spotlight After the NIH, FDA, and GAO Push

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A conversation between

Elizabeth (Lizzy) Crist, Business Development Manager & Technical Lead (USA), AIM Biotech and

Henning Mann, PhD, Founder & CEO, HM.BioConsulting, former Sen. Dir. Applied Science, Nortis Inc.,

Executive Intro

With the FDA, NIH, and GAO each advancing the shift toward human-based preclinical models, Organ-on-Chip (OoC) and broader Microphysiological Systems (MPS) technologies have been moved into the spotlight and given unprecedented key direction and support. FDA Modernization Acts 2.0 and 3.0 formally permit human model data in place of animal testing; NIH is doubling down on MPS funding and comparability programs; and GAO’s 2025 report explicitly calls for “fit-for-purpose validation” and “cross-platform standardization.”

AIM Biotech is part of the center of this transformation. The company’s standardized, automation-compatible MPS platforms, idenTx® 40, organiX™, and the new Cell Systems line, are designed to make high-fidelity human biology accessible, reproducible, and ready for regulatory use.

In this interview, Lizzy Crist and I unpack how AIM Biotech is leveraging the regulatory trifecta to expand impact at scale, helping the global life sciences community move from animal reliance to human relevance.

OoC and NAMs in the Spotlight:

Henning: The past year has been a turning point for the field. The moves from FDA, NIH and GAO have many new stakeholders talking about MPS, validation frameworks, and fit-for-purpose models, from regulators to pharma and biotech R&D. What changed for AIM Biotech as this policy wave hit? 

Lizzy:

The past year has really marked a turning point in how advanced biological research tools are integrated into regulatory and drug development frameworks. For years, AIM and other MPS developers have been building systems that faithfully mirror human biology, but broad adoption has been slow, partly because the regulatory and validation structures weren’t fully in place.

That landscape is changing quickly. The FDA Modernization Acts and monoclonal antibody (mAb) roadmap, along with the GAO’s recent guidance on fit-for-purpose validation, provide a clearer pathway for using human-based data in submissions. This gives our customers - and all OoC/ NAM customers, particularly in pharma and biotech - the confidence to integrate MPS in their development processes.

The NIH’s ongoing support complements this by encouraging collaborations and comparability studies. This is critical because it’s one thing to have a great platform in a single lab, and another to have it recognized as reliable across the field. For AIM, our approach has always been to model and validate specific human biological processes with rigor. By doing so, we provide tools that are not only human-relevant but also scalable, reproducible, and aligned with the drug development and regulatory contexts of use.

With these combined shifts, MPS are no longer just a promising technology, but instead they are becoming essential tools in drug development.

The policy wave reframes MPS as implementation science: the question is no longer if human-relevant models should be used, but where they best fit and how they’re validated.

Evolving FDA, NIH, and GAO initiatives are shaping a clearer framework for integrating microphysiological systems into research and regulatory practice. Within this environment, aligning R&D with standardized methods, reproducible biology, and collaborative validation supports both scientific credibility and regulatory acceptance. The broader 3Rs principles, Replacement, Reduction, and Refinement, underscore how purposeful, transparent approaches can advance human-relevant models more effectively than added complexity.

Henning: Besides the new opportunities and levels of credibility and relevance that these new initiatives provide, how are you as AIM Biotech leveraging these new initiatives directly a) to your advantage and b) to advance the OoC/ NAM field as a whole with your own developments? 

Lizzy: These announcements and policy shifts give model developers a clear opportunity to engage with biopharma and biotech companies to incorporate MPS data for decision-making and regulatory submissions. It helps catalyze conversations about where and how MPS can fit into internal workflows and regulatory strategies.

At AIM, we have focused on standardization of cells and biological readouts in our R&D. This is reflected in our recently launched Cell Systems kits and assay-ready solutions, where TERT-immortalized cell sources were validated in AIM’s vascularization and angiogenesis assays. We’re collaborating with partners like Nikon to provide imaging analysis solutions so that users can apply standardized approaches to analyze those assays.

Every individual step forward benefits the field as a whole. When an MPS provider develops a robust, validated model, it not only strengthens their own offering but also helps set the standard and build credibility for human-relevant models across the industry.

Henning: A Follow-Up Question: The 3Rs Initiative (Replacement, Reduction, Refinement) - how does it play into this context? 

Lizzy: The broader movement toward Replacement, Reduction, and Refinement (the 3Rs) in preclinical research is gaining momentum as regulators and industry increasingly recognize the potential of human-relevant models. The overarching goal is to reduce reliance on animal testing while maintaining high scientific rigor and ensuring patient safety. Initiatives like the 3Rs Collaborative and the FNIH’s VQN program are part of this broader effort, bringing together MPS developers, biopharma teams, and regulatory experts to define validation and qualification strategies for specific contexts of use. 

At AIM, we are actively participating in these initiatives to better understand where MPS and other NAMs can be most impactful in reducing animal use and align our R&D strategy. While full replacement of animal models remains a high bar, these collaborative efforts help clarify specific use cases where MPS can provide reliable, human-relevant data that informs drug development decisions. Every study and model that demonstrates reproducibility, scalability, and translational relevance moves the field forward–not just for AIM, but for the entire ecosystem of human-based preclinical research.

Choosing the Right Platform for the Right Question

The Organ-on-Chip (OoC) field today spans a spectrum of designs: from high-complexity systems modeling multiple tissues to simplified platforms that strike a balance between throughput and fidelity.

As just a few of the leading examples: companies like Emulate deploy integrated, instrumented platforms that support perfusion, mechanical actuation, and high-content imaging in automated formats (e.g. their AVA™ system). On the midsize end, CN Bio offers the PhysioMimix® line to support flexible configurations for single- and multi-organ studies, and TissUse has built multiorgan “HUMIMIC” chips that allow interconnected organ modules. In parallel, multiwell platforms offer more streamlined approaches, such as well-plate geometry with varying key elements, for example like MIMETAS with their OrganoPlate® supporting perfused 3D tissues with microfluidic flow and co-culture capabilities, or Altis Biosystems with their membrane-based RepliGut system. At the simplest end lie organoid, tumoroid and spheroid models in static well plates such as InSphero; scalable and accessible but lacking flow, gradients, and vascular interfaces.

Each platform carries trade-offs in engineering complexity, throughput, compatibility with automation, and reproducibility across labs – and clearly as a place and application it is ideally suited and delivering for. The choice of system should thus depend on the biological question in play: whether you require high fidelity (vascular) interfaces or high sample numbers for screening.

Henning: Walk me through AIM’s platforms. How should scientists think about choosing between idenTx® and organiX™?

Lizzy: AIM Biotech is a leading developer of organ-on-chip platforms designed to make physiologically relevant 3D cell culture accessible to every lab. Our systems are compatible with standard lab workflows, require no proprietary equipment, and deliver a low cost per data point. This combination of usability and scientific rigor has led to over 200 peer-reviewed publications by researchers worldwide. In addition to our off-the-shelf platforms, we also collaborate with biopharma partners to provide custom assay development services that help translate these models into their internal drug screening and development processes.

Both of AIM’s platform families—idenTx® and organiX™—are built on the same core architecture and design principles. Each features our three-channel microfluidic design, which recreates physiological tissue-fluid interfaces and supports the establishment of flow and chemical gradients. This enables researchers to generate perfusable microvascular networks, angiogenic sprouting, and directed 3D cell migration, for example. AIM’s platforms also include a gas-permeable laminate in place of a traditional coverslip, allowing efficient gas exchange without the need for pumps or rockers.

Both systems are SBS-compliant and fully compatible with automated liquid handling and in situ imaging, which allows integration into existing lab infrastructure. A major advantage of AIM’s technology is that it requires no proprietary hardware, such as plate rockers or perfusion systems, making it highly scalable and cost-effective.

The key distinction between the platforms comes down to tissue size and experimental intent. The idenTx® 40 platform is optimized for smaller tissue constructs and higher experimental throughput, making it ideal for screening studies, target validation, or mechanistic assays where you want statistically robust datasets across many conditions.

The organiX™ platform, by contrast, was engineered to support larger (up to 2 mm), more complex 3D tissues, such as organoids, tumor spheroids, and patient-derived biopsies. Its open-top design allows users to culture, perfuse, and retrieve tissues intact for downstream applications like histology and spatial omics.

In short, both platforms deliver the same core biological fidelity, it’s just a matter of what size your tissues are and what questions you’re aiming to answer. 

MPS Validation: Simplicity Over Complexity

In MPS development, there are competing approaches ranging from simplistic to quite complex. Simplicity may be equivalent to clarity of purpose and outweigh complexity, however, undisputedly, there are other, more intricate and complex approaches which are very successful as well. For each type of system there are ideal applications, but a field-wide understanding of what systems are ideal to establish for which type of context does not exist. Defining the specific biological function to model, and validating it with clear, quantitative benchmarks, yields data that is interpretable, reproducible, and aligned with regulatory expectations. 

Henning: Validation of MPS models can be complex and intimidating. How does AIM approach validation in a way that’s meaningful, actionable, and aligned with regulatory expectations? 

Lizzy: At AIM, we believe you don’t need to recreate the entire human body–or even every component of a specific organ–to generate meaningful human data. Instead, we focus on the key biological function(s) the model is designed to capture, adding complexity only where it serves the scientific purpose.

In our systems, that can mean modeling neovascularization, vascular barrier integrity, or immune cell-mediated tumor killing. By concentrating on these defined biological processes, we can establish clear, quantitative benchmarks that demonstrate both structure and function.

Ultimately, our goal is to make validation efforts data-driven, transparent, and directly tied to their intended use. This kind of focused validation provides the clarity that both the FDA and GAO are advocating for–and, in turn, gives our partners greater scientific and regulatory confidence in the data our models produce.

Context-of-Use (CoU): Path to Adoption

As the field matures, defining precisely how and where a model is intended to be used and would produce most useful data has become essential. Establishing a clear Context-of-Use (CoU), the link between a model and its specific, intended application in a regulatory, research, or clinical setting is critical for adoption. This helps to ensure that data are both interpretable and actionable. The growing emphasis on context marks an evolution from demonstrating biological sophistication to demonstrating regulatory and decision-making relevance.

Henning: “Context” has become a new key phrase across the community. How do you interpret that phrase in practice?

Lizzy: In practice, Context-of-Use, or CoU, is what turns a sophisticated biological model into a tool that can inform regulatory and development decisions. It’s about clearly defining the biological question, the endpoints you’ll measure, and how the data will be used, and then aligning that with the appropriate validation strategy. This clarity allows our partners to integrate MPS data confidently into their decision-making and, ultimately, regulatory submissions.

For AIM, the conversation shifts from “Can this model replicate human biology?” to “Can this model support a go/no-go decision in drug development?” The exciting part is that defining CoUs doesn’t stifle innovation; it actually accelerates adoption. Once a CoU is well-defined and supported with robust data, regulators, pharma teams, and CROs all understand how to interpret the results. That’s when MPS truly evolves from a research tool into a trusted platform for decision-making.

The Hardware Philosophy: Simplicity Enables Scale

Organ-on-Chip and other NAM technologies span a wide range—from simple static systems to complex, multi-component platforms with varying engineering needs, readouts, and investment requirements. Having come from the more “hardware-heavy” side of the field with the Nortis pump–platform–chip system, I’ve seen how complexity can both empower and hinder adoption. AIM Biotech takes a different approach, emphasizing simplicity and standardization to make microphysiological systems accessible and scalable across laboratories.

Henning: AIM’s designs stand out because they don’t need pumps, tubing, or rockers. Why did you take that approach?

Lizzy: At AIM, we’ve always believed that simplicity is what enables scale. Most labs don’t want to overhaul their existing infrastructure just to adopt MPS technology. From the beginning, we designed our systems to function like standard cell culture plates, meaning users only need to be proficient with handling pipettes to use our cultureware. Additionally, the platforms do not require any plate rocking or external perfusion systems, allowing users to place them directly in standard incubators and image the plates on existing microscopes. 

By removing pumps, tubing, and external hardware, we lowered the technical and financial barrier to entry and let scientists focus on the biology, not the plumbing. It’s this accessibility that allows both new and experienced users, including those without microfluidics or engineering backgrounds, to generate high-quality, human-relevant data right away.

Importantly, AIMs platforms are compatible with automated liquid handling systems, which enable fully automated cell culture setup, media exchange, and maintenance workflows. This same compatibility extends to high-content imaging and analytical systems, allowing researchers to streamline data acquisition and analysis while maintaining consistency across large experimental datasets.

And because our platform operates on familiar lab workflows, it can be easily scaled and reproduced across different teams, partners, and CROs–ensuring consistency from discovery through development. 

Henning: The geometry itself drives flow via capillary and hydrostatic forces.

Lizzy: Exactly. The geometry itself uses gravity to drive transient flow through capillary and hydrostatic forces, so there’s no need for pumps or external perfusion systems. Most users do not require continuous flow for their specific application. This simplicity not only keeps the platform affordable but also minimizes variability between users and labs. For studies requiring continuous perfusion, AIM provides accessories that enable syringe or peristaltic pumps to deliver controlled flow while maintaining the simplicity of the core workflow.

The recent GAO report emphasized that the lack of standardization remains a major barrier to broader MPS adoption. At AIM, we see our design philosophy as part of the solution. By providing a standardized, easy-to-use format, we make it far easier for researchers across institutions to reproduce results and build confidence in the data.

Back to simplicity vs. complexity: While simplicity lowers barriers to adoption, not every biological question can - or should - be studied in the simplest possible way. Certain physiological processes demand more controlled and dynamic environments. Vascular or tubular systems, for instance, require continuous flow to model shear stress and vessel remodeling, while some co-culture systems are best maintained under static or low-flow conditions to preserve barrier integrity. Achieving the right balance between simplicity and functional realism is key. 

Henning: What about calls for specific flow speeds and sheer forces, consistency of flow and direction of flow, especially in vascular systems?

Lizzy: That’s a great question and one that comes up often in the context of vascular modeling. Our platforms are designed to enable gravity-driven interstitial flow through controlled differences in media volumes between channels. This setup generates physiologically relevant flow rates and shear forces that are sufficient to trigger vasculogenesis, angiogenesis, and barrier maturation–all without requiring pumps or tubing.

That said, we recognize that certain studies benefit from precise control over flow velocity or direction. For those applications, AIM’s idenTx 3 and idenTx 9 platforms are fully compatible with syringe pumps, enabling continuous perfusion and tunable shear stress.

This flexibility allows researchers to start with passive flow for simplicity and scalability, and then move to active perfusion when their biological question demands tighter control. 

Validating the Vasculature: Function Over Form

Among the many systems modeled on-chip, vasculature remains one particularly demanding, technically and biologically. Replicating blood vessel structure is one challenge, replicating its function as a dynamic, selective barrier is another. This is even more true to tubular systems such as kidney proximal tubuli. True validation therefore requires more than visual confirmation of vessel formation; it must demonstrate physiological behavior such as permeability, transport, and responsiveness to stimuli. 

Henning: As a scientist and developer of some of the earliest models I have to ask for a science-heavy tangent: having personally worked for years on various vascular and kidney models, and found that functionality is the real test, how do you validate vascular integrity and flow in your chips?

Lizzy: Absolutely, and I agree that function is the real test of any vascular model. At AIM, we focus on validating both phenotype and function to ensure our vasculature behaves like it does in vivo.

We start by confirming that the morphology and spatial organization of the endothelial and supporting stromal cells mimic native tissue architecture. Using immunofluorescent staining, we assess the expression of key cell-specific and adhesion markers, as well as transport proteins that define the vascular subtype being modeled.

Once the structure and phenotype are validated, we move to functional assays. We routinely quantify vascular permeability using fluorescent tracers of defined molecular weights to measure solute transport over time. Beyond that, we’ve extended our analyses to include non-fluorescent compound transport, using ELISA or LC-MS, to directly quantify drug concentrations in both the vascular and tissue compartments.

In short, we’re not only looking at whether vessels form, but whether they actually function as physiological barriers and transport interfaces.

Henning: Are there target markers, e.g. transport or barrier proteins, that you have evidenced to be present as part of tissue relevance validation? What is the weight you put on immunofluorescence of (spatial) marker expression, proteome and transcriptome during tissue validation?

Lizzy: We take a multidimensional approach to validation. Image-based IF quantification confirms spatial expression of key vascular and barrier markers such as CD31, VE-cadherin, and transport proteins. We pair this with functional permeability assays to measure barrier integrity and solute transport. Additionally, transcriptomic and cytokine analyses provide deeper molecular insights, showing how cells respond and communicate within the tissue.

Our blood-brain barrier (BBB) model is a good example of this approach in practice. We’ve validated tight junction and transporter expression, such as ZO-1, Claudin-5, and P-gp, through both imaging and gene expression analysis. Functional assays further demonstrate selective permeability and receptor-mediated transcytosis, for example, via the transferrin receptor, confirming both passive and active transport mechanisms. Importantly, data generated using our BBB model were recently included in an IND filing by a biopharma partner, underscoring the model’s robustness and translational relevance.

Together, these validation layers provide a comprehensive view of structure and function, ensuring each model is human-relevant and fit for its intended use.

From Validation to Standardization: Advancing Reproducibility in MPS

As regulatory agencies increasingly endorse human-relevant data, the focus around Organ-on-Chip and broader microphysiological systems (MPS) is shifting toward integration and operational readiness. For biopharma organizations, the next frontier lies in making these models scalable, automatable, and suitable for regulatory inclusion. However, this transition requires not only scientific credibility but also workflow compatibility and standardized endpoints that map to recognized regulatory metrics. Yet, standardization and reproducibility remain persistent bottlenecks. Despite significant progress in validation and protocol refinement, variability in lab practices, assay design, and cell sourcing continues to challenge comparability and confidence in the data. Addressing these issues requires open, transparent methodologies, harmonized benchmarks, and standardized biological systems that reduce user-dependent variation while maintaining scientific rigor.

Henning: How do you keep results consistent across a wide community of users?

Lizzy: Consistency across a large user base starts with transparency and accessibility. All of our protocols, user guides, and product details are publicly available, and we continuously refine them based on user feedback and new insights, supported by a portfolio of more than 200 peer-reviewed publications using AIM’s platforms.

In that context, two main elements of standardization stand out: the cultureware and the biological materials. Our cultureware is fully standardized—injection-molded, SBS-compliant, and built on a 384-well plate footprint—ensuring compatibility and reproducibility across laboratories. 

The launch of our Cell Systems product line takes this further by combining our cultureware with standardized biology in the form of kits and assay-ready plates that are shipped pre-loaded with biological materials. For example, AngioPrime is an assay-ready angiogenesis kit, and the VasQ Kit provides users with the building blocks to generate perfusable microvascular networks. This approach dramatically reduces variability in cell sourcing and handling, which are some of the biggest drivers of inconsistency across labs, as noted in the GAO report. Our goal is simple: make complex human biology plug-and-play while maintaining scientific rigor, creating a practical path to global reproducibility. 

From Organoids to Organ-on-Chip: Overcoming the Static Barrier

Organoid and spheroid cultures have earned favor for their simplicity, scalability, and ability to recapitulate certain tissue features, but they remain fundamentally static models lacking perfusion, gradients, and extracellular or vascular elements. In contrast, Organ-on-Chip platforms overlay fluidic dynamics and engineered microenvironments precisely with the intention to emulate physiological behavior. However, integrating those added features brings challenges: complex microfabrication, bubble management, and difficulty in maintaining reproducibility across labs.

Henning: Organoid (and spheroid and tumoroid) cultures have their own advantages: simple, inexpensive, highly scalable. Where do organoid cultures fall short, and how does AIM Bio address the need for compartmentalization, more comprehensive 3D environments while maintaining standardization and reproducibility to fill the gap to static cultures? 

Lizzy: Organoids, spheroids, and tumoroids cultured in standard well-plates are powerful tools—they’re simple, cost-effective, and highly scalable, which makes them attractive for screening applications and basic mechanistic studies. However, these models are typically maintained as free-floating aggregates in media, without a 3D scaffold or structural confinement. As a result, they lack the extracellular matrix (ECM) support needed to reproduce key physiological processes such as directed 3D cell migration, tumor invasion into surrounding tissue, or immune cell infiltration through a matrix.

In static culture formats, tissues are also deprived of perfusion and chemical gradients, which limit their ability to model drug transport, vascularization, and cytokine or nutrient distribution—processes that are inherently dynamic in vivo. Without vascular or stromal interfaces, critical interactions between cell types can’t be fully captured.

With idenTx® and organiX™, we aim to address these gaps by combining the biological fidelity of organoids with the architectural and fluidic control of OoC systems. These platforms introduce 3D ECM and perfusable vascular networks that support dynamic biological phenomena such as angiogenesis, vasculogenesis, immune cell trafficking, and physiologically relevant drug penetration.

We see organoids are the starting material—valuable for their biological complexity—and idenTx® and organiX™ as providing the environment that unlocks their functional potential. By enabling vascularization, perfusion, and compartmentalization within a standardized, user-friendly format, AIM’s platforms advance organoid research toward more in vivo-like tissue models. Importantly, the open-top design of organiX™ allows for intact tissue retrieval and downstream analyses, including histology and spatial omics, providing deeper insight into these complex 3D systems.

In short, this isn’t about replacing organoids, but about evolving them—pairing biological sophistication with microengineered control to bring organoid cultures closer to living human physiology.

Automation, IND Readiness, and the Industry Shift

As the FDA and GAO move toward broader acceptance of New Approach Methodologies (NAMs), the focus for many developers has shifted from proving scientific validity to demonstrating operational readiness. For Organ-on-Chip technologies to influence real regulatory decisions, they must learn to integrate more seamlessly into existing discovery and development pipelines, and to deliver recognized endpoints in formats compatible with automation and high-throughput workflows. 

Henning: With FDA and GAO aligning around NAMs, how is AIM helping sponsors translate chip data into regulatory submissions?

Lizzy: While we offer drug screening services, custom model development, and pilot studies, the ultimate goal is to empower drug developers to adopt our technology in-house. Our services help translate complex biology into clinically relevant insights with recognized endpoints like permeability, cytotoxicity, and immune activation, ensuring the data aligns with regulatory expectations.

On the scalability and automation side, our plate-based architecture integrates seamlessly with automated liquid handlers and imaging platforms. We also collaborate with instrumentation partners to standardize workflows for cell culture, imaging, and data analysis.

This approach makes complex 3D assays reproducible, automatable, and scalable, enabling biopharma and CROs to run these models themselves as part of their internal workflows.

Our approach has been validated by IND submissions featuring AIM assay data that have been approved by the FDA.

Henning: This is what we have seen as necessary for pharma to increase adoption for a long time, thank you.

What’s Next

It is exciting to see Organ-on-Chip technologies evolving and maturing from specialized research tools into standardized, automation-ready platforms capable of producing human-relevant data at scale. AIM Biotech’s idenTx® and organiX™ systems exemplify this evolution, balancing physiological fidelity with operational simplicity and regulatory readiness.

By addressing key challenges in reproducibility, validation, and accessibility, AIM is helping to close the gap between early-stage research and translational applications. As policy, industry, and science align, the next chapter centers on integration: combining biology, automation, and analytics into seamless workflows that bring human-based modeling directly into mainstream drug development.

Henning: Where do you see AIM Biotech heading in the next phase of development?

Lizzy: Looking ahead, AIM Biotech is focused on expanding our Cell Systems portfolio into new applications, including the BBB and other complex tissue models. At the same time, we’re partnering with AI/ML and instrumentation companies to further increase throughput, speed, and reproducibility, making predictive, human-relevant data more accessible to the life sciences community. Our goal is to continue enabling researchers, drug developers, and CROs to adopt these models in-house, accelerating decision-making and advancing human-relevant drug development.

Henning: That’s the future the field has been pushing toward — integrated, robust, data-rich systems that merge biology, automation, and analytics into one seamless framework.

Lizzy, thank you for taking the time for this conversation. :)

Key Takeaways

• Regulatory alignment between the FDA, NIH, and GAO is accelerating the mainstream adoption of human-based preclinical models.

• AIM Biotech’s idenTx®, organiX™, and Cell Systems platforms combine standardization, throughput, and biological fidelity.

• Fit-for-purpose validation emphasizes reproducibility and relevance over complexity.

• Automation and AI analytics are redefining scalability and objectivity in data capture.

Summary

Organ-on-Chip technologies are no longer experimental luxuries but they’re operational assets. With the policy framework finally aligned, platforms like AIM Biotech’s are demonstrating what the next generation of preclinical research will look like: reproducible, regulatory-ready, and distinctly human.

The industry needs better evidence to drive adoption, not just better chips. AIM Biotech wants to help deliver exactly that.

Resources:

Most pertinent AIM Publications, FDA, NIH, GAO Article, Other Material (3Rs)

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