Animal models often fall short of predicting human outcomes, creating costly translational failures. Human-on-a-Chip systems address this by reproducing key aspects of human physiology to generate clinically relevant insights into the safety and efficacy of therapeutics. Combined with quantitative PK/PD modeling, these platforms deliver human-relevant preclinical insights and enable research into rare diseases where models are limited or non-existent. This talk covers three applications:

First, a cardiac ischemia model that imposes controlled hypoxia and reperfusion within a multi-organ context. Contractile force, electrophysiology, and injury biomarkers quantify damage and recovery enabling evaluation of candidate therapeutics.

Second, a patient-specific neuromuscular junction (NMJ) model for Charcot-Marie-Tooth type 2S. Using iPSC-derived motoneurons and skeletal muscle from the patient alongside healthy controls, we recapitulated NMJ dysfunction and quantified rescue by the client’s therapeutic, as measured by functional readouts. This N-of-1 study supported the FDA’s decision to grant Orphan Drug Designation of a sponsor’s therapeutic illustrating how these platforms can guide therapies for diverse genetic disorders.

Third, we extend our multi-organ PK/PD capabilities to the first published Digital Twin informed by an organ-on-a-chip system, in which longitudinal biological data informed in silico models to predict response and improve translatability.

Together, these studies show how integrated human biology and quantitative modeling can reduce reliance on animal studies, de-risk development, and shorten the path from preclinical insight to clinical decisions.

Learning Objectives:

1. Describe the principles of multi-organ Human-on-a-Chip systems, and list which clinically relevant readouts are used to model cardiac ischemia and recovery.

2. Describe how a Human-on-a-Chip informed Digital Twin is established and explain its potential to improve drug development.

3. Evaluate the integration of organ-on-a-chip data with quantitative PK/PD modeling and digital twin approaches to improve clinical translatability.

From 12-1 PM PT on the day of the event, Labroots is excited to offer a variety of interactive networking opportunities designed to help you engage, explore, and expand your network.

Connect with fellow attendees in the social space through Speed Networking, chat with poster authors during our live Poster Discussion, and earn bonus points by visiting booths in our Exhibit Hall. See you there!

Traditional animal models and simplified cell cultures often fail to capture human biology, limiting progress in biomedical research and drug development. Emerging microfluidic "Organ-on-Chip" technologies provide biomimetic in vitro models that more accurately replicate human tissues and physiological responses. This session will highlight how these platforms are transforming basic and translational research in human health.

Learning Objectives:

1. Describe the design and function of human organ chips as advanced in vitro models of human physiology.

2. Explain how organ chip technologies can be applied to study disease mechanisms, drug responses, and toxicity.

3. Evaluate the potential of organ chips to complement or replace traditional preclinical models in advancing human health research.

Designing robust and effective flow cytometry experiments requires careful consideration of fluorochrome selection, panel design, and up-to-date immune cell subset information. In this talk, we will explore how the FluoroFinder platform goes beyond simple panel building or spectral viewing to provide a holistic suite of tools that streamline the entire experimental workflow. From vendor-integrated product search and the comprehensive Dye Directory, to the CellTypes tool for current immune subset markers, FluoroFinder brings essential resources together in one cohesive platform.  

Attendees will learn how to:

• Leverage the IntelliPanel automated panel design tool.

• Validate panel combinations with instrument-specific settings using the Spectral Viewer.

• Take advantage of premium features such as inventory management, automated product suggestions, auto-antigen density settings, and supplier preferences.  

Designed with user experience and the expansion of fluorescence knowledge in mind, FluoroFinder empowers researchers to create well-informed, functional, and optimized panel designs efficiently, helping them achieve their brightest research yet.

Protein structures are now being resolved at the atomic level, but deciphering their molecular organization in the cell remains a challenge. Super-resolution microscopy enables the use of fluorescent-based molecular localization tools to study molecular structure at the nanoscale level in the intact cell, bridging the mesoscale gap to classical structural biology methodologies. SuperResNET is an integrated machine learning-based analysis software for visualizing and quantifying 3D point cloud data acquired by single molecule localization microscopy (SMLM). The computational modules of SuperResNET include correction for multiple blinking of a single fluorophore, denoising, segmentation (clustering), and feature extraction, which are then used for cluster group identification, modularity analysis, blob retrieval and visualization in 2D and 3D. More recent updates to SuperResNET allow two-channel interaction distance analysis to determine how two proteins interact within macromolecular assemblies. SuperResNET can be effectively and easily applied to any SMLM event list from which it rapidly learns macromolecular architecture in the intact cell. I will describe the ability of network graph analysis software (SuperResNET) to determine molecular structure from dSTORM and MinFlux single molecule localization microscopy. Use cases to be described include molecular analysis of the nucleopore complex, structural changes to clathrin coated pits by inhibitors of clathrin endocytosis and the identification and structural characterization of caveolae and non-caveolar caveolin-1 scaffolds.

Learning Objectives:

1. Explain how SMLM breaks the diffraction barrier

2. Compare structure determination by SuperResNET to that obtained by cryoEM

3. Describe the structure and function of Cav1 scaffolds and caveolae

Embodying intelligence into materials requires engineering systems that can autonomously sense, adapt, and respond to environmental stimuli, similar to the dynamic behaviours of living organisms. Realizing this in practical devices remains a scientific grand challenge with direct implications for soft robotics, bioengineering, and medicine. Researchers have previously developed stimuli-responsive hydrogels and biohybrid constructs that interface with living systems; however, these devices often remain tethered, constrained, or limited to specific environments, such as patterned surfaces. In this talk, I present my research on untethered, thermoresponsive hydrogel robots that crawl autonomously across unpatterned surfaces. I designed multisegmented bilayer gelbots composed of active poly(N-isopropylacrylamide) (pNIPAM) and passive polyacrylamide (pAAM), connected by suspended linkers. We validated the experiments using finite element simulations and proved these robots consistently achieve unidirectional motion through spontaneous asymmetries in contact forces generated during an actuation cycle. I further validated the model by demonstrating that I could tune gelbot displacement through design parameters such as linker stiffness, morphology, and number of bilayer segments. This framework charts a path toward untethered, intelligent soft robots with applications in targeted drug delivery, minimally invasive surgery, and programmable bio-actuation.

Learning Objectives:

1. Describe how thermoresponsive hydrogels enable autonomous movement in untethered soft robots.

2. Explain how design parameters such as linker stiffness, morphology, and bilayer segmentation influence gelbot displacement.

3. Assess potential biomedical and engineering applications of untethered hydrogel-based soft robots.

Cells in the body never experience the 21 percent oxygen levels of a standard incubator, yet much of biomedical research is still carried out under these artificial conditions. This webinar highlights why adopting physiologically relevant oxygen levels is essential for accurate, reproducible science. Dr. Krista Rantanen will explain how shifting from traditional normoxia to physioxia can transform cell culture studies, improve drug development models, and reveal hidden biological effects that high oxygen levels mask. Join this session to see how small changes in experimental oxygen conditions can make a big difference in advancing discovery and translational research.

Early detection of safety liabilities of new therapies is a critical biopharmaceutical challenge. Addressing this challenge could significantly advance drug discovery. Advanced human cell models, including microphysiological systems (MPS), aim to recapitulate the architecture, cell-to-cell interactions, and microenvironment of a given tissue, making them more representative of complex in vivo biology than standard two-dimensional culture. Hence, human MPS are particularly well-suited suited to enhancing translation of pre-clinical model outcomes to clinical settings.

In Clinical Pharmacology and Safety Sciences at AstraZeneca, we are developing advanced human cell models tailored to various organs and safety applications, depending on the context of use. This presentation will showcase one example of successful adoption of MPS for pre-clinical safety assessment: our human 3D static and fluidic (MPS) bone marrow (BM) models. Our models recapitulate key aspects of living BM, maintaining stem/progenitor cells and supporting differentiation into erythroid, myeloid and megakaryocyte lineages. This allows capture of lineage-specific haematotoxicity associated with monotherapy and combination therapies, informing candidate drug selection, and guiding oncology drug combination dosing and scheduling. Integrating data from these models with Quantitative Systems Toxicology modeling approaches is crucial for accurate safety assessments and clinical translation. 

Despite the potential of advanced cell models to enhance the human relevance of pre-clinical safety assessments, challenges to their widespread adoption and development in the pharmaceutical industry remain. These challenges include a lack of standardization, high costs and time requirements, and low sample quantities for downstream analyses. This presentation will also address these challenges and present opportunities to further improve advanced cell models and thereby drive their adoption in the industry.

Learning Objectives:

1. Describe how advanced human cell models, including MPS, enhance the translation of pre-clinical outcomes to clinical settings.

2. Illustrate how human bone marrow MPS capture lineage-specific hematotoxicity to inform drug selection and dosing strategies.

3. Discuss current challenges to adopting advanced cell models in the pharmaceutical industry and propose opportunities for improvement.

So-called new approach methodologies (NAMs) including human cell-based microphysiological systems (MPS) are poised to revolutionize preclinical science and improve the success rate of candidate therapeutics in clinical trials. To achieve these goals, it will be critical to capture aspects of individual physiological differences such as biological sex and hormone status in microphysiological systems and other NAMs. Sex-specific cell culture methods and MPS can enhance our understanding of how biological sex influences health and disease. Our laboratory has demonstrated baseline sex differences in numerous 2D culture and MPS bioassays when a common cell culture medium is used for both sexes. To address this limitation, we developed sex-specific culture methods based on culturing female cells with estradiol and male cells with dihydrotestosterone, the concentrations of which can be tuned to yield sex-equivalent baselines in select 2D and MPS bioassays. This talk will emphasize the application of these culture methods to create sex-specific MPS models of diabetic retinopathy. Sex-matched combinations of primary human retinal microvascular endothelial cells and ocular fibroblasts were used to construct MPS models of an endothelial barrier and vascular beds. Estradiol protected against pathological changes induced by diabetic culture conditions, such as increased barrier permeability and basement membrane thickening, in female but not male models. Dihydrotestosterone failed to protect against pathological changes in both female and male models. These results are compatible with clinical observations of increased incidence and severity in male patients. Further refinement of sex-specific MPS will enable the investigation of sex-based precision therapies that target sex hormone signaling in diabetic retinopathy and other diseases. 

Learning Objectives:

1. Describe how new approach methodologies (NAMs) and microphysiological systems (MPS) can improve preclinical research and therapeutic development.

2. Differentiate the impact of sex-specific cell culture methods on baseline responses in 2D and MPS bioassays.

3. Interpret findings from sex-specific MPS models of diabetic retinopathy to evaluate implications for precision therapies.

Peripheral neuropathy (PN) is a dose-limiting side effect of chemotherapeutic and antibody drug conjugate (ADC) treatment which significantly impacts patients’ quality of life. Despite a high clinical incidence of PN across monomethyl auristatin E (MMAE)-ADCs, it has not been predicted from standard preclinical toxicology studies. Advanced cell models including microphysiological systems (MPS) have the potential to bridge this gap and improve the predictive assessment of PN, enhancing the early selection of safer ADCs and improving clinical success. 

To model PN in vitro, axonal outgrowth MPS model incorporating human iPSC-derived peripheral neurons was employed. Neurons were embedded in extracellular matrix in the OrganoPlate®, a 3D microfluidic culture platform with 40 chips. The axons extend into an adjacent layer of gel, while the dendrites and soma remain in the somal compartment. Toxicity was assessed over three timepoints (48, 72, 96 h) and a clinically relevant concentration range, by labeling the axonal networks with calcein-AM and quantifying axonal outgrowth following confocal microscopy.

Our findings demonstrate the success of our MPS in vitro model to capture chemotherapeutic- and ADC-induced neurotoxicity, which was observed as a dose- and time-dependent disruption of the neurite network following compound exposure. Importantly, the compounds tested could be ranked by the level of neurotoxicity induced, highlighting the potential value of in vitro models as tools to select molecules with an improved PN toxicity profile for further progression, circumventing dependence on animal toxicology models. 

Learning Objectives:

1. Analyze how advanced cell models including micrphysiological systems (MPS) may bridge the translational gap between preclinical safety models of peripheral neuropathy (PN) and the clinic.

2. Interpret how to test a MPS of peripheral neuropathy (PN) to better select molecules for an improved PN profile.

3. Analyze axonal outgrowth data from an MPS model to assess dose- and time-dependent neurotoxicity of chemotherapeutics and ADCs.