How Human-Relevant Models and Spatial Profiling Can Drive Precision Medicine

3D Biology and Spatial Profiling - Expert Insights with the Life Sciences companies of Danaher Visit DHRLS.CO 08 Important Considerations 12 Main Challenges 20 Solutions Table of Contents 06 Introduction to Human-Relevant Models and Spatial Profiling 28 Additional Resources 4 5 Abcam provides highly validated research tools including antibodies and assays to accelerate scientific, diagnostic and therapeutic research. IDT manufactures products used in diagnostic tests for many forms of cancer and most inherited and infectious diseases. IDT’s oligonucleotides are instrumental for decoding genomic DNA from the millions of crop varieties around the world, helping to develop crops that will withstand droughts, diseases and pest outbreaks. Aldevron provides critical nucleic acids and proteins used to make gene and cell therapies, gene editing technologies, DNA and RNA vaccines. Leica Microsystems develops leading-edge microscopes and scientific instruments to power technological advances and touch lives in meaningful ways. For more than 80 years, Beckman Coulter has been a trusted partner for laboratory professionals, enabling researchers to explore complex disease research and biological challenges by providing centrifuges, automated liquid handling systems and advanced cell culture and genomics solutions, play a critical role in life sciences. Molecular Devices provides highperformance bioanalytical measurement solutions for life science research, pharmaceutical and biotherapeutic development. Products include powerful platforms for high-throughput screening, genomic and cellular analysis, colony selection and microplate detection. The Life Sciences Companies of Danaher Genedata transforms data into intelligence with innovative enterprise software solutions that incorporate extensive biopharma R&D domain knowledge. Multinational biopharmaceutical organizations and cutting-edge biotechs around the globe rely on Genedata to digitalize and automate data-rich and complex R&D processes. From early discovery all the way to the clinic, Genedata solutions help maximize the ROI in R&D expenditure. Phenomenex is a global technology leader committed to developing novel analytical chemistry solutions that solve the separation and purification challenges. From drug discovery and pharmaceutical development to food safety and environmental analysis, Phenomenex chromatography solutions accelerate science and give researchers the tools they require to improve global health and wellbeing IDBS provides purpose-built software solutions to address the data management challenges prominent across the BioPharma lifecycle and supply chain. At SCIEX, our mission is to deliver solutions for the precision detection and quantification of molecules, empowering our customers to protect and advance the wellness and safety of all. The company was founded in 1970 to develop analytical instrumentation-based sensor technology for use in space. Since then, SCIEX has made its advanced analytical technology, including Mass Spectrometers & Capillary Electrophoresis Systems and available to the worldwide scientific community. Human-relevant models and spatial profiling are transforming drug discovery by providing more predictive, human-like data compared to traditional animal models and 2D cultures. Human-relevant models, such as organoids and 3D cell cultures, better mimic human biology, improving disease modeling, drug screening and precision medicine. Spatial profiling further enhances these insights by mapping cellular interactions and biomarker distribution, aiding in personalized treatments for cancer, neurodegenerative diseases and autoimmune disorders. These approaches reduce reliance on animal testing, aligning with regulatory shifts and improving early toxicity assessments. By bridging the gap between preclinical research and clinical trials, human-relevant models and spatial profiling accelerate drug development, ensuring safer, more effective treatments reach patients faster. The Life Sciences companies of Danaher provide integrated solutions for humanrelevant models and spatial profiling, addressing the need for more predictive models in drug discovery. With advanced imaging, automation and AI-driven analysis, we enhance data accuracy, optimize drug response insights and drive the next generation of precision medicine. Introduction to HumanRelevant Models and Spatial Profiling 3D Biology and Spatial Profiling 6 7 How can we understand the trade-offs between translatability and scalability in different cellular model systems? Important Considerations for Human-Relevant Models The expense of screening and developing drug candidates necessitates costeffective technologies that can more accurately recapitulate human physiology and response. Currently, screening potential candidates is primarily accomplished through simple bioassays and animal models. While these approaches provide information on drug safety, toxicity, efficacy and pharmacokinetic action, they have inherent limitations. This is evident by the high drug failure rate during clinical trials. 8 9 2 days We see a way to reduce time to assay from 17 days to just 2 days with experiment-ready human-relevant models. Molecular Devices 3D Ready Organoids High clinical trial failure rates Preclinical models often produce data that don’t accurately reflect human physiological responses Limited translatability Simple bioassays and animal models lack the complexity of human biology, reducing relevance and reliable data High cost Animal studies are costly, which limits scalability, requires significant resources and raises ethical concerns Need for better models The need for more relevant data earlier in drug development highlights a need for preclinical models that enable high-throughput screening of multiple candidates 9 The drug discovery and development fields are eagerly adopting microphysiological systems, such as organoids, to augment their research and offset clinical translation issues. These systems offer several key advantages: Improved physiological relevance – Accurately represents human physiology and pathology better than simple monolayer cell cultures Ethical benefits – Organoids reduce the reliance on animal testing and align with societal preferences for humane research practices Regulatory recognition – Recognized as a New Alternative Method in drug development by the FDA Modernization Act 2.0 Versatile applications – Serve as a valuable platform for small and large molecule testing, safety screening, toxicity and biomarker discovery Immortalized cell lines are widely used in drug discovery due to their wellcharacterized properties, ability to mimic diseases and ease of manufacturing. This makes them suitable for disease recapitulation and identification in cell-based models. However, limitations in translatability were encountered. In contrast, patient-derived organoids offer improved translatability as they closely resemble their tissue of origin, making them more physiologically relevant and better at predicting therapeutic outcomes. Why is light sheet microscopy wellsuited for long-term live imaging of 3D human-relevant models? Important Considerations for Imaging Human-Relevant Models Researchers use 3D imaging to study the development and dynamics of complex biological systems in detail, down to the single-cell level. This can reveal differences from experimental manipulations or compare the control and treatment. For example, the presence or absence of specific cells or changes to their morphology (e.g., shape, volume, length, area, etc.) are informative parameters. As a particularly gentle imaging technique, light sheet microscopy provides an unbiased view of processes over time. Light sheet microscopy is well suited for thick, delicate or dynamic samples such as tumoroids, spheroids or organoids. The noninvasive nature and its ability to acquire 3D data make it well-suited for time-lapse imaging studies. Light sheet microscopy can increase our understanding of complex biological systems in developmental biology, neuroscience, cell biology, drug discovery, cancer research and other fields. 10 11 Experience the key benefits of imaging large and complex samples with Leica Microsystems’ light sheet microscopy solutions: Capture sharp, uniformly illuminated images of large-volume specimens over extended periods Easily mount samples and maintain experimental protocols with minimal disruption Make on-the-fly adjustments during experiments for greater flexibility and convenience Study complex samples such as patient-derived tumoroids, spheroids and organoids with reliable, precise and versatile technology Choose from stand-alone systems or integrated solutions for fast, gentle volumetric imaging Push the boundaries of research with advanced imaging tools and AI-driven analysis software designed for high performance and reproducibility Watch the full webinar to discover: ɉ How to standardize human-relevant model culture with purpose-built automation to increase reproducibility ɉ Cutting-edge imaging and AI-based image analysis for deep characterization of human-relevant models ɉ Strategies for collaboration to scale your human-relevant model programs Bridging the Gap: Advancing Human-Relevant Models for Real-World Impact Webinar Light sheet microscopy is a technique enabling imaging of organoids and larger samples. It excites the sample parallel to the focal plane, perpendicular to the detection objective, providing optical sectioning with a thin excitation plane. This reduces phototoxicity and photobleaching while allowing high-speed imaging. For long-term imaging of humanrelevant models, minimizing phototoxicity is crucial to prevent ROS generation and thermal damage from intense laser exposure. 12 13 Increasing complexity in cellular biology presents challenges, as highlighted by the scientific community’s emphasis on scaling, reproducibility and accessing large, diverse model populations with batch consistency. One way to achieve the required reproducibility is by providing platform technologies that help industrialize these processes, converting manual approaches into more reliable, routine ones through automation. Main Challenge: Reproducibility What are the main challenges associated with using human-relevant models? Drugs fail in clinical trials because data generated across pre-clinical R&D and CMC don’t always provide the necessary clinical predictive power or relevancy. Monolayer cell cultures and animal models are limited in predicting adverse effects and accurately reflecting the physiological conditions of human tissues. Additionally, they often fail to replicate the complex structure, cellular interactions and functional responses of native tissues. In contrast, organoid systems are becoming more widely used as pre-clinical models because they: ɉ Recapitulate key features of cellular architecture and function ɉ Provide relevant, translatable data on drug functionality, kinetics and toxicity ɉ Present a more cost-effective and ethical solution than animal models However, manual culturing and maintenance of organoids and other complex 3D microphysiological models is cumbersome and fails to meet the demand for large-scale drug screening studies. The process starts with a 2D pre-culture phase, progressing to 3D cell culture and organoid formation, which typically takes weeks. Manual handling increases inter-batch variability, potentially undermining the consistency and reliability of organoid data. 14 15 The goal should always be to avoid risks such as poor imaging resolution, non-reproducible results and wasted resources. This starts with selecting the right antibodies when building your panel. A properly planned spatial profiling experiment can deliver high-quality data, including the identification of new biomarkers, by leveraging antibodies that accurately target the intended antigen without cross-reactivity. Your panel must also be validated for your assay. This attention to detail enhances the overall robustness and validity of the findings. Main Challenge: Antibody Specificity and Sensitivity How does antibody specificity and sensitivity impact multiplex and spatial profiling experiments? Precise detection of biomarkers, antigens and identified targets in multiplex experiments largely hinges on the specificity and sensitivity of the antibodies used. In the realm of spatial profiling, particularly when characterizing human-relevant models, assay-validated and highly specific antibodies are essential. Promiscuous antibodies increase off-target binding, which can call into question the reliability of the data obtained. Prioritizing antibody specificity and sensitivity is paramount to advancing your understanding of complex biological systems. • Inaccurate, non-reproducible results can lead to unreliable interpretations of complex biological phenomena • Lost samples lead to the need for repeated experiments and result in the loss of important materials, including primary tumor samples • Increased spending on reagents, equipment and time for troubleshooting and reevaluating experiments 16 17 When imaging 3D human-relevant models, we often want to image samples for days or weeks, which isn’t always easy with many platforms. We aim for high resolution, relatively fast imaging and enough temporal resolution to observe cell divisions and movements without causing phototoxicity or photobleaching. Conventional microscopes typically require prolonged light exposure, which can harm the sample. Main Challenge: Phototoxicity and Photobleaching What are the main challenges when imaging 3D human-relevant models? Evaluation of 3D models through microscopy remains the principal method for assessing physiological responses and obtaining accurate, high-resolution imaging results. However, using conventional imaging techniques presents its challenges: ɉ Prolonged and repetitive exposure to intense light, elevated temperatures or toxic imaging agents can cause phototoxicity and compromise cell viability ɉ High-intensity laser exposure during manual optimization of imaging parameters can lead to photobleaching, which impacts the accuracy of results ɉ Maintaining culture-like conditions to ensure accurate evaluation of organoid growth and morphology over time ɉ Difficult image acquisition and resolution due to light scattering and attenuation of the depth and opacity of the samples 18 19 Swift insights and connectivity across departments, organizations and external collaborators are fueling the labs of the future. Automated and AI-driven assay analysis is table stakes for global analytical teams. Organizations that embrace advanced digital tools to contextualize their scientific data will benefit from more efficient research processes. Main Challenge: Data Analysis What challenges do researchers face when characterizing complex organoid models? Organoid screening is increasingly leveraged in drug discovery due to its ability to model complex tissue architecture and cellular interactions. However, fully characterizing these multicellular, heterogeneous systems demands a broad array of assays—including imaging, luminescence, cytokine profiling, calcium signaling and gene expression analysis. Manual assay analysis and gathering data from multiple tools can prove cumbersome and unreliable. ɉ The diversity of data types introduces significant challenges in assay analysis and data integration ɉ Manual processing and the use of different tools slow down analysis workflows and introduce inconsistencies that compromise data reliability ɉ Improper or fragmented analysis practices can create noise, reduce reproducibility and hinder the translational potential of organoid-based findings The pressure to move drugs to clinical trials faster has increased the demand for scalable, high-throughput screening models. 3D organoid challenges, like reproducibility, scalability and labor-intensive protocols, shouldn’t limit their broader adoption. To address these limitations, Molecular Devices has developed the CellXpress.ai® Automated Cell Culture System—a fully integrated platform that automates and standardizes both 2D and 3D cell culture. This system enhances reproducibility, scalability and efficiency to enable high-content organoid culturing and screening through: This purpose-built platform makes advanced cell models more accessible for drug discovery by improving assay reliability and throughput. CellXpress.ai, an automated fed-batch bioreactor for industrializing organoid culture, especially for iPSC and PDO models needing a matrix. It enables continuous perfusion, large-scale production of up to 18 million uniform organoids per batch, boosting capacity 25x over manual methods. The system supports drug perturbation, speeding up patient-derived organoid research. It integrates liquid handling and a high-capacity incubator (up to 154 plates) for automated feeding, seeding and passaging. Its unified software eliminates the need to manage multiple instruments, using AI, machine learning, K² analysis and neural networks for imageguided decisions, automating culture progression and industrializing human-relevant models. Molecular Devices CellXpress.ai Automated Cell Culture System 20 21 Solution: Industrializing Human-Relevant Models What advancements are being made in automating and scaling cell culture to support humanrelevant biological models? 25x We see a way to boost in-house organoid production by 25 times compared to culturing cells by hand. Molecular Devices CellXpress.ai™ Automated Cell Culture System Automated cell monitoring using built-in incubation, liquid handling, media exchange, reagent addition and imaging Automated quality control and sample tracking throughout the entire lifetime of 2D and 3D cell cultures Built-in imaging to track the cell journey and provides imagebased decision-making AI-powered software that acquires and analyzes data, automates complex workflows and scheduling and streamlines processes to reduce variability Read the full App Note to discover: ɉ Automated and scalable workflow for organoid handling and screening ɉ Deep learning segmentation (SINAP) and phenotypic classification (Phenoglyphs™) via IN Carta® Image Analysis Software ɉ High-throughput and reproducible results with reduced manual intervention ɉ Enhanced physiological relevance for intestinal toxicity assessment AI-enabled toxicity screening using human intestinal organoids Application Note Choosing fully validated antibodies is essential for improving the quality of insights gained from imaging workflows. When antibodies show high specificity and sensitivity and are validated for your specific application, the results accurately reflect the true biological context. This accuracy allows for more reliable interpretation of complex spatial relationships and the distribution of biomarkers within tissues. Abcam’s mission is to keep your research moving forward. For that, you need reagents you can trust to deliver reliable, accurate results. Their leading quality management system works from the very beginning of product development to after product launch to ensure the high standards of antibody quality you expect. Their quality is backed by the following: Our comprehensive portfolio of antibodies is designed to empower scientists worldwide in their quest to unravel the fundamental complexities of biology and disease and drive scientific breakthroughs. We offer a vast selection of highly cited antibodies, including monoclonal and polyclonal antibodies, along with an unmatched range of recombinant monoclonal antibodies. Explore Abcam’s validation process from beginning to end and find out how premium recombinant antibodies can help you. 22 Solution: Fully Validated Antibodies How does vendor quality control impact antibody specificity, sensitivity and reliability? Biophysical characterization and quality control(QC) confirm antibody identity at the molecular level, ensuring the very highest batch-to-batch consistency Application screening based on the target product profile Knock-out validation including the use of positive and negative cell lines, gives you ultimate confidence in your antibody’s quality Abcam’s leading quality management system ensures antibodies perform as indicated for their specific applications. Their process includes biophysical characterization, application-specific testing and knockout validation to confirm the antibody identity. 23 Utilizing cutting-edge imaging technologies significantly enhances the study of biological systems by reducing photobleaching and phototoxicity. This allows researchers to capture high-resolution images over extended periods, ensuring the integrity of delicate samples while unveiling intricate cellular dynamics. Evaluation and extracting actionable insights through microscopy remains the principal method for assessing complex cell models and tissue samples. Leica Microsystems’ portfolio includes purpose-built imaging platforms that provide the required deep characterization of organoids while minimizing laser-induced artifacts. Leica Microsystems’ Viventis Deep combines multi-view and multi-position light-sheet imaging to increase spatio-temporal resolution of your complex biological systems at the cellular level. Its open-top configuration and multi-position capabilities enable efficient, parallel data collection across diverse conditions. Leica Microsystems’ Mica is a purpose-built microhub that makes microscopy accessible to more scientists, enabling easier live cell imaging under physiological-like conditions. By eliminating over 85% of setup steps needed to get to the first image and automating imaging settings, Mica empowers users to quickly generate higher-quality, accurate results with confidence and minimal technical input. This results in 33% less time to the first image and 4x more data with 100% correlation. Leica Microsystems’ Cell DIVE Multiplex Imaging Solution is a precise, open multiplexing solution that helps researchers deepen their understanding of the tissue microenvironment by offering outstanding spatial mapping of single cells within context. Unveil whole tissue imaging down to the single cell level, automatically calibrated and corrected to enable quality analysis downstream. Leica Microsystems Viventis Deep Leica Microsystems Mica Leica Microsystems Cell DIVE Multiplex Imaging Solution 24 25 Solution: Advanced Imaging Platforms What innovations are helping reduce phototoxicity and photobleaching in spatial profiling and multiplex imaging? 50% We see a way to train users 50% faster to image organoids and 3D cultures. Leica Microsystems Mica – The world’s first Microhub Read the full App Note to discover: ɉ Challenges encountered when imaging 3D culture models ɉ Key considerations for imaging organoids and spheroids ɉ Solutions for examining dynamic processes in organoids and spheroids in real-time ɉ Going deeper into 3D with correlative light and electron microscopy (CLEM) Advancing 3D Culture Imaging: Unleashing the power of microscopy Application Note Integrating Leica Microsystems’ Aivia AI Image Analysis Software can overcome subjectivity and poor reproducibility during image analysis. Aivia is a uniquely innovative and complete 2-to-5D image visualization, analysis and interpretation platform designed for the reliable processing and reconstruction of highly complex images. Aivia AI Image Analysis Software Key Benefits: ɉ Get to insights faster with a 69% speedup in 3D analysis pipelines ɉ Over 45 microscopy file formats supported ɉ Easy to use machine learning segmentation and classification tools Genedata Screener Key Benefits: ɉ 360° view of organoid data in minutes ɉ Automate and standardize assay analysis ɉ Speed up decision-making Genedata Screener automates data capture and analysis needed for functional characterization of 3D organoid systems. It ensures that data is analyzed the right way and the same way, every time. The software also incorporates AI to enable entirely automated, unbiased analyses of organoid images collected across assays for faster decision-making. Removing subjectivity and increasing reproducibility Automating data capture and analysis 26 27 Imaging assays used in drug discovery and development have become increasingly complex. As organoid research continues to evolve, implementing robust analytical tools is becoming imperative for streamlining the application of 3D culture testing. AI-driven analysis methods have the potential to deliver high-quality results in an automated, unbiased way and yield biological insights not accessible via manual methods. Solution: Unbiased Insight Creation What impact does data analysis have on translational research using human-relevant models? 74% 50% We see a way to reduce time from raw image to fully analyzed data by up to 74%. Leica Microsystems Aivia AI Image Analysis Software We see a way to increase assay sensitivity by 50% using AI-based phenotypic classification Genedata Genedata Screener Lung Organoids as an Assay Model for In Vitro Assessment of Toxicity Effects by 3D High-Content Imaging and Analysis Exploring the Tumor Immune Landscape Using Multiplexed Imaging and AI-Powered Spatial Analysis 3D Tissue Imaging: From Fast Overview to High Resolution with One Click From Imaging to Insight: Cell Cycle Mapping in Tumors with Advanced Multiplexing & Spatial Profiling Scale Up Your Screening: Integrating Automation Into 3D Biology for Therapeutic Drug Discovery See How the CellXpress.ai Automated Cell Culture System Transforms Cardiovascular Research How to Choose and Use Antibodies Transforming Research with Spatial Proteomics Workflows 28 29 Additional Resources Application Note Webinar Application Note Webinar Webinar Webinar Application Note Application Note For research use only. Not for use in diagnostic procedures. ©2025 DH Life Sciences, LLC, DH Tech. Dev. Pte. Ltd., Genedata AG, Leica Microsystems CMS GmbH, Wetzlar, Germany. Subject to modifications., Molecular Devices, LLC., ID Business Solutions, Ltd. All rights reserved. LEICA and the Leica Logo are registered trademarks of Leica Microsystems IR GmbH. Trademarks and/or registered trademarks mentioned herein, including associated logos, are the property of AB Sciex Pte. Ltd. or their respective owners in the United States and/or certain other countries. Visit DHRLS.CO Our experts apply Danaher’s life science technologies and proven solutions, working with you to design and implement integrated workflow solutions that can dramatically reduce time & costs of bringing advanced therapies to market.