Upscaling Organoid Research for Sharper Biological Insights

Upscaling organoid research for sharper biological insights. For research use only. Not for use in diagnostic procedures. Upscaling organoid research for sharper biological insights.2 Organoids provide an opportunity to create cellular models of human disease, which can be used to understand underlying disease mechanisms and identify possible treatments. However, the culture and analysis of organoids presents complex challenges, especially when it comes to scaling up for drug discovery purposes. This guide will help you navigate these challenges and find innovative solutions to enhance organoid research. Unravel the mysteries of human disease Upscaling organoid research for sharper biological insights. 3 The organoid research workflow An organoid experiment can take between 7-10 weeks, requiring many steps that bear equally as many potential sources of error. To scale up, standardize and achieve greater biological insights, researchers need to rely on automation and multi-dimensional datasets. Organoid Formation Phenotyping Pertubation, CRISPRi/RNAi or Compounds (2) PhenoVue™ probes & cell painting assays HIVE CLX™ scRNA sequencing Detection Assays: Luminescence, Alpha, and HTRF® Cellular Imaging (4) Transcriptomics (5) Cell Health & Marker detection (6) Analysis 2D or 3D Pre-culture, CRISPR gene editing Cell Seeding for 3D culture (2) Media exchange (2) and growth control (3) 2. JANUS® liquid handler 1. Cellaca™ cell counter 3. Celigo Image Cytometer or or Cell counting (1) ULA 5. HIVE scRNAseq 6. VICTOR® Nivo™ plate reader 4. Opera Phenix® Plus high-content imager Hydrogel DOME Repeat until full maturation Upscaling organoid research for sharper biological insights. 4 Seamless science from culture to insights with automation Scale up your organoid workflows by integrating market-leading platforms. Our flexible, modular workstation solutions allow you to: Gain back time Ensure skilled researchers aren’t tied to cell culture See everything Resolve the subtlest phenotypic changes with high-end imaging Reproduce results Remove human error and technical sources of heterogeneity Increase scale Rapid processing provides the capacity to increase experiment scale Upscaling organoid research for sharper biological insights. 5 Nathan Gödde, Ph.D., Manager Australian Organoid Facility University of Queensland, Australia “The modular design of our custom-built Cell::Explorer system future proofs our facility so we can keep pace with the rapid growth and demand for the kinds of biologically complex models we make.” Ben Hopkins, Ph.D., Asst. Professor Genetic and Genomic Sciences, Mount Sinai School of Medicine, New York, USA “Our workstation integrating the CLS and Phenix high content imagers allows us to rapidly test thousands of treatments across hundreds of patient derived organoid models in a highly reproducible and stable manner, so we can rapidly identify tumor specific drug sensitivities.” Dr. Lynn McGarry, High-Content Imaging Lead, CRUK Beatson Institute, Glasgow, UK “What we get from the Opera Phenix/plate::handler combo is the ability to combine high-content with high-throughput.” Organoid research stories We have helped leading institutions discover new ground with automated solutions for organoid development and analysis. Our custom workstations are helping researchers address their organoid challenges every day. Read their stories. Upscaling organoid research for sharper biological insights. 6 Nathan Gödde, PhD, University of Queensland, Australia Flexibility run many different organoid experiments. “Need Testimonial.” Ben Hopkins, PhD, Mount Sinai School of Medicine, New York, USA Speed rapidly test patient-derived samples. “Our workstation integrating the CLS and Phenix high content imagers allows us to rapidly test thousands of treatments across hundreds of patient derived organoid models in a highly reproducible and stable manner, so we can rapidly identify tumor specific drug sensitivities.” Dr. Lynn McGarry, CRUK Beatson Institute, Glasgow, UK Simplicity automates the part of the process that matters to you “What we get from the Opera Phenix/plate::handler combo is the ability to combine high-content with high-throughput. Xingyu Zhou, Central South University, Changsha, China Hands free, multi-modal system for long-term experiments “Need Testimonial.” LEARN MORE LEARN MORE LEARN MORE LEARN MORE Meet our customers The goal: Providing quality-assured and standardized organoids at a greater scale and innovating complex 3D biological research. The build: Custom-built explorer G3 organoid/3D workstation with HEPA-filtered enclosure for organoid culture, monitoring, and high-content imaging. The solution: The AOF can now automate a range of protocols for organoid production and can phenotype effects from various treatments using high-content assays. Through automation, their organoids are much more affordable at scale. Class 100 enclosure with 4x HEPA filter units Liconic 37°C incubator Plate::handler robotic arm Liconic 4°C incubator JANUS liquid handler Celigo image cytometer Opera Phenix Plus HCS system Case study: Australian Organoid Facility (AOF), University of Queensland, Australia Nathan Gödde, Ph.D., Manger Australian Organoid Facility Upscaling organoid research for sharper biological insights. 7 Nathan Gödde, PhD, University of Queensland, Australia Flexibility run many different organoid experiments. “Need Testimonial.” Ben Hopkins, PhD, Mount Sinai School of Medicine, New York, USA Speed rapidly test patient-derived samples. “Our workstation integrating the CLS and Phenix high content imagers allows us to rapidly test thousands of treatments across hundreds of patient derived organoid models in a highly reproducible and stable manner, so we can rapidly identify tumor specific drug sensitivities.” Dr. Lynn McGarry, CRUK Beatson Institute, Glasgow, UK Simplicity automates the part of the process that matters to you “What we get from the Opera Phenix/plate::handler combo is the ability to combine high-content with high-throughput. Xingyu Zhou, Central South University, Changsha, China Hands free, multi-modal system for long-term experiments “Need Testimonial.” LEARN MORE LEARN MORE LEARN MORE LEARN MORE Meet our customers The goal: To establish functional drug testing of multiple treatment options in patient-derived cancer organoids within clinically relevant time frames. Need to fit into a very small laboratory. The build: Custom-built explorer G3 organoid/3D workstation with HEPA-filtered enclosure for culture, non-contact compound dispensing, multi-mode detection, and live cell high-content imaging. The solution: Within 3 years, Mount Sinai School of Medicine have tested 200 patient-derived samples for drug sensitivity. After organoid expansion, they can test 338 drugs with 6-point dose-response curves in triplicate over 14 days. They can also test drug combinations to identify agents that cooperate. Case study: Mount Sinai School of Medicine, USA Ben Hopkins, Ph.D., Asst. Professor Genetic and Genomic Sciences HEPA filter units Liconic 37°C incubator Echo liquid handler JANUS liquid handler Operetta CLS system Opera Phenix Plus HCS system Victor Nivo plate reader JANUS liquid handler Upscaling organoid research for sharper biological insights. 8 Nathan Gödde, PhD, University of Queensland, Australia Flexibility run many different organoid experiments. “Need Testimonial.” Ben Hopkins, PhD, Mount Sinai School of Medicine, New York, USA Speed rapidly test patient-derived samples. “Our workstation integrating the CLS and Phenix high content imagers allows us to rapidly test thousands of treatments across hundreds of patient derived organoid models in a highly reproducible and stable manner, so we can rapidly identify tumor specific drug sensitivities.” Dr. Lynn McGarry, CRUK Beatson Institute, Glasgow, UK Simplicity automates the part of the process that matters to you “What we get from the Opera Phenix/plate::handler combo is the ability to combine high-content with high-throughput. Xingyu Zhou, Central South University, Changsha, China Hands free, multi-modal system for long-term experiments “Need Testimonial.” LEARN MORE LEARN MORE LEARN MORE LEARN MORE Meet our customers Case study: Cruk Beatson Institute Glasgow, UK Dr. Lynn McGarry, High-Content Imaging Lead Plate::handler Random access racks Opera Phenix Plus HCS system The goal: Perform high-quality confocal imaging at high throughput. Need to handle large numbers of plates. The build: Opera Phenix combined with plate::handler and random-access racks. The solution: The Beatson Institute can run high-throughput HCS screens in 2D and projects in 3D in 384 well format. In 2D, they have processed up to 800 plates. In a colorectal cancer project with 3D organoids, they analyzed batches of 12 plates to identify novel drugs or novel drug combinations. Upscaling organoid research for sharper biological insights. 9 5. 1. 4. The Components Efficiently schedule and manage protocol steps, including dynamic and static scheduling Extract quantitative multi-parametric data from organoids at the single-cell level Perform media exchanges and compound additions, handle hydrogels and generates dome cultures Analyze cell health or biomarkers from 3D culture supernatants 6. Analysis 2. 3. Automate the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. 7. 8. 9. 10. Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spin down liquids in plates Wash plates Upscaling organoid research for sharper biological insights. 10 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 1Organoid workstation Everyone wants more hours in their day. You’ll gain back valuable time with our automated organoid platform that operates 24/7, streamlining routine lab work. Our explorer G3 organoid/3D workstation is a flexible, modular workstation that automates the formation and culture of organoid and spheroid models, followed by image-based phenotyping and marker analysis using multimode detection. The workstation is customizable according to your applications. All key instruments and software are provided by Revvity, so you can be sure of a cohesive and seamless workflow. explorer G3 organoid/3D workstation Upscaling organoid research for sharper biological insights. 11 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 2 Schedule protocols Now you can standardize your processes, ensuring consistent protocols and reducing human bias. Plate::works scheduling & control software Increase throughput and efficiency with parallel methods and sample tracking, and use the workstation at capacity. You can create workflows simply by using the intuitive drag-and-drop interface for instrument icons. Upscaling organoid research for sharper biological insights. 12 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 3 Move liquids To err is human. You can now minimize errors and create reproducible cultures by pipetting defined volumes with automated liquid handling. The JANUS liquid handler enables you to reliably automate media exchanges and compound additions, handle hydrogels such as matrigel with a cold block, and generate dome cultures. JANUS liquid handler Upscaling organoid research for sharper biological insights. 13 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 4 Monitor organoids You can trust these images now more than ever. With whole well imaging you never miss your cells or organoids. Celigo image cytometer Accurately count your cells and analyze organoid health and maturation during the growth phase or as the endpoint. Upscaling organoid research for sharper biological insights. 14 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 5 Confocal 3D imaging See what you have been missing. Hardware designed to capture every phenotypic detail. Opera Phenix Plus high-content imaging system The Opera Phenix Plus enables you to identify the position of organoids for imaging at higher resolution and extracts quantitative multi-parametric data from organoids at the single cell level. Upscaling organoid research for sharper biological insights. 15 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 6 Detect analytes Ready to fast-track your research? Our powerful microplate readers produce better results – every time. Get swift and reliable cell health detection for 3D cultures by measuring ATP-based luminescence with a one-step addition. Multimode plate reader & detection reagents Upscaling organoid research for sharper biological insights. 16 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 7 Image analysis From pixels to numbers, extract quantitative phenotypic information from your high-content images. Analyze complex cellular models in 3D, reliably discriminate phenotypes, and transform biological data into knowledge. Harmony image analysis software Upscaling organoid research for sharper biological insights. 17 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 8 Data analysis Our unified data analysis software guides you all the way — from numbers to conclusions. You can quickly process, analyze, share, and store the vast volumes of data generated by high-content screening and cellular imaging of 3D objects to get answers sooner. Intuitive apps are available for all assay instrument data from HTS, HCS, SPR, and in vivo in Signals VitroVivo® software. Signals VitroVivo data analysis software Upscaling organoid research for sharper biological insights. 18 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 9 Enabling reagents Achieve human-relevant results with reliable, ready-to-use reagents. Hydrogels - automation compatible • Animal free • Reproducible • Stable at room temperature • Tunable stiffness Fluorescent probes and kits – optimized for HCS • Cell painting kits • Organelle dyes • Functional dyes • Secondary antibodies Upscaling organoid research for sharper biological insights. 19 5. 1. 4. The Components Efficiently schedules and manages protocol steps, including dynamic and static scheduling Extracts quantitative multi-parametric data from organoids at the single-cell level Performs media exchanges and compound additions, handles hydrogels and generates dome cultures Detect analytes Schedule protocols Move liquids Analyzes cell health or biomarkers from 3D culture supernatants 6. Analysis 2. Organoid workstation* 3. Confocol 3D Imaging* Monitor organoids* Automates the formation and analysis of organoids and spheroids, providing flexibility and customization Analyze organoid health and maturation during the growth phase or as endpoint Click the yellow button to learn more about each component. Image analysis Data analysis 7. 8. 9. Enabling reagents 10. Reliable consumables Incubate samples Incubate samples at 4°C and 37°C Move plates Protect samples Seal and peel your plates Centrifuge Efficiently spins down liquids in centrifuge plates Wash plates 10 Reliable consumables Rely on carefully designed and produced consumables for maximum accuracy and precision. ULA-coated microplates for the reliable generation of organoids or spheroids. Plus, precise disposable tips and reservoirs or throughs for on-deck storage of liquids - choose the best option based on your specific application needs. Microplate pipet tips and reservoirs www.revvity.com Ready to start building your workstation today? Share your challenges with us, and we’ll help you create the right solution to match your needs. For a complete listing of our global offices, visit www.revvity.com Copyright ©2023, Revvity, Inc. All rights reserved. 1271254 (1112103) Revvity, Inc. 940 Winter Street Waltham, MA 02451 USA www.revvity.com