A Journey with the BD Rhapsody™ Single-Cell Analysis System
Explore the TechnologyImagine trying to understand a complex recipe by tasting the entire finished dish all at once. You might get a general sense of the flavor, but you'd miss how each individual ingredient contributes to the whole.
For decades, scientists faced a similar challenge when studying biological tissues—analyzing "bulk" samples containing millions of cells masked critical differences between individual cells. The rapid evolution of single-cell sequencing technology has revolutionized this approach, allowing researchers to investigate cell-to-cell variations that were previously invisible, revealing new cell types and providing unprecedented insights into developmental processes and disease mechanisms 1 .
Single-cell analysis enables researchers to see beyond population averages and explore cellular heterogeneity at unprecedented resolution.
Simultaneous measurement of multiple molecular layers from the same cells provides a comprehensive view of cellular function.
At the forefront of this revolution is the BD Rhapsody™ Single-Cell Analysis System, a powerful platform that enables researchers to capture multimodal information from thousands of single cells in parallel. This technology goes beyond traditional methods by allowing simultaneous measurement of multiple aspects of biology—gene expression, protein abundance, immune receptor sequences, and more—from the very same cells 2 .
The BD Rhapsody™ system employs a distinctive microwell-based approach that sets it apart from other technologies. The process begins with a specially designed cartridge containing an array of over 220,000 microscopic wells. A dilute cell suspension is loaded onto this cartridge, and individual cells gently settle into the microwells through gravity—a stark contrast to methods that rely on potentially stressful microfluidic channels 3 .
The true innovation of the BD Rhapsody™ system lies in its ability to perform "multiomic" analysis—simultaneously capturing different types of molecular information from the same single cells. This comprehensive approach includes:
Whole Transcriptome Analysis or targeted panels
Measurement using oligo-conjugated antibodies
Analysis for T-cell receptors and B-cell receptors
This multimodal capability is transformative because measuring several aspects of biology simultaneously from the same cells provides a more complete picture of cellular identity and function than could ever be achieved by separate experiments 5 .
To understand the real-world impact of this technology, consider a key experiment focused on characterizing exhausted T cells—a critical cell population in cancer immunotherapy. When T cells face chronic exposure to antigens, such as in tumors or persistent infections, they can enter a dysfunctional "exhausted" state that limits their ability to fight disease 3 .
Researchers used the BD Rhapsody™ system to perform deep characterization of CD8+ T cells undergoing chronic stimulation. They analyzed both gene expression and protein markers simultaneously, allowing them to identify distinct subpopulations that would have been invisible with conventional methods.
The experimental procedure followed these key steps:
CD8+ T cells isolated and stimulated for 14 days
Cells stained with BD® AbSeq Antibody-Oligonucleotides
Cells loaded onto BD Rhapsody™ Single-Lane Cartridge
| Marker | Subpopulation 1 Expression | Subpopulation 2 Expression | Biological Significance |
|---|---|---|---|
| CD38 | High | Low | Activation/Metabolic marker |
| CD39 | High | Moderate | Immunosuppressive enzyme |
| CD94 | Low | High | NK cell receptor |
| Additional genes (mRNA) | Distinct profile | Different distinct profile | Functional state determinants |
Table 1: Protein and Gene Expression in Exhausted T-cell Subpopulations 3
This finding was significant because understanding the heterogeneity within exhausted T cells could help explain why some patients respond to immunotherapies while others don't, potentially leading to more targeted and effective treatments. The simultaneous measurement of proteins and mRNA provided a multidimensional view that neither modality alone could deliver, highlighting the power of multiomic analysis 3 .
The BD Rhapsody™ ecosystem comprises a comprehensive suite of instruments, reagents, and analytical tools that work together to enable robust single-cell multiomics research.
| Tool Category | Specific Products | Function in Workflow |
|---|---|---|
| Instruments | BD Rhapsody™ Scanner, BD Rhapsody™ Express System | Visualize single-cell capture, provide quality metrics, perform cell partitioning |
| Sample Preparation | BD® OMICS-Guard Sample Preservation Buffer, BD® Single-Cell Multiplexing Kit | Protect transcriptomic/proteomic information for up to 72 hours, combine up to 24 samples |
| RNA Analysis | BD Rhapsody™ WTA Amplification Kits, BD Rhapsody™ Targeted mRNA Panels | Unbiased whole transcriptome capture or focused analysis of hundreds of genes |
| Protein Analysis | BD® AbSeq Assay, BD® OMICS-One Protein Panels | Simultaneously detect tens to hundreds of protein markers via oligo-conjugated antibodies |
| Specialized Applications | BD Rhapsody™ TCR/BCR Next Assay, BD Rhapsody™ ATAC-Seq Kits | Characterize immune receptor repertoires, profile chromatin accessibility |
| Bioinformatics | BD Rhapsody Sequence Analysis Pipeline, BD Cellismo™ Data Visualization Tool | Process sequencing data, visualize single-cell results for biological insights 4 8 |
Table 2: The BD Rhapsody™ Research Toolkit 4 8
This comprehensive toolkit enables researchers to design complete workflows from sample preparation to data analysis, with the flexibility to focus on specific biological questions while maintaining the potential for unexpected discoveries 4 8 .
The utility of any scientific instrument depends on its ability to generate reliable, reproducible data. The BD Rhapsody™ system has demonstrated excellent performance across multiple metrics that matter to researchers.
| Performance Measure | Result | Research Impact |
|---|---|---|
| Cell Capture Rate | Superior across various cell types | Maximizes valuable sample utilization |
| Multiplet Rate | Low | Reduces data ambiguity from multiple cells |
| Technical Reproducibility | High correlation between replicates (R² >0.95) | Enables confident interpretation of results |
| Biological Reproducibility | Minimal batch effects | Facilitates multi-center, longitudinal studies |
| Bead Stability | Beads with cDNA can be stored for months | Enables experimental flexibility, archiving |
| Inter-site Consistency | Minimal user-to-user and site-to-site variability | Supports collaborative, translational research 3 |
Table 3: BD Rhapsody™ System Performance Metrics 3
These performance characteristics make the system particularly valuable for translational, multi-center, and multi-cohort studies where consistency and reproducibility are paramount. The ability to archive and subsequently pool beads from different experiments also provides remarkable operational efficiency and standardization capabilities 3 .
As the BD Rhapsody™ platform reaches significant adoption milestones—with the 1,000th system recently placed at Cambridge University's Addenbrooke's Hospital—the technology continues to evolve 6 . Researchers like Dr. Andrew Conway Morris are using these systems to decipher biological mechanisms at single-cell resolution "with resolution previously not possible," ultimately aiming to translate these findings into treatments that improve patient outcomes 6 .
The future promises even more powerful tools, including new assays like the BD OMICS-One™ WTA Next Assay for increased genetic information at lower cost-per-cell, enhanced sample preservation solutions, and robust automation to further standardize workflows 6 .
Emerging technologies that preserve tissue architecture context while enabling single-cell analysis.
Growing accessibility of bioinformatics platforms for collaborative research and data sharing.
Growth of single-cell analysis platforms in research institutions
As we stand at this frontier of biological exploration, technologies like the BD Rhapsody™ Single-Cell Analysis System provide not just a window into the invisible world of cellular heterogeneity, but an entire laboratory for understanding it—one cell at a time.