Single-cell functional analysis enables scientists to examine the unique characteristics of each cell within organs, tissues, and cell cultures. Unlike bulk-cell analysis, single-cell analysis allows the characterization of rare cell types and investigates cellular variation. It also helps determine a cell's molecular content, spatial and temporal transformations, and microenvironment. Technological advancements in single-cell omics, single-cell RNA sequencing, and functional assays have played a crucial role in uncovering disease mechanisms and offering high-throughput molecular profiling across different modalities.
Vikram Devgan, PhD
Vice President of Global Marketing and Product Management
Bruker Cellular Analysis
In this Innovation Spotlight, Vikram Devgan, vice president of Global Marketing and Product Management at Bruker Cellular Analysis, discusses the benefits and limitations of traditional single-cell analysis. He also explains how the Beacon Discovery system, equipped with advanced features including optofluidics, functional cell biology assays, live single-cell imaging, and multiomic data, enables researchers to unravel invaluable biological insights and develop new therapies more efficiently.
What is single-cell functional analysis, and which areas of research benefit the most from this type of inquiry?
Single-cell functional analysis examines the behavior and biological responses of individual cells over time, providing insights into dynamic processes such as cytokine secretion, cytotoxicity, motility, activation, proliferation, and cell-cell interactions. Unlike genomic or transcriptomic profiling, which provides static snapshots, functional analysis reveals what cells do, not just what they are programmed to do.
The fields that benefit the most include cell therapy development, immuno-oncology, antibody discovery, vaccine research, infectious disease, autoimmune disease research, and functional immunology. Researchers can better understand immune responses, identify rare but potent cells, and improve therapeutic candidate selection by analyzing functional heterogeneity at the single-cell level.
How do traditional instruments for single-cell functional analysis work and what are their limitations?
Traditional instruments include flow cytometers, droplet-based single-cell platforms, microwell-based single-cell instruments, and ELISpot readers. These systems either provide endpoint measurements, hold a low temporal resolution, or have limited assay capacity typically constrained to one or two assays per cell, making it impossible to track multiple behaviors across time in the same cell. Certain conventional instruments also require cell lysis, fixation, or labeling, which restrict analyzing the same live cell repeatedly. These limitations hinder in-depth functional insights needed for cell therapy and antibody discovery, where multimodal and temporal functional data can be critical for selecting the most effective candidates.
Which innovations help improve live cell imaging and analysis?
Over the years, several technological advancements have significantly improved live cell analysis. For instance, microfluidics and high-content imaging are powerful combinations that allow precise cell handling and detailed high-parameter and temporal analysis. Optofluidics enable researchers to rapidly manipulate and analyze single cells by controlling light and fluid flow at the micro- and nanoscale. Another important innovation is artificial intelligence (AI)-powered image analysis, which offers an accurate and accelerated interpretation of complex cellular behaviors. In addition, non-destructive, multiplexed assays have allowed scientists to analyze the same cells over time repeatedly.
How does the Beacon Discovery platform work and who would benefit the most from this instrument?
The Beacon Discovery platform is a benchtop optofluidic system that empowers live single-cell functional analysis. It enables researchers to perform sequential, multiplexed functional assays on the same cell across multiple time points. Beacon Discovery seamlessly links functional data to sequencing from the same cell for deeper scientific breakthroughs.
With the ability to screen thousands of live T cells and perform multiple functional assays per cell, including dynamic cytotoxicity, cytokine secretion, and cell surface marker expression, scientists can comprehensively evaluate T cell potential and connect it with T cell receptor sequencing and transcriptomics data for the same cells. For antibody discovery, this includes running multimodal functional assays, such as antigen specificity, cross-reactivity, affinity, membrane-bound antigen cell-binding, ligand blocking, and internalization, on tens of thousands of single B cells. Scientists may directly export and sequence the most promising antibody-secreting cells, enabling a truly end-to-end antibody discovery workflow with a single platform.
Bruker Cellular Analysis developed the Beacon Discovery platform, which is a reliable, high-throughput, cutting-edge platform that enables scientists to study different aspects of a single cell with high precision, supporting critical scientific research and drug discovery.
Bruker Cellular Analysis
Beacon Discovery could benefit many stakeholders, particularly biopharma companies and academic researchers. For instance, translational laboratories in biopharma companies could use this system for antibody discovery and cell therapy development. Academic researchers could use the Beacon Discovery platform to study immune function, therapeutic mechanisms, and translational biomarker discovery. Furthermore, core labs requiring an accessible, compact, flexible, and proven live single-cell analysis solution could use this device.
How does the Beacon Discovery platform improve upon traditional analyses?
Beacon Discovery addresses several limitations of traditional systems by introducing multiple advanced features. It supports longitudinal studies of live single cells by allowing researchers to track cellular behavior over days or even weeks. Incorporating multiple functional assays on a single platform promotes a comprehensive multiparametric analysis without compromising cell viability.
Beacon Discovery offers high-resolution image-based analysis and functional data for deeper biological insights. Furthermore, this platform promotes a simplified workflow by reducing multiple instrument requirements and manual intervention. Finally, the system lowers the barrier to entry with a smaller footprint and a more cost-effective solution relative to previous Beacon systems. These advantages directly impact antibody discovery and cell therapy development, where rapid screening and in-depth characterization of individual cell behavior are essential.
What excites you the most about the recent advancements and future of single-cell functional analysis?
The most exciting advancement in single-cell research is the shift toward dynamic, multimodal, and integrated analysis of living cells. This research opens the door to discovering rare, high-potency immune cells or antibody-secreting B cells that drive therapeutic responses. Through advanced single-cell analysis, researchers may uncover temporal patterns in cell behavior that static assays miss. It also promises to accelerate therapeutic development in antibody discovery and cell therapies by enabling rapid, function-based candidate screening.
As platforms like Beacon Discovery make these capabilities more accessible, the next decade could transform how we design and optimize biologics, immunotherapies, and personalized medicine strategies.
