Resolve Biosciences: Next-Level Single-Cell Spatial Profiling

Advancements in molecular biology have made it possible to study cells with remarkable precision, leading to breakthroughs in disease research and therapeutic development. Traditional methods often struggle to capture the complex spatial organization of tissues at a single-cell level, limiting our understanding of cellular interactions within their native environments.

Resolve Biosciences addresses this challenge by offering next-level single-cell spatial profiling technology. This approach enables researchers to visualize gene expression and cellular structures with unprecedented detail, providing deeper biological insights.

Single-Cell Spatial Profiling

Understanding cellular behavior within its native tissue environment requires spatial context. Single-cell spatial profiling preserves the physical relationships between cells while capturing molecular signatures at an individual level. Unlike bulk sequencing, which averages signals across heterogeneous populations, this method retains tissue architecture, allowing researchers to dissect cellular heterogeneity with granularity. By mapping gene expression patterns directly onto tissue sections, scientists can uncover how cells interact, differentiate, and respond to their surroundings in ways traditional sequencing cannot resolve.

This technique maintains spatial integrity while delivering high-resolution molecular insights. Resolve Biosciences’ Molecular Cartography™ leverages barcoded probes to detect RNA transcripts in situ, ensuring gene expression data remains anchored to its original cellular location. This method eliminates tissue dissociation, which can disrupt native organization and obscure critical interactions. Retaining spatial information allows researchers to identify distinct cellular niches, track lineage trajectories, and pinpoint rare cell populations that might otherwise be lost in bulk analyses.

Beyond individual cells, this approach enables the study of microenvironments that drive tissue function and pathology. In oncology, spatial transcriptomics reveals how tumor cells interact with stromal and immune components, influencing disease progression and therapeutic resistance. In neuroscience, it maps gene expression across brain regions, shedding light on molecular underpinnings of neurodegenerative disorders. These insights are possible because spatial profiling retains tissue architecture, allowing researchers to correlate molecular activity with structural organization.

High-Resolution Imaging Mechanics

Achieving high-resolution imaging in single-cell spatial profiling requires optical precision, molecular detection sensitivity, and computational reconstruction. Advanced fluorescence microscopy techniques enable visualization of individual RNA molecules within intact tissue samples. Resolve Biosciences’ Molecular Cartography™ employs high-efficiency barcoded probes and sequential fluorescence hybridization, capturing spatially resolved gene expression data with subcellular accuracy. This method surpasses traditional in situ hybridization by allowing multiplexed detection of thousands of transcripts simultaneously while preserving spatial context.

A key challenge in high-resolution imaging is the diffraction limit of light, which restricts the ability to resolve structures smaller than approximately 200 nanometers. To overcome this, Molecular Cartography™ integrates super-resolution imaging strategies such as structured illumination microscopy (SIM) and stochastic optical reconstruction microscopy (STORM). These techniques enhance spatial resolution by leveraging patterned illumination and single-molecule localization, enabling researchers to distinguish molecular interactions within densely packed cellular environments.

Beyond optical advancements, accuracy relies on robust signal amplification and noise reduction. Molecular Cartography™ employs error-correcting barcodes and optimized probe designs to minimize background fluorescence and enhance detection specificity. This ensures even low-abundance transcripts are reliably identified. Computational deconvolution algorithms refine image reconstruction, compensating for optical aberrations and improving fidelity. These enhancements enable researchers to visualize complex cellular architectures with clarity, facilitating identification of subtle transcriptional variations that drive tissue function and pathology.

Targeted Gene Expression Analysis

Analyzing gene expression at the single-cell level requires a precise and scalable method for detecting specific transcripts while maintaining spatial fidelity. Targeted gene expression analysis refines this process by focusing on predefined sets of genes, allowing researchers to investigate molecular pathways with specificity. Resolve Biosciences’ Molecular Cartography™ employs a multiplexed barcoding system that hybridizes directly to RNA transcripts, ensuring only sequences of interest are captured. This minimizes signal dilution from irrelevant genes and enhances detection of subtle transcriptional differences between neighboring cells.

Unlike broad-spectrum transcriptomic approaches that generate massive datasets requiring extensive computational filtering, targeted analysis streamlines data acquisition and interpretation. Selecting genes associated with specific biological processes—such as cellular differentiation, metabolic regulation, or disease progression—allows scientists to construct detailed expression maps without noise from irrelevant transcripts. This precision is particularly valuable when low-abundance RNA molecules play a significant role, as targeted methods amplify detection sensitivity while preserving spatial resolution.

The effectiveness of targeted gene expression analysis also depends on maintaining quantitative accuracy across diverse tissue types. Resolve Biosciences’ approach incorporates error-correction algorithms to distinguish true signals from background noise, ensuring expression levels reflect biological reality. This is particularly important in heterogeneous tissue environments, where gene activity can vary dramatically between adjacent cells. By refining probe design and optimizing hybridization conditions, Molecular Cartography™ ensures even weakly expressed genes are detected with high fidelity, enabling researchers to explore subtle transcriptional differences that drive cellular identity and function.

Tissue-Level Mapping Strategies

Mapping gene expression across entire tissue sections requires preserving spatial organization while capturing molecular diversity. Unlike single-cell techniques that focus on individual transcriptional profiles, tissue-level mapping emphasizes broader cellular interactions. Resolve Biosciences’ Molecular Cartography™ employs high-density spatial barcoding, allowing researchers to visualize gene expression gradients across complex tissue landscapes. This is particularly valuable for studying structured tissues such as the liver, where zonation patterns dictate metabolic function, or the brain, where distinct molecular signatures define regional specialization.

A challenge in tissue-level mapping is maintaining resolution without sacrificing coverage. Molecular Cartography™ utilizes sequential hybridization cycles that enable multiplexed transcript detection across expansive tissue samples. Layering these cycles allows researchers to construct comprehensive gene expression atlases that reveal localized variations in cellular activity. This is especially useful in developmental biology, where spatially restricted gene expression guides tissue morphogenesis. For example, key signaling pathways such as Wnt and Notch exhibit highly localized expression patterns that influence organ formation. Capturing these spatial dynamics in situ provides a more accurate representation of biological processes than traditional dissociative methods.

Multi-Parameter Detection Approaches

Extracting meaningful insights from single-cell spatial profiling requires analyzing multiple molecular features simultaneously. Multi-parameter detection approaches enhance this capability by integrating various data modalities within a single experiment, allowing researchers to correlate gene expression with additional biological markers such as protein abundance, chromatin accessibility, or metabolic activity. Resolve Biosciences’ Molecular Cartography™ facilitates this level of multiplexing through combinatorial barcoding strategies that enable detection of diverse molecular targets without compromising spatial resolution. Layering different biological data allows scientists to construct comprehensive models of cellular function, capturing the interplay between transcriptional activity and downstream regulatory mechanisms.

One advantage of multi-parameter detection is resolving functional heterogeneity within complex tissues. In cancer biology, transcriptomic profiling may reveal differential gene expression between tumor and stromal cells, but integrating protein-level data can uncover post-transcriptional modifications driving oncogenic signaling. This approach has been particularly effective in identifying therapeutic targets, as certain drug-resistant cell populations exhibit distinct proteomic signatures not apparent at the RNA level. Similarly, in developmental biology, combining transcriptomic and epigenetic data allows researchers to track lineage-specific regulatory changes influencing cell fate decisions. These insights are possible through techniques that preserve spatial organization while capturing multiple molecular dimensions, reinforcing the value of high-throughput, multi-parameter profiling in modern biological research.