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Single Cell BCR Profiling Service

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Unlocking the Repertoire: The Single Cell Imperative

Fig.1 B cells. (Creative Biolabs AI)

The humoral immune response, a cornerstone of adaptive immunity, is orchestrated by B lymphocytes, which recognize an immense diversity of antigens via their B cell receptors (BCRs). The BCR is a membrane-bound immunoglobulin composed of a heavy (VH) and a light (VL) chain, the variable domains of which form a unique, antigen-binding paratope. Upon antigen encounter, B cells undergo a sophisticated process of clonal selection, somatic hypermutation (SHM), and class switch recombination to produce high-affinity antibodies that neutralize pathogens and confer long-term immunological memory. A comprehensive understanding of these processes is paramount for the development of effective vaccines, diagnostics, and therapeutics.

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Limitations of Traditional Bulk Sequencing

Single Cell BCR Sequencing: A Transformative Solution

Key Advantage Impact
Preserves VH-VL pairing Enables faithful reconstruction of native antibodies
Single Cell resolution Captures repertoire diversity at the individual B cell level
Dual-modality analysis (BCR + transcriptome) Links clonotype with functional state, lineage, and phenotype
Real-time tracking Monitors immune responses during infection or vaccination
Microenvironment insights Dissects B cell dynamics in cancer and autoimmune diseases

Creative Biolabs provides a state-of-the-art Single Cell BCR Profiling Service designed to empower researchers to explore these frontiers with unprecedented precision and depth.

Engineering High-Fidelity Pairing Platform

At the core of our service is the proprietary platform, an integrated system engineered for high-throughput, high-fidelity Single Cell immune repertoire analysis. Our platform is built upon a sophisticated microfluidic technology that couples Single Cell partitioning with a unique emulsion-based linkage PCR methodology. This approach physically isolates individual B cells in nano-liter scale droplets, creating discrete reaction chambers for cell lysis, mRNA capture, and reverse transcription.

Key Platform Features:

High-Fidelity Native Pair Preservation

Our emulsion-based linkage PCR ensures the endogenous pairing of VH and VL chains is maintained, which is critical for the functional reconstruction of monoclonal antibodies.

High-Throughput Single Cell Resolution

The platform is capable of analyzing thousands of individual B cells per sample, providing the necessary depth to accurately capture the diversity of the B cell repertoire, including rare clones.

Integrated Transcriptomic Analysis

The platform seamlessly integrates 5' gene expression profiling, enabling the direct correlation of BCR sequence with the transcriptional signature of the same cell, thereby elucidating its functional status (e.g., naïve, memory, or plasma cell).

Robust Bioinformatic Pipeline

We provide a comprehensive analysis suite that delivers clonotype definition, somatic hypermutation analysis, isotype distribution, and clonal lineage reconstruction, presenting complex data in a clear, publication-ready format.

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From Sample to Insight: Our End-to-End Workflow

The Single Cell BCR Profiling Service at Creative Biolabs is a comprehensive, end-to-end solution designed to deliver maximal insight with minimal client-side burden. Our process is refined for precision and efficiency:

  • 1. Initial Consultation and Experimental Design

    Every project begins with a detailed consultation with our scientific team to define experimental goals, select appropriate sample types, and establish a clear project timeline.

  • 2. Sample Preparation and Quality Control

    We accept a wide range of input materials, including peripheral blood mononuclear cells (PBMCs), purified B cells, and Single Cell suspensions derived from complex tissues such as tumors or lymph nodes. A key advantage of our workflow is its compatibility with both live and cryopreserved cells, offering significant logistical flexibility for sample collection and shipment. Upon receipt, each sample undergoes rigorous quality control, including cell viability and concentration assessment, to ensure optimal data generation.

  • 3. Single Cell Capture and Barcoding

    Viable single cells are loaded onto our microfluidic system for high-efficiency capture and partitioning into emulsion droplets along with magnetic beads for mRNA capture and barcoding reagents.

  • 4. Paired VH:VL Linkage and Library Construction

    Following reverse transcription and barcoding within the droplets, our proprietary emulsion linkage PCR is performed to generate paired VH:VL amplicons. These products are then used to construct next-generation sequencing libraries, which are indexed and quantified prior to sequencing.

  • 5. Next-Generation Sequencing and Data Analysis

    Libraries are sequenced on our high-throughput platform. The resulting data is processed through our specialized bioinformatics pipeline to perform error correction, V(D)J annotation, pairing, clonotype assembly, and, if requested, integrated analysis with the 5' gene expression data.

  • 6. Data Delivery

    Clients receive a comprehensive data package containing raw sequencing files, processed data tables, and a detailed report summarizing key findings, including clonal frequencies, SHM rates, isotype usage, and publication-quality figures illustrating the repertoire landscape.

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Powering the Next Breakthrough: From Discovery to Deep Research

The high-resolution data generated by our service has transformative potential across numerous domains of biomedical research and development:

Therapeutic Antibody Discovery

Rapidly identify and screen naturally occurring, high-affinity human antibodies with their native chain pairings from convalescent patients or vaccinated donors. This accelerates the discovery-to-clinic pipeline for novel monoclonal antibody therapeutics against infectious agents, cancer antigens, and other targets.

Vaccine Efficacy and Design

Delineate the precise B cell clonal lineages that expand and evolve in response to vaccination. This allows for the molecular-level assessment of vaccine efficacy, identification of epitopes targeted by neutralizing antibodies, and rational design of next-generation immunogens.

Onco-Immunology

Interrogate the B cell repertoire within the tumor microenvironment to understand the role of tumor-infiltrating B lymphocytes (TIL-Bs). Characterizing their clonality and functional states can uncover novel prognostic biomarkers and therapeutic targets for immunotherapy.

Autoimmunity and Infectious Disease Research

Deconstruct the B cell-mediated pathology in autoimmune diseases by identifying and characterizing autoreactive clones. In infectious disease, our service enables the tracking of antigen-specific B cell dynamics, providing critical insights into pathogenesis and protective immunity.

Immune System Monitoring

Longitudinally monitor the reconstitution and health of the B cell compartment in settings such as hematopoietic stem cell transplantation, immunodeficiency disorders, or during therapeutic interventions. It can also be applied to monitor for minimal residual disease (MRD) in B cell malignancies.

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The Creative Biolabs Advantage: Precision, Flexibility, and Expertise

Choosing Creative Biolabs for your Single Cell BCR profiling needs provides several distinct advantages:


Unparalleled VH:VL Pairing Fidelity

Our core technology is specifically designed to preserve the endogenous heavy and light chain pairing, eliminating the ambiguity and artifacts associated with computational pairing methods.


Logistical Superiority with Non-Live Cells

Our assay's unique tolerance for non-live cells dramatically simplifies logistics. Researchers can work with fixed or cryopreserved samples from remote clinical sites without compromising data integrity, reducing costs and expanding experimental possibilities.


High-Throughput and Cost-Effective

We have optimized our protocols to minimize reagent consumption while maximizing cell throughput, making deep, Single Cell repertoire analysis more accessible and affordable without sacrificing quality.


Deep Scientific Expertise

Our team consists of seasoned immunologists and bioinformaticians who provide expert guidance from experimental design to data interpretation, ensuring your project yields the most impactful results. We offer customized analysis and collaborative support to help you achieve your research objectives.

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FAQs

  1. Q: What sample types are compatible with the Single Cell BCR Profiling Service?

    A: We accommodate a diverse range of sample types, including fresh or cryopreserved PBMCs, sorted B cell populations (e.g., via FACS), and Single Cell suspensions from dissociated tissues like tumors, lymph nodes, and spleens. Our protocol's flexibility with non-viable cells provides a significant advantage for precious or difficult-to-process samples.

  2. Q: What are the primary sample submission requirements?

    A: For optimal results, we recommend a cell viability of >70% with a concentration between 500 and 2,000 cells/μL in a volume of at least 200 μL. The suspension buffer should be free of calcium and magnesium ions. However, we encourage you to contact us to discuss your specific sample, as we can often optimize protocols for challenging inputs.

  3. Q: How many cells are typically analyzed per sample?

    A: Our platform is highly scalable, routinely analyzing between 1,000 and 10,000 cells per sample. This range provides sufficient depth to profile complex repertoires and identifies rare B cell clones. The precise number can be tailored to your experimental goals and budget.

  4. Q: Can I obtain transcriptome data from the same single cells?

    A: Absolutely. Our platform is designed for multi-omic analysis, integrating full-length, paired V(D)J repertoire sequencing with 5' gene expression profiling. This allows you to directly link a B cell's clonal identity with its functional phenotype, activation state, and metabolic profile.

  5. Q: How does your platform guarantee the native pairing of heavy and light chains?

    A: The fidelity of our pairing is ensured by the physical compartmentalization of single cells in our emulsion droplet system. Each droplet acts as an independent micro-reactor, ensuring that the mRNA transcripts for both the heavy and light chains originate from a single B cell. Our downstream linkage PCR then physically connects these transcripts into a single sequencable molecule, providing an unambiguous record of the native pair.

  6. Q: What can I expect in the final data deliverables?

    A: Clients receive a comprehensive data package that includes raw sequencing data (FASTQ files) and a detailed, publication-ready bioinformatics report. This report contains V(D)J gene annotation, paired VH:VL sequences, clonotype frequencies and distributions, somatic hypermutation analysis, isotype usage statistics, and clonal lineage trees. For integrated projects, this is accompanied by a full Single Cell gene expression analysis. Please contact us for more information and a detailed quote.

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Resources

Use the resources in our library to help you understand your options and make critical decisions for your study.

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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