SELEX (Systematic Evolution of Ligands by EXponential Enrichment) is the gold-standard process for discovering aptamers—single-stranded DNA or RNA molecules that bind to a specific target with high affinity and specificity, similar to antibodies.
Magnetic Bead SELEX is a widely used variant where the target molecule is immobilized on magnetic beads. This format offers significant advantages in automation, handling, and efficiency.
Developing aptamers in-house is time-consuming, requires specialized expertise, and involves significant optimization. A professional service provides:
Expertise & Experience: Knowledge of library design, PCR optimization, and counter-selection strategies.
Specialized Equipment: Access to automated magnetic separation systems, NGS, and bioinformatics.
Time & Cost Efficiency: Faster turnaround (typically 2-4 months) than setting up a new lab.
Higher Success Rate: Proven protocols to avoid common pitfalls like PCR bias or selection of non-specific binders.
Phase 1: Project Design & Target Preparation
Consultation: You define the target (e.g., a protein, small molecule, cell), desired affinity (Kd), and application (diagnostics, therapeutics, sensors).
Target Immobilization: The service provider chemically conjugates your target to the surface of magnetic beads (e.g., streptavidin-biotin, NHS-amine coupling). A “negative selection” bead (without target) is also prepared to remove non-specific binders.
Phase 2: The SELEX Cycles (Iterative Selection & Amplification)
This core cycle is repeated 8-15 times.
Incubation: A vast, random synthetic oligonucleotide library (10¹⁴ – 10¹⁵ unique sequences) is incubated with the target-bound beads.
Binding & Washing: Magnetic separation is used to easily wash away unbound and weakly bound sequences.
Elution: Tightly bound aptamers are eluted (e.g., by heat, denaturants, or competitive elution).
Amplification: The eluted pool is amplified by PCR (for DNA SELEX) or RT-PCR (for RNA SELEX).
Stringency Increase: In later rounds, conditions (washing time, salt concentration, competitor molecules) become stricter to select for the highest-affinity binders.
Phase 3: Sequencing & Identification
Next-Generation Sequencing (NGS): The enriched pool from the final rounds is sequenced to identify thousands of candidate sequences.
Bioinformatics Analysis: Clustering algorithms identify sequence families, consensus motifs, and predicted structures. The most promising candidates (e.g., 10-50 sequences) are synthesized.
Phase 4: Characterization & Validation
Primary Screening: Candidate aptamers are tested for binding (e.g., via flow cytometry, ELISA-like assays, or biolayer interferometry).
Affinity Measurement: The dissociation constant (Kd) of top hits is determined (e.g., Surface Plasmon Resonance – SPR, or MicroScale Thermophoresis – MST).
Specificity Testing: Binding is tested against related targets or in complex matrices (e.g., serum) to confirm specificity.
Functional Assay: If applicable, testing in the final application (e.g., inhibition of protein function, cell internalization).
Flexible Targets: Proteins, peptides, small molecules, whole cells, viruses, or even post-translational modifications.
Library Options: DNA libraries (more stable, cheaper), RNA libraries (more structural diversity), or modified nucleotides (nuclease resistance, higher affinity).
Automation: Often performed on liquid handlers with magnetic modules for high reproducibility and reduced hands-on time.
Delivery: Final report including candidate sequences, binding data (Kd), specificity profiles, and recommended next steps.
Diagnostics: Biosensors, lateral flow assays, ELISA replacements.
Therapeutics: Targeted drug delivery, antagonists.
Research Tools: Cell sorting, protein detection, imaging agents.
Biotechnology: Affinity purification, quality control.
Proven Track Record: Ask for case studies or publications with targets similar to yours.
Technical Capabilities: Do they offer Next-Generation Sequencing (NGS) and SPR/MST for characterization?
Clarity of Deliverables: Understand exactly what data and materials you will receive.
Project Timeline & Cost: A standard project ranges from $20,000 to $60,000+ and takes 3-6 months, depending on complexity.
| Method | Advantages | Best For |
|---|---|---|
| Magnetic Bead SELEX | Easy washing, automatable, high purity, handles diverse targets. | Most protein and small molecule targets. The most common service. |
| Cell-SELEX | Discovers aptamers to native cell-surface markers, no need for purified target. | Whole live cells, cancer cell targeting, biomarker discovery. |
| Capillary Electrophoresis SELEX | Very high stringency and resolution based on mobility shift. | Extremely high-affinity aptamers for soluble targets. |
| In Silico SELEX | Computational screening; fast and cheap for initial candidates. | Pre-screening or complementing wet-lab SELEX (not a standalone service). |
Using a professional Magnetic Bead SELEX Screening Service is the most efficient path to obtain high-quality, validated aptamers for your specific target. By outsourcing this technically demanding process, you leverage specialized expertise and infrastructure to de-risk and accelerate your aptamer development project.
Next Step: Contact potential providers with a clear description of your target, desired aptamer properties (Kd, application), and ask for a detailed project proposal and quote.
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