Small molecules are some of the most valuable—and most difficult—targets in molecular recognition. They include metabolites, drugs, toxins, cofactors, and signaling compounds that often weigh only a few hundred Daltons. Developing expertise in aptamers to small molecules means mastering a set of selection and validation strategies that differ substantially from protein-target aptamer work, because small molecules offer fewer contact points, weaker “handles” for separation, and more ways to generate false positives. This article explains how small-molecule aptamers are discovered, why selection is uniquely challenging, how advanced SELEX variants improve success rates, and what “good” looks like when you engineer an aptamer into a sensor, assay, or therapeutic concept. 1) What makes small-molecule aptamers special? Aptamers are single-stranded DNA or RNA sequences that fold into 3D shapes able to bind a target through non-covalent interactions—hydrogen bonding, π–π stacking, electrostatics, and shape complementarity. For proteins, large surfaces provide many contacts, so binding can be robust even when the selection workflow is imperfect. Small molecules are different: Tiny binding interface: fewer interaction opportunities means affinity can be harder to evolve and easier to mis-measure. Separation is tricky: in classic SELEX you often immobilize the target; immobilization can change the target’s presentation…
Negative aptamer selection—often called negative selection or counter-selection—is a deliberate filtering step in SELEX(Systematic Evolution of Ligands by EXponential enrichment) designed to remove sequences that bind to the wrong things. Instead of enriching binders to your intended target, negative selection enriches your final pool for what you actually want in real-world use: high specificity, low background, and minimal cross-reactivity. In modern aptamer discovery, negative selection is not “optional polish.” It is one of the most effective ways to prevent selection artifacts—like aptamers that bind to beads, linkers, tags, surfaces, common matrix components, or closely related off-target molecules—from dominating your pool. 1) What “Negative Aptamer Selection” Means (and Why It Exists) During SELEX, you start with a huge randomized DNA/RNA library and iteratively enrich sequences that bind. The catch is that many sequences bind strongly to unintended components in the experimental system: immobilization substrates (e.g., beads, membranes) affinity tags or capture molecules (e.g., streptavidin–biotin systems) blockers, serum proteins, plastic, or assay buffers structurally similar molecules (analogs) that you must not bind Negative selection introduces a decoy binding step: you expose the library to an unwanted target (or “negative target”), then discard the sequences that bind it and keep…
Aptamers are short, single-stranded nucleic acids—typically ~20–100 nucleotides—that fold into defined 3D shapes and bind targets (proteins, small molecules, ions, cells) with high affinity and specificity. They are often described as “chemical antibodies,” but they behave differently: their binding comes from nucleic-acid folding + surface complementarity, and their performance is tightly linked to sequence chemistry, structure, and degradation pathways. When your core question is “DNA aptamers or RNA aptamers?”, the best answer is not a slogan. It’s a decision based on (1) structural needs, (2) stability environment, (3) manufacturability, (4) modification strategy, and (5) application constraints. 1) The Fundamental Difference: Structural Vocabulary vs Environmental Toughness RNA aptamers: richer folding vocabulary RNA has a 2′-OH group on the ribose, which expands hydrogen-bonding possibilities and supports a larger “structural vocabulary” (hairpins, internal loops, bulges, pseudoknots, complex tertiary contacts). In practice, this often means more diverse and intricate 3D conformations, which can translate into excellent binding performance for some targets. Takeaway: Choose RNA when the target demands highly nuanced shape recognition (e.g., challenging protein surfaces or structured RNA targets). DNA aptamers: generally more chemically stable and simpler DNA lacks the 2′-OH group and is typically more resistant to base-catalyzed…
CELL-SELEX (Cell-Based Systematic Evolution of Ligands by EXponential enrichment) is a selection strategy used to discover nucleic-acid aptamers—short single-stranded DNA or RNA molecules that fold into shapes capable of binding cellular targets with high affinity and specificity. What makes CELL-SELEX AND BIOMARKER DISCOVERY such a powerful pairing is that cell-SELEX can enrich binders against native cell-surface features (often membrane proteins, glycoproteins, lipids, or complex epitopes) without needing to know the target in advance. This is especially valuable in biomarker discovery, where the “best” marker may be unknown, heterogeneous, or highly dependent on the cellular context. 1) What CELL-SELEX Is (and Why It Matters for Biomarkers) Traditional SELEX often starts with a purified target (e.g., a recombinant protein). In cell-SELEX, the “target” is a living cell population that represents a phenotype you care about—such as a disease subtype, drug-resistant cells, activated immune cells, or a specific differentiation stage. The selection process enriches aptamers that bind those cells while removing sequences that bind irrelevant or shared features. Why this matters for biomarkers: Native conformation is preserved. Cell-surface proteins keep their natural folding, post-translational modifications, and membrane context—features that can be lost in purified preparations. Unbiased discovery. You can discover binding…
“Aptamer fields” can be understood as the interconnected research and application areas where aptamers—short, single-stranded DNA or RNA molecules—are designed and used as highly selective binding agents (often described as “chemical antibodies”) for targets ranging from proteins and small molecules to whole cells. This article explains what defines the aptamer fields, how aptamers are created, where they’re used, and what technical trends are shaping the space. 1) What Are Aptamers (and Why They Matter in Aptamer Fields)? Aptamers are typically ~20–100 nucleotides long and fold into 3D structures that bind specific targets with high affinity and specificity. Unlike antibodies (biological proteins), aptamers are nucleic acids, which affects how they are discovered, synthesized, modified, and integrated into devices. Key reasons aptamers have become a “field” rather than a niche tool: Programmability: sequence-controlled design and chemical modification Manufacturability: scalable synthesis routes compared with biological production Versatility: diagnostics, biosensing, therapeutics, imaging, and research reagents 2) The Core Engine: SELEX and How Aptamers Are Discovered Most aptamers are generated using SELEX (Systematic Evolution of Ligands by EXponential enrichment), an iterative in-vitro selection process that enriches sequences that bind a chosen target. In common workflows, a large random library is…
CUSTOM APTAMER DISCOVERY & DEVELOPMENT is the process of creating target-specific single-stranded DNA or RNA aptamers—short nucleic acids that fold into 3D shapes capable of binding proteins, small molecules, cells, vesicles, or other targets with antibody-like selectivity. Most custom programs rely on SELEX (Systematic Evolution of Ligands by EXponential enrichment), then refine “hits” into robust, application-ready binders through sequencing-driven analysis and post-selection optimization. 1) What Aptamers Are (and Why They’re Used) Aptamers are typically ~15–90 nucleotides long and can be engineered to bind targets across a wide size range (from small molecules to whole cells). They’re attractive because they are chemically synthesized (batch-to-batch consistency), can be readily labeled (fluorophores, biotin, etc.), and are generally thermally stable and re-foldable—features that often simplify assay development and manufacturing. Common aptamer use cases Diagnostics & biosensors (capture probes, signal transducers, point-of-care formats) Targeted delivery & therapeutics research (cell-directed binding, payload delivery concepts) Affinity purification & analytical workflows (pull-downs, enrichment, separations) 2) The Core Workflow in Custom Aptamer Discovery A custom program is best thought of as a pipeline with four linked decisions: target format → selection strategy → analytics → optimization. Step A — Target Definition and “Bindability” Planning…
