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…
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…
Aptamers are short single-stranded DNA or RNA molecules that fold into 3D structures capable of binding targets (proteins, small molecules, cells, or even complex particles) with high specificity and affinity. “Aptamer methods” usually refers to the full pipeline: library design → selection (SELEX) → enrichment monitoring → sequencing & bioinformatics → candidate optimization → biophysical/functional validation → stability engineering. Modern platforms improve speed and hit quality by combining smarter selection pressures with microfluidics and next-generation sequencing. 1) Core Aptamer Selection Method: SELEX (Systematic Evolution of Ligands by EXponential Enrichment) 1.1 Classical SELEX workflow (baseline method) Start with a random oligonucleotide library (often 10^13–10^15 unique sequences) Incubate library with the target Partition bound vs unbound sequences Elute binders Amplify (PCR for DNA; RT-PCR + transcription for RNA) Repeat iterative rounds with increasing stringency until enrichment is achieved Why it works: each round increases the fraction of sequences that can bind under the imposed conditions (buffer, temperature, competitor molecules, etc.). Why it’s hard: classical SELEX can be slow, labor intensive, and prone to amplification bias—hence the rise of “advanced SELEX” platforms. 1.2 “Stringency engineering” (how you make aptamers useful) Selection success often depends less on the target itself…
