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| Method | Description | Reference |
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| Atomic force microscopy (AFM)-SELEX | AFM-SELEX uses a dynamic atomic force microscopy tip to pick up and visualize aptamer-target complexes. This SELEX requires only one round of selection. | [99]
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| Automated SELEX | This SELEX uses automated systems for the procedure to reduce the time and labour required. | [34]
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| Blended SELEX | In this technique, a lead chemical compound is attached covalently or non-covalently to a nucleic acid library. Each nucleic acid conjugate in the starting library is a variant of the chemical compound moiety and allows up to 1015 variants of the small molecule to be screened for the most active of these composite assemblies. | [100]
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| Cell-SELEX | Cell-SELEX generates aptamers that can bind specifically to a cell of interest. Commonly, a cancer cell line is used as the target to generate aptamers that can differentiate that cell from other cancers or normal cells. | [101]
|
| Capillary electrophoresis (CE)-SELEX | The separation of bound and nonbound oligonucleotides is performed using capillary electrophoresis. | [102]
|
| Chimeric SELEX | Chimeric SELEX uses two or more different oligonucleotide libraries for production of chimeric aptamers with more than one wanted feature or function. Each of the parent libraries will be selected first to a distinct feature; the resulting aptamers are then fused together. | [103]
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| Conditional SELEX | This SELEX uses regulator molecules during the selection, thus, allowing aptamer binding to the target to be regulated. | [104]
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| Counter selection/ subtractive SELEX | This technique employs additional rounds of SELEX to remove sequences that bind to similar target structures. | [44]
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| Covalent/ Crosslinking SELEX | This process is used to select aptamers that contain reactive groups which are capable of covalent linking to a target protein. | [105]
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| Deconvolution SELEX | Deconvolution SELEX is used to generate aptamers for complex targets. Typically selection is performed on mixtures (or a cell). Once aptamers have been generated, a second part of SELEX involves discriminating which aptamers bind to which parts of the complex mixture. | [106]
|
| Electrophoretic mobility shift assay (EMSA)-SELEX | The partitioning step of SELEX occurs through the use of electrophoretic mobility shift assay (EMSA) at every round. | [107]
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| Expression cassette SELEX | This is a special form of blended SELEX that involves transcription factors and optimizes aptamer activity for gene therapy applications. | [108]
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| Fluorescence-activated cell sorting (FACS) SELEX | This SELEX makes use of fluorescence-activated cell sorting to differentiate and separate aptamer-bound cells. | [59]
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| FluMag SELEX | Here the library is modified with fluorescein instead of radiolabels for quantification purposes. Additionally, the target is immobilized to magnetic beads instead of agarose. | [109]
|
| Genomic SELEX | The SELEX library is constructed from an organism’s genome and target proteins and metabolites from the same organism are used to elucidate meaningful interactions. | [110]
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| In vivo SELEX | In vivo SELEX uses transient transfection in an iterative procedure in cultured vertebrate cells to select for RNA-processing signals. | [111]
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| Indirect SELEX | The target used in the selection is not the aptamer binder; however, it becomes required for aptamer binding to the new target. | [112]
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| Mod-SELEX | Mod-SELEX uses a library of oligonucleotides with chemical substitutions that result in nuclease-resistant aptamers. | [113]
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| Multivalent aptamer isolation (MAI) SELEX | This process is used to generate aptamer pairs for a given target. | [114]
|
| Microfluidics SELEX | This SELEX uses microfluidic technologies, creating an automatic, and miniature SELEX platform for fast aptamer screening. | [115, 116] |
| Monolex | Monolex involves a single affinity chromatography step, followed by physical segmentation of the affinity material, to obtain the highest affinity aptamers. | [117]
|
| Multiplexed massively parallel SELEX | This allows analysis of large numbers of transcription factors in parallel through the use of affinity-tagged proteins, bar-coded selection oligonucleotides, and multiplexed sequencing. | [118]
|
| Multi-stage SELEX | Multistage SELEX is a modified version of chimeric selex. Here, the fused aptamer components then go through an additional selection with all the targets. | [119]
|
| Negative selection | An additional step, performed typically at the beginning of selection, removes sequences that have an affinity for the selection matrix. | [48]
|
| Next generation SELEX | This SELEX uses designed oligonucleotide libraries that tile through a pre-mRNA sequence. The pool is then partitioned into bound and unbound fractions, which are quantified by a two-color microarray. | [120]
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| Non-SELEX (NCEEM) | This process involves repetitive steps of partitioning with no amplification steps. | [121]
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| Photo SELEX | Aptamers bearing photo-reactive groups that can photo cross-link to a target and/or photo activate a target molecule are used. | [122]
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| Primer-free SELEX | This SELEX involves removal of the primer-annealing sequences from the library prior to selection, preventing unwanted primer-based secondary structures. | [123]
|
| Serial analysis of gene expression (SAGE) or high- throughput SELEX | SAGE SELEX links oligomers from SELEX with longer DNA molecules that can be efficiently sequenced. | [124]
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| Spiegelmer technology | The aptamer selection is performed with the natural D-nucleic acids but on the opposite enantiomer of the chiral target molecule. After sequencing, the aptamers are synthesized as L-isomers for binding to the desired enantiomer of the target. | [125]
|
| Slow off-rate modified aptamers (SOMAmer) | The selection is performed with oligonucleotide libraries that are uniformly functionalized at the 5′-position resulting in high-quality aptamers. | [28]
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| Tailored SELEX | This is an integrated method to identify aptamers with only 10 fixed nucleotides through ligation and removal of primer binding sites within the SELEX process. | [126]
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| Target expressed on cell surface (TECS) SELEX | Recombinant proteins on the cell surface are used directly as the selection target. | [127]
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| Tissue-SELEX | This method is for generating aptamers capable of binding to tissue targets. | [106]
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| Toggle-SELEX | The selection is performed on different targets in alternating rounds. | [128]
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| Yeast Genetic SELEX | This method optimizes in vitro selected aptamers by creating a library of degenerate aptamers and performing a secondary selection in vivo using a yeast three (one)-hybrid system. | [129]
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