###### Abstract  
The development of sensitive and selective assays for protein biomarkers and other biological analytes is important for advancing the fields of clinical diagnostics and bioanalytical chemistry. The potential advantages of using aptamers in electrochemical sandwich assays are being increasingly recognized. These assays may include an aptamer as both capture and detection agent or a combination of an aptamer with a different partner such as an antibody, a lectin or a nanomaterial. The second binding partner in the sandwich structure is typically conjugated to a redox marker, a catalyst or an enzyme that can be used to generate the signal needed for electrochemical detection. Nanoparticles and other nanostructures can be used as the carriers for multiple molecules of the detection partner and thereby increase the signal. Nanostructured surfaces can be used to increase surface area and improve electron transfer. Sensitive electrochemical methods including impedance, differential and square-wave voltammetry and chronocoulometry have been used for electrochemical signal read-out. Impressive results have been achieved using electrochemical sandwich assays in terms of limit of detection and linear range for a growing range of analytes. The recent progress for this type of assay for proteins and other biomarkers is the subject of this review. assy; sandwich assay; aptamer; protein; electrochemistry; biomarker +
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of aptamer-based electrochemical sensors in medical diagnostics is reviewed including strategies based on hybridization and changes in aptamer conformation [1]. An interesting earlier review concerning electrochemical sandwich assays is also presented [2]. The most common electrochemical detection strategies are those that detect a peak current and those that detect an accumulation of charge by binding a redox marker to the surface-bound oligonucleotides associated with the detection part of the sandwich structure. **Scheme 1. ** A sample of some of the sandwich assay structures that are possible and that are discussed in this review. (**A**) an aptamer-analyte-aptamer sandwich with capture aptamers bound to a nanoparticle-modified electrode surface with the detection aptamers bound to a nanoparticle that also is labeled by an enzyme, (**B**) an aptamer-analyte-antibody sandwich on a nanostructured layer which has continuous nanoscale features to which capture aptamers are bound with the detection antibodies then bound to a nanoparticle in the form of antibody-enzyme conjugates, (**C**) aptamer-modified magnetic nanoparticles captured on an electrode surface using a magnet so that an aptamer-analyte-(antibody-enzyme conjugate) sandwich structure can be formed, and (**D**) a nanocomposite surface containing materials such as carbon nanotubes and polymers with adsorbed or covalently attached aptamers forming a sandwich with a glycoprotein for which the glycan structure is bound by a lectin-enzyme conjugate. There are numerous other possibilities. The linkage of aptamers to surfaces or nanoparticles may be by the use of thiolated aptamers, the use of bioconjugation reactions, biotin-streptavidin interactions or by physisorption. Enzymes may be linked to aptamers or antibodies using biotin-streptavidin interactions, or bioconjugation reactions. The analyte is most often a protein biomarker but can also represent other possibilities such as a cell, a bacterium, a peptide, or some other biomolecule. Electrochemical approaches to detecting biomarkers for a wide range of diseases are under intensive development focusing on specific proteins, peptides, and oligonucleotidestides [3]. Electrochemical detection of specific protein biomarkers is a key technology under development for the diagnosis of cancer and other diseases in clinical and point-of-care settings [4]. Electrochemical immunosensors based on antibodies and antibody sandwich complexes have become a highly popular approach [5; 6; 7].