Their detection and monitoring can thus inform on therapy efficacy and dose optimization. Due to the low concentration (low nM to pM) at which antibodies are commonly found in clinical samples, methods for antibody detection must be not only specific and selective but also highly sensitive. The enzyme-linked immunosorbent assay (ELISA), probably the most widely used approach for antibody detection, uses enzymatic amplification as a way to achieve very low limits of detection. However, this approach has the disadvantage of requiring reagent-intensive processes and multiple wash and reaction steps which result in relatively high costs and limit the applicability of this method at the point of care. Radioimmunoassay (RIA), another highly sensitive method for antibody detection, uses radioactively labelled antigens to provide information on antigen/antibody binding. However, this approach is also not without limitation as it requires the use and disposal of radioactive material, has cross-reactivity with matrix components and inter-batch variability. In an effort to develop analytical platforms for antibody detection that are suitable for the point of care, we and other research groups have recently demonstrated several approaches that take advantage of the programmability and versatility of synthetic DNA to build nanoscale antibody-responsive devices. In these systems, synthetic DNA strands are used as molecular scaffolds to conjugate recognition elements (i.e. antigens) and signaling tags and are rationally designed to provide a signal when the target antibody binds to the antigens. In the last 10 years, several sensors using antigen-conjugated DNA strands and different sensing strategies (such as binding-induced conformational change, co-localization and steric hindrance) have been described. The advantages of such DNA-based systems include their great versatility and programmability. Indeed, by simply changing the recognition elements conjugated to the synthetic DNA strands, it is possible to recognize, in principle, any target antibody. Also, the programmability of DNA-DNA interactions along with the ability to use different orthogonal signal labels (both fluorescent and electrochemical) allows multiplexed detection of different antibodies in the same solution. These detection platforms are also characterized by high specificity, fast response time and slow-cost. Despite the above advantages, however, all these approaches based on the use of antigen-conjugated DNA strands share a common limitation: due to the direct nature of the assays and the inherent instrumental limitations, the lowest antibody concentrations (limit of detection) that can be measured by these approaches is inevitably higher than those obtained by other indirect techniques such as ELISA. This important limitation ultimately impacts the potential use of these DNA-based platforms as point-of-care devices.