Signal Processing for Single Biomolecule Identification Using Nanopores: A Review

Nanopore sensors provide an innovative platform for rapid and label-free biomolecule detection. The analytical information extracted from resistive pulse sensing (RPS) measurement, though powerful has several limitations. To address these challenges, various signal conditioning algorithms have been researched which include efficient clustering and classification of data, applying probabilistic models to reduce information overlap and also leveraging transient analysis of ionic current instead of the steady state RPS measurement. Additionally, as the current is typically in few picoampere regime with high transition rates, its faithful measurement requires precision instrumentation like a patch clamp amplifier with low noise and high bandwidth. However, for practical deployment of such systems, it is necessary to develop portable electronic interface. Significant efforts have been directed globally to develop on-chip customized integrated circuits with low noise, high bandwidth amplifiers. Thus, it is absolutely timely and pertinent to conduct a review on the various signal processing schemes and electronic interfaces for single biomolecule identification using nanopores which will enable to comprehend the current status for its deployment as a commercial platform for genomics and ultrasensitive detection. To the best of our knowledge, the data extraction methodologies and electronic interface schemes for nanopores have not yet been summarized. In this paper, a comprehensive review emphasizing the signal processing algorithms for DNA sequencing and protein identification in complex analyte using functionalized and non-functionalized nanopores has been presented along with the on-chip low noise electronic interfaces required for field deployable measurement.