Enhancing the Performance of DNA Surface-Hybridization Biosensors through Target Depletion

• DOI: 10.1021/acs.langmuir.9b01761
• Publication Date: 2019-08-21T18:39:03Z
• Authors: Stefanos K. Nomidis; Michal Szymonik; Tom Venken; Enrico Carlon; Jef Hooyberghs
• Keywords: Hybridization probe; Langmuir adsorption model; Sequence (biology)

DNA surface-hybridization biosensors utilize the selective hybridization of target sequences in solution to surface-immobilized probes. In this process, is usually assumed be excess, so that its concentration does not significantly vary while hybridizing surface-bound If initially at low concentrations and/or if number probes very large and have high affinity for target, may get depleted. paper we analyze equilibrium kinetics case strong depletion, by extending Langmuir adsorption model. We focus, particular, on detection a small amount single-nucleotide "mutant" sequence (concentration $c_2$) solution, which differs one or more nucleotides from an abundant "wild-type" $c_1 \gg c_2$). show depletion can give rise strongly-enhanced sensitivity biosensors. Using representative values rate constants free energies, find regime could detect relative $c_2/c_1$ are up three orders magnitude smaller than conventional approach. The surprisingly rich, exhibits non-monotonic with no counterpart no-depletion case. Finally, that, alongside enhanced sensitivity, approach offers possibility sample enrichment, substantially increasing mutant over wild-type sequence.