A strategy is described for continuous monitoring of multiple latent tuberculosis infection (LTBI) biomarkers, specifically of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2). Silver nanoparticles acting as mass signal amplifiers were linked to respective antibodies to form mass nanoprobes for increasing the mass loaded on the surface of the quartz crystal microbalance (QCM). This results in enhanced sensitivity. The mass nanoprobes can be oxidatively dissolved by hydrogen peroxide that avoided the steric hindrance caused by the scale effect of mass nanoprobes. This offers the option of signal recovery monitoring. By using this method, IFN-γ, TNF-α and IL-2 can be monitored serially. The frequency shifts caused by TNF-α, IFN-γ and IL-2, respectively, are reversible. Hence, the biomarkers can be continuously quantified. Compared to multichannel QCM sensing, the new method avoids acoustic interference and has a simplified instrumental setup. The assay is simple, accurate, sensitive, and inexpensive. Graphical abstract Silver nanoparticles as the mass signal amplifiers were linked with the antibodies to form mass nanoprobes for enhancing the monitoring sensitivity. With the introduction of H2O2 to dissolve the mass nanoprobes attached on sensing interface, a signal recovery QCM strategy is established for real-time and continuous monitoring of three LTBI biomarkers.
Keywords: Monitoring sensitivity; Multi-analyte detection; Multiplex immunoassay; On-line monitoring; Soluble mass nanoprobes.