Direct detection of whole bacteria using a nonlinear acoustic resonator

• Published in: Sensors and actuators. B, Chemical Chemical, 2020-08, Vol.316, p.128086, Article 128086
• Main Authors: Khobragade, Shilpa, Da Silva Granja, Carlos, Sandström, Niklas, Efimov, Igor, Ostanin, Victor P, van der Wijngaart, Wouter, Klenerman, David, Ghosh, Sourav K
• Format: Article
• Language: English
• Subjects: Acoustic properties; Acoustic resonance; Acoustics; anharmonic acoustic aptasensor; Bacteria; Buffer solutions; E coli; label-free direct rapid biosensor; Mathematical analysis; Microfluidics; nonlinear acoustic sensor; Nonlinear response; Nonlinearity; Parameter sensitivity; portable microfluidic biosensor; quartz crystal microbalance; Quartz crystals; Resonators; whole bacterial detection
• ISSN: 0925-4005; 1873-3077; 1873-3077
• DOI: 10.1016/j.snb.2020.128086

•Direct detection of whole bacteria using nonlinear response of a quartz resonator.•Specificity distinctly higher due to unique transduction specificity.•Sensitivity and quantification improved over traditional acoustic parameters.•Microfluidic cell and aptamer assist rapid and specific detection under flow.•Theoretical model relates experimental data with quartz nonlinearity coefficient. Direct detection of whole vegetative bacteria was investigated employing a quartz crystal resonator (QCR) in its nonlinear regime. Escherichia coli (E. coli) in buffer solution under flow was captured on a QCR in a microfluidic cell using a whole-cell anti-E.coli aptamer. The nonlinear distortion in QCR response due to the ‘pull’ from surface-bound bacteria was measured in realtime as the change in third Fourier harmonic (3f) current and compared with shifts in the traditional acoustic parameters of resonance frequency and dissipation. The change in 3f current showed superior quantitative correlation with E. coli concentrations (105-108 cfu/mL) and at least an order of magnitude better sensitivity than shifts in the traditional acoustic parameters. Most interestingly, underpinned by the strength of bacteria-QCR pull, the nonlinear acoustic principle demonstrated a unique specificity in transduction, even in a mixed sample with another gram-negative bacteria, that can supplement the specificity of the bioreceptors. An analytical expression was derived to quantitatively relate the competing influence of shifts in dissipation and nonlinearity coefficient of the QCR on the change in 3f current. This study demonstrates the potential for reliable direct readout of bioreceptor-mediated binding of whole vegetative bacteria from complex samples using a nonlinear acoustic resonator.