Single cell detection with micromechanical oscillators

The ability to detect small amounts of materials, especially pathogenic bacteria, is important for medical diagnostics and for monitoring the food supply. Engineered micro- and nanomechanical systems can serve as multifunctional, highly sensitive, immunospecific biological detectors. We present a resonant frequency-based mass sensor, comprised of low-stress silicon nitride cantilever beams for the detection of Escherichia coli (E. coli)-cell-antibody binding events with detection sensitivity down to a single cell. The binding events involved the interaction between anti-E. coli O157:H7 antibodies immobilized on a cantilever beam and the O157 antigen present on the surface of pathogenic E. coli O157:H7. Additional mass loading from the specific binding of the E. coli cells was detected by measuring a resonant frequency shift of the micromechanical oscillator. In air, where considerable damping occurs, our device mass sensitivities for a 15 μm and 25 μm long beam were 1.1 Hz/fg and 7.1 Hz/fg, respectively. In both cases, utilizing thermal and ambient noise as a driving mechanism, the sensor was highly effective in detecting immobilized anti-E. coli antibody monolayer assemblies, as well as single E. coli cells. Our results suggest that tailoring of oscillator dimensions is a feasible approach for sensitivity enhancement of resonant mass sensors.