Single cell detection with micromechanical oscillators

Abstract

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.