Single cell detection with micromechanical oscillators

TLDR

Detecting small amounts of material, especially pathogenic bacteria, is critical for medical diagnostics and food safety, and engineered micro‑ and nanomechanical systems provide highly sensitive, immunospecific detection. The authors present a resonant‑frequency mass sensor using low‑stress silicon nitride cantilever beams capable of detecting Escherichia coli–antibody binding events down to a single cell. The sensor operates by immobilizing anti‑E. coli O157:H7 antibodies on cantilever beams, binding to O157 antigen on bacterial surfaces, and detecting the resulting mass loading through shifts in resonant frequency.

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.