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.

Cantilever biosensors for detection of viruses and bacteria

“…Эта бактерия может служить индикатором качества воды [11]. Детектирование отдельной клетки E.coli было продемонстрировано с помощью кантилеверного сенсора в резонансном режиме [12] (рис.3). Однако в данной работе для повышения чувствительности измерения про Fig.3.…”

“…Однако в данной работе для повышения чувствительности измерения про Fig.3. Single E. Coli bacterium on the surface of the cantilever [12] #5 / 67 / 2016 chip of few millimeters is already shown. IBM has demonstrated the location of the 100 cantilevers on 1 mm 2 .…”

“…This bacterium may serve as an indica tor of water quality [11]. The detec tion of individual E. coli cell was demonstrated using the cantile ver sensor in a resonant mode [12] (Fig.3). However, in this project, for sensitivity increase measurements were carried out in vacuum and required stage of drying.…”

Integrated MEMS/NEMS Resonant Cantilevers for Ultrasensitive Biological Detection

“…With precise optical detection of atomic force microscopy (AFM), a single cell or virus has been sensed in air environment [8,9]. In ultrahigh vacuum, the resonant cantilevers even showed the mass resolution as high as attogram level [10].…”

“…Differently, the dynamic detecting method employs the cantilever as a resonator. Induced by specific mass adsorbate, a shift in the resonant frequency is read out as the sensing signal [7][8][9][10][11].…”