In an era of potential bioterrorism and pandemics of antibiotic-resistant microbes, bacterial contaminations of food and water supplies is a major concern. There is an urgent need for the rapid, inexpensive and specific identification of bacteria under field conditions. Here we describe a method that combines the specificity and avidity of bacteriophages with fluctuation analysis of electrical noise. The method is based on the massive, transitory ion leakage that occurs at the moment of phage DNA injection into the host cell. The ion fluxes require only that the cells be physiologically viable (i.e., have energized membranes) and can occur within seconds after mixing the cells with sufficient concentrations of phage particles. To detect these fluxes, we have constructed a nano-well, a lateral, micron-size capacitor of titanium electrodes with gap size of 150 nm, and used it to measure the electrical field fluctuations in microliter (mm3) samples containing phage and bacteria. In mixtures where the analyte bacteria were sensitive to the phage, large stochastic waves with various time and amplitude scales were observed, with power spectra of approximately 1/f2 shape over at 1 - 10 Hz. Development of this SEPTIC (SEnsing of Phage-Triggered Ion Cascades) technology could provide rapid detection and identification of live, pathogenic bacteria on the scale of minutes, with unparalleled specificity. The method has a potential ultimate sensitivity of 1 bacterium/microliter (1 bacterium/mm3).
This paper presents a nanowell device that detects the nano-scale electric field fluctuations due to ion cascade in bacteria. Solid-state nano devices allow for the measurement and analysis of fluctuation on the single cell or molecule scale, which can offer orders of magnitude higher sensitivity than microscopic measurements through conventional sensors. We fabricated a nanowell that is a 150nm wide gap in the middle of a titanium line on LiNbO3 substrate. The noise in the electrical current through this gap is measured. When bacteria are infected by bacteriophage, a large amount of ions are released, which yields spatiotemporal fluctuations of electric potential captured by this nanowell. It was demonstrated that this technology can be used to identify bacteria within minutes using the high specificity of phage/bacteria interaction. The perspective of building a biochip with hundreds of nano devices, immobilized phages and microfluidic channels so as to identify a large variety of bacteria is also discussed in this paper.