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.
Fatal injury of bacteria opens transmembrane ion pathways that create temporary ion clouds around the cells. This ion release transiently charges bacteria yielding spatiotemporal fluctuations of the electrical field which show up like a "fatal scream" in thermal noise. The effect has recently been demonstrated with the specific injuries caused by bacteriophage infections (King, et al, in press) and suggested for identification of bacteria with extraordinary speed and selectivity. Calculations indicate that the detection and identification of a single bacterium can be achieved with natural (wild) phages with reasonable efforts within a time window of 10 minutes. However the potential applicability of the agent-triggered ion cascade reaches much beyond that, including other kinds of injuries, such as those induced by antibiotics, ageing, poisoning, etc. Considerations and open questions about the physical aspects of the fluctuations and their detectability are discussed in this talk.
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 (mm<sup>3</sup>) 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/f<sup>2</sup> 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/mm<sup>3</sup>).
We propose a new way of pattern recognition which can distinguish different stochastic processes even if they have the same power density spectrum. Known crosscorrelation techniques recognize only the same realizations of a stochastic process in the two signal channels. However, crosscorrelation techniques do not work for recognizing independent realizations of the same stochastic process because their crosscorrelation function and cross spectrum are zero. A method able to do that would have the potential to revolutionize identification and pattern recognition, techniques, including sensing and security applications. The new method we are proposing is able to identify independent realizations of the same process, and at the same time, does not give false alarm for different processes which are very similar in nature. We demonstrate the method by using different realizations of two different types of random telegram signals, which are indistinguishable with respect to power density spectra (PDS). We call this method bispectrum correlation coefficient (BCC) technique.
The error rate in a current-controlled logic processor dominated by shot noise has been investigated. It is shown that the error rate increases very rapidly with increasing cutoff frequency. The maximum clock frequency of the processor, which works without errors, is obtained as a function of the on-state current. The information channel capacity of the system is also studied.
The tunneling rate of single electronic tunneling (SET) transistor at nonzero temperature has been analyzed. A stability condition, which allows one bit flip error/year, is used. The aspects of dissipation and performance are studied, for a single SET and for a microprocessor built of SETs, versus the size.