Single molecule sensors in which nanoscale pores within biological or artificial membranes act as mechanical gating elements are very promising devices for the rapid characterization and sequencing of nucleic acid molecules. The two terminal electrical measurements of translocation of polymers through single ion channels and that of ssDNA molecules through protein channels have been demonstrated, and have sparked tremendous interest in such single molecule sensors. The prevailing view regarding the nanopore sensors is that there exists no electrical interaction between the nanopore and the translocating molecule, and that all nanopore sensors reported to-date, whether biological or artificial, operate as a coulter-counter, i.e., the ionic current measured across the pore decreases (is mechanically blocked) when the DNA molecule transverses through the pore. We have fabricated nanopore "channel" sensors with a silicon oxide inner surface, and our results challenge the prevailing view of exclusive mechanical interaction during the translocation of dsDNA molecules through these channels. We demonstrate that the ionic current can actually increase due to electrical gating of surface current in the channel due to the charge on the DNA itself.As a first step toward the ultimate goal of single-molecule DNA sequencing using nanopore sensors, one must first identify the key mechanical and electrical variables that control the translocation of the molecules through the nanopores. First, a nanopore used for characterization and sequencing of a single molecule must have a diameter of less than the persistence length (∼50 nm for dsDNA) to avoid any signal averaging from thermally induced conformational changes. Second, the pores must be chemically stable and mechanically robust under a wide variety of conditions of use. Third, and finally, the mechanical and electrical interaction between the nanopores and the single molecules must be well characterized. Toward this end, the electrical detection of translocation of polymers through single ion channels has been demonstrated. 1-2 Subsequently, the pioneering studies of the use of R-hemolysin protein pore within a lipid bilayer for the translocation of single strands of DNA molecules using a voltage bias across the membranes sparked tremendous interest in such single molecule sensors. [3][4][5][6][7][8] The normal ionic current through the protein pore in a lipid bilayer would detectably reduce as a polyanionic chain of ssDNA molecules traversed through the pore, even allowing the distinction between polycytosine and polyadenine molecules, thus demonstrating the potential of single base discrimination in these sensors. 4,5 Despite these advantages, robust integration of these biological sensors within practical devices is quite problematic, and a mechanical pore 9,10 provides numerous advantages over biological pores. Besides the obvious advantages of being able to drastically change ambient conditions such as pH, electric field, and temperature without distorting the s...

Reports of DNA translocation measurements have been increasing rapidly in recent years due to advancements in pore fabrication and these measurements continue to provide insight into the physics of DNA translocations through MEMS based solid state nanopores. Specifically, it has recently been demonstrated that in addition to typically observed current blockages, enhancements in current can also be measured under certain conditions. Here, we further demonstrate the power of these nanopores for examining single DNA molecules by measuring these ionic currents as a function of the applied electric field and show that the direction of the resulting current pulse can provide fundamental insight into the physics of condensed counterions and the dipole saturation in single DNA molecules. Expanding on earlier work by Manning and others, we propose a model of DNA counterion ionic current and saturation of this current based on our experimental results. The work can have broad impact in understanding DNA sensing, DNA delivery into cells, DNA conductivity, and molecular electronics.

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Biomedical or Biological Micro-Electro-Mechanical-Systems (BioMEMS) have in recent years become increasingly prevalent and have found widespread use in a wide variety of applications such as diagnostics, therapeutics and tissue engineering. This paper reviews the interdisciplinary work performed in our group in recent years to develop microintegrated devices to characterize biological entities. We present the use of electrical and mechanically based phenomena to perform characterization and various functions needed for integrated biochips. One sub-system takes advantage of the dielectrophoretic effect to sort and concentrate bacterial cells and viruses within a micro-fluidic biochip. Another subsystem measures impedance changes produced by the metabolic activity of bacterial cells to determine their viability. A third sub-system is used to detect the mass of viruses as they bind to micro-mechanical sensors. The last sub-system described has been used to detect the charge on DNA molecules as it translocates through nanopore channels. These devices with an electronic or mechanical signal output can be very useful in producing practical systems for rapid detection and characterization of cells for a wide variety of applications in the food safety and health diagnostics industries. The paper will also briefly discuss future prospects of BioMEMS and its possible impact and on bionanotechnology.