On-board amplifiers can alleviate the space requirements of integration, although a recent review estimated that a cost-effective integration would be limited to 1000 amplifiers in a 600 mm 2 chip area. 27− 29 Nonoptical approaches to reading multiple pores, namely, tunneling-based or fluid wells, are both limited by the need for a network of parallel electrodes and/or fluid conduits that lead to macroscale contacts. Indeed, various schemes have been proposed and demonstrated for multiplexed detection, which include optical approaches, 14− 19 field effect/tunneling-based detection, 20− 26 and fluid wells connected to electrode arrays. However, a critical requirement for this is that each pore in the sensor array is monitored independently, which in the case of electrical detection requires advanced microfluidics and integrated circuitry. Furthermore, the ability to introduce sensors tailored for different molecules on a single device can afford complex mixture analysis at unprecedentedly small volumes. Multiplexed detection from an array of sensors can considerably speed up measurements, thereby reducing the molecular/biological sample requirement. 10− 13ĭue to the stochastic nature of single-molecule detection using nanopores, many discrete molecular observations are required in order to obtain statistically significant data for a sample. Over the past decade, nanopore-based techniques have shown great promise in a wide range of biophysical and biomedical applications, including DNA, 1, 2 RNA, 3 and protein sequencing 4− 6 drug discovery 7 single-molecule biophysics 8, 9 and proteomics. A characteristic transient drop in the ionic conductance of the pore is observed for each passing molecule, which is used to determine its identity.
In a typical nanopore measurement, an insulating membrane separates two chambers containing an electrolyte solution analyte molecules in the solution are electrophoretically driven across the barrier via a nanometer-scale aperture contained in the membrane. Nanopores offer a unique capability of sensing and manipulating single molecules in a label-free manner.
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