Tech Briefs

Multiple biomarkers would be detected rapidly in small samples.

Arrays of nanosensors for detecting biomolecules associated with breast cancer are undergoing development. It has been proposed to construct the arrays as silicon-based large-scale integrated circuits, each array containing possibly thousands of nanosensors, for rapid, simultaneous detection of molecules of many different species of interest. Some or all of the nanosensors in a given array could be based on a detection principle involving changes in electrical conduction in biofunctionalized nanowires. Alternatively, some or all of the nanosensors in a given array could be based on a detection principle involving changes in the vibrational resonance frequencies of nanocantilevers. By exploiting the experience of the semiconductor and microelectromechanical systems (MEMS) industries, it should be possible to mass-produce such nanosensor arrays at low cost. The development work thus far has included computational simulations of the operation of nanosensors based on the aforementioned detection principles, and fabrication and testing of individual nanosensors and small nanosensor arrays.

This Array of Nanosensors includes gold electrodes connected by functionalized 100-nm-thick silicon wires having various widths from 200 to 300 nm. A single 10-μm-wide silicon strip between electrodes 3 and 4 serves as a control. Electrode 5 serves as a reference or gate electrode for field-effect operation.

The most recently reported development efforts have been focused on electrical-conductance-based nanosensors. A sensor of this type comprises one or more boron-doped silicon nanowires supported between gold electrodes on an electrically insulating layer of silicon oxide. Such a sensor or an array of such sensors is fabricated on a silicon-on-insulator substrate by electron-beam lithography, micromachining, and other processes that are well established in the semiconductor and MEMS industries. The doping is effected by ion implantation and the doping concentration is chosen to obtain the desired starting electrical resistivity. In some cases, electrical-conductance-type nanosensors have been fabricated with gate electrodes placed nearby to demonstrate that these nanosensors could be operated in a manner analogous to that of field-effect transistors (FETs), with all the advantages of amplification, reproducibility, and sensitivity afforded by FETs.

After fabrication of a nanowire-type sensor array as described thus far, all parts except the nanowires are masked with poly(methyl methacrylate) by an established process involving coating and electron-beam lithography. Then the nanowires are functionalized in a process that typically includes exposure to a solution containing the desired sensitizing substance or its precursor. In the case of the experimental nanosensor array shown in the figure, the solution consisted of aminopropyltriethoxysilane in methanol.

In addition to electrodes with nanowires between them, the experimental array shown in the figure includes a reference or gate electrode used to demonstrate operation utilizing the field effect. In the experiments, the nanosensors were used to measure the pH (the logarithm of the reciprocal of the hydrogen- ion concentration). The gate electrode was used to locally set the potential of a sample of a solution of buffer and protein to which the array was exposed. The estimated sample volume sensed was about 1 femtoliter.

In general, the effect of changing pH can be mimicked by changing the gate voltage. This fact can be exploited to increase sensitivity and control by adjusting the gate voltage to change the local hydrogen-ion concentration past the nominal chosen pK value (the negative logarithm of an equilibrium constant) of a selected bimolecular group. In effect, the local pH in a few femtoliters of solvent near a nanosensor can be controlled by adjusting the gate voltage to adjust the ion concentration. By thus changing the local hydrogen-ion concentration past the nominal chosen pK value, one could control the ability of the group to bind or not bind. Hence, through control of gate voltages, one could effect selective coating of nanowires with specific antibodies or peptides. It is planned to investigate such selective coating using cancer biomarker substances specific to breast cancer.

This work was done by Shyamsunder Erramilli of Boston University for the Army Research Laboratory. ARL-0007

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