Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Abstract

Detection of proteins and nucleic acids is dominantly performed using optical fluorescence based techniques, which are more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging. In this paper, we discuss our study of the electrical properties of nucleic acids and proteins at the nanoscale using a nanoelectronic probe we have developed, which we refer to as the Nanoneedle biosensor. The nanoneedle consists of four thin film layers: a conductive layer at the bottom acting as an electrode, an oxide layer on top, and another conductive layer on top of that, with a protective oxide above. The presence of proteins and nucleic acids near the tip results in a decrease in impedance across the sensing electrodes. There are three basic mechanisms behind the electrical response of DNA and protein molecules in solution under an applied alternating electrical field. The first change stems from modulation of the relative permittivity at the interface. The second mechanism is the formation and relaxation of the induced dipole moment. The third mechanism is the tunneling of electrons through the biomolecules. The results presented in this paper can be extended to develop low cost point-of-care diagnostic assays for the clinical setting. V C 2013 AIP Publishing LLC. [http://dx

Modeling of Integrated Nanoneedle-Microfluidic System for Single Cell Temperature Measurement

“…The electrical measurement was done to determine the effect of the cell conductivity on the nanoneedle. According to the literature, single cell viability could be detected by measuring the current flow inside a cell using dual nanoprobes made of tungsten [2]. This triggered the possibility that the cell conductivity could affect the temperature measurement.…”

“…Cell intracellular temperature has been proven a vital element in most cellular activates. Recently, many attempts by researchers focused on developing sensors that have high accuracy and do not cause any damages to the cells, such as nanogap biosensors [1], nanoneedle biosensors [2,3], and sensors using extended-gate field-effect transistors [4,5].…”

“…The rigidity of Tungsten and the small size of the nanoneedle ensure higher chances of penetration. Equations (1) and (2) [26] present the working principle of the sensor. (2) V is the voltage (V), I is the current (A), R is the resistance (Ohm), (ρ) is related the resistivity which relates resistance to temperature, and T is the temperature (K).…”

Quantifying spatio-temporal dynamics of biomarker pre-concentration and depletion in microfluidic systems by intensity threshold analysis

“…2 Micro/nanofluidic device methodologies are routinely applied towards enabling analyte preconcentration within physiologically relevant media [3][4][5] for reducing target diffusion time towards the sensor 6 and thereby enhancing detection sensitivity. 7 Selective pre-concentration also enables analyte enrichment over interfering proteins and small molecules, 8 which is especially relevant given the wide concentration range of proteomic biomarkers within typical biofluids (mg/ml-pg/ml).…”

Digital microfluidic assay for protein detection

“…Such miniaturization can be accomplished by scaling down the optical readout instrumentation, but also by using electronic detection, which offers the added benefit of being low in cost (11). To date, several attempts at label-free electronic detection, such as detection based on impedance spectroscopy at the surface of microelectrodes (12), capacitive sensing-based approaches (13)(14)(15), and field affect transistor-based approaches (16), have been made with varying success. The main challenge with these approaches is the requirement for operation in low salt concentrations.…”