Characterization of a gold coated cantilever surface for biosensing applications

Abstract

Cantilever based sensors are a promising tool for a very diverse spectrum of biological sensors. They have been used for the detection of proteins, DNA, antigens, bacteria viruses and many other biologically relevant targets. Although cantilever sensing has been described for over 20 years, there are still no viable commercial cantilever-based sensing products on the market. Several reasons can be found for this – a lack of detailed understanding of the origin of signals being an important one. As a consequence application-relevant issues such as shelf life and robust protocols distinguishing targets from false responses have received very little attention.Here, we will discuss a cantilever sensing platform combined with an electrochemical system. The detected surface stress signal is modulated by applying a square wave potential to a gold coated cantilever. The square wave potential induces adsorption and desorption onto the gold electrode surface as well as possible structural changes of the target and probe molecules on the cantilever surface resulting in a measurable surface stress change. What sets this approach apart from regular cantilever sensing is that the quantification and identification of observed signals due to target-probe interactions are not only a function of stress value (i.e. amplitude), but also of the temporal evolution of the stress response as a function of the rate and magnitude of the applied potential change, and the limits of the potential change.This paper will discuss three issues that play an important role in future successful applications of cantilever-based sensing. First, we will discuss what is required to achieve a large surface stress signal to improve sensitivity. Second, a mechanism to achieve an optimal probe density is described that improves the signal-to-noise ratio and response times of the sensor. Lastly, lifetime and long term measurements are discussed.

Microfluidic techniques for high throughput single cell analysis

“…Figure 1 provides an overview of microfluidic-enabled technologies and their ability to analyze and isolate increasingly rare single cells from increasingly large populations. Properties of selectively immobilized cells have been directly characterized using static and quasi-static techniques such as MEMS resonant sensing[11], atomic force microscopy (AFM)[12,13] (Figure 1a), and fluorescence microscopy[14]. As microfabrication schemes and fluid control techniques advanced, the selectivity and number of cells that could be simultaneously analyzed increased[1,15].…”

Sensitivity measurement of a cantilever-based surface stress sensor

“…A three-electrode electrochemical system, with the cantilever connected as the working electrode, is used to apply potentials to the surface of the cantilever. Ions are directed to the surface and these accumulated charges cause a substantially larger measurable change in the surface stress 8,12,24 over conventional surface stress measurements at open-circuit potentials.…”

“…In recent years, several nano and micromechanical structures have been described as possible biosensor platforms. [1][2][3][4][5] Here we focus on cantilever-based sensors which have been used for the mechanical detection of a vast variety of biological targets such as DNA, [6][7][8][9][10][11][12][13][14][15] antigens, 16 proteins, 17,18 bacteria, [19][20][21] and viruses. 22 The most common detection principles in these mechanical sensors due to biological binding effects are changes in surface stress [23][24][25][26][27] and mass.…”

“…12 An important consequence of this is that the magnitude of the observed stress signal is proportional to the area of exposed clean gold. 8 In this study, a gold-coated cantilever sensor is used to measure surface stress changes upon exposure to a 1 mM NaCl or NaClO 4 solution under potential control. A three-electrode electrochemical system, with the cantilever connected as the working electrode, is used to apply potentials to the surface of the cantilever.…”

Selectivein situpotential-assisted SAM formation on multi electrode arrays

“…In some applications, a partially coated sensor surface is desired [21][22][23]. Peterson et al [24] have shown that surfacetethered single stranded DNA, when in a low surface density regime, is desired as probe hybridization proceeds with relatively fast kinetics.…”