Cees J.M. van Rijn

Arrays of dual nanomechanical resonators for selective biological detection.

Arrays of small nanomechanical resonators with dual geometry have been fabricated for sensitive biological detection. The arrays consist of silicon nitride resonating 100 nm thick cantilevers with sensing gold areas alternately placed on the free and fixed cantilever ends. The Au areas act as sensing regions as can be functionalized by means of thiol chemistry. The nanomechanical arrays provide a double flavor of the adsorbed molecules: the added mass reported by the cantilevers with the Au area at the tip and the nanoscale elasticity reported by the cantilevers with the Au area at the clamp. The devices were applied for DNA detection based on Watson-Crick pairing rules. The proposed design for nanomechanical resonators provides higher specificity for DNA sensing in comparison with conventional single cantilevers. The nanoscale elasticity induced by the DNA hybridization arises from the intermolecular interactions between the adsorbates bound to the cantilever and the surface stress.

Wet and dry etching techniques for the release of sub-micrometre perforated membranes

For the production of microsieves we studied the release of perforated silicon nitride membranes from a silicon substrate. During the release by KOH etching the pressure build-up due to hydrogen gas formation can be quite large and cause rupture of the membrane. We explored the use of anisotropic etching with an SF6/O2 plasma to replace KOH etching. For sub-micrometre pores excellent results were obtained.

Shedding Light on Axial Stress Effect on Resonance Frequencies of Nanocantilevers

The detection back-action phenomenon has received little attention in physical, chemical, and biological sensors based on nanomechanical systems. We show that this effect is very significant in ultrathin bimetallic cantilevers, in which the laser beam that probes the picometer scale vibration largely modifies the resonant frequencies of the system. The light back-action effect is nonlinear, and some resonant frequencies can even be reduced to a half with laser power intensities of 2 mW. We demonstrate that this effect arises from the stress and strain generated by the laser heating. The experiments are explained by two-dimensional nonlinear elasticity theory and supported by finite element simulations. The found phenomenology is intimately connected to the old unsolved problem about the effect of surface stress on the resonance frequency of singly clamped beams. The results indicate that to achieve the ultimate detection limits with nanomechanical resonators one must consider the uncertainty due to the detection back-action.

A low-power readout circuit for nanowire based hydrogen sensor

This paper presents a fully integrated lock-in amplifier intended for nanowire gas sensing. The nanowire will change its conductivity according to the concentration of an absorbing gas. To ensure an accurate nanowire impedance measurement, a lock-in technique is implemented to attenuate the low frequency noise and offset by synchronous demodulation or phase-sensitive detection (PSD). The dual-channel lock-in amplifier also provides both resistive and capacitive information of the nanowire in separate channels. Measurement results of test resistors and capacitors show a 2% resolution in the resistance range 10-40k@W and a 3% resolution in the capacitance range 0.5-1.8nF. Moreover, a 28.7-32.1k@W impedance variation was measured through the lock-in amplifier for a single palladium nanowire that was exposed to a decreasing hydrogen concentration (10% H2 in N2 to air). The chip has been implemented with UMC 0.18@mm CMOS technology and occupies an area of 2mm^2. The power consumption of the readout circuit is 2mW from a 1.8V supply.

A generic microfluidic biosensor of G protein-coupled receptor activation – impedance measurements of reversible morphological changes of reverse transfected HEK293 cells on microelectrodes

Impedance spectroscopy of cell lines on interdigitated electrodes (IDEs) is an established method of monitoring receptor-specific cell shape changes in response to certain analytes. Normally, assays are done in multiwells making it a bulky, static and single use procedure. Here, we present a biosensor allowing sequential application of biological test samples with an automated microfluidic system. It is capable of monitoring relative changes in impedance using castellated IDEs of 250–500 μm diameter, covered with stable or reverse transfected HEK293 cells. Reversible activation of the Neurokinin 1 (NK1) receptor in stable cell lines was observed in response to a series of 5 minute exposures from 1 pM–10 nM of the specific ligand Substance P (SP) using impedance measurements at 10 mV and 15 kHz. An optimal flow speed of 10 μl min−1 was chosen for the 10 μl flow cell. The EC50 of ∼10 pM was about 10 times lower than the EC50 based on measuring changes in the calcium ion concentration. The method was also shown to work with reverse transfected cells. Plasmid DNA encoding the NK1 gene was spotted onto the electrodes and pre-incubated with a transfection agent. The overlaid HEK293 cells were subsequently transfected by the underlying DNA. After challenge with SP, the cells induced an activation response similar to the stable cell line. The microfluidic micro-electrode reverse transfection system opens up possibilities to perform parallel measurements on IDE arrays with distinct receptors per IDE in a single flow channel.