Double-side-coated nanomechanical membrane-type surface stress sensor (MSS) for one-chip-one-channel setup.

With their capability for real-time and label-free detection of targets ranging from gases to biological molecules, nanomechanical sensors are expected to contribute to various fields, such as medicine, security, and environmental science. For practical applications, one of the major issues of nanomechanical sensors is the difficulty of coating receptor layers on their surfaces to which target molecules adsorb or react. To have measurable deflection, a single-side coating is commonly applied to cantilever-type geometry, and it requires specific methods or protocols, such as inkjet spotting or gold-thiol chemistry. If we can apply a double-side coating to nanomechanical sensors, it allows almost any kind of coating technique including dip coating methods, making nanomechanical sensors more useful with better user experiences. Here we address the feasibility of the double-side coating on nanomechanical sensors demonstrated by a membrane-type surface stress sensor (MSS) and verify its working principle by both finite element analysis (FEA) and experiments. In addition, simple hand-operated dip coating is demonstrated as a proof of concept, achieving practical receptor layers without any complex instrumentation. Because the double-side coating is compatible with batch protocols such as dip coating, double-side-coated MSS represents a new paradigm of one-chip-one-channel (channels on a chip are all coated with the same receptor layers) shifting from the conventional one-chip-multiple-channel (channels on a chip are coated with different receptor layers) paradigm.

Two dimensional array of piezoresistive nanomechanical Membrane-type Surface Stress Sensor (MSS) with improved sensitivity.

We present a new generation of piezoresistive nanomechanical Membrane-type Surface stress Sensor (MSS) chips, which consist of a two dimensional array of MSS on a single chip. The implementation of several optimization techniques in the design and microfabrication improved the piezoresistive sensitivity by 3~4 times compared to the first generation MSS chip, resulting in a sensitivity about ~100 times better than a standard cantilever-type sensor and a few times better than optical read-out methods in terms of experimental signal-to-noise ratio. Since the integrated piezoresistive read-out of the MSS can meet practical requirements, such as compactness and not requiring bulky and expensive peripheral devices, the MSS is a promising transducer for nanomechanical sensing in the rapidly growing application fields in medicine, biology, security, and the environment. Specifically, its system compactness due to the integrated piezoresistive sensing makes the MSS concept attractive for the instruments used in mobile applications. In addition, the MSS can operate in opaque liquids, such as blood, where optical read-out techniques cannot be applied.

Parallel AFM imaging and force spectroscopy using two-dimensional probe arrays for applications in cell biology.

Atomic force microscopy (AFM) investigations of living cells provide new information in both biology and medicine. However, slow cell dynamics and the need for statistically significant sample sizes mean that data collection can be an extremely lengthy process. We address this problem by parallelizing AFM experiments using a two-dimensional cantilever array, instead of a single cantilever. We have developed an instrument able to operate a two-dimensional cantilever array, to perform topographical and mechanical investigations in both air and liquid. Deflection readout for all cantilevers of the probe array is performed in parallel and online by interferometry. Probe arrays were microfabricated in silicon nitride. Proof-of-concept has been demonstrated by analyzing the topography of hard surfaces and fixed cells in parallel, and by performing parallel force spectroscopy on living cells. These results open new research opportunities in cell biology by measuring the adhesion and elastic properties of a large number of cells. Both properties are essential parameters for research in metastatic cancer development.

Nanomechanical membrane-type surface stress sensor.

Nanomechanical cantilever sensors have been emerging as a key device for real-time and label-free detection of various analytes ranging from gaseous to biological molecules. The major sensing principle is based on the analyte-induced surface stress, which makes a cantilever bend. In this letter, we present a membrane-type surface stress sensor (MSS), which is based on the piezoresistive read-out integrated in the sensor chip. The MSS is not a simple "cantilever," rather it consists of an "adsorbate membrane" suspended by four piezoresistive "sensing beams," composing a full Wheatstone bridge. The whole analyte-induced isotropic surface stress on the membrane is efficiently transduced to the piezoresistive beams as an amplified uniaxial stress. Evaluation of a prototype MSS used in the present experiments demonstrates a high sensitivity which is comparable with that of optical methods and a factor of more than 20 higher than that obtained with a standard piezoresistive cantilever. The finite element analyses indicate that changing dimensions of the membrane and beams can substantially increase the sensitivity further. Given the various conveniences and advantages of the integrated piezoresistive read-out, this platform is expected to open a new era of surface stress-based sensing.

Sub-ppm detection of vapors using piezoresistive microcantilever array sensors.

The performance of microfabricated piezoresistive cantilever array sensors has been evaluated using various vapors of volatile organic compounds including alkanes with different chain length from 5 (n-pentane) to 14 (n-tetradecane). We demonstrate that piezoresistive microcantilever array sensors have the selectivity of discriminating individual alkanes in a homologous series as well as common volatile organic compounds according to principal component analysis. We developed a new method to evaluate the sensitivity, taking advantage of the low vapor pressures of alkanes with longer chains, such as n-dodecane, n-tridecane and n-tetradecane, under saturated vapor conditions. This method reveals sub-ppm sensitivity and the cantilever response is found to follow the mass of evaporated analytes as calculated using a quantitative model based on the Langmuir evaporation model.