We set up a label-free direct binding assay for the detection of noncoding RNAs. The assay is based on nanomechanical cantilever arrays for the detection of surface stress induced by immobilized biomolecules and their interaction partners. We used various means to significantly reduce the drift of the cantilever readout that was a prominent feature in experiments with readout in stationary fluid before and after sample injection. Major improvements were achieved by focusing on a faster system equilibration (for instance temperature control and diffusion independence). Experimental protocols were improved to provide user-friendly and less time-consuming measurements. Further enhancements were achieved by, for example, using pre-gold-coated cantilever array wafers compared to individually prepared ones and a directly implemented data analysis tool as real-time feature of the measurement software. We have demonstrated picomolar specific biomarker target detection and can easily distinguish modified targets with single-nucleotide mismatches that hybridize with lower affinity.

Peter Noy

Roger Steiner

Joerg Voelkle

Martin Hegner

Christof Fattinger

Instrument for Label-Free Detection of Noncoding RNAs

We demonstrate the use of an astigmatic detection system (ADS) for resonance frequency identification of polymer microcantilever sensors. The ADS technology is based on a DVD optical head combined with an optical microscope (OM). The optical head has a signal bandwidth of 80 MHz, allowing thermal fluctuation measurements on cantilever beams with a subnanometer resolution. Furthermore, an external excitation can intensify the resonance amplitude, enhancing the signal-  to-noise ratio. The full width at half maximum (FWHM) of the laser spot is 568 nm, which facilitates read-out on potentially submicrometer-sized cantilevers. The resonant frequency of SU-8 microcantilevers is measured by both thermal fluctuation and excited vibration measurement modes of the ADS.

En-Te Hwu

Hsien-Shun Liao

Filippo G. Bosco

Ching-Hsiu Chen

Stephan Sylvest Keller

Anja Boisen

Kuang-Yuh Huang

An Astigmatic Detection System for Polymeric Cantilever-Based Sensors

Early detection of protein aggregation is of great importance in the field of neurodegenerative diseases. The successful detection of the aggregation of the protein <i>α</i>-synuclein in a quantitative, label-free manner by functionalising a microcantilever with <i>α</i>-synuclein monomers and operating it in dynamic mode in the presence of <i>α</i>-synuclein monomers in solution is reported. A total mass of 6 ng of <i>α</i>-synuclein was detected over 9 hours on the surface of the cantilever. The result is compared to conventional fluorescence measurements of <i>α</i>-synuclein aggregation under similar conditions. It is found that the label-free cantilever detection method requires a concentration of protein 50 times smaller than that of the current method and indicated potential for significantly faster response times.

Jason Jensen

Margherita Farina

Giampaolo Zuccheri

Wilfried Grange

Quantitative, Label-Free Detection of the Aggregation of <i>α</i>-Synuclein Using Microcantilever Arrays Operated in a Liquid Environment

Cantilever array-based sensor devices widely utilise the laser-based optical deflection method for measuring static cantilever deflections mostly with home-built devices with individual geometries. In contrast to scanning probe microscopes, cantilever array devices have no additional positioning device like a piezo stage. As the cantilevers are used in more and more sensitive measurements, it is important to have a simple, rapid, and reliable calibration relating the deflection of the cantilever to the change in position measured by the position-sensitive detector. We present here a simple method for calibrating such systems utilising commercially available AFM cantilevers and the equipartition theorem.

Rohit Mishra

Rapid and Reliable Calibration of Laser Beam Deflection System for Microcantilever-Based Sensor Setups

Hepatitis B surface antigen (HBsAg) concentrations were measured using a piezoelectric microcantilever sensor (PEMS) developed by the authors. The developed PEMS is label-free and detects the sensing signal electrically. It was designed to measure the mass of biomolecules attached to it using an accurate mass-microbalancing technique; its probe area is confined to the end of the cantilever, and its equivalent spring constant is relatively high to minimize the effect of changes in the surface stress when the biomolecules are attached to it. The “dip- and-dry” technique was used to enable the probe area of the sensor to react with reagents in controlled environmental conditions. HBsAg was detected by an immunoreaction whereas the reaction time, antibody density, and its area on the probe were kept at a constant level. The mass of the detected HBsAg was measured in the range of 0.1–100 ng/mL.

Sangkyu Lee

Jongyun Cho

Yeolho Lee

Sangmin Jeon

Hyung Joon Cha

Wonkyu Moon

Measurement of Hepatitis B Surface Antigen Concentrations Using a Piezoelectric Microcantilever as a Mass Sensor

The qualitative agreement between experimental measurements of the <svg style="vertical-align:-1.90608pt;width:12.325px;" id="M2" height="12.925" version="1.1" viewBox="0 0 12.325 12.925" width="12.325"  xmlns="http://www.w3.org/2000/svg">
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</svg> factors and flexural resonance frequencies in air of microcantilevers and calculations based on the compressible fluid model of Van Eysden and Sader (2009) is presented. The <svg style="vertical-align:-1.90608pt;width:12.325px;" id="M3" height="12.925" version="1.1" viewBox="0 0 12.325 12.925" width="12.325"  xmlns="http://www.w3.org/2000/svg">
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</svg> factors and resonance frequencies observed on two sets of cantilever arrays were slightly lower than those predicted by the model. This is attributed to the individual design and geometry of the microfabricated hinged end of the cantilever beams in the array.

Predictions of the Compressible Fluid Model and its Comparison to Experimental Measurements of <svg style="vertical-align:-2.2932pt" height="14.3125" version="1.1" viewBox="0 0 13.175 14.3125" width="13.175" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.4)"><path id="x1D444" d="M745 361q0 -134 -83.5 -233t-214.5 -130l16 -11q97 -67 250 -132l-8 -23q-76 3 -131 16q-81 19 -242 125l-20 13q-129 8 -209 91t-80 208q0 160 116 271t289 111q136 0 226.5 -83t90.5 -223zM645 356q0 127 -57.5 201.5t-169.5 74.5q-126 0 -210.5 -104.5t-84.5 -248.5&#xA;q0 -97 46 -166.5t129 -87.5l84 15l29 -19q104 21 169 121.5t65 213.5z" /></g></svg> Factors and Flexural Resonance Frequencies for Microcantilevers

We present a fibre-optic-based device for the automated readout of microcantilever arrays for fast microorganism growth detection. We determined the ability of our device to track shifts in resonance frequency due to an increase in mass on the cantilever surface or changes in mechanical stiffness. The resonance frequency response of 7 <i>μ</i>m thick agarose-functionalised cantilevers was tracked as humidity levels were varied revealing a mass responsivity of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>~</mml:mo><mml:mi></mml:mi><mml:mn>51</mml:mn><mml:mo>±</mml:mo><mml:mn>1</mml:mn></mml:math> pg/Hz. The resonance response of microcantilevers coated with <i>Aspergillus niger (A. niger)</i> spores was monitored for &gt;48 h revealing a growth detection time of &gt;4 h. The growth of mycelium along the cantilevers surface is seen to result in an increase in resonance frequency due to the reinforcement of the cantilever structure. The use of our fibre optic detection technique allows data to be recorded continuously and faster than previously reported.

N. Maloney

G. Lukacs

N. Nugaeva

W. Grange

J. P. Ramseyer

J. Jensen

M. Hegner

Fibre Optic Readout of Microcantilever Arrays for Fast Microorganism Growth Detection

About this journal

<p><em>Journal of Sensors</em> publishes research focused on all aspects of sensors, from their theory and design, to the applications of complete sensing devices.</p>


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<p>Chief Editor, Professor Harith Ahmad, is currently the director of the Photonics Research Center, University of Malaya, Malaysia. His current research is in the exploration of various 2D and 3D nanomaterials for optoelectronics applications.</p>


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Journal of Sensors - Table of contents 2012

title

Journal of Sensors publishes research focused on all aspects of sensors, from their theory and design, to the applications of complete sensing devices.

Journal of Sensors