High throughput label-free platform for statistical bio-molecular sensing.

Sensors are crucial in many daily operations including security, environmental control, human diagnostics and patient monitoring. Screening and online monitoring require reliable and high-throughput sensing. We report on the demonstration of a high-throughput label-free sensor platform utilizing cantilever based sensors. These sensors have often been acclaimed to facilitate highly parallelized operation. Unfortunately, so far no concept has been presented which offers large datasets as well as easy liquid sample handling. We use optics and mechanics from a DVD player to handle liquid samples and to read-out cantilever deflection and resonant frequency. Also, surface roughness is measured. When combined with cantilever deflection the roughness is discovered to hold valuable additional information on specific and unspecific binding events. In a few minutes, 30 liquid samples can be analyzed in parallel, each by 24 cantilever-based sensors. The approach was used to detect the binding of streptavidin and antibodies.

[1]  Hans-Jørgen Albrechtsen,et al.  Sorption of the herbicide dichlobenil and the metabolite 2,6-dichlorobenzamide on soils and aquifer sediments. , 2004, Environmental science & technology.

[2]  V. Dravid,et al.  MOSFET-Embedded Microcantilevers for Measuring Deflection in Biomolecular Sensors , 2006, Science.

[3]  M. Jakobsen,et al.  A quantitative enzyme-linked immunoassay for the detection of 2, 6-dichlorobenzamide (BAM), a degradation product of the herbicide dichlobenil. , 2000, Journal of immunological methods.

[4]  Thomas Thundat,et al.  Thermal and ambient-induced deflections of scanning force microscope cantilevers , 1994 .

[5]  John E Sader,et al.  Effect of surface stress on the stiffness of cantilever plates. , 2007, Physical review letters.

[6]  Javier Tamayo,et al.  Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films. , 2008, Nature nanotechnology.

[7]  Murali Krishna Ghatkesar,et al.  Quantitative time-resolved measurement of membrane protein-ligand interactions using microcantilever array sensors. , 2009, Nature nanotechnology.

[8]  Joe T. Lin,et al.  Microfabricated Centrifugal Microfluidic Systems: Characterization and Multiple Enzymatic Assays , 1999 .

[9]  Hans-Jürgen Butt,et al.  Calculation of thermal noise in atomic force microscopy , 1995 .

[10]  J. Thaysen,et al.  Environmental sensors based on micromachined cantilevers with integrated read-out , 2000, Ultramicroscopy.

[11]  M. Roukes,et al.  Toward single-molecule nanomechanical mass spectrometry , 2005, Nature nanotechnology.

[12]  Anja Boisen,et al.  Cantilever Sensors: Nanomechanical Tools for Diagnostics , 2009 .

[13]  Anja Boisen,et al.  Characterization system for resonant micro- and nanocantilevers , 2005 .

[14]  Hao Jiang,et al.  Bimaterial Microcantilevers as a Hybrid Sensing Platform , 2008 .

[15]  Wenmiao Shu,et al.  Investigation of biotin-streptavidin binding interactions using microcantilever sensors. , 2007, Biosensors & bioelectronics.

[16]  Javier Tamayo,et al.  Effect of the adsorbate stiffness on the resonance response of microcantilever sensors , 2006 .

[17]  Matthew A Cooper,et al.  Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance. , 2008, Nature nanotechnology.

[18]  Raj Mutharasan,et al.  In situ cell detection using piezoelectric lead zirconate titanate-stainless steel cantilevers , 2003 .

[19]  Masakazu Aono,et al.  Sub-ppm detection of vapors using piezoresistive microcantilever array sensors , 2009, Nanotechnology.

[20]  Anja Boisen,et al.  Self-aligned cantilever positioning for on-substrate measurements using DVD pickup head , 2010 .

[21]  Gerber,et al.  Atomic force microscope. , 1986, Physical review letters.

[22]  H. Craighead,et al.  Single cell detection with micromechanical oscillators , 2001 .

[23]  Javier Tamayo,et al.  Real-time profile of microcantilevers for sensing applications , 2005 .

[24]  Christiane Ziegler,et al.  Cantilever-based biosensors , 2004, Analytical and bioanalytical chemistry.

[25]  Peter Vettiger,et al.  Sequential position readout from arrays of micromechanical cantilever sensors , 1998 .

[26]  John E. Sader,et al.  Effect of surface stress on the stiffness of cantilever plates. , 2007 .

[27]  Nanomechanoelectronic signal transduction scheme with metal-oxide-semiconductor field-effect transistor-embedded microcantilevers , 2009 .

[28]  Srinath Satyanarayana,et al.  Nano-chemo-mechanical sensor array platform for high-throughput chemical analysis , 2006 .

[29]  Marc Madou,et al.  Lab on a CD. , 2006, Annual review of biomedical engineering.

[30]  Ing-Shouh Hwang,et al.  Simultaneous detection of translational and angular displacements of micromachined elements , 2007 .

[31]  N. Amer,et al.  Novel optical approach to atomic force microscopy , 1988 .

[32]  Tae Song Kim,et al.  Immunoassay of prostate-specific antigen (PSA) using resonant frequency shift of piezoelectric nanomechanical microcantilever. , 2005, Biosensors & bioelectronics.

[33]  H. Craighead,et al.  Micro- and nanomechanical sensors for environmental, chemical, and biological detection. , 2007, Lab on a chip.

[34]  James K. Gimzewski,et al.  Observation of a chemical reaction using a micromechanical sensor , 1994 .