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Cantilever Array for Proteomic and Genomics Applications
Within these subprojects, we are working on new nanomechanical sensors suitable for proteomic or
genomic detection.
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A) Genomic sensing: Upon hybridization of ssDNA with its complementary target
dsDNA is formed |
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B) Cantilever array: Lever dimensions 500μm long, 100μm wide and
0.45μm thick at an array pitch of 250 μm
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C) Proteomic sensing: Upon antigen binding a protein-protein complex is
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The results reported in the first phase are based on a combination of the topical fields of
nanotechnology and molecular biology contributing to the development of innovative tools for
genomics and proteomics.
We developed a diagnostic tool for gene fishing and transcript detection using cantilever array
sensors. The nanomechanical sensors bear the potential to revolutionize the field of fast and
reliable medical diagnostics, since physiological sensitivity of cantilever sensors in liquid
environment for genomic experiments is established for the first time. Individual genes can now
be detected and analyzed for polymorphism without amplification or labeling. The triggered
expression level of an individual gene relevant for cancer or viral infections can be measured
depending on external factors such as drugs or other agents and, furthermore, individual genes can
be detected in a complete RNA background. These achievements eliminate time-consuming biochemical
preparative steps in in-vitro diagnostic studies of drug response biomarkers in clinical samples
where speed and cost efficiency are crucial. Hybridization detection takes place within
tens of minutes in contrast to other methods like gene chips (microarrays) where such analyses
require many hours.
In the field of protein cantilevers we show that the method also performs extremely well in
proteomics. In particular, we designed a new nanomechanics-based immunosensor featuring label-free
detection whose sensitivity achieves the performance of commercially available techniques, such as
Surface Plasmon Resonance (SPR). The sensitivity of the method was reached by application of
genetically engineered single-chain Fv antibody fragments (scFv) as receptor molecules (in
collaboration with the University of Zurich). The fragments were attached to the sensor surface
in an oriented manner. Our array enables simultaneous measurements of multiple targets in parallel.
Utilizing small, oriented antibody fragments, we improved the sensitivity of the method by more than
two orders of magnitude as compared to randomly oriented entire antibody molecules.
Achieving nanomechanical sensitivity in the lower picomolar range has the potential to combine
genomics and proteomics within the same assay. We show a method and a tool that basically can
address a wide range of functions within a cell such as analysis of proteins (membrane and soluble),
transcriptions factors, RNA transcription. The scalable format and the fast analysis will pave the
way to design a future portable device which can be applied in the field of personalized medicine,
where combined label-free analysis of a small amount of biological material is required to probe
the response from an individual to allow specific drug treatment.
Nanomechanics - the Link to Biology and Chemistry
Hans Peter Lang, Martin Hegner and Christoph Gerber
Chimia 56 (2002) 515-519
Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array
Rachel McKendry, Jiayun Zhang, Youri Arntz, Torsten Strunz, Martin Hegner, Hans Peter Lang, Marko K. Baller, Ulrich Certa, Ernst Meyer, Hans-Joachim Güntherodt, and Christoph Gerber
PNAS, July 23, 2002, Vol. 99, No. 15 9783–9788
Label-free protein assay based on a nanomechanical cantilever array
Y. Arntz, J. D. Seelig, H. P. Lang, J. Zhang, P. Hunziker, J. P. Ramseyer, E. Meyer, M. Hegner and Ch. Gerber
Nanotechnology 14 (2003) 86-90
Rapid functionalization of cantilever array sensors by inkjet printing
Alexander Bietsch, Jiayun Zhang, Martin Hegner, Hans Peter Lang and Christoph Gerber
Nanotechnology 15, 873-880 (2004)
Inkjet Deposition of Alkanethiolate Monolayers and DNA Oligonucleotides on Gold: Evaluation of Spot Uniformity by Wet Etching
Alexander Bietsch, Martin Hegner, Hans Peter Lang, and Christoph Gerber
Langmuir, 20 (12), 5119 -5122, 2004
Cantilever array sensors
Hans Peter Lang, Martin Hegner and Christoph Gerber
Materials Today, Volume 8, Issue 4, Pages 30-36
Biological Single Molecule Applications and advanced Biosensing
Hegner, M. et al.
J. Chrom. Lib. 68, 241 (2003)
RealTime Mass Sensing by Nanomechanical Resonators in Fluid
Ghatkesar M. K. et al.
Proc. IEEE Sensors 2004 1060 (2004)
scFv functionalized cantilever arrays
Backmann, N. et al.
submitted to PNAS
Label free gene fishing in total RNA
Zhang, J. et al.
submitted to Nature
Contact:
Christoph Gerber |
Martin Hegner |
Hans Peter Lang |
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Institute of Physics, University of Basel, Switzerland
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