Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array.
We report a microarray of cantilevers to detect multiple unlabeled biomolecules simultaneously at nanomolar concentrations within minutes. Ligand-receptor binding interactions such as DNA hybridization or protein recognition occurring on microfabricated silicon cantilevers generate nanomechanical bending, which is detected optically in situ. Differential measurements including reference cantilevers on an array of eight sensors can sequence-specifically detect unlabeled DNA targets in 80-fold excess of nonmatching DNA as a background and discriminate 3' and 5' overhangs. Our experiments suggest that the nanomechanical motion originates from predominantly steric hindrance effects and depends on the concentration of DNA molecules in solution. We show that cantilever arrays can be used to investigate the thermodynamics of biomolecular interactions mechanically, and we have found that the specificity of the reaction on a cantilever is consistent with solution data. Hence cantilever arrays permit multiple binding assays in parallel and can detect femtomoles of DNA on the cantilever at a DNA concentration in solution of 75 nM.
IBM Research, Zurich Research Laboratory, 8803 Rüschlikon, Switzerland.
Rachel
R
McKendry
Jiayun
J
Zhang
Youri
Y
Arntz
Torsten
T
Strunz
Martin
M
Hegner
Hans Peter
HP
Lang
Marko K
MK
Baller
Ulrich
U
Certa
Ernst
E
Meyer
Hans-Joachim
HJ
Güntherodt
Christoph
C
Gerber
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D020411:Oligonucleotide Array Sequence Analysis; D012680:Sensitivity and Specificity; D013816:Thermodynamics
D009838:Oligodeoxyribonucleotides; D004247:DNA