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Immunoassay of prostate-specific antigen (PSA) using resonant frequency shift of piezoelectric nanomechanical microcantilever.

In Biosensors Bioelectronics on 15 April 2005 by Lee, J. H., Hwang, K. S., et al.

We designed and fabricated the nanomechanical Pb(Zr0.52Ti0.48)O3 (PZT) cantilever; we demonstrated a novel electrical measurement, under a controlled ambient temperature and humidity, for label-free detection of a prostate-specific antigen (PSA); and we achieved a detection sensitivity as low as 10 pg/ml. For the fabrication of our nanomechanical PZT cantilevers, we used composite layers of Ta/Pt/PZT/Pt/SiO2 on a SiN(x) supporting layer for electrical self-sensing without external oscillators. This method allows PSA proteins to be detected via a simple electrical measurement of the resonant frequency change generated by the molecular interaction of the antigen (Ag) and the antibody (Ab). The resonant frequency shifted due to the specific binding of the PSA Ag to its Ab which is immobilized via calixcrown self-assembled monolayers on an Au surface deposited on a nanomechanical PZT cantilever. We determined the resonant frequency shift as the value of -172 Hz and -273 Hz, when the concentration of PSA Ag was 1 ng/ml, with the cantilever dimensions of 100 microm x 300 microm and 50 microm x 150 microm, respectively. Theoretical and experimental analysis suggests that the minimum detectable sensitivity for a resonant frequency shift due to a PSA Ag-Ab interaction depends on the dimensions of the nanomechanical PZT cantilever. These results also demonstrate that the experimentally measured resonant frequency shift is larger than that calculated theoretically due to the compressive stress of the PSA Ag-Ab interaction.

Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers.

In Biosensors Bioelectronics on 15 April 2005 by Wee, K. W., Kang, G. Y., et al.

We report an electro-mechanical biosensor for electrical detection of proteins with disease markers using self-sensing piezoresistive micro-cantilevers. Electrical detection, via surface stress changes, of antigen-antibody (Ag-Ab) specific binding was accomplished through a direct nano-mechanical response of micro-fabricated self-sensing micro-cantilevers. A piezoresistive sensor measures the film resistance variation with respect to surface stress caused by biomolecules specific binding. When specific binding occurred on a functionalized Au surface, surface stress was induced throughout the cantilever, resulting in cantilever bending and resistance change of the piezoresistive layer. The cantilever biosensors were used for the detection of prostate specific antigen (PSA) and C-reactive proteins (CRP), which are a specific marker of prostate cancer and cardiac disease. From the above experiment, it was revealed that the sensor output voltage was proportional to the injected antigen concentration (without antigen, 10 ng/ml, 100 ng/ml, 1 microg/ml). PSA and CRP antibodies were found to be very specific for their antigens, respectively. This indicated that the self-sensing micro-cantilever approach is beneficial for detecting disease markers, and our piezoresistive micro-cantilever sensor system is applicable to miniaturized biosensor systems.

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