Karolyn M. Hansen

Bioassay of prostate-specific antigen (PSA) using microcantilevers.

Diagnosis and monitoring of complex diseases such as cancer require quantitative detection of multiple proteins. Recent work has shown that when specific biomolecular binding occurs on one surface of a microcantilever beam, intermolecular nanomechanics bend the cantilever, which can be optically detected. Although this label-free technique readily lends itself to formation of microcantilever arrays, what has remained unclear is the technologically critical issue of whether it is sufficiently specific and sensitive to detect disease-related proteins at clinically relevant conditions and concentrations. As an example, we report here that microcantilevers of different geometries have been used to detect two forms of prostate-specific antigen (PSA) over a wide range of concentrations from 0.2 ng/ml to 60 μg/ml in a background of human serum albumin (HSA) and human plasminogen (HP) at 1 mg/ml, making this a clinically relevant diagnostic technique for prostate cancer. Because cantilever motion originates from the free-energy change induced by specific biomolecular binding, this technique may offer a common platform for high-throughput label-free analysis of protein–protein binding, DNA hybridization, and DNA–protein interactions, as well as drug discovery.

Detection of pH variation using modified microcantilever sensors

A micromechanical technique for measuring solution pH using modified silicon (SiO2) and silicon nitride (Si3N4) microcantilevers is described. As the modified surface of the cantilever accumulates charge proportional to the pH of the surrounding liquid, the cantilever undergoes bending due to the differential surface stress. Results are presented for chemically modified (4-aminobutyltriethoxysilane, 11mercaptoundecanoic acid) and metal-modified (Au/Al) surfaces over a pH range 2‐12. Aminosilane-modified SiO2/Au cantilevers performed robustly over pH range 2‐8 (49 nm deflection/pH unit), while Si3N4/Au cantilevers performed well at pH 2‐6 and 8‐12 (30 nm deflection/pH unit). The influences of other ions on cantilever bending were found to be negligible below 10 ˇ2 M concentration.

Nanomechanical Sensor Array for Detection of Biomolecular Bindings: Toward a Label-Free Clinical Assay for Serum Tumor Markers

A label-free technique capable of rapidly screening human blood samples simultaneously for multiple serum tumor markers would enable accurate and cost-effective diagnosis of cancer before physiological symptoms appear. Recently, microfabricated, bimaterial cantilever sensors have been demonstrated to detect DNA hybridization and antigen-antibody binding at clinically relevant concentrations. Cantilever sensors deflect measurably under the surface stress resulting when biomolecules immobilized on one surface of the sensor interact with their binding partners [1]. We present an array of cantilever sensors (silicon nitride with a gold coated surface) capable of simultaneously interrogating 100 different biomolecular interactions.Copyright