Novel Glucose Biosensor Based on the Microcantilever

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Novel Glucose Biosensor Based on the Microcantilever Jianhong Pei1, Fang Tian, and Thomas Thundat* Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6123 1 Present address: Nova Biomedical Corporation, 200 Prospect Street Waltham, MA 02454 * To whom correspondence should be addressed. Fax: +1(865) 574-6210; email: [email protected] ABSTRACT We report a novel technique for micromechanical detection of biologically relevant glucose by immobilization of glucose oxidase (GOx) onto a microcantilever surface. Microfabricated cantilevers have recently attracted considerable interest in the development of a wide range of novel physical, chemical, and biological sensors. This paper describes the combination of this novel technology with enzyme specificity to construct a highly selective glucose biosensor. The enzyme-functionalized microcantilever undergoes bending due to a change in surface stress induced by the reaction between glucose and the GOx immobilized on the cantilever surface. The common interferents for glucose detection in other detection schemes have been tested and have shown no effect on the measurement of blood glucose level by this technique. INTRODUCTION Recent advances in designing and fabricating microcantilever beams capable of detecting extremely small forces, mechanical stresses, and mass additions offer the promising prospects of physical, chemical, and biological sensing with unprecedented sensitivity and dynamic range [13]. Microcantilevers, the simplest micro-electro-mechanical-system (MEMS) components, are easily micromachined and mass-produced. Molecular adsorption, when confined to one surface of a cantilever, results in differential surface stress that leads to cantilever bending. The transduction mechanism of a microcantilever sensor is based on the changes in the deflection and resonance frequency induced by environmental factors in the medium in which the cantilever is maintained. The surface stress can be calculated from the magnitude of cantilever bending by using Stoney’s formula [4]: z=

3(1 − γ )L2 dσ , t2E

(1)

where z is the cantilever deflection, dσ is the differential surface stress, γ is the Poisson’s ratio, E is the Young’s modulus for the substrate and L and t are the length and thickness of the cantilever, respectively. In recent years, the unique ability of biomolecules to recognize other molecules has been investigated in the development of microcantilever-based biosensors. Microcantilever-based biosensors can offer many advantages over other biosensor designs; for example, the microcantilevers can easily be fabricated into multiple-element arrays, and the sensor does not require the use of external probes or labeling. General applications of this label-free detection

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method have been shown for DNA hybridization, the detection of single-base mismatches [5,6], and nanomechanical motion induced by antibody-antigen interaction [7, 8]. Diabetes mellitus is a disease in which cells fail to take up glucose due to either a lack of insulin (T