Efficient maintenance of glucose homeostasis is a major challenge in diabetes therapy, where accurate and reliable glucose level detection is required. Though several methods are currently used, these suffer from impaired response and often unpredictable drift, making them unsuitable for long-term therapeutic practice. In this study, we demonstrate a method that uses a functionalized atomic force microscope (AFM) cantilever as the sensor for reliable glucose detection with sufficient sensitivity and selectivity for clinical use. We first modified the AFM tip with aminopropylsilatrane (APS) and then adsorbed glucose-specific lectin concanavalin A (Con A) onto the surface. The Con A/APS-modified probes were then used to detect glucose by monitoring shifts in the cantilever resonance frequency. To confirm the molecule-specific interaction, AFM topographical images were acquired of identically treated silicon substrates which indicated a specific attachment for glucose-Con A and not for galactose-Con A. These results demonstrate that by monitoring the frequency shift of the AFM cantilever, this sensing system can detect the interaction between Con A and glucose, one of the biomolecule recognition processes, and may assist in the detection and mass quantification of glucose for clinical applications with very high sensitivity. 1. Introduction Diabetes mellitus (DM) is a serious public health concern that causes illness, disability, and death throughout the world. Clinical diabetes therapy requires precise monitoring and maintaining of blood glucose levels as close to normal as possible to reduce the risk of emergency complications such as the retinopathy, nephropathy, and hypo- and hyperglycemia [1–3]. To date, existing sensing techniques have been demonstrated, such as glucose-based noninvasive glucose sensors and enzyme-based biosensors; however, impaired responses and unpredictable drift make these unsuitable for long-term therapeutic practice [3]. Therefore, the development of new diagnostic tools for reliable glycemic control with sufficient sensitivity and selectivity is of clinical interest. In order to solve these problems, microcantilever-based sensors have been proposed, which have high sensitivity, low detection limits, and broad application in the fields of chemistry, biotechnology, detection, and medical science [4, 5]. This sensing system has significant advantages over other sensor technologies, such as high surface-to-volume ratio, fast response time, and low cost of fabrication [4], and further, has proven effective in DNA hybridization and,
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