We present non-invasive methods for improving the sensitivity of label-free biosensors that offer the advantage of rapid and real-time detection but suffer from relatively low sensitivity. We present detection of cancer markers using the Quartz Crystal Microbalance and demonstrate that 2 order-of-magnitude amplification in sensitivity can be achieved by forming sandwich or "piggy back" layers using antibodies and functionalized gold nanoparticles. We also discuss detection of aptazymes i.e. RNA-based enzymatic macromolecules and their potential as signal amplifying agents in biosensors.
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