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Figure 40: Schematic representation of functions performed by the biosensor based on the DNA add-ons. a) proteins applied to the surface of DNA origami sense concentration of the selected analytes, based on either immunochemical or enzymatic principles, b) the signal from the sensor undergoes a selected logical function (AND, OR, XOR…), depending on the specific analysis and c) creates a readout signal that can be detected.
Biosensors are analytical devices that combine a biological sensing element, a signal transducer and an output/reader device. Proteins, such as enzymes or antibodies, are essential for the specificity of biosensors and represent the core of the vast majority of biological sensing elements.
This led us to the idea of using DNA origami add-ons as a platform for creation of biosensors. The advantage of using DNA origami as a biosensor platform is primarily that it can be used to combine several elements whose spatial position can be precisely defined.
This allows us to integrate detection of several analytes into one assembly and furthermore connect sensing with signal transducer, potential implementations of a logical operator and an output signal, such as e.g. optical signal.

We have demonstrated that ZFP fusions can be combined with luciferase that generates light and with a fluorescent protein that can exhibit fluorescence depending on the proximity to the luciferase that generates the excitation signal. In this example the output only occurs in case of the existence and spatial proximity of both elements, constituting a logical AND operator.

Biosensors based on this type of platform could be used to follow several analytes simultaneously, which is in fact typical for many health-related applications but also for analysis of other complex samples. Stability of DNA origami in biological fluids has been demonstrated before (Mei, 2011), therefore in vivo applications might be feasible. Optical signal in the infrared region might provide the ability of transmitting the signal through the tissue. Moreover, one can imagine that DNA origami could be used as a nanoanalytical platform for following-up the cellular or organism's physiological state (e.g. ATP levels, glucose levels in blood etc.) potentially even in real-time.

  • Mei Q, Wei X, Su F, Liu Y, Youngbull C, Johnson R, Lindsay S, Yan H, Meldrum D (2011) Stability of DNA origami nanoarrays in cell lysate. Nano Lett. 11:1477-82.

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