Simultaneous topography imaging and molecular recognition with low crosstalk and high sensitivity

Atomic force microscope has been used to recognize biomolecules through a functionalize tip. In order to achieve simultaneous topography imaging and molecular recognition, existing method such as PicoTREC (commercialized by Agilent Inc.) extracts the topography image from the lower amplitude of the cantilever oscillation while extracts recognition image from the upper amplitude of the cantilever oscillation. To avoid crosstalk between topography and recognition images, PicoTREC requires using cantilever with small quality factor (Q≈1). Such low Q, however, results in low force sensitivity, thus a large tip-sample interaction force during imaging, which is destructive to the soft biological samples. In this paper, we propose an innovative method for simultaneous topography imaging and molecular recognition using cantilever with high Q but with minimized crosstalk. For cantilever with large quality factor (Q>10) in liquid, the upper part and lower part of the cantilever's oscillation becomes symmetric. The topography information that exists in the lower amplitude of the deflection signal also exists in the upper amplitude. Because of the symmetry of the deflection signal, the topography information in the upper amplitude can be cancelled by the lower amplitude. However, the control system will conversely respond to the decrease of the amplitude caused by the molecule binding. So taking use of the lower amplitude, the topography crosstalk in the upper amplitude can be cancelled and the molecule recognition information can be kept. So using this method, high-Q cantilever can be used for simultaneous topography and molecular recognition without crosstalk. The high-Q cantilever will result in high-force sensitivity that will be less destructive to the soft biological samples. This technique will make the simultaneous topography imaging and molecular recognition possible on soft biological sample surfaces, such as the cell membrane. In this paper, the simulation is utilized to demonstrate the principle of our proposed method, and then initial experiments are also performed to validate our method.