Importance of controlling nanotube density for highly sensitive and reliable biosensors functional in physiological conditions

Biosensors utilizing carbon nanotube field-effect transistors have a tremendous potential to serve as the basis for the next generation of diagnostic systems. While nanotubes have been employed in the fabrication of multiple sensors, little attention has previously been paid to how the nanotube density affects the biosensor performance. We conducted a systematic study of the effect of density on the performance of nanotube biosensors and discovered that this parameter is crucial to achieving consistently high performance. We found that devices with lower density offer higher sensitivity in terms of both detection limit and magnitude of response. The low density nanotube devices resulted in a detection limit of 1 pM in an electrolyte buffer containing high levels of electrolytes (ionic concentration ∼140 mM, matching the ionic strength of serum and plasma). Further investigation suggested that the enhanced sensitivity arises from the semiconductor-like behavior - strong gate dependence and lower capacitance - of the nanotube network at low density. Finally, we used the density-optimized nanotube biosensors to detect the nucleocapsid (N) protein of the SARS virus and demonstrated improved detection limits under physiological conditions. Our results show that it is critical to carefully tune the nanotube density in order to fabricate sensitive and reliable devices.