What are nanosensors and why are they important in medical applications?

Advances in the fabrication and uses of semiconducting, metallic, and insulating materials with dimensions on the nanoscale – the scale of a billionth of a meter – are opening novel means of measuring and sensing quantities with spatial precision on the nanoscale. For example, spherical nanocrystals only a few billionths of a meter in diameter may be fabricated in ways that facilitate the tuning of their optical properties. The nanocrystals serve as tiny light bulbs that emit light of a desired wavelength – red, orange, green, infrared, or ultraviolet as examples – and they are used to label cells, tissues, and biomolecules. In the alliance, such tiny nanocrystals have been used for luminescent labeling of biomolecules on the surfaces of cancer cells, to detect antigen molecules, to cleave DNA molecules, to observe the dynamics of integrins of cellular surfaces, to inject charges into T-shaped molecular junctions, and for luminescent labeling of carbon nanotubes (CNTs). These nanocrystals have also been studied in this alliance to explore their uses as nanosensors that detect local changes in electric fields in the nanoscale regime. As an example of the alliance’s CNT advances, see publications of Prof. Megaridis et al.

The alliance focuses on the use of manmade nanostructures and their integration with nanoscale biological structures, including biomolecule structures. Sensing at the molecular level is absolutely critical for accurate and rapid biomedical diagnostics, but molecular-level sensing must be augmented with signal integration and processing techniques in order to realize the full potential of nanosensor technology in biomedicine. In many situations, the integration of multiple physiological signals is essential to exploiting nanotechnology in medical applications. For example, nanosensors of neuronal action potentials must simultaneously record the neuronal impulses of multiple neurons to obtain useful neuronal signals. Moreover, diagnosis of physiological conditions requires knowledge of pH, membrane potentials as well as levels of oxygen, CO2, glucose, NO, and amino acids. Hence, the integration and interpretation of the outputs of multiple nanosensors is a key focus of the alliance. Indeed, the critical importance of molecular-level sensing in biological systems as well as tools and techniques for molecular-level sensing in biological systems is manifested by the pervasive role of biomolecular processes in cellular activity.

Biosensing modalities being explored in this alliance include: CNT-based transistors as biosensors; quantum-dot (QD)--functionalized DNA for sensing the electrical transport properties of DNA; QD-functionalized ion channels for sensing the effect of QD-dipole-induced fields on the conductivity of ion channels; carbon-nanotube-based (CNT-based) transistors as sensors of the properties of quantum-dot--functionalized DNA where the quantum dots (QDs) provide a means of optically injecting carriers into the DNA; AFM/STM-based tracking combined with optical tracking of QD-functionalized transmembrane proteins including integrins and receptors; and tracking the transport of QD-encapsulating phospholipid micelles through cell membranes. Essential to developing these biomolecular sensing modalities is a basic understanding of the interaction between manmade nanostructures and biomolecules; accordingly, experimental studies of biomolecular sensing modalities are supported by parallel theoretical investigations.