Nanoscale imaging and sensing for biomedical applications

THE last two decades have witnessed the explosion of nanoscale materials for biology imaging. Recent integrative research efforts have included: nanotechnology (fabrication and application) as a tool in developing new and improving existing optical imaging techniques for real-time subwavelength imaging of cellular processes; developing the next generation of nanobiosensors for improving biological/chemical sensing applications; using nanoparticles (NP)/nanostructures for optical engineering of methodologies for targeting and treatment of diseases; and very large scale and/or very sensitive detection down to single molecule level for drug discovery and diagnostics applications, such as nanoarrays. The use of nanostructures and NPs for biological imaging applications is currently undergoing a revolution with the incorporation of new kinds of microscopic techniques that allow the visualization of tissues, cells, proteins, and macromolecular structures at all levels of resolution, functional states, chemical composition and dynamic analysis by using photonic studies of nanoscale interactions in biology and medicine. Owing to the high sensitivity, high resolution, and the wealth of contrast mechanisms, imaging and fluorescence detection is the most versatile and widely used visualization modality to study nanostructure and function of biological systems and the molecular process in living organisms without perturbing them. Molecular imaging and flow cytometry is an evolving field of imaging sciences, which involves the development of microscopic techniques for live cell analysis and imaging by super resolution and macroscopic techniques to monitor molecular events in living organism. The breakthrough of super-resolution techniques allows researchers to obtain images with a higher resolution than the diffraction limit (1). However, the use of nanostructures and NPs for biological imaging applications is also facing important challenges. Because imaging requires exogenous probes to enhance imaging contrast or provide signal readout, the nanomaterials and probes performance largely determines the detection limit and sensitivity. The intrinsic poor penetration of UV and visible light limits their broad applications in biology. Therefore, promising nanostructures and combination of nanostructures and fluorescent dyes that exhibit high photostability, long fluorescence lifetime, strong absorption, and/or emission in the near-infrared (NIR) region are highly desirable. A NP is a collection of atoms or molecules with much higher intensity of absorbance and emissions compared to small molecular probes, which can provide strong local contrast in biological imaging. Two-photon fluorescent probes simultaneously absorb two infrared (IR) or NIR photons. Using IR or NIR light for excitation can minimize the light scattering and suppress the background signal, which allows imaging of living tissues up to about one millimeter in depth (2). Applications of nanostructure probes for molecular imaging are increasing rapidly for recording events from single live cells to whole animals with high sensitivity and