Label-free nanoscale chemical mapping of intracellular structures

Imaging with nanoscale spatial resolution is of prime importance for understanding biology on an intracellular level, but optical diffraction sets a resolution limit which prevents this for standard optical microscopes. Specialist techniques such as super-resolution fluorescence and electron microscopy surpass this limit, but both require stains or labels to generate image contrast, which can be toxic, make quantification hard, and may even perturb sample biology.

We demonstrate a technique for label-free nanoscale chemical mapping using a probe-based optical microscope illuminated with a mid-infrared quantum cascade laser. The mid infrared wavelengths excite vibrational modes of functional groups found naturally in cells, removing the need for stains and labels. We demonstrate the technique by chemically mapping intracellular structures in human myeloma cells and comparing with electron micrographs of the same cell line. We perform the mapping at multiple wavelengths, selectively targeting proteins and nucleic acids in cells, with a spatial resolution of 30nm. We expect that this technique can be applied to study nanoscale biochemical markers of disease, as well as nanotherapeutics and medicine.