Deep-Tissue Serial Sectioning Microscope

The Deep-Tissue Serial Sectioning Microscope accommodates large biological samples such as the organs of a mouse. In such samples, high-resolution optical imaging is traditionally limited to only the surface layer because light scattering and absorption prevents focusing deeper. The approach we are employing is to repeatedly image a small (a few hundred micrometers thick) layer of the sample at a time and then mechanically remove the imaged section to expose deeper layers. Imaging and sectioning is fully automated and allows for gap-less, high-resolution imaging of large volumes (see http://dx.doi.org/10.1038/nmeth.1854 for a reference). This method is currently acquiring two-photon fluorescence signals, but we will extend it further by implementing a novel contrast mechanism, adding access to non-fluorescent targets for applications such as locating and imaging sparse melanoma cells in excised lymph nodes.

Lattice Light-Sheet Microscope

Lattice light-sheet microscopy is a modified version of light sheet fluorescence microscopy that increases image acquisition speed while decreasing damage to cells caused by phototoxicity. This microscope is ideally suited to image small biological samples, ranging from intracellular components to small organisms such as fruit flies. The strength of this technology lies in the combination of high spatial resolution and high acquisition speed. The method uses a structured light sheet to excite fluorescence in successive planes of a specimen, generating a time series of 3D images that can provide information about dynamic biological processes such as cellular interactions. It is a novel combination of techniques including Light sheet fluorescence microscopy, Bessel beam microscopy, and Super-resolution microscopy (specifically structured illumination microscopy - SIM).

Multimodal Pump-Probe Microscope (planned)

Optical pump-probe microscopy is a recently developed technique that can measure electronic and vibrational dynamics of materials at high spatial (sub-micron) and temporal (sub-picosecond) resolution. This nonlinear optical technique accesses contrast mechanisms that do not require fluorescence, such as transient absorption and gain, nonlinear phase, and stimulated Raman processes. Pump-probe microscopes can therefore generate three-dimensional maps of structure or even function in materials that are not suitable to conventional microscopy techniques (such as confocal or multi-photon fluorescence microscopy).