Next-Generation Optical Contrasts for Characterization of Biological Tissue, Hard Matter, and Cultural Heritage Objects

With support from the Chemical Measurement and Imaging (CMI) Program in the Division of Chemistry, Drs. Martin Fischer and Warren Warren at Duke University will develop optical microscopy techniques to investigate the three-dimensional structure and function of a wide range of materials, including biological tissue and pigments used in historical artwork.

Traditionally, these complex materials pose severe challenges for optical imaging and often the samples need to be cut open to investigate layers below the surface. Newly developed imaging methods allow for three-dimensional imaging without sample destruction and the investigators are developing techniques to extend the range of chemical contrast, the depth of imaging, and the ability to interpret the results.

This development has the potential to detect microscopic changes in skin and artwork during the onset of deterioration, which could aid in early diagnosis and better choice of treatment options. The methods developed by this program benefit academic research and could lead to a device of great interest to biomedical researchers and conservators alike.

Multiple ultrafast laser pulses can interact with matter via a wide range of nonlinear processes. The investigators have pioneered an imaging method, pump-probe microscopy, that turns such interactions into detectable contrast for imaging with low average power at high speeds and they have demonstrated applications in biological tissue, historical artworks, and engineered materials.

The signals acquired with this microscopy method depend on many parameters, such as the laser pulse wavelengths, inter-pulse delay, relative polarization, and detection direction. The range of parameters presents a challenge due to the complexity of the response, but also an opportunity for recording images using multiple parameters to provide different contrast types and a diverse and comprehensive view of the sample.

The investigators are developing a pump-probe microscopy platform that can efficiently, safely, and rapidly acquire multi-modal, multi-parameter data sets that provide images with molecular specificity for biology and cultural heritage. Specifically, the investigators and their team will pursue the following research goals: (i) systematically investigate and model the dependence on imaging and sample parameters (i.e., wavelength, polarization, scattering angle) to separate the complex set of nonlinear optical interactions and decompose the images into fundamental components; and (ii) develop a coherent femtosecond pulse shaping and detection approach for efficient multi-modal and multi-parameter acquisition.

The research seeks to develop a microscope that will be able to non-invasively extract comprehensive molecular and structural information in biological tissue and historical artwork.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.