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Northwestern University

Hybrid Microscopy

(Supported by NSF-MRI, AFOSR, W.M. Keck Foundation, Intel, SRC, Hitachi, ANL, State of Illinois, NSF-ECS, NSF-INT, DARPA, Baxter, CMRC, NMH)

The coupling of electron microscopy with complementary characterization methods is essential for the morphological, chemical and functional analysis of soft and hybrid materials. Advancements in the imaging of soft materials focuses on two core challenges: The soft component has inherently low contrast because of low atomic number elements, and soft materials are highly susceptible to beam damage.

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Work in this group addresses low contrast by introducing a variety of contrast enhancement mechanisms. This includes staining with heavy metals, as applied to biological materials such as proteins and embedded and sectioned cells. Low voltage imaging using scanning electron microscopy further improves contrast, takes advantage of the numerous signals available in SEM for surface and compositional analysis, and allows for high-throughput screening of numerous samples. We are also investigating the modulation of the electron beam for contrast enhancement and electron dose reduction, both computationally and experimentally, including the addition of a phase plate and adaptive sampling. Finally, electron diffraction holds additional information that can be extracted to improve imaging at lower doses.

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Correlative imaging, particularly with light microscopy, provides essential complementary analysis when combined with EM. We have particularly used correlative imaging for the analysis of chromatin in cell nuclei, where EM provides high-resolution structural information while fluorescence microscopy highlights the distribution of chromatin in the cell through specific labeling. Electron tilt tomography gives key insight into the three-dimensional structure of chromatin.

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Finally, high-throughput structural screening and analysis for soft and hybrid nanomaterials is made possible through the automated characterization of nanoparticle megalibraries. This involves a cycle of identification of target particles, data acquisition, data analysis, and library synthesis, all performed through adaptive sampling for the controlled acquisition of images, diffraction, or compositional information. This process is accomplished in real-time through integration in microscopy soft/hardware.

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Representative Publications:

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