Contact-free neuroimaging microscope images the structure of materials

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Decades of research have been dedicated to improving contact-free neuroimaging techniques that allow users to image neurons in the brain. Recently, Anatoly Efimov and Evan Perillo (Center for Integrated Nanotechnologies, MPA-CINT) have developed an advanced microscopy system that visualizes materials’ internal and surface structure through nonlinear-optical interaction induced by external lasers. The unique system provides multiple image contrast mechanisms, including sensitivity to vibrational resonances and quasi-static electric fields in the sample. This capability, combined with the expertise of CINT scientists, could offer novel modalities for sample imaging and diagnostics in biology, chemistry, and materials sciences for CINT users.

Efimov and Perillo designed the microscope to send femtosecond laser pulses to a sample in the mid-infrared frequency range, enabling users to probe both transparent and opaque materials. The tool can use both laser scanning and sample scanning to obtain the image. Because the excitation path of the microscope is all-reflective, there are no issues with attenuation, dispersion, and chromatic aberrations typical for standard refractive microscopes. Photon counting detectors are used for extremely low light levels typically encountered in nonlinear imaging modalities. The microscope can accommodate electrical and electrophysiology probes for sample connectivity. Available image contrasts include multiple-photon fluorescence, vibrationally resonant harmonic and sum-frequency generation, and coherent and stimulated Raman processes. The lasers’ wavelengths can be tuned continuously in the 1-5 micrometer range, letting the user target vibrational resonances in molecules and enhance specific nonlinear interactions. Excitation lasers can be temporally synchronized and variably delayed to enable pump-probe interrogation of the sample and allow for time-based image contrast, such as lifetime and delayed response.

The instrument was designed and built with funding from a Laboratory Directed Research and Development (LDRD) project titled “Sensitive Optical Super-Resolution Neuroimaging,” which aims to image the quasi-DC electric field of the neuronal action potential. Such chemical imaging of live neurons yields an intrinsic high-contrast signal that lets users study high-speed firing events in large groups of neurons. In a broader scope, the system could be used to image electric fields in materials and samples relevant to the Laboratory’s Science of Signatures and Materials for the Future science pillars. The work supports the Laboratory’s Energy Security and Global Security mission areas.

Efimov and Perillo are preparing the instrument for use in the lab. They plan to continue testing the microscope’s sensitivity limits to the DC electric field using lithography-manufactured non-biological samples and to explore lateral resolution limits, field of view extents, and imaging speeds. The pair conducts baseline experiments with simple biological samples to reproduce past results from literature.

CINT is a DOE Office of Basic Energy Sciences user facility operated by Sandia National Laboratories and Los Alamos National Laboratory that offers access to a unique combination of expertise and equipment for nanoscale science research center. Technical contact: Anatoly Efimov

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Caption 1

Figure. An image of mammalian compact bone taken by the new neuroimaging microscope. The signal originates from second harmonic generation of collagen within the osteons of the bone. Image size is 0.75 mm by 1 mm.