Understanding metabolism is indispensable to unraveling the mechanistic basis of many physiological and pathological processes. However, in situ metabolic imaging tools are still lacking. Herein we introduce a framework for mid-infrared (MIR) metabolic imaging by coupling the emerging high-information-throughput MIR microscopy with specifically designed IR-active vibrational probes. Three categories of small vibrational tags including azide bond, 13 C-edited carbonyl bond and deuterium-labeled probes are presented to interrogate various metabolic activities in cells, small organisms and mice. Two MIR imaging platforms are implemented including broadband Fourier transform infrared (FTIR) microscopy and discrete frequency infrared (DFIR) microscopy with a newly incorporated spectral region (2000–2300 cm −1 ). Our technique is uniquely suited for metabolic imaging with high-information-throughput. In particular, we performed single-cell metabolic profiling including heterogeneity characterization, and large-area metabolic imaging at tissue/organ level with rich spectral information.

Chemical imaging in the field of vibrational spectroscopy is developing into a promising tool to complement digital histopathology. Applications include screening of biopsy tissue via automated recognition of tissue/cell type and disease state based on the chemical information from the spectrum. For integration into clinical practice, data acquisition needs to be speeded up to implement a rack based system where specimens are rapidly imaged to compete with current visible scanners where 100's of slides can be scanned overnight. Current Fourier transform infrared (FTIR) imaging with focal plane array (FPA) detectors are currently the state-of-the-art instrumentation for infrared absorption chemical imaging, however recent development in broadly tunable lasers in the mid-IR range is considered the most promising potential candidate for next generation microscopes. In this paper we test a prototype quantum cascade laser (QCL) based spectral imaging microscope with a focus on discrete frequency chemical imaging. We demonstrate how a protein chemical image of the amide I band (1655 cm(-1)) of a 2 × 2.4 cm(2) breast tissue microarray (TMA) containing over 200 cores can be measured in 9 min. This result indicates that applications requiring chemical images from a few key wavelengths would be ideally served by laser-based microscopes.

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We use Monte Carlo simulations to examine self-heating in ultra-short silicon devices when quasiballistic transport conditions dominate. The generated phonon spectrum in strained silicon is found to be different from bulk silicon at low electric fields, but essentially the same under high fields. Joule heat dissipation in ultra-short devices occurs almost entirely in their drain region, since transport across the channel is quasiballistic. The results of this work can be used to gauge the electro-thermal performance of ultra-scaled device geometries.

Accurate early diagnosis is critical to patient survival, management and quality of life. Biofluids are key to early diagnosis due to their ease of collection and intimate involvement in human function. Large-scale mid-IR imaging of dried fluid deposits offers a high-throughput molecular analysis paradigm for the biomedical laboratory. The exciting advent of tuneable quantum cascade lasers allows for the collection of discrete frequency infrared data enabling clinically relevant timescales. By scanning targeted frequencies spectral quality, reproducibility and diagnostic potential can be maintained while significantly reducing acquisition time and processing requirements, sampling 16 serum spots with 0.6, 5.1 and 15% relative standard deviation (RSD) for 199, 14 and 9 discrete frequencies respectively. We use this reproducible methodology to show proof of concept rapid diagnostics; 40 unique dried liquid biopsies from brain, breast, lung and skin cancer patients were classified in 2.4 cumulative seconds against 10 non-cancer controls with accuracies of up to 90%.

Anisotropic molecular alignment occurs ubiquitously and often heterogeneously in three dimensions (3D). However, conventional imaging approaches based on polarization can map only molecular orientation projected onto the 2D polarization plane. Here, an algorithm converts conventional polarization-controlled infrared (IR) hyperspectral data into images of the 3D angles of molecular orientations. The polarization-analysis algorithm processes a pair of orthogonal IR transition-dipole modes concurrently; in contrast, conventional approaches consider individual IR modes separately. The orthogonal-pair polarization IR (OPPIR) method, introduced theoretically but never demonstrated experimentally, was used to map the 3D orientation angles and the order parameter of the local orientational distribution of polymer chains in a poly(ε-caprolactone) film. The OPPIR results show that polymer chains in the semicrystalline film are aligned azimuthally perpendicular to the radial direction of a spherulite and axially tilted from the film normal direction. This newly available information on the local alignments in continuously distributed molecules helps to understand the molecular-level structure of highly anisotropic and spatially heterogeneous materials.