The potential advantages of infrared spectroscopic imaging for examination of cells and tissue biopsies for cancer histopathology is high, however there are fundamental limitations of FTIR that must first be addressed. One limitation is that Infrared spectroscopy lacks the sensitivity to detect biomarkers of disease directly. With cancer being one of the leading causes of death and its increasing prevalence, it is important to develop tools that can rapidly screen and enable rapid and simultaneous fingerprinting of biologic content and metabolic state. To address these limitations, probed Infrared spectroscopy is being explored. We report the successful synthesis, characterization, and application of metal carbonyl loaded nanoparticle probes for the detection of breast cancer biomarkers.
Chemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the bottom-up design of its optical train facilitates dual-axis galvo laser scanning of a diffraction-limited focal point over large areas using custom infinity-corrected objectives. The data quality enables applications of modern machine learning and capabilities not previously feasible. Distinct from conventional approaches that focus on morphological investigations or immunostaining, this development makes label-free imaging of minimally processed tissue practical.
Quantum cascade lasers (QCLs) have presented a new chapter for the development of infrared spectroscopy for its high throughput and ability to tune to absorption bands of interest. However, compared to conventional thermal sources, the output stability of QCLs is a limiting factor. Specifically, the noise associated with pulse-to-pulse instability is of specific concern as we design faster and more sensitive spectrometers. Here, we demonstrate a dual-detector approach to reference measurements with the intensity illuminating the sample in real-time per individual laser pulse. We integrate this concept into our custom point-scanning confocal IR microscope. Results show double the SNR and a 10-fold shorter response time with the proposed method versus a single detector approach, all while being lock-in amplifier free. We characterize the controllable parameters and discuss the trade-offs required for a unified system capable of collecting high-quality point spectra as well as whole-slide spectral imaging.
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