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Register a new userHigh-Speed Coherent Raman Fingerprint Imaging of Biological Tissues
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Charles H. Camp Jr.
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We have developed a coherent Raman imaging platform using broadband coherent anti-Stokes Raman scattering (BCARS) that provides an unprecedented combination of speed, sensitivity, and spectral breadth. The system utilizes a unique configuration of laser sources that probes the Raman spectrum over 3,000 cm$^{-1}$ and generates an especially strong response in the typically weak Raman fingerprint region through heterodyne amplification of the anti-Stokes photons with a large nonresonant background (NRB) while maintaining high spectral resolution of $<$ 13 cm$^{-1}$. For histology and pathology, this system shows promise in highlighting major tissue components in a non-destructive, label-free manner. We demonstrate high-speed chemical imaging in two- and three-dimensional views of healthy murine liver and pancreas tissues and interfaces between xenograft brain tumors and the surrounding healthy brain matter.
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Laser speckle can provide a powerful tool that may be used for metrology, for example measurements of the incident laser wavelength with a resolution beyond that which may be achieved in a commercial device. However, to realise highest resolution requires advanced multi-variate analysis techniques, which limit the acquisition rate of such a wavemeter. Here we show an arithmetically simple method to measure wavelength changes with dynamic speckle, based on a Poincar`e descriptor of the speckle pattern. We demonstrate the measurement of wavelength changes at femtometer-level with a measurement time reduced by two orders of magnitude compared to the previous state-of-the-art, which offers promise for applications such as speckle-based laser wavelength stabilisation.
We have developed a system combining a back-illuminated Complementary-Metal-Oxide-Semiconductor (CMOS) imaging sensor and Xilinx Zynq System-on-Chip (SoC) device for a soft X-ray (0.5-10 keV) imaging spectroscopy observation of the Sun to investigate the dynamics of the solar corona. Because typical timescales of energy release phenomena in the corona span a few minutes at most, we aim to obtain the corresponding energy spectra and derive the physical parameters, i.e., temperature and emission measure, every few tens of seconds or less for future solar X-ray observations. An X-ray photon-counting technique, with a frame rate of a few hundred frames per second or more, can achieve such results. We used the Zynq SoC device to achieve the requirements. Zynq contains an ARM processor core, which is also known as the Processing System (PS) part, and a Programmable Logic (PL) part in a single chip. We use the PL and PS to control the sensor and seamless recording of data to a storage system, respectively. We aim to use the system for the third flight of the Focusing Optics Solar X-ray Imager (FOXSI-3) sounding rocket experiment for the first photon-counting X-ray imaging and spectroscopy of the Sun.
High resolution optical microscopy is essential in neuroscience but suffers from scattering in biological tissues. It therefore grants access to superficial layers only. Recently developed techniques use scattered photons for imaging by exploiting angular correlations in transmitted light and could potentially increase imaging depths. But those correlations (`angular memory effect) are of very short range and, in theory, only present behind and not inside scattering media. From measurements on neural tissues and complementary simulations, we find that strong forward scattering in biological tissues can enhance the memory effect range (and thus the possible field-of-view) by more than an order of magnitude compared to isotropic scattering for $sim$1,mm thick tissue layers.
Recently optical whispering-gallery-mode resonators (WGMRs) have emerged as promising platforms to achieve label-free detection of nanoscale objects and to reach single molecule sensitivity. The ultimate detection performance of WGMRs are limited by energy dissipation in the material they are fabricated from. Up to date, to improve detection limit, either rare-earth ions are doped into the WGMR to compensate losses or plasmonic resonances are exploited for their superior field confinement. Here, we demonstrate, for the first time, enhanced detection of single-nanoparticle induced mode-splitting in a silica WGMR via Raman-gain assisted loss-compensation and WGM Raman lasing. Notably, we detected and counted individual dielectric nanoparticles down to a record low radius of 10 nm by monitoring a beatnote signal generated when split Raman lasing lines are heterodyne-mixed at a photodetector. This dopant-free scheme retains the inherited biocompatibility of silica, and could find widespread use for sensing in biological media. It also opens the possibility of using intrinsic Raman or parametric gain in other systems, where dissipation hinders the progress of the field and limits applications.
High-resolution optical microscopy suffers from a low contrast in scattering media where a multiply scattered wave obscures a ballistic wave used for image formation. To extend the imaging depth, various gating operations - confocal, coherence, and polarization gating - have been devised to filter out the multiply scattered wave. However, these gating methods are imperfect as they all act on the detection plane located outside a scattering medium. Here, we present a new gating scheme, called space gating, that rejects the multiply scattered wave directly at the object plane inside a scattering medium. Specifically, we introduced a 30 $mu$m-wide acoustic focus to the object plane and reconstructed a coherent image only with the ballistic wave modulated by acousto-optic interaction. This method allows us to reject the multiply scattered wave that the existing gating methods cannot filter out and improves the ratio of the ballistic wave to the multiply scattered wave by more than 100 times for a scattering medium more than 20 times thicker than its scattering mean free path. Using the coherent imaging technique based on space gating, we demonstrate the unprecedented imaging capability - phase imaging of optically transparent biological cells fully embedded within a scattering medium - with a spatial resolution of 1.5 $mu$m.
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