Imaging single chiral nanoparticles in turbid media using circular-polarization optical coherence microscopy

Abstract

Optical coherence tomography (OCT) is a widely used structural imaging method. However, it has limited use in molecular imaging due to the lack of an effective contrast mechanism. Gold nanoparticles have been widely used as molecular probes for optical microcopy based on Surface Plasmon Resonance (SPR). Unfortunately, the SPR enhanced backscattering from nanoparticles is still relatively weak compared with the background signal from microscopic structures in biological tissues when imaged with OCT. Consequently, it is extremely challenging to perform OCT imaging of conventional nanoparticles in thick tissues with sensitivity comparable to that of fluorescence imaging. We have discovered and demonstrated a novel approach towards remarkable contrast enhancement, which is achieved by the use of a circular-polarization optical coherence microscopy system and 3-dimensional chiral nanostructures as contrast agents. By detecting the circular intensity differential depolarization (CIDD), we successfully acquired high quality images of single chiral nanoparticles underneath a 1-mm-thick tissue -mimicking phantom.

Polarized light interaction with tissues

“…OCT is an interferometric technique providing high-resolution cross-sectional tissue images by detection of the intensity of a low-coherence light reflected from tissue layers or other inhomogeneities. 2,5,274 To study complex anisotropic tissues possessing microscopic fibrous structures, including collagen fibers and nerve fibers, a conventional OCT was improved by enabling measurements of signal polarization characteristics, which is the PS-OCT. 2,5,9,15,21,22,61,62,66,67,103,129,132,163,202,[256][257][258][259][260]268 In-depth measurements of Stokes parameters allow for determination of tissue birefringence (phase retardation), dichroism (diattenuation), and optic-axis orientation. Advanced PS-OCT systems give the possibility for tissue imaging by measurements of a full Jones matrix 103,202,239,241,242 or Mueller matrix 61,62,67,202,239 for each pixel, as well as representing results of imaging in the form of the Poincaré sphere.…”

“…A novel approach toward significant enhancement of image contrast of OCT microscopy was recently demonstrated. 268 It is based on the combination of a circular-polarization OCT system with 3-D chiral nanostructures as contrast agents. By detecting the circular intensity differential depolarization, high-quality images of single chiral nanoparticles underneath a 1-mmthick tissue-mimicking phantom were successfully acquired.…”

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

“…65,66 These tissues are turbid compared with the 24 hpf embryo, and we could only find one report of OCM imaging on 24 hpf zebrafish 67 in which the signal seemed comparable with our data, relatively weak, presumably due to the transparency of the embryo. There have been efforts to use OCM for imaging with molecular contrast such as detecting backscattered light from gold nanoparticles conjugate to antibodies for immunodetection 68,69 and using spectral domain detection to look for absorption signatures of specific molecules such as hemoglobin. There have been efforts to use OCM for imaging with molecular contrast such as detecting backscattered light from gold nanoparticles conjugate to antibodies for immunodetection 68,69 and using spectral domain detection to look for absorption signatures of specific molecules such as hemoglobin.…”

Polarization sensitive optical coherence microscopy for brain imaging

“…Sensitivity and accuracy of polarization measurements have to be guaranteed in the highly scattering medium. Previous reports on PS-OCM succeeded to visualize muscle structures [12] and chiral nanoparticles in scattering medium [13]. Quantitative analysis of birefringence and the axis of anisotropy have yet to be investigated.…”