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.

Figure 1. Schematic of CP-OCM Setup.

Red lines represent free space optical paths and green lines represent fiber guided optical paths. SLD: Super-luminescence laser diode; FC: fiber coupler/collimator. LP: linear polarizer; BS: beam splitter; QWP: quarter-wave plate; M: mirror; SM: scanning mirror; SL: scanning lens; TL: tube lens; OBJ: objective; HWP: half-wave plate.

Figure 2. PCN array.

(a) Geometry of a Plasmonic chiral nanoparticle array (inset: 3D sketch of an individual L-PCN) (b) SEM image of a single L-PCN (inset: SEM image of the bottom nanorod before the dielectric layer was deposited). Scale bars: 100 nm. (c) FDTD simulated backscattering (depolarization component) intensities for LCP (blue) and RCP (red) incident beams, respectively, from the L-PCN.

Figure 3. Tissue phantom.

(a) Schematic and (b) photo of the tissue phantom.

Figure 4. Enface images of the L-PCN array.

(a) Conventional OCT image. (b) CIDS image. (c) CIDD image. Scale bars: 10 μm. (d) Normalized signal intensities along a line across several PCN's.

Figure 5. L-PCN, R-PCN, and NR comparison.

Normalized Line profile of CDR for LCP illumination (Purple line), RCP illumination (Green line) and CIDD (Red line) for (a) L-PCN, (b) R-PCN and (c) NRs, respectively. (d) Weber contrast for L-PCN, R-PCN and NR.

Figure 6. Imaging PCN's through tissue phantom.

(a) 2D en-face CIDD image of PCN's; (b) Weber contrast comparison between CIDD, CDR_L, and CDR_R.