A Caltech Library Service

Imaging with Second-Harmonic Generation Nanoparticles


Hsieh, Chia-Lung (2011) Imaging with Second-Harmonic Generation Nanoparticles. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/WCS2-FD82.


Second-harmonic generation nanoparticles show promise as imaging probes due to their coherent and stable signal with a broad flexibility in the choice of excitation wavelength. In this thesis, we developed and demonstrated barium titanate nanoparticles as second-harmonic radiation imaging probes. We studied the absolute second-harmonic generation efficiency of the nanoparticles on single-particle level. The polarization dependent second-harmonic signal of single nanoparticles was studied in detail. From the measured polar response, we were able to find the orientation of the nanoparticle. We developed a biochemical interface for using the second-harmonic nanoprobes as biomarkers, including in vitro cellular imaging and in vivo live animal imaging. The nanoparticles were surface functionalized with primary amine groups for stable colloidal dispersion. We achieved specific labeling of the second-harmonic nanoprobes via immunostaining where the antibodies were covalently conjugated onto the nanoparticles. We observed no toxicity of the functionalized nanoparticles to biological cells. The coherent second-harmonic signal radiated from the nanoparticles offers opportunities for new imaging techniques. Using interferometric detection, namely harmonic holography, both amplitude and phase of the second-harmonic field can be captured. Through digital beam propagation, three-dimensional field distribution, reflecting three-dimensional distribution of the nanoparticles, can be reconstructed. We achieved a scan-free three-dimensional imaging of nanoparticles in biological cells with sub-micron spatial resolution by using the harmonic holographic microscope. We further exploited the coherent second-harmonic signal for imaging through scattering media by performing optical phase conjugation of the second-harmonic signal. We demonstrated an all-digital optical phase conjugation of the second-harmonic signal originated from a nanoparticle by combining harmonic holography and dynamic computer generated holography using a spatial light modulator. The phase-conjugated second-harmonic scattered field retraced the scattering trajectory and formed a clean focus on the nanoparticle placed inside a scattering medium. The nanoparticle acted as a beacon of light; it helped us find the tailored wavefront for concentrating light at the nanoparticle inside the scattering medium. We also demonstrated imaging through a thin scattering medium by raster-scanning the phase-conjugated focus in the vicinity of the beacon nanoparticle, in which a clear image of a target placed behind a ground glass diffuser was obtained.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Nonlinear optics; second-harmonic generation; nanoparticles; microscopy; cell imaging; surface functionalization; bioconjugation; three-dimensional imaging; holography; optical phase conjugation; imaging through scattering media
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Electrical Engineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Psaltis, Demetri
Thesis Committee:
  • Psaltis, Demetri (chair)
  • Perona, Pietro
  • Rutledge, David B.
  • Yang, Changhuei
  • Painter, Oskar J.
  • Daraio, Chiara
Defense Date:16 March 2011
Record Number:CaltechTHESIS:04082011-064907780
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6281
Deposited By: Chia-Lung Hsieh
Deposited On:17 May 2011 23:05
Last Modified:09 Oct 2019 17:08

Thesis Files

PDF - Final Version
See Usage Policy.


Repository Staff Only: item control page