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Label-free Detection of Single Molecule Using Microtoroid Optical Resonators


Su, Tsu-Te Judith (2014) Label-free Detection of Single Molecule Using Microtoroid Optical Resonators. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/EHWP-DH17.


Being able to detect a single molecule without the use of labels has been a long standing goal of bioengineers and physicists. This would simplify applications ranging from single molecular binding studies to those involving public health and security, improved drug screening, medical diagnostics, and genome sequencing. One promising technique that has the potential to detect single molecules is the microtoroid optical resonator. The main obstacle to detecting single molecules, however, is decreasing the noise level of the measurements such that a single molecule can be distinguished from background. We have used laser frequency locking in combination with balanced detection and data processing techniques to reduce the noise level of these devices and report the detection of a wide range of nanoscale objects ranging from nanoparticles with radii from 100 to 2.5 nm, to exosomes, ribosomes, and single protein molecules (mouse immunoglobulin G and human interleukin-2). We further extend the exosome results towards creating a non-invasive tumor biopsy assay. Our results, covering several orders of magnitude of particle radius (100 nm to 2 nm), agree with the 'reactive' model prediction for the frequency shift of the resonator upon particle binding. In addition, we demonstrate that molecular weight may be estimated from the frequency shift through a simple formula, thus providing a basis for an ``optical mass spectrometer'' in solution. We anticipate that our results will enable many applications, including more sensitive medical diagnostics and fundamental studies of single receptor-ligand and protein-protein interactions in real time. The thesis summarizes what we have achieved thus far and shows that the goal of detecting a single molecule without the use of labels can now be realized.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:microtoroid, frequency-locking, single-molecule, biosensing, optical resonator, whispering gallery mode
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Rees, Douglas C.
Group:Kavli Nanoscience Institute
Thesis Committee:
  • Rees, Douglas C. (chair)
  • Phillips, Robert B.
  • Vahala, Kerry J.
  • Davis, Mark E.
  • Bjorkman, Pamela J.
Defense Date:30 May 2014
Non-Caltech Author Email:judithsu (AT)
Record Number:CaltechTHESIS:05302014-140200007
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8446
Deposited By: Tsu-Te Su
Deposited On:03 Jun 2014 19:25
Last Modified:04 Oct 2019 00:05

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