Conventional and photonic crystal fiber based two -photon fluorescence biosensing

2004 2004

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Abstract (summary)

Optical fiber probes are widely used in the biomedical field for applications such as optical microscopy, endoscopy, and optical biopsy. Due to their flexibility and small size, optical fibers offer a minimally invasive light interface for imaging and spectroscopic analysis of internal tissue. The development of fluorescent probes for studies of biological processes has increased the importance of developing optical methods for quantitative, in vivo diagnosis.

In this dissertation, we discuss the development of a novel two-photon optical fiber fluorescence (TPOFF) probe for real time, in vivo, quantitative fluorescence measurements in biological samples. In order to understand and optimize two-photon excitation through an optical fiber, pulse propagation effects must be considered. We found a simple phenomenological scaling behavior for the energy dependence of the pulse width for negatively pre-chirped pulses propagating in a normally dispersive fiber. As a consequence of this scaling behavior, the dependence of two-photon fluorescence (TPF) on the pulse intensity becomes sub-quadratic.

The TPOFF probe employs a scheme where the same single-mode fiber (SMF) is used for both the excitation and collection of TPF. Using this fiber probe, we show quantification of tumor fluorescence both ex vivo and in vivo. In ex vivo measurements of tumors developed from cells expressing the green fluorescence protein (GFP), the TPOFF probe detected fluorescence from tumors with as little as 0.3% GFP cells. These results were similar to flow cytometry analysis of isolated cells from the tumors. The TPOFF measurements of GFP tumors in live, anesthetized mice showed a linear relationship between the measured fluorescence and the percentage of GFP expressing cells. The TPOFF probe was also used in targeted binding experiments of Herceptin antibody and folic acid-dendrimer nanoparticle conjugates.

To improve the sensitivity of the TPOFF probe, a double-clad photonic crystal fiber (DCF) was employed. This fiber combines the advantages of both single mode fibers (high excitation efficiencies) and multimode fibers (high collection efficiencies). When we compare the through-fiber TPF signal from a Rhodamine dye gel collected by an SMF and DCF, we observe over an order of magnitude signal enhancement.

Indexing (details)

0752: Optics
Identifier / keyword
Pure sciences; Biosensing; Fiber-optic probes; Multiphoton fluorescence; Photonic crystal; Two-photon fluorescence
Conventional and photonic crystal fiber based two -photon fluorescence biosensing
Myaing, Mon Thiri
Number of pages
Publication year
Degree date
School code
DAI-B 65/10, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
9780496096152, 049609615X
Norris, Theodore B.
University of Michigan
University location
United States -- Michigan
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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