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Wide Field-of-view Microscopes and Endoscopes for Time-lapse Imaging and High-throughput Screening

Citation

Han, Chao (2015) Wide Field-of-view Microscopes and Endoscopes for Time-lapse Imaging and High-throughput Screening. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9SF2T49. http://resolver.caltech.edu/CaltechTHESIS:01302015-101318815

Abstract

Wide field-of-view (FOV) microscopy is of high importance to biological research and clinical diagnosis where a high-throughput screening of samples is needed. This thesis presents the development of several novel wide FOV imaging technologies and demonstrates their capabilities in longitudinal imaging of living organisms, on the scale of viral plaques to live cells and tissues.

The ePetri Dish is a wide FOV on-chip bright-field microscope. Here we applied an ePetri platform for plaque analysis of murine norovirus 1 (MNV-1). The ePetri offers the ability to dynamically track plaques at the individual cell death event level over a wide FOV of 6 mm × 4 mm at 30 min intervals. A density-based clustering algorithm is used to analyze the spatial-temporal distribution of cell death events to identify plaques at their earliest stages. We also demonstrate the capabilities of the ePetri in viral titer count and dynamically monitoring plaque formation, growth, and the influence of antiviral drugs.

We developed another wide FOV imaging technique, the Talbot microscope, for the fluorescence imaging of live cells. The Talbot microscope takes advantage of the Talbot effect and can generate a focal spot array to scan the fluorescence samples directly on-chip. It has a resolution of 1.2 μm and a FOV of ~13 mm2. We further upgraded the Talbot microscope for the long-term time-lapse fluorescence imaging of live cell cultures, and analyzed the cells’ dynamic response to an anticancer drug.

We present two wide FOV endoscopes for tissue imaging, named the AnCam and the PanCam. The AnCam is based on the contact image sensor (CIS) technology, and can scan the whole anal canal within 10 seconds with a resolution of 89 μm, a maximum FOV of 100 mm × 120 mm, and a depth-of-field (DOF) of 0.65 mm. We also demonstrate the performance of the AnCam in whole anal canal imaging in both animal models and real patients. In addition to this, the PanCam is based on a smartphone platform integrated with a panoramic annular lens (PAL), and can capture a FOV of 18 mm × 120 mm in a single shot with a resolution of 100─140 μm. In this work we demonstrate the PanCam’s performance in imaging a stained tissue sample.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:microscopy, endoscopy, time-lapse imaging, high-throughput screening
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Electrical Engineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Yang, Changhuei
Thesis Committee:
  • Yang, Changhuei (chair)
  • Tai, Yu-Chong
  • Choo, Hyuck
  • Ismagilov, Rustem F.
  • Lai, Lily L.
Defense Date:27 January 2015
Record Number:CaltechTHESIS:01302015-101318815
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:01302015-101318815
DOI:10.7907/Z9SF2T49
Related URLs:
URLURL TypeDescription
http://dx.doi.org/0.1039/C3AN02323KDOIArticle adapted for ch. 2
http://dx.doi.org/10.1364/OL.37.005018DOI1st article adapted for ch. 3
http://dx.doi.org/10.1021/ac303356vDOI2nd article adapted for ch. 3
http://dx.doi.org/10.1364/BOE.6.000607DOIArticle adapted for ch. 4
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8763
Collection:CaltechTHESIS
Deposited By: Chao Han
Deposited On:26 Mar 2015 21:43
Last Modified:09 Mar 2016 17:35

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