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Sensors 2012, 12(5), 5650-5669; doi:10.3390/s120505650
Review

Time-Domain Fluorescence Lifetime Imaging Techniques Suitable for Solid-State Imaging Sensor Arrays

1,* , 2
, 3
, 4
, 4
, 5
, 2
, 4
 and 4
1 Department of Engineering and Design, School of Engineering and Informatics, University of Sussex, Brighton BN1 9QT, UK 2 Division of Cancer Research & Randall Division of Cell and Molecular Biophysics, Richard Dimbleby Department of Cancer Research, Guy’s Campus, London SE1 1UL, UK 3 SUPA, COSMIC, School of Physics and Astronomy, The University of Edinburgh, The King’s Buildings, Mayfield Road, Edinburgh EH9 3JZ, Scotland, UK 4 Institute for Integrated Micro and Nano Systems, The School of Engineering, The University of Edinburgh, The King’s Buildings, Mayfield Road, Edinburgh EH9 3JL, Scotland, UK 5 Queensland Brain Institute, University of Queensland, St. Lucia, QLD 4072, Australia
* Author to whom correspondence should be addressed.
Received: 24 March 2012 / Revised: 18 April 2012 / Accepted: 26 April 2012 / Published: 2 May 2012
(This article belongs to the Special Issue Sensing at the Nano-Scale: Chemical and Bio-Sensing)
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Abstract

We have successfully demonstrated video-rate CMOS single-photon avalanche diode (SPAD)-based cameras for fluorescence lifetime imaging microscopy (FLIM) by applying innovative FLIM algorithms. We also review and compare several time-domain techniques and solid-state FLIM systems, and adapt the proposed algorithms for massive CMOS SPAD-based arrays and hardware implementations. The theoretical error equations are derived and their performances are demonstrated on the data obtained from 0.13 μm CMOS SPAD arrays and the multiple-decay data obtained from scanning PMT systems. In vivo two photon fluorescence lifetime imaging data of FITC-albumin labeled vasculature of a P22 rat carcinosarcoma (BD9 rat window chamber) are used to test how different algorithms perform on bi-decay data. The proposed techniques are capable of producing lifetime images with enough contrast.
Keywords: fluorescence lifetime imaging microscopy; FLIM; CMOS; single-photon avalanche diode; single-decay; multi-decay; time-domain FLIM; lifetime based sensing fluorescence lifetime imaging microscopy; FLIM; CMOS; single-photon avalanche diode; single-decay; multi-decay; time-domain FLIM; lifetime based sensing
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Li, D.-U.; Ameer-Beg, S.; Arlt, J.; Tyndall, D.; Walker, R.; Matthews, D.R.; Visitkul, V.; Richardson, J.; Henderson, R.K. Time-Domain Fluorescence Lifetime Imaging Techniques Suitable for Solid-State Imaging Sensor Arrays. Sensors 2012, 12, 5650-5669.

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