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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
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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 (CC BY 3.0).

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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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