improving biomedical applications with a time-resolved ...€¦ · improving biomedical...
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András Kufcsák1, Katjana Ehrlich2,3, Mike Tanner2,3, Robert Henderson1, Nikola Krstajić1,3
1. Institute for Integrated Micro and Nano Systems, School of Engineering, University of Edinburgh, Edinburgh, United Kingdom
2. Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Science, Heriot-Watt University, Edinburgh, UK
3. EPSRC IRC Hub in Optical Molecular Sensing & Imaging, Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Improving biomedical applications with a time-resolved CMOS SPAD sensor
ACKNOWLEDGEMENTS
We would like to thank Engineering and Physical Sciences Research Council(EPSRC, United Kingdom) Interdisciplinary Research Collaboration grantEP/K03197X/1 for funding this work. The work presented here includes the effortsof a large team too numerous to mention individually.
REFERENCES[1] L. Marcu, P. M. W. French, D. S. Elson, “Fluorescence Lifetime Spectroscopy and Imaging: Principles and Applications in Biomedical Diagnostics,” (CRC, 2014)[2] A. Erdogan et al., “A 16.5 Giga Events/s 1024 × 8 SPAD Line Sensor with per-pixel Zoomable 50ps-6.4ns/bin Histogramming ,” VLSI Symposium (2017)
Email: [email protected]
The Proteus project focuses on developing a fibre optic based system for detection of lung diseases of critically ill patients in vivo in situ, through the use of fluorescent smart probes.
TIME RESOLVED FLUORESCENCE SPECTROSCOPY
We built a system providing time-correlated single photon counting (TCSPC) time-resolved fluorescence spectra (TRFS) in 8.3 ms. Such systems can be used to measure changes in spectral fluorescence intensity and lifetime in real time advancing the study of Försterresonance energy transfer or protein folding dynamics [1]. The fluorescence intensity of
chlorophyll A in an intact leaf showed a fast rise in approximately 100 ms, and then a slow relaxation in 2 minutes. We measured not just intensity but changes in lifetime spectrally.
THE RA-I LINE SENSOR
THE PROTEUS PROJECT
A compromise between sampling in time and spectral resolution: decays of a single wavelength (0.4 nm width) for every 50 ms (top), or no spectral information but decays every 8 ms and less noise (bottom).
More efficient photon collection and direct lifetime estimation in centre of mass mode (CMM). Lifetime estimates are shown for two spectral bands over the first 40 ms of the measurement, for every 166.6 us (top) and every 16.6 ms(bottom).
The applied sensor is a single photon avalanche diode (SPAD) based CMOS sensor with 256x2 pixels, with 4-4 SPADs for detection in the red and blue spectra. The sensor can work in photon counting mode, or time-resolved mode for TCSPC and CMM. Efficient time-stamping of photons is provided by 256 parallel time-to-digital converters (TDCs).
Dark count rate (DCR) at different bias voltages for red SPADs (left). DCR is around 1000 counts per second (CPS) at 1.2 V excess bias voltage (20.46 V).
The TDC resolution has an average of 426 ps (right). FWHM of the instrument response function (IRF) is between 0.6-1.5 ns (bottom right). New sensor version is designed with improved properties [2].
Plan to deploy CMOS SPAD line sensors into this system for video rate spectral fluorescence lifetime imaging (FLIM) and detection of various physiological parameters in the lung.
Additional time-gating can be applied in each mode with adjustable location and width of 1.4 ns resolution (left).