Abstract

Single-photon avalanche photodiode (SPAD) image sensors offer time-gated photon counting, at high binary frame rates of >100 kFPS and with no readout noise. This makes them well-suited to a range of scientific applications, including microscopy, sensing and quantum optics. However, due to the complex electronics required, the fill factor tends to be significantly lower (< 10%) than that of EMCCD and sCMOS cameras (>90%), whilst the pixel size is typically larger, impacting the sensitivity and practicalities of the SPAD devices. This paper presents the first characterisation of a cylindrical-shaped microlens array applied to a small, 8 micron, pixel SPAD imager. The enhanced fill factor, ≈50% for collimated light, is the highest reported value amongst SPAD sensors with comparable resolution and pixel pitch. We demonstrate the impact of the increased sensitivity in single-molecule localisation microscopy, obtaining a resolution of below 40nm, the best reported figure for a SPAD sensor.

© 2018 Optical Society of America

Full Article  |  PDF Article
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2017 (1)

B. Eggart, M. Scheible, and C. Forthmann, “Beyond the Diffraction Limit,” Optik Photonik 12(2), 26–29 (2017).
[Crossref]

2016 (6)

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

B. Aull, “Geiger-Mode Avalanche Photodiode Arrays Integrated to All-Digital CMOS Circuits,” Sensors (Basel) 16(4), 495 (2016).
[Crossref] [PubMed]

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

2015 (2)

2014 (3)

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

J. M. Pavia, M. Wolf, and E. Charbon, “Measurement and modeling of microlenses fabricated on single-photon avalanche diode arrays for fill factor recovery,” Opt. Express 22(4), 4202–4213 (2014).
[Crossref] [PubMed]

2013 (1)

E. R. Fossum, “Modeling the performance of single-bit and multi-bit quanta image sensors,” IEEE J. Electron. Dev. Soc. 1(9), 166–174 (2013).
[Crossref]

2012 (2)

S. Saurabh, S. Maji, and M. P. Bruchez, “Evaluation of sCMOS cameras for detection and localization of single Cy5 molecules,” Opt. Express 20(7), 7338–7349 (2012).
[Crossref] [PubMed]

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

2011 (1)

2006 (3)

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

S. T. Hess, T. P. Girirajan, and M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91(11), 4258–4272 (2006).
[Crossref] [PubMed]

Abbas, T. A.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

Al Abbas, T.

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Almer, O.

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

Ameer-Beg, S. M.

Antolovic, I. M.

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

Aull, B.

B. Aull, “Geiger-Mode Avalanche Photodiode Arrays Integrated to All-Digital CMOS Circuits,” Sensors (Basel) 16(4), 495 (2016).
[Crossref] [PubMed]

Barber, P.

Betzig, E.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Bonifacino, J. S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Borkovec, J.

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Bruchez, M. P.

Bruschini, C.

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

A. C. Ulku, C. Bruschini, X. Michalet, S. Weiss, and E. Charbon, “A 512×512 SPAD Image Sensor with Built-In Gating for Phasor Based Real-Time siFLIM,” in Proceedings of IISW (IISS, 2017), pp. 234–237.

Buller, G. S.

Burri, S.

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

Chang, C.-C.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Charbon, E.

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

J. M. Pavia, M. Wolf, and E. Charbon, “Measurement and modeling of microlenses fabricated on single-photon avalanche diode arrays for fill factor recovery,” Opt. Express 22(4), 4202–4213 (2014).
[Crossref] [PubMed]

A. C. Ulku, C. Bruschini, X. Michalet, S. Weiss, and E. Charbon, “A 512×512 SPAD Image Sensor with Built-In Gating for Phasor Based Real-Time siFLIM,” in Proceedings of IISW (IISS, 2017), pp. 234–237.

Cheng, S.-C.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Coelho, S.

Cox, R.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Dalgarno, P. A.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

Dammeyer, T.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Davidson, M. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Davies, A.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

De Munck, K.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Della Rocca, F. M.

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Devauges, V.

Donati, S.

Duncan, R. R.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

Dutton, N.

Dutton, N. A. W.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

Eggart, B.

B. Eggart, M. Scheible, and C. Forthmann, “Beyond the Diffraction Limit,” Optik Photonik 12(2), 26–29 (2017).
[Crossref]

Forthmann, C.

B. Eggart, M. Scheible, and C. Forthmann, “Beyond the Diffraction Limit,” Optik Photonik 12(2), 26–29 (2017).
[Crossref]

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Fossum, E. R.

E. R. Fossum, “Modeling the performance of single-bit and multi-bit quanta image sensors,” IEEE J. Electron. Dev. Soc. 1(9), 166–174 (2013).
[Crossref]

Gasparini, L.

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

Gietl, A.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Girirajan, T. P.

S. T. Hess, T. P. Girirajan, and M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91(11), 4258–4272 (2006).
[Crossref] [PubMed]

Golanski, D.

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Grant, L. A.

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

Gyongy, I.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

Hagen, G. M.

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Haspeslagh, L.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Henderson, R. K.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

S. P. Poland, N. Krstajić, J. Monypenny, S. Coelho, D. Tyndall, R. J. Walker, V. Devauges, J. Richardson, N. Dutton, P. Barber, D. D. U. Li, K. Suhling, T. Ng, R. K. Henderson, and S. M. Ameer-Beg, “A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging,” Biomed. Opt. Express 6(2), 277–296 (2015).
[Crossref] [PubMed]

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Henrion, Y.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

Herzig, H. P.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Hess, H. F.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Hess, S. T.

S. T. Hess, T. P. Girirajan, and M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91(11), 4258–4272 (2006).
[Crossref] [PubMed]

Hoebe, R.

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

Holmes, A. J.

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

Holzmeister, P.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Hsieh, J. C.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Huang, C.-H.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Intermite, G.

Kagami, M.

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

Krížek, P.

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Krstajic, N.

Li, D. D. U.

Lin, K.-F.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Lindwasser, O. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Lippincott-Schwartz, J.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Lussana, R.

Maji, S.

Martini, G.

Mason, M. D.

S. T. Hess, T. P. Girirajan, and M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91(11), 4258–4272 (2006).
[Crossref] [PubMed]

Massari, N.

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

Matsubara, H.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

McCarthy, A.

Michalet, X.

A. C. Ulku, C. Bruschini, X. Michalet, S. Weiss, and E. Charbon, “A 512×512 SPAD Image Sensor with Built-In Gating for Phasor Based Real-Time siFLIM,” in Proceedings of IISW (IISS, 2017), pp. 234–237.

Miyashita, T.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Monypenny, J.

Naessens, K.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Ng, T.

Niclass, C.

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

Ogawa, M.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

Ohta, M.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

Olenych, S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Ottevaere, H.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Ovesný, M.

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Parmesan, L.

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

Patterson, G. H.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Pavia, J. M.

Pellegrini, S.

T. A. Abbas, N. A. W. Dutton, O. Almer, S. Pellegrini, Y. Henrion, and R. K. Henderson, “Backside illuminated SPAD image sensor with 7.83μm pitch in 3D-stacked CMOS technology,” In Proceedings of IEDM (IEEE, 2016).
[Crossref]

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Perenzoni, D.

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

Perenzoni, M.

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

Poland, S. P.

Puers, R.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Rae, B.

T. Al Abbas, N. A. W. Dutton, O. Almer, F. M. Della Rocca, S. Pellegrini, B. Rae, D. Golanski, and R. K. Henderson, “8.25µm Pitch 66% Fill Factor Global Shared Well SPAD Image Sensor in 40nm CMOS FSI Technology,” in Proceedings of IISW (IISS, 2017), pp. 97–100.

Randone, E.

Ren, X.

Resetar, T.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Richardson, J.

Rickman, C.

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

Rosmeulen, M.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Saurabh, S.

Scheible, M.

B. Eggart, M. Scheible, and C. Forthmann, “Beyond the Diffraction Limit,” Optik Photonik 12(2), 26–29 (2017).
[Crossref]

Schmied, J. J.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Soga, M.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

Sougrat, R.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Steinhauer, C.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Stoppa, D.

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

Suhling, K.

Süss, A.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Švindrych, Z.

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Taghizadeh, M.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Taghizadeh, M. R.

Takai, I.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

Thienpont, H.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Tinnefeld, P.

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Tosi, A.

Tseng, L.-Y.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Tyndall, D.

Ulku, A. C.

A. C. Ulku, C. Bruschini, X. Michalet, S. Weiss, and E. Charbon, “A 512×512 SPAD Image Sensor with Built-In Gating for Phasor Based Real-Time siFLIM,” in Proceedings of IISW (IISS, 2017), pp. 234–237.

Van Hoof, C.

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

Villa, F.

Völkel, R.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Waddie, A. J.

Walker, R. J.

Warburton, R. E.

Weiss, S.

A. C. Ulku, C. Bruschini, X. Michalet, S. Weiss, and E. Charbon, “A 512×512 SPAD Image Sensor with Built-In Gating for Phasor Based Real-Time siFLIM,” in Proceedings of IISW (IISS, 2017), pp. 234–237.

Wolf, M.

Woo, H. J.

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Wu, K.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Yamashita, T.

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

Yang, H.-M.

S.-C. Cheng, C.-C. Chang, K.-F. Lin, C.-H. Huang, L.-Y. Tseng, H.-M. Yang, K. Wu, and J. C. Hsieh, “Lens Solution for Intensity Enhancement in Large-Pixel Single-Photon Avalanche Diode,” in Proceedings of IISW (IISS, 2017), pp. 284–287.

Zappa, F.

Bioinformatics (1)

M. Ovesný, P. Křížek, J. Borkovec, Z. Švindrych, and G. M. Hagen, “ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging,” Bioinformatics 30(16), 2389–2390 (2014).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Biophys. J. (1)

S. T. Hess, T. P. Girirajan, and M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91(11), 4258–4272 (2006).
[Crossref] [PubMed]

IEEE J. Electron. Dev. Soc. (1)

E. R. Fossum, “Modeling the performance of single-bit and multi-bit quanta image sensors,” IEEE J. Electron. Dev. Soc. 1(9), 166–174 (2013).
[Crossref]

IEEE J. Solid-State Circuits (2)

C. Niclass, M. Soga, H. Matsubara, M. Ogawa, and M. Kagami, “A 0.18-µm CMOS SoC for a 100-m-Range 10-Frame/s 200 × 96-Pixel Time-of-Flight Depth Sensor,” IEEE J. Solid-State Circuits 49(1), 315–330 (2014).
[Crossref]

M. Perenzoni, N. Massari, D. Perenzoni, L. Gasparini, and D. Stoppa, “A 160×120 Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging,” IEEE J. Solid-State Circuits 51(1), 155–167 (2016).
[Crossref]

IEEE Trans. Electron Dev. (1)

I. M. Antolovic, S. Burri, C. Bruschini, R. Hoebe, and E. Charbon, “Nonuniformity Analysis of a 65-kpixel CMOS SPAD Imager,” IEEE Trans. Electron Dev. 63(1), 57–64 (2016).
[Crossref]

J. Lightwave Technol. (1)

J. Opt. A, Pure Appl. Opt. (1)

H. Ottevaere, R. Cox, H. P. Herzig, T. Miyashita, K. Naessens, M. Taghizadeh, R. Völkel, H. J. Woo, and H. Thienpont, “Comparing glass and plastic refractive microlenses fabricated with different technologies,” J. Opt. A, Pure Appl. Opt. 8(7), S407–S429 (2006).
[Crossref]

Nat. Methods (1)

J. J. Schmied, A. Gietl, P. Holzmeister, C. Forthmann, C. Steinhauer, T. Dammeyer, and P. Tinnefeld, “Fluorescence and Super-resolution Standards based on DNA Origami,” Nat. Methods 9(12), 1133–1134 (2012).
[Crossref] [PubMed]

Opt. Express (3)

Optik Photonik (1)

B. Eggart, M. Scheible, and C. Forthmann, “Beyond the Diffraction Limit,” Optik Photonik 12(2), 26–29 (2017).
[Crossref]

Sci. Rep. (1)

I. Gyongy, A. Davies, N. A. W. Dutton, R. R. Duncan, C. Rickman, R. K. Henderson, and P. A. Dalgarno, “Smart-aggregation imaging for single molecule localisation with SPAD cameras,” Sci. Rep. 6(1), 37349 (2016).
[Crossref] [PubMed]

Science (1)

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Sensors (Basel) (3)

T. Resetar, K. De Munck, L. Haspeslagh, M. Rosmeulen, A. Süss, R. Puers, and C. Van Hoof, “Development of Gated Pinned Avalanche Photodiode Pixels for High-Speed Low-Light Imaging,” Sensors (Basel) 16(8), 1294 (2016).
[Crossref] [PubMed]

I. Takai, H. Matsubara, M. Soga, M. Ohta, M. Ogawa, and T. Yamashita, “Single-photon avalanche diode with enhanced NIR-sensitivity for automotive LIDAR systems,” Sensors (Basel) 16(4), 459 (2016).
[Crossref] [PubMed]

B. Aull, “Geiger-Mode Avalanche Photodiode Arrays Integrated to All-Digital CMOS Circuits,” Sensors (Basel) 16(4), 495 (2016).
[Crossref] [PubMed]

Other (12)

N. A. W. Dutton, L. Parmesan, A. J. Holmes, L. A. Grant, and R. K. Henderson, “320×240 oversampled digital single photon counting image sensor,” in Proceedings of VLSI Circuits Symposium (IEEE, 2014), pp. 1–2.

I. Gyongy, N. Calder, A. Davies, N.A.W. Dutton, P. Dalgarno, R. Duncan, C. Rickman, and R. K. Henderson, “256×256, 100kfps, 61% Fill-factor SPAD Image Sensor for Time-Resolved Microscopy Applications,” IEEE Trans. Electron. Dev. (in press).
[Crossref]

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Figures (7)

Fig. 1
Fig. 1 a) Micrograph of SPAD sensor, detailed in [6], viewed from top, b) close up on pixel array with and without microlens, c) cross-sectional diagram of microlens array, d) electron microscope image of microlens array showing cylindrical structure
Fig. 2
Fig. 2 a) Focusing of collimated light by a perfectly aligned microlens array (illustration only), b) A mismatch in the lateral position of the microlens with respect to the SPAD array reduces the amount of light that is focused onto photo-sensitive areas c) By tilting the sensor relative to the light source, the focused light can be directed back onto the photo-sensitive areas, limiting the effect of the mismatch, d) Measured concentration factor versus tilt angle
Fig. 3
Fig. 3 The effect of microlensing on SPAD response, in terms of a) average output versus exposure for 650 nm light (based on 1000 bit-planes at each exposure level), b) average output versus exposure for 450 nm light, c) concentration factor versus microlens height for different microlens replications, compared with simulation results.
Fig. 4
Fig. 4 Uniformity in response across SPAD array after DCR correction, obtained under diffused 650 nm light, as indicated by a) aggregated image frame without microlens (sum of 2 × 106 bit-planes with a mean count rate of ≈0.07 photons/pixel/bit-plane), b) histogram of pixel values (photon counts) without microlens, c) aggregated image frame with microlens (sum of 2 × 106 bit-plane with a mean count rate of ≈0.12 photons/pixel/bit-plane) d) histogram of pixel values with microlens.
Fig. 5
Fig. 5 Three-channel fluorescence microscopy image of BPAE cell, obtained using a) SPAD without microlens (sum of 330 bit-planes per channel, equating to 33 ms exposure/channel), b) SPAD with microlens (same summation as A) c) sCMOS (33ms exposure per channel), d) profile plots across F-actin filaments in the green channel and highlighted by the yellow lines in A-C, obtained with the three cameras. The microlensed SPAD is seen to reproduce several peaks in the profile that are buried in noise in the non-microlensed case.
Fig. 6
Fig. 6 Comparison of the measured photon transfer curve for the SPAD camera (with/without microlens) with those of EMCCD, ICCD and sCMOS (based on noise models). The assumed camera parameters {EQE, rms readout noise, gain, excess noise factor, dark count rate} are as follows: EMCCD = {90%, 20 e-, 200, 1.41, 0.001 cps}, ICCD = {50%, 4.8 e-, 200, 1.6, 0.1 cps}, sCMOS = {80%, 1.4 e-, 1, 1, 0.05 cps}.
Fig. 7
Fig. 7 a) Representative super-resolution images of individual GATTA-PAINT 40G HiRes nanorulers acquired using EMCCD (left), SPAD without microlens (centre) or SPAD with microlens (right). Scale bar = 50 nm. Box plots comparing 40G HiRes nanorulers acquired using EMCCD (black), SPAD without microlens (blue) or SPAD with microlens (red): b) Number of localisations per nanoruler, c) number of nanorulers detected, d) number of photons detected for each localization, e) uncertainty in localization, f) distance between fluorescent points on nanorulers and g) fwhm of the fluorescent points on nanorulers. Grey box represents the manufactured distance between fluorescent point (40 ± 5 nm), if the FWHM is above this box then individual fluorescent points would not be resolvable.A minimum of 25 nanorulers were analysed per experiment, the results are from at least 4 experiments. The horizontal line within the box indicates the median, boundaries of the box indicate the 25th- and 75th-percentile and the whiskers indicate the 5th- and 95th-percentile. The “□” marked in the box indicates the mean and “-” indicates the maximum and minimum values. Statistical significance was tested with Kruskal-Wallis one-way analysis of variance followed by Dunn’s post hoc test for multiple comparisons or for C) ordinary one-way analysis of variance followed by Tukey’s post hoc test for multiple comparisons. **P<0.001, ***P<0.0005, ****P<0.0001.

Tables (2)

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Table 1 ThunderSTORM settings for single molecule localisation

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Table 2 Comparison of high fill factor SPAD imagers

Equations (1)

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SNR= mean(coun t lightON )mean(coun t lightOFF ) var(coun t lightON ) .

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